The presence of HIV-1 DNA sequences in DNA from peripheral blood mononuclear cells (PBMCs) was investigated in a two-stage polymerase chain reaction ('double' PCR) using four sets of nested primers. The PBMCs tested were obtained from 46 children born to HIV-seropositive mothers, seven 'control' children born to HIV-seronegative mothers and seropositive fathers, and 45 healthy adult blood donors who were HIV seronegative. Nine of the children had symptomatic HIV infection and other laboratory features characteristic of HIV infection: all nine were PCR-positive with each set of primers in each of their 22 blood samples tested. The remaining 44 children had no clinical or laboratory evidence of HIV infection, and each of their 50 samples was PCR-negative with each set of primers, as were all blood donor samples. PCR-positive samples were tested in more detail using two of the sets of primers, which spanned hypervariable regions in the env gene. Polyacrylamide gel electrophoresis of DNA amplified from these regions yielded patterns of amplified DNA length variation which were characteristic for each child, and which changed little with time (in serial samples obtained over periods of 3–7 months). This excluded contamination as a cause of PCR positivity. This is the first report of the use of a double PCR for the diagnosis of HIV infection. The results demonstrate the specificity of this PCR method in diagnosis, with failure to reveal in this cohort any cases of vertically transmitted HIV-1 infection in addition to those already confirmed by conventional laboratory techniques.


We compare the absolute positions of methanol maser sites with those of typical tracers of young massive stellar objects, such as ultra-compact Hii regions, outflows and hot molecular cores. We have selected thirteen star-forming regions for which we have produced VLBI maps of 6.7 and 12.2 GHz methanol masers, and for which complementary high resolution images are available in the literature. These sources are namely: IRAS 20126+4104, NGC 7538, S 252, G 31.28+0.06, W 75N, S 255, S 269, Mon R2, G 9.62+0.20, Cep A, W 51, G 59.78+0.06 and G 29.95-0.02. Eight of the methanol maser sources coincide in position within 2000 AU with outflows and/or hot molecular cores, i.e. phenomena occuring at the earliest stage of massive star formation. Only two sources coincide in position with hyper-compact Hii regions. We conclude that 6.7 and 12.2 GHz methanol masers are likely to be one of the first signposts of massive star formation and perhaps the first signpost of a massive protostar.


In the sport domain, game-strategy efficacy is the belief that coaches can lead teams or athletes to a successful performance in competition. Developmentally-focused youth sport coaches, however, may define success differently to those working in other contexts. Researchers suggest that if youth sport coaches define successful performances in terms of winning only, the psychosocial development of young athletes could be hindered. Therefore, scholars and practitioners need to understand how developmentally-focused youth sport coaches cultivate their game-strategy efficacy beliefs to improve coach education and personal development programs. The purpose of this study was to explore UK developmentally-focused youth sport coaches' game-strategy efficacy beliefs and to examine the sources and outcomes of perceived efficacy. A secondary focus was the generation of practically relevant and useable findings that developmentally-focused youth sport coaches could utilise. Data was obtained by interviewing 10 male youth sport coaches and analysed using an interpretive description methodology. Results are presented as a representative bricolage from the perspective of two fictional coaches who either have high or low game-strategy efficacy. These results highlighted sources of game-strategy efficacy within the UK developmentally-focused youth sport context, including acknowledgement, playing experience, relationships with athletes and peers, results, self-image, and success. Additionally, two outcomes of game-strategy efficacy included releasing control and self-evaluation. The findings offer coaches a chance to explore their own game-strategy efficacy beliefs against others in similar positions while opening a dialogue between research findings and those in the field.


Delay-tolerant networks (DTNs) have the potential to interconnect devices in regions that current networking technology cannot reach. To realize the DTN vision, routes must be found over multiple unreliable, intermittently-connected hops. In this paper we present a practical routing protocol that uses only observed information about the network. We designed a metric that estimates the average waiting time for each potential next hop. This learned topology information is distributed using a link-state routing protocol, where the link-state packets are "flooded" using epidemic routing. The routing is recomputed each time connections are established, allowing messages to take advantage of unpredictable contacts. A message is forwarded if the topology suggests that the connected node is "closer" to the destination than the current node. We demonstrate through simulation that our protocol provides performance similar to that of schemes that have global knowledge of the network topology, yet without requiring that knowledge. Further, it requires significantly less resources than the alternative, epidemic routing, suggesting that our approach scales better with the number of messages in the network. This performance is achieved with minimal protocol overhead for networks of approximately 100 nodes.


One explanation for the absence of higher mass red supergiants (16.5 M☉ ≲ M ≲ 25 M☉) as the progenitors of Type IIP supernovae (SNe) is that they die in failed SNe creating black holes. Simulations show that such failed SNe still eject their hydrogen envelopes in a weak transient, leaving a black hole with the mass of the star's helium core (5–8 M☉). Here we show that this naturally explains the typical masses of observed black holes and the gap between neutron star and black hole masses without any fine-tuning of stellar mass loss, binary mass transfer, or the SN mechanism, beyond having it fail in a mass range where many progenitor models have density structures that make the explosions more likely to fail. There is no difficulty including this ∼20% population of failed SNe in any accounting of SN types over the progenitor mass function. And, other than patience, there is no observational barrier to either detecting these black hole formation events or limiting their rates to be well below this prediction.


In this article, we outline a conceptual framework for dealing with implementation problems of business ethics. To the extent that implementation consumes scarce resources, it is from the economic point of view a problem of production. As such, it can be analyzed with the customary tools of economic analysis. In our comparative approach, we contrast the production of business ethics with the spontaneous emergence of business ethics in the market process. We also compare it to forced ethics (the imposition of ethical codes of conduct by private parties) and to fiat ethics (imposition by legislation and other authoritarian acts). Guido Hulsmann, "The Production of Business Ethics," Journal of Markets & Morality 11, no. 2 (Fall 2008): 275-299


Until recently it has been too easy to overlook Small and Medium-size Enterprises in the analysis of environmental impact of particularly the manufacturing sector (ibid 2003). SMEs continue to grow, so do their environmental impacts. SMEs are faced by such challenges as difficulty in raising capital, limited managerial skills, regulatory constraints, limited extension services and difficulty in getting access to technology The study found out that SMEs where copies of environment related laws existed and staffs were aware of the laws, respondents indicated involvement in environmental management practices.  It is thus concluded that legal provisions influenced adoption of good environmental management practices by Small and Medium-size Manufacturing enterprises. Key words: Legal Requirements. Environmental Concern. Sustainability Practices


The northeastern San Juan Mountains, the least studied portion of this well-known segment of the Southern Rocky Mountains Volcanic Field are the site of several newly identified and reinterpreted ignimbrite calderas. These calderas document some unique eruptive features not described before from large volcanic systems elsewhere, as based on recent mapping, petrologic data, and a large array of newly determined high-precision, laser-fusion 40Ar/39Ar ages (140 samples). Tightly grouped sanidine ages document exceptionally brief durations of 50–100 k.y. or less for individual Oligocene caldera cycles; biotite ages are more variable and commonly as much as several hundred k.y. older than sanidine from the same volcanic unit. A previously unknown ignimbrite caldera at North Pass, along the Continental Divide in the Cochetopa Hills, was the source of the newly distinguished 32.25-Ma Saguache Creek Tuff (~400–500 km3). This regionally distinctive crystal-poor alkalic rhyolite helps fill an apparent gap in the southwestward migration from older explosive activity, from calderas along the N-S Sawatch locus in central Colorado (youngest, Bonanza Tuff at 33.2 Ma), to the culmination of Tertiary volcanism in the San Juan region, where large-volume ignimbrite eruptions started at ca. 29.5 Ma and peaked with the enormous Fish Canyon Tuff (5000 km3) at 28.0 Ma. The entire North Pass cycle, including caldera-forming Saguache Creek Tuff, thick caldera-filling lavas, and a smaller volume late tuff sheet, is tightly bracketed at 32.25–32.17 Ma. No large ignimbrites were erupted in the interval 32–29 Ma, but a previously unmapped cluster of dacite-rhyolite lava flows and small tuffs, areally associated with a newly recognized intermediate-composition intrusion 5 × 10 km across (largest subvolcanic intrusion in San Juan region) centered 15 km north of the North Pass caldera, marks a near- caldera-size silicic system active at 29.8 Ma. In contrast to the completely filled North Pass caldera that has little surviving topographic expression, no voluminous tuffs vented directly from the adjacent Cochetopa Park caldera, which is morphologically beautifully preserved. Instead, Cochetopa Park subsided passively as the >500 km3 Nelson Mountain Tuff vented at 26.9 Ma from an "underfit" caldera (youngest of the San Luis complex) 30 km to the SW. Three separate regional ignimbrites were erupted sequentially from San Luis calderas within an interval of less than 50–100 k.y., a more rapid recurrence rate for large explosive eruptions than previously documented elsewhere. In eruptive processes, volcanic compositions, areal extent, duration of activity, and magmatic production rates and volumes, the Southern Rocky Mountains Volcanic Field represents present-day erosional remnants of a composite volcanic field, comparable to younger ignimbrite terranes of the Central Andes.


Magnetotherapy effects on cerebral hemodynamics were studied using rheoencephalography (REG). When the treatment results and changes in cerebral hemodynamics were compared it was evident that normalization or improvement of vascular status in vertebrobasilar and carotid territories registered at REG results in better hearing. This confirms the role of vascular factor in pathogenesis of neurosensory hypoacusis of different etiology and effectiveness of magnetotherapy in such patients.


The nature of the cognitive processes that give rise to moral judgment and behavior has been a central question of psychology for decades. In this paper, we suggest that an often ignored yet fruitful stream of research for informing current debates on the nature of moral cognition is social influence. We introduce what we call the "social-moderation-of-process" perspective, a methodological framework for leveraging insights from social influence research to inform debates in moral psychology over the mechanisms underlying moral cognition and the moral domains in which those mechanisms operate. We demonstrate the utility of the social-moderation-of-process perspective by providing a detailed example of how research on social influence in behavioral ethics can be utilized to test a research question related to a debate between two prominent theories in moral psychology. We then detail how researchers across the field of moral psychology can utilize our social-moderation-of-process perspective.


By comparing the reconciliation between Germans and Jews in the aftermath of World War II and that between Serbs and Bosniaks in post-Dayton Bosnia, this article argues that reconciliation can be a ''simpler'' affair in some cases than in others. More specifically, reconciliation between victims and perpetrators is more easily facilitated when both parties do not have to live in the same state and imagine themselves as part of the same political community, as in the case of Germans and Jews. By arguing that the success of German–Jewish reconciliation lies, first and foremost, in the fact that victims and perpetrators did not have to live in the same state in the aftermath of genocide, this article challenges the dominant view that the success of German–Jewish reconciliation was due to the ''three Rs'' of retribution, restitution, and reconstruction. It also challenges the persistent tendency to invoke German–Jewish reconciliation as a model for reconciliation in other post-genocide societies, such as Bosnia. While reconciliation in the German– Jewish case amounted to the establishment of good bilateral relations between two sovereign nation-states, reconciliation in divided societies such as Bosnia is intertwined with, and inseparable from, the project of state and nation building and therefore much more difficult.


Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease which can affect most organ systems including skin, joints and the kidney. Clinically, SLE is a heterogeneous disease and shares features of several other rheumatic diseases, in particular primary Sjögrens syndrome (pSS) and systemic sclerosis (SSc), why it is difficult to diagnose The pathogenesis of SLE is not completely understood, partly due to the heterogeneity of the disease. This study demonstrates that metabolomics can be used as a tool for improved diagnosis of SLE compared to other similar autoimmune diseases. We observed differences in metabolic profiles with a classification specificity above 67% in the comparison of SLE with pSS, SSc and a matched group of healthy individuals. Selected metabolites were also significantly different between studied diseases. Biochemical pathway analysis was conducted to gain understanding of underlying pathways involved in the SLE pathogenesis. We found an increased oxidative activity in SLE, supported by increased xanthine oxidase activity and an increased turnover in the urea cycle. The most discriminatory metabolite observed was tryptophan, with decreased levels in SLE patients compared to control groups. Changes of tryptophan levels were related to changes in the activity of the aromatic amino acid decarboxylase (AADC) and/or to activation of the kynurenine pathway.


Thesis: S.M., Massachusetts Institute of Technology, Department of Mechanical Engineering, in conjunction with the Leaders for Global Operations Program at MIT, 2017.


Insurgent organizations have become major players in criminal enterprises around the world. However, research examining why some participate in crime while others do not remains underdeveloped. Analyzing newly collected annual data on 140 insurgent groups from 1998 to 2012, we examine the conditions driving insurgents' participation in drug crimes, extortion, smuggling, kidnapping for ransom, and robbery. We find that control of territory positively affects involvement in all types of crime. However, we also find notable differences in the conditions driving participation in episodic crimes versus crimes that require institutional investments. Institutional crimes are, with the exception of smuggling, more likely to occur as insurgent groups age, whereas efforts to cultivate legitimacy—as indicated by the ongoing provision of social services—substantially reduces the probability of involvement in episodic crimes. We discuss how this latter effect is reflective of a legitimacy trade-off that emerges for groups pursuing both social support and material resources.


Altered expression of the human septin gene, SEPT9, and its murine homologue, Sept9, has been implicated in neoplasia. However, their role(s) in oncogenesis remains poorly understood. We found amplification of SEPT9 in 67% of breast cancer cells (BCC) when compared with immortalized human mammary epithelial cells (IHMEC) as well as high levels of SEPT9 expression in the majority (61%) of the BCCs studied, unlike IHMECs. Expression profiling of variant SEPT9 transcripts and translated products revealed that high expression of the variant, SEPT9_v1, in contrast to other variants, was widespread in BCCs (55% of the BCCs) but not in IHMECs. High expression of SEPT9_v1 was also observed in primary breast cancer samples by immunohistochemical studies. We subsequently examined the phenotypic consequences of SEPT9_v1 expression in human breast cells. Retroviral expression of SEPT9_v1 in IHMEC cell culture models showed that SEPT9_v1 accelerated growth kinetics, stimulated cell motility, promoted invasion in Matrigel Transwell assays, increased genomic instability with the development of aneuploidy, and stimulated morphologic changes. Significant cytokinesis defects and disruption of tubulin microfilaments were also observed by immunofluorescence when SEPT9_v1 was ectopically expressed in IHMECs. Furthermore, SEPT9_v1 markedly enhanced neoplastic transformation in Hs578T cells, a BCC with no endogenous expression of the SEPT9_v1 isoform. Small interfering RNA-mediated and short hairpin RNA-mediated inhibition of SEPT9_v1 expression in two BCCs with high levels of endogenous SEPT9_v1 expression inhibited neoplastic growth properties of the cells. Taken together, our findings suggest that increased SEPT9_v1 expression contributes to the malignant pathogenesis of some breast tumors.


We study the unique characteristics of neutrino bursts from the black-hole-forming collapse of non-rotational massive stars, which is a definite branch among other core-collapse supernovae. We clarify that the neutrino signals from the failed supernovae are short and energetic, being different from the ordinary supernova neutrinos, by performing the numerical simulations of the general relativistic neutrino-radiation hydrodynamics with the neutrino reactions rates. Based on the calculated spectra of neutrino emission, we predict that the number of neutrino detection at the Super-Kamiokande is large enough to discuss the detailed differences of the neutrino signals using the sets of equation of state including hyperons and quarks. Therefore, the massive stellar collapse with the short neutrino burst is an important target of neutrino astronomy to probe the properties of dense matter.


The increasing need for vegetable oil about 5 million a year accompanied by the human population growth with the average increase 0.9% requires a consistent effort for Indonesia as the largest CPO producer in the world. The efforts to increase the palm oil plantation production faces not only the constraint of the low plantation product but also the lack of downstream palm oil industry development, in addition, there is not any special fund for the plantation. For that reason , it is necessary to make an improvement effort for the revitalization of the palm oil plantation in North Sumatera-Indonesian through the big potential benefits of North Sumatera by modelling palm oil plantation revitalization, to facilitate the relevant parties to find the solution of the constraints of palm oil plantation revitalization so that it can support the CPO agroindustry development in North Sumatera. The implementation of palm oil plantation revitalization in North Sumatera is very low, that is only 17.5 % out of the planned one. It indicates that it becomes the constraint of the palm oil plantation revitalization in North Sumatera. The result of the research shows that several dominant factors influencing the success of the revitalization are among others the land availability and the replanting, the increased productivity of plantation and CPO agroindustry, and the plantation financing. Therefore, it is recommended that the relevant parties such as government , plantation companies, banks and-and farming community be able to synergize so that various influencing factors can be optimized and the increase in the revitalization is maximized.


Data from subsurface temperature measurements provide widely used and vital input data for maturity modeling_ Because maturity calculations are very sensitive to thermal history, and because reconstruction of the thermal history begins with the modern temperature profile, accurate knowledge of true formation temperatures is vital. Temperature data used in maturity modeling come from a variety of sources, including BHTs derived from single logging runs, BHTs obtained from multiple logging runs at the same depth and corrected using the Horner plot method, RFTs, DSTs, and production tests (PTs)_ However, temperatures obtained using most of these techniques require some correction before they represent true formation temperatures. Unfortunately, the need for these corrections is not generally recognised, leading most modelers to consistently underestimate modern subsurface temperatures_ Such errors can lead to major errors in subsequent calculations of hydrocarbon generation and cracking, and can thus have profound effects on exploration decisions_ In an effort to evaluate the accuracy of data from single logging runs, Horner plots, RFTs, and DSTs or PTs, an extensive temperature data base was developed for the Malay Basin. Basal heat flows calculated for many wells using each type of temperature data were compared. It was found that all other temperature data considerably underestimated subsurface temperatures compared to DSTIPT data, which were assumed to represent true formation temperatures. Results were analyzed using two different statistical approaches, which gave quite consistent conclusions, and average correction factors for each type of temperature data were developed. To be equivalent to heat flows calculated from DSTI PT temperatures, heat flows calculated using single BHT data already subjected to a standard 10% correction had to be corrected upward by an additional 16%, those calculated from Horner plot extrapolations by an additional 14%, and those obtained from uncorrected RFT data by 9%. Measured subsurface temperatures were corrected using a more complex set of equations that take surface temperature (T.) into account. The corrected subsurface temperature To is given by one of the following formulas, where Tb is the uncorrected temperature from a single logging run, Th is the extrapolated temperature obtained from a Horner plot, and Tr is the uncorrected RFT temperature. To = (1.1 eTb - T.)e1.16 + T. To = (Th - T.)e1.14 + T. To = (Tr - T.)e1.09 + T. Although these correction factors were developed for the Malay Basin, evidence presented by other workers suggests that corrections are needed in other basins as well, and that the magnitude of the corrections suggested here is reasonable for other areas. Future work should test these hypotheses and extend this calibration to ·other types of basins in other parts of the world. The correction factors established in this study only represent statistical averages, and cannot be expected to work well in all cases. Whenever DST or PT data are available, they should be weighted considerably more heavily than any other type of data, even those corrected by the best methods available. In the absence ofDST or PT data, however, these correction methods will greatly increase our confidence in subsurface temperatures from RFTs or from wireline logs.


Recent cases involving religious businesses owners who object to providing services for same-sex weddings and resulting lawsuits have generated a vigorous academic and popular debate. That debate centers in part on the proper role of religion in the market. This article develops three theories of the proper relationship between commerce and religion and applies them to these conflicts. The first approach would apply the norms of liberal democratic governments to market actors. The second approach posits that any market outcome is legitimate so long as it results from voluntary contracts. These approaches yield contradictory and indeterminate advice on the conflicts involving same-sex weddings and religious business owners. In place of them, this article defends the doux commerce theory, which argues that markets manage social pluralism but only so long as they are largely disconnected from deeper moral or political struggles. Under this theory, the outcome of the debate over religious businesses and same-sex marriage should be empirically contingent. Aggressive antidiscrimination laws may be necessary to insure meaningful access to the market, but where instances of religious discrimination are rare, there is no compelling justification for punishing idiosyncratic religious behavior. Indeed, doing so will tend to degrade the value of markets. Religious business owners and same-sex couples have made dueling claims about injured dignity. Gays and lesbians insist that religious exemptions from antidiscrimination laws assault their dignity, while religious believers claim that without such exemptions the law assaults their dignity. The doux commerce approach does not require that we resolve this intractable dispute. Rather, it counsels in favor of maintaining the market as an ideologically blase space where we may peacefully and productively interact in the face of deep disagreements.


This paper introduces VibPress, a software technique that enables pressure input interaction on mobile devices by measuring the level of vibration absorption with the built-in accelerometer when the device is in contact with a damping surface (e.g., user's hands). This is achieved using a real-time estimation algorithm running on the device. Through a user evaluation, we provide evidence that this system is faster than previous software-based approaches, and accurate as hardware-augmented approaches (up to 99.7% accuracy). With this work, we also provide an insight about the maximum number of pressure levels that users can reliably distinguish, reporting usability metrics (time, errors and cognitive load) for different pressure levels and types of gripping gestures (press and squeeze).


Differentiation of adipogenic precursor cells into mature adipocytes is a complex process. Adipocyte differentiation is characterized by the expression of several adipocyte-specific genes, which occurs in an ordered fashion, and is orchestrated by a set of interacting transcription factors. The most prominent transcription factors involved in this process are the γ form of peroxisome proliferator activated receptors (PPAR) and the various members of the CAAT enhancer binding proteins (α β, and γ). In addition to PPARγ and the C/EBPs, several other transcription factors, including ADD-1 (SRE-BP), HMGI-C, are involved in regulating the differentiation process. Altered activity and/or expression of these transcription factors, will change the expression of target genes in the differentiating cells, ultimately resulting in the differentiated adipocyte phenotype. Modulation of these transcription factors by either pharmacological or dietary manipulations might influence adipocyte differentiation and prove beneficial in the prevention and treatment of obesity


This paper argues that the central object of constitutional interpretation is the Constitution, which is an intentional lawmaking act rather than a text floating free in the world, and that the point of such interpretation is primarily to understand the meaning that those who made the Constitution intended to convey by promulgating the text in question. The paper develops these claims by way of a critique of Cass Sunstein's recent argument that there is nothing that interpretation just is, contending that he misunderstands the way that intention works in language use in general and that the alternatives to intentionalism that he outlines each fail. The radical interpretive choice for which he argues is ruled out by the nature of the Constitution. The final part of the paper considers the various ways in which one might understand the Constitution as an object requiring interpretation and outlines the significance that this understanding has for interpretive practice.


For the first time in 400 years a number of leading common law nations have, fairly simultaneously, embarked on charity law reform leading to an encoding of key definitional matters in charity legislation. This book provides an analysis of international case law developments on the ever growing range of issues now being generated by clashes between human rights, religion and charity law. Kerry O'Halloran identifies and assesses the agenda of 'moral imperatives', such as abortion and gay marriage that delineate the legal interface and considers their significance for those with and those without religious belief. By assessing jurisdictional differences in the law relating to religion/human rights/charity the author provides a picture of the evolving 'culture wars' that now typify and differentiates societies in western nations including the USA, England and Wales, Ireland, Australia, Canada and New Zealand.


PURPOSE
Current commercially available small animal irradiators provide limited software tools for treatment planning. We report on the implementation of an in-house treatment planning system, Metropolis, for micro-irradiator and compare its capabilities with those of the vendor-supplied system, TPS(XRAD).

METHODS
The 225 kV beam of the micro-irradiator was commissioned using both ion chamber and radiographic film (EBT3). Dose calculation in Metropolis was verified by comparing with measured dose in phantom. Starting from a 3D CT image of a tumor-bearing mouse, the same treatment plans were designed in the two systems. In TPS(XRAD), a treatment point was selected on a CT slice, two orthogonal beams were defined based on tumor size on the CT slice, and isocenter depth was computed from a body contour determined by image thresholding. In Metropolis, structures (outer, tumor, and lung) were contoured on CT images, beams were defined based on tumor volume coverage on beams-eye-view (BEV), 3D dose calculation was performed, and plan was evaluated based on dose distribution and dose-volume histogram (DVH).

RESULTS
Measured dose in phantom agreed with Metropolis calculation within 3% for all collimators. The beam-on-times calculated by the two systems agreed within 1% at isocenter. Whereas TPS(XRAD) provides only beam-on-time for each beam, Metropolis capabilities include various image segmentation tools, multimodality image registration, verification of target coverage and normal tissue sparing using BEV, 3D isodose distribution overlaid on CT images, and DVH. DVH inspection of the two-beam treatment plan reveals a tumor dose variation (D95 : 388 and D05 : 401 cGy) and dose to lung (Dmean: 84 cGy) for a prescribed isocenter dose of 400 cGy.

CONCLUSION
By implementing a clinical TPS for a small animal irradiator system, both efficient planning and precise plan evaluation become possible, allowing the full potential of advanced micro-irradiator radiation treatment planning to be conducted for pre-clinical experimentation.


Although it has long been understood that a well-constructed data set ought to be filled with complexities and contradictions, observations that challenge or contradict analytic interpretations are not often given sufficiently serious attention in the methodological qualitative health literature. When researchers attempt to produce comprehensive or "holistic" findings, they all too often set aside or gloss over the negative cases that fail to conform to their emerging interpretive generalizations. In this article, the authors challenge fellow qualitative health researchers to engage actively in identifying and exploiting both actual and theoretical exceptions as a valuable analytic strategy. They argue that heightened sensitivity for negative cases uncovers the assumptive claims deriving from our various methodological orientations and illuminates alternative explanations. They propose that thoughtful attention to contradictory or challenging observations can deepen our expectations about the kinds of knowledge products that qualitative research ought to yield, thereby helping us advance the credibility of our findings and the ultimate utility of our empirical conclusions.


The objective of this paper is to present the role of law in structuring and regulating the state- civil society relationship and the extent of the challenge globalization poses to this triangular relationship. While there are a number of different conceptualizations and formulations of the state- civil society relationship, it is only through a legal framework that this relationship is formally defined. The article begins by providing a conceptual framework for the state and civil society distinction and then introduces the evolution of law into a legal system as the precondition for differentiating the civil society as a non-state actor. A comparative evaluation of civil society development in totalitarian, liberal and welfare state systems provides an analytical backdrop for the contemporary transformations generated by globalization and how that affects legal systems, states and civil societies within the realm of the nation-state as well as in the larger context of a global political economic structure.


In a move towards a more informed understanding of the concept of satisfaction, this study aims
to explore how thirty dermatology patients describe what it
means to be satisfied with their healthcare. This was undertaken by adopting a qualitative research approach, using an in-depth semi-structured interview methodology.
It was conducted within the context of a randomised controlled trial of telemedicine in dermatology (RCT). A secondary aim was to evaluate the extent to which the methodological approach of the study (interpretative
phenomenological analysis) was successful in eliciting such descriptions. The findings reveal patient satisfaction as being a complex and fluid construct underpinned by a range of values, beliefs, attitudes and experiences. Individual
participant descriptions of satisfaction emphasise the importance of 1) receiving a diagnosis treatment and cure, 2) minimum waiting time for appointments and treatment 3) the need to receive adequate information and explanations 4)
receiving individualised personal care and 5) the need
for participants to feel as though they were being taken seriously and 6) the importance of practitioner characteristics/good communication. Perhaps the most significant observation was the sequential nature of satisfaction, which was defined, redefined and re-evaluated
by participants throughout the
interview process. This study also identified a continuum of satisfaction across patients' definitions of being
'satisfied' as opposed to 'very satisfied' with healthcare. The method of data analysis (interpretative phenomenological analysis-IPA) was a useful approach to guide the analysis
identifying and exploring themes relevant to eliciting the
meaning of satisfaction. However, limitations to this methodology were apparent over the course of the study, and alternative methodology, contextualised interpretative phenomenological analysis has been postulated. It is suggested that the journey for a definitive notion of patient satisfaction, can only be meaningfully directed by accepting some form of refinement of phenomenological methods as a means of adding sophistication to existing
quantitative studies.


In the course of the last 50 years our knowledge about the epidemiology, aetiology, pathogenesis, prevention, and treatment of addiction has increased dramatically. Since the 1980s treatment providers have had at their disposal effective psychotherapeutic interventions whereby insightful forms of treatment have been largely replaced by cognitive behavioural therapy aimed at bringing about changes in behaviour. Since the 1990s more and more pharmacological interventions have also been introduced and recently some new neurophysiological interventions have been carefully tested. Finally, considerable progress has been made in assigning patients to the most suitable forms of treatment.


Within the Influenza Monitoring Vaccine Effectiveness in Europe (I-MOVE) project we conducted a multicentre case–control study in eight European Union (EU) Member States to estimate the 2011/12 influenza vaccine effectiveness against medically attended influenza-like illness (ILI) laboratory-confirmed as influenza A(H3) among the vaccination target groups. Practitioners systematically selected ILI / acute respiratory infection patients to swab within seven days of symptom onset. We restricted the study population to those meeting the EU ILI case definition and compared influenza A(H3) positive to influenza laboratory-negative patients. We used logistic regression with study site as fixed effect and calculated adjusted influenza vaccine effectiveness (IVE), controlling for potential confounders (age group, sex, month of symptom onset, chronic diseases and related hospitalisations, number of practitioner visits in the previous year). Adjusted IVE was 25% (95% confidence intervals (CI): -6 to 47) among all ages (n=1,014), 63% (95% CI: 26 to 82) in adults aged between 15 and 59 years and 15% (95% CI: -33 to 46) among those aged 60 years and above. Adjusted IVE was 38% (95%CI: -8 to 65) in the early influenza season (up to week 6 of 2012) and -1% (95% CI: -60 to 37) in the late phase. The results suggested a low adjusted IVE in 2011/12. The lower IVE in the late season could be due to virus changes through the season or waning immunity. Virological surveillance should be enhanced to quantify change over time and understand its relation with duration of immunological protection. Seasonal influenza vaccines should be improved to achieve acceptable levels of protection.


Telling a cause from its effect using observed time series data is a major challenge in natural and social sciences. Assuming the effect is generated by the cause through a linear system, we propose a new approach based on the hypothesis that nature chooses the "cause" and the "mechanism generating the effect from the cause" independently of each other. Specifically we postulate that the power spectrum of the "cause" time series is uncorrelated with the square of the frequency response of the linear filter (system) generating the effect. While most causal discovery methods for time series mainly rely on the noise, our method relies on asymmetries of the power spectral density properties that exist even in deterministic systems. We describe mathematical assumptions in a deterministic model under which the causal direction is identifiable. In particular, we show a scenario where the method works but Granger causality fails. Experiments show encouraging results on synthetic as well as real-world data. Overall, this suggests that the postulate of Independence of Cause and Mechanism is a promising principle for causal inference on observed time series.


With the exponential growth of the Internet of Things, people now expect every household appliance to be smart and connected. At the same time, smartphones have become ubiquitous in our daily life. Their continuous performance improvement and their compatibility with a broad range of radio protocols as WiFi, Bluetooth Low Energy (BLE) or NFC make them the most convenient way to interact with these smart objects. However, providing wireless connectivity with BLE or NFC means adding an extra chipset and an antenna, increasing the object size and price. Previous works already have demonstrated the possibility of receiving information through visible light using an unmodified smartphone thanks to its camera. Also, LED-to-LED communication for smart devices like toys has been shown previously. However, past efforts in LED to camera communication for IoT device communication have been limited.

In this work, we design LightIoT, a bidirectional visible-light communication (VLC) system between a low-cost, low-power colored LED that is part of an IoT device and an off-the-shelf smartphone. The IoT device is thus able to send and receive information through its LED, while the smartphone uses its camera to receive data and its flashlight to send information. We implement and experimentally evaluate a LED-to-camera VLC system, designed specifically for small LEDs. The proposed solution exploits the rolling shutter effect of unmodified smartphone cameras and an original decoding algorithm, achieving a throughput of nearly 2 kb/s. Based on the insight gained from an extensive experimental study, we model, for the first time in the literature, the LED-to-camera communication channel. We propose a Markov-modulated Bernoulli process model, which allows us to easily study the performance of different message retransmission strategies. We further exploit this model to implement a simulator for LED-to- Camera communications performance evaluation.

In order to achieve bi-directional communications, we evaluate flashlight-to- LED communications using non-rooted smartphones and small LEDs. With these constraints, our implementation achieves a throughput of 30 bits/second. While limited, this is enough for a feed-back channel coming to support the required redundancy mechanisms. Some of these redundancy mechanisms are based on random linear coding, never tested previously in VLC. Therefore, we design and implement, for the first time in the literature, a pseudo random linear coding scheme especially fitted for line-of-sight LED-to-camera conditions. Experimental evaluation highlights that this type of approach increases the goodput up to twice compared to classical retransmission strategies.

Finally, we compare the energy consumption of LightIoT with the one of a BLE module with similar activity. Our results show that using the LED for communication purposes reduces the energy consumption under a normal usage behavior.


The 1860s are considered the 'Golden Age' of illustrated periodicals, a time when the 'knockabout' humour of the 1840s, which was dominated by illustrators such as Cruikshank, Doyle and Phiz, gave way to a more considered style grounded in serious artistic principles, allowing for deeper expression and emotion in artistic output. "Illustrated Periodicals of the 1860s" provides a new and informative approach to the study of 'sixties' periodicals, revealing the previously unstudied area of the complex interrelationships between the various parties involved in the production of these magazines: publishers, editors, artists, engravers and authors. The book considers the effects of these relationships on creative output, both artistic and literary, and in so doing provides a detailed, historical reconstruction of the essential character of the periodicals of that era. The book includes over 120 reproductions of engravings and preparatory drawings, almost all of them original size.


The objective of artistic style learning is to synthesize a new image from a source image with the style learnt from example images. Existing example-based texture synthesis (EBTS) techniques model style with low-level statistical properties. These methods work well with some artistic styles such as oil painting, but have difficulties in preserving image details and features for other styles such as pencil hatching. In this article, an improved artistic style-learning algorithm with feature-based texture synthesis (FBTS) is introduced. Compared with existing EBTS methods, in our FBTS algorithm, image details and features are better defined with a feature field generated from the source image. Also, an improved L2 neighborhood distance metric which provides better measures of perceptual similarity is proposed. Results and comparisons are given to demonstrate the effectiveness of the FBTS algorithm with applications in the areas of stylized shading and artistic style transfer.


Most field campaigns aim at helping in specified scientific or practical tasks, such as modeling, prediction, optimization, or management. Often these tasks involve binary decisions or seek answers to yes/no questions under uncertainty, e.g., Is a model adequate? Will contamination exceed a critical level? In this context, the information needs of hydro(geo)logical modeling should be satisfied with efficient and rational field campaigns, e.g., because budgets are limited. We propose a new framework to optimize field campaigns that defines the quest for defensible decisions as the ultimate goal. The key steps are to formulate yes/no questions under uncertainty as Bayesian hypothesis tests, and then use the expected failure probability of hypothesis testing as objective function. Our formalism is unique in that it optimizes field campaigns for maximum confidence in decisions on model choice, binary engineering or management decisions, or questions concerning compliance with environmental performance metrics. It is goal oriented, recognizing that different models, questions, or metrics deserve different treatment. We use a formal Bayesian scheme called PreDIA, which is free of linearization, and can handle arbitrary data types, scientific tasks, and sources of uncertainty (e.g., conceptual, physical, (geo)statistical, measurement errors). This reduces the bias due to possibly subjective assumptions prior to data collection and improves the chances of successful field campaigns even under conditions of model uncertainty. We illustrate our approach on two instructive examples from stochastic hydrogeology with increasing complexity.


New Zealand marine fishing activities create many types of environmental externalities. Legislation requires that the externalities be internalised and fisheries management agencies must choose from a wide range of instruments which are best suited to the task. Selection of best instruments can be aided by following a hierarchical decision process, which first screens the universe of instruments to produce a likely set, then tests that list against implementation criteria to establish the feasible set. Instruments in the feasible set can be evaluated against a range of environmental, Treaty of Waitangi, economic, socio-cultural and management criteria. This approach to selection can be formalised in decision support software to provide a useful tool for fisheries management agencies.


ABSTRACT Paleogene arkoses of the Auvergne region of France represent the type arkose originally described by Brongniart (1826). They are alluvial-fan and fluvial deposits including traction-current sandstones (arenites) and matrix-rich debris-flow deposits (wackes). Locally, they have been extensively altered by geothermal waters related to nearby Tertiary-Holocene volcanic activity. The alteration is typified by leaching of detrital grains and precipitation of ubiquitous chert cement. The average Gazzi-Dickinson composition of unaltered arenites is Q40F60L0, with K/F (potash feldspar/total feldspar) = 0.63. Altered arenites have an average composition of Q55F43L2, with K/F= 0.73, reflecting loss of plagioclase due to intense a teration. When secondary chert is included with detrital quartz and chert, the altered rocks have an average composition of Q66F32L1, emphasizing silica enrichment associated with alteration. Holocene sands derived from crystalline basement of the Massif Central have the same provenance as the Paleogene sandstones. They have an average Gazzi-Dickinson composition of Q46F49L5 with K/F = 0.52 and compare favorably with their unaltered ancient counterparts. Arkosic alluvium at Roosevelt Hot Springs, Utah is believed to represent a modern analog for alteration of the Auvergne sandstones. The alluvium has been altered and cemented with silica by geothermal waters at near-surface conditions in the epithermal zone. Chemical analyses of 130 sand and rock samples demonstrate original sediment compositions and changes due to hydrothermal alteration. Holocene sands and unaltered Paleogene clastics are compositionally similar and show variation trends similar to feldspathic clastics derived from granitic basement in other basins. Silica enrichment in the altered sandstones causes dilution of all other elements as an effect of constant summation. Consequently, most element abundances decline proportionately with silica dilution. Na and Rb, however, are reduced below the levels predicted by dilution due to plagioclase and biotite destruction. As a result, K/Rb ratios are higher in the altered sandstones. Ba, S, SO4, As, and Sb are enriched in the altered rocks by precipitation from hydrother al solutions. Barium is in barite as fracture-filling veins and scattered patches in sandstone matrix. Destruction of mafic minerals during alteration released Fe, Co, Cr, Ni, Zn, Pb, and Th that later precipitated as oxides and sulfides in fractures and locally in chert matrix in the sandstones.


This paper reports on a conducted study, measuring the perceptions of post-graduate students on the effectiveness of serious games in the classroom. Four games were used (Project Management Exercise, "Winning Margin" Business Simulation, Management of Change and Management of Product Design and Development) with scenarios ranging from product design to project management. The games might be classified as Team-Based Mixed-Reality (TBMR) games. The games were conducted over the period October 2010 to May 2011and the questionnaires conducted during June 2011. The results, from a sample size of 80 of largely international students, indicated a clear ranking of emotions experienced when participating in the games with "Exciting" outweighing "Apprehensive", "Bored" and Indifferent". The majority of students indicated that both "their team winning" and "showing their personal competence" were important to them. However 70% said that working in teams was valuable in itself implying that team-working was a strong element in the conclusion that the games were of value. For all four games, over 60% said that conflict was valuable and over 75% said participating improved their "working in teams" skills. The value of feedback was rated highly, as was improved motivation. Over 60% said that the participation in the games was more useful than lectures on the same topic.


There is great interest in elucidating how stem cells regulate their proliferative state, endowing them with the property of self-renewal. Tsai and McKay report that nucleolar proteins may contribute to this phenomenon. Their study has identified a nucleolar protein called nucleostamin that is expressed in central nervous system stem cells, embryonic stem cells, and several cancer cell lines. Its expression decreased when stem cells differentiated, suggesting that it functions to maintain cell proliferation. However, overexpression of nucleostamin prevented cells from entering mitosis and increased cell death. This effect was dependent on the expression of p53, a tumor suppressor protein that also coimmunoprecipitated with nucleostamin from cell extracts. Nucleostamin also harbors a guanosine triphosphate-binding domain that the authors propose regulates nucleolar localization. R. Y. L. Tsai, R. D. G. McKay, A nucleolar mechanism controlling cell proliferation in stem cells and cancer cells. Genes Dev. 16, 2991-3003 (2002). [Abstract] [Full Text]


The U.S. Geological Survey, in cooperation with Jefferson County and the Jefferson Valley Conservation District, sampled groundwater in southwestern Montana to evaluate the occurrence and concentration of naturally-occurring radioactive constituents and to identify geologic settings and environmental conditions in which elevated concentrations occur. A total of 168 samples were collected from 128 wells within Broadwater, Deer Lodge, Jefferson, Lewis and Clark, Madison, Powell, and Silver Bow Counties from 2007 through 2010. Most wells were used for domestic purposes and were primary sources of drinking water for individual households. Water-quality samples were collected from wells completed within six generalized geologic units, and analyzed for constituents including uranium, radon, gross alpha-particle activity, and gross beta-particle activity. Thirty-eight wells with elevated concentrations or activities were sampled a second time to examine variability in water quality throughout time. These water-quality samples were analyzed for an expanded list of radioactive constituents including the following: three isotopes of uranium (uranium-234, uranium-235, and uranium-238), three isotopes of radium (radium-224, radium-226, and radium-228), and polonium-210. Existing U.S. Geological Survey and Montana Bureau of Mines and Geology uranium and radon water-quality data collected as part of other investigations through 2011 from wells within the study area were compiled as part of this investigation. Waterquality data from this study were compared to data collected nationwide by the U.S. Geological Survey through 2011. Radionuclide samples for this study typically were analyzed within a few days after collection, and therefore data for this study may closely represent the concentrations and activities of water being consumed locally from domestic wells. Radioactive constituents were detected in water from every well sampled during this study regardless of location or geologic unit. Nearly 41 percent of sampled wells had at least one radioactive constituent concentration that exceeded U.S. Environmental Protection Agency drinking-water standards or screening levels. Uranium concentrations were higher than the U.S. Environmental Protection Agency maximum contaminant level (MCL) of 30 micrograms per liter in samples from 14 percent of the wells. Radon concentrations exceeded a proposed MCL of 4,000 picocuries per liter in 27 percent of the wells. Combined radium (radium-226 and radium-228) exceeded the MCL of 5 picocuries per liter in samples from 10 of 47 wells. About 40 percent (42 of 104 wells) of the wells had gross alphaparticle activities (72-hour count) at or greater than a screening level of 15 pCi/L. Gross beta-particle activity exceeded the U.S. Environmental Protection Agency 50 picocuries per liter screening level in samples from 5 of 104 wells. Maximum radium-224 and polonium-210 activities in study wells were 16.1 and 3.08 picocuries per liter, respectively; these isotopes are constituents of human-health concern, but the U.S. Environmental Protection Agency has not established MCLs for them. Radioactive constituent concentrations or activities exceeded at least one established drinking-water standard, proposed drinking-water standard, or screening level in groundwater samples from five of six generalized geologic units assessed during this study. Radioactive constituent concentrations or activities were variable not only within each geologic unit, but also among wells that were completed in the same geologic unit and in close proximity to one another. Established or proposed drinking-water standards were exceeded most frequently in water from wells completed in the generalized geologic unit that includes rocks of the Boulder batholith and other Tertiary through Cretaceous igneous intrusive rocks (commonly described as granite). Specifically, of the wells completed in the Boulder batholith and related rocks sampled as part of this study, 24 percent exceeded the MCL of 30 micrograms per liter for uranium, 50 percent exceeded the proposed alternative MCL of 4,000 picocuries per liter for radon, and 27 percent exceeded the MCL of 5 micrograms per liter for combined radium-226 and radium-228. Elevated radioactive constituent values were detected in samples representing a large range of field properties and water types. Correlations between radioactive constituents and 2 Radiochemical Constituents in Groundwater of Jefferson County and Surrounding Areas, Southwestern Montana pH, dissolved oxygen, and most major ions were not statistically significant (p-value > 0.05) or were weakly correlated with Spearman correlation coefficients (rho) ranging from -0.5 to 0.5. Moderate correlations did exist between gross beta-particle activity and potassium (rho = 0.72 to 0.82), likely because one potassium isotope (potassium-40) is a beta-particle emitter. Total dissolved solids and specific conductance also were moderately correlated (rho = 0.62 to 0.71) with gross alpha-particle and gross beta-particle activity, indicating that higher radioactivity values can be associated with higher total dissolved solids. Correlations were evaluated among radioactive constituents. Moderate to strong correlations occurred between gross alpha-particle and beta-particle activities (rho = 0.77 to 0.96) and radium isotopes (rho = 0.78 to 0.92). Correlations between gross alpha-particle activity (72-hour count) and all analyzed radioactive constituents were statistically significant (p-value < 0.05), and therefore, gross alpha-particle activity likely may be used as a screening tool for determining the presence of radionuclides in area waters. In this study, gross alpha-particle activities of 7 picocuries per liter or greater were associated with all radioactive constituents whose concentrations exceeded drinking-water standards or screening levels. Radiochemical results varied temporally in samples from several of the thirty-eight wells sampled at least twice during the study. The time between successive sampling events ranged from about 1 to 10 months for 29 wells to about 3 years for the other 9 wells. Radiochemical constituents that varied by greater than 30 percent between sampling events included uranium (29 percent of the resampled wells), and radon (11 percent of the resampled wells), gross alpha-particle activity (38 percent of the resampled wells), and gross betaparticle activity (15 percent of the resampled wells). Variability in uranium concentrations from two wells was sufficiently large that concentrations were less than the MCL in the first set of samples and greater than the MCL in the second. Sample holding times affect analytical results in this study. Gross alpha-particle and gross beta-particle activities were measured twice, 72 hours and 30 days after sample collection. Gross alpha-particle activity decreased an average of 37 percent between measurements, indicating the presence of short-lived alpha-emitting radionuclides in these samples. Gross beta-particle activity increased an average of 31 percent between measurements, indicating ingrowth of longer-lived beta-emitting radionuclides.


We present the first massively distributed architecture for deep reinforcement learning. This architecture uses four main components: parallel actors that generate new behaviour; parallel learners that are trained from stored experience; a distributed neural network to represent the value function or behaviour policy; and a distributed store of experience. We used our architecture to implement the Deep Q-Network algorithm (DQN). Our distributed algorithm was applied to 49 games from Atari 2600 games from the Arcade Learning Environment, using identical hyperparameters. Our performance surpassed non-distributed DQN in 41 of the 49 games and also reduced the wall-time required to achieve these results by an order of magnitude on most games.


In this paper, we had studied that different types of classical raga music evokes different feelings and emotions. Certain raags produces peace happiness,cheerfullness, sad and Depression mood. According to Indian aesthetics, each poem or musical composition produces a certain rasa (emotion). Local Binary Patterns (LBP) have been well exploited for facial image analysis in the existing work, the LBP histograms are extracted from local facial regions, and used as a whole for the regional description. In this empirical paper we studied LBP Histogram (LBP) bins for the task of facial expression recognition while listening to Indian classical ragas. Our experiments illustrate that the selected LBP bins provide a compact and discriminative facial expression representation. The selected LBP bins will be used to obtain the best recognition performance rate on collected database. The local binary pattern (LBP) operator is defined as a grayscale invariant texture measure, derived from a general definition of texture in a local neighborhood. Due to its discriminative power and computational simplicity, the LBP texture operator has become a popular approach in various applications, including visual inspection, image retrieval, remote sensing, biomedical image analysis, motion analysis, environment modeling, and outdoor scene analysis .Subjective evaluation shows that Indian classical raags evokes certain emotions & feelings which can be reflect on the human face and was evaluated using LBP approach. Keyword LBP, Facial Expression Analysis, Histogram, Classical raags, Emotional Face Expression.


Data Acquisition Systems (DAS) are the basis for building monitoring tools that enable the supervision of local and remote systems. DASs are complex systems. It is difficult for developers to compare proprietary generic DAS products and/or standards, and the design of a specific DAS is costly. In this paper we propose a role-based use case model of a generic DAS. This model gives DAS developers an abstraction of the generic functionalities of DASs; it enables them to compare existing products and standards; and it provides the DAS developers that aim to develop a specific DAS with a starting point for the design of a specific DAS. We have found that a role-based use case model of a generic system has many advantages. We propose patterns and techniques that are useful for the development of role-based use case models of generic systems.


Low-Energy Processes for Unconventional Oil Recovery fills a gap in oil and gas literature. Today, in our globalized society, the oil industry has to demonstrate how oil recovery can be done responsibly over the life-cycle of the project, clearly articulating energy efficiency as well as limiting CO2 and environmental footprints of the chosen recovery processes. The authors bring together their complementing expertise to provide the reader with an in-depth discussion of a range of alternative recovery techniques. Most recovery methods included are focused on heavy oil recovery, but some have applications in light oil reservoirs as well. With the recent industry drive and focus to recover hydrocarbons from tight rock and shale resources, a chapter has also been devoted to shale oil recovery.


Mutations in the genes that encode the gap junction proteins connexin 26 (Cx26, encoded by GJB2 ) and Cx30 ( GJB6 ) are the leading cause of hereditary hearing loss. That said, the Cx30 p.Ala88Val (A88V) mutant causes Clouston syndrome, but not hearing loss. Here, we report that the Cx30-A88V mutant, despite being toxic to inner ear-derived HEI-OC1 cells, conferred remarkable long-term protection against age-related high frequency hearing loss in Cx30 A88V/A88V mice. During early development, there were no overt structural differences in the cochlea between genotypes, including a normal complement of hair cells; however, the supporting cell Cx30 gap junction plaques in mutant mice were reduced in size. In adulthood, Cx30 A88V/A88V mutant mice had a reduction of cochlear Cx30 mRNA and protein, yet a full complement of hair cells. Conversely, the age-related high frequency hearing loss in Cx30 +/+ and Cx30 +/A88V micewas due to extensive loss of outer hair cells. Our data suggest that the Cx30-A88V mutant confers long-term hearing protection and prevention of hair cell death, possibly via a feedback mechanism that leads to the reduction of total Cx30 gap junction expression in the cochlea.


Intracellular pH sensing is of importance and can be used as an indicator for monitoring the evolution of various diseases and the health of cells. Here, we developed a new class of surface-functionalized MXene quantum dots (QDs), Ti3C2, by the sonication cutting and hydrothermal approach and further explored their intracellular pH sensing. The functionalized Ti3C2 QDs exhibit bright excitation-dependent blue photoluminescence (PL) originating from the size effect and surface defects. Meanwhile, Ti3C2 QDs demonstrate a high PL response induced by the deprotonation of the surface defects. Furthermore, combining the highly pH sensitive Ti3C2 QDs with the pH insensitive [Ru(dpp)3]Cl2, we developed a ratiometric pH sensor to quantitatively monitor the intracellular pH values. These novel MXene quantum dots can serve as a promising platform for developing practical fluorescent nanosensors.

publisher-specific, author manuscript: http://rsc.li/journals-terms-of-use


Drawing on bog turtle research work with UNCG students, we designed the pilot box turtle study at Bethany Community Middle School (BCMS) in accordance with one already underway at Davidson College under the leadership of Biology Professor Dr. Mike Dorcas. The BCMS Box Turtle Project, initiated in 2001, involved middle school students, their teachers, UNCG faculty and graduate students, and interested individuals in the Bethany community studying box turtles on the school grounds and adjacent property. The radio-tracking phase of the project was completed in 2004, but the mark-recapture study continues due to the dedication of Sarah Seymour, the BCMS science teacher. This project is described in detail in an article published in Science Scope, which is included as Appendix A. Please note that many of the tools and techniques described herein for studying box turtles can be applied to the study of other reptiles and amphibians (herpetofauna).


This paper presents our work towards a decentralized reconfiguration strategy for self-reconfiguring modular robots, assembling furniture-like structures from Roombots (RB) metamodules. We explore how reconfiguration by locomotion from a configuration A to a configuration B can be controlled in a distributed fashion. This is done using Roombots metamodules—two Roombots modules connected serially—that use broadcast signals, lookup tables of their movement space, assumptions about their neighborhood, and connections to a structured surface to collectively build desired structures without the need of a centralized planner.


This Report is one of the deliverables of the Global System Dynamics and Policies (GSD) Project (www. globalsystemdynamics.eu) which is coordinated and funded by the Future & Emerging Technologies Division of the European Commission (Work Package 3: Appendix A). Chapter 1 provides an introduction to economic growth models in the context of macro problems such as resource depletion and ecosystem degradation. The first Chapter examines the standard 'textbook' models within the larger framework of different worldviews and the various ways in which these models can be improved. In Chapter 2 we provide the reader with an overview of the literature on Complex Systems Science (CSS) in the search for better 'elementary models for a sustainable economy' – which was the title used for a workshop held in Utrecht in January 2010 (Appendix B). This overview is in fact biased as it is largely based on the contributions of workshop participants. It contains brief descriptions of economic growth engine models, supply-demand mechanisms at microlevel, evolutionary economics models, generalised utility function formulations, income distribution mechanisms, agent-based models of economic behaviour, energy and knowledge as production factors and the incorporation of catastrophic regime shifts and provision of services in ecosystems. The description of this rapidly growing field is, of course, incomplete. In subsequent chapters we describe some research done in the context of the GSD project. We first report on the SusClime model, which has been used to explore the role of decision making rules in the transition to renewable (noncarbon) energy sources to offset natural resource depletion and climate change. This has led to the use of a model in which utility-maximising strategies are simulated in a world of finite oil reserves and climate change. The utility loss for a competitive strategy (where each region optimises for itself) is compared against a cooperative strategy (where a central planner optimises) and is shown for a set of modelling experiments. Strengthening the science-policy interface is partly a matter of legitimacy – hence the importance of simple, interactive models and simulation games about (the perception of) macro-problems. In the last chapter a brief description is given of an MSc research project done on the perception and behaviour of climate change risks under uncertainty.


Abstract Tropical cyclones (TC) under different climate conditions in the Northern Hemisphere have been investigated with the Max Planck Institute (MPI) coupled (ECHAM5/MPI-OM) and atmosphere (ECHAM5) climate models. The intensity and size of the TC depend crucially on resolution with higher wind speed and smaller scales at the higher resolutions. The typical size of the TC is reduced by a factor of 2.3 from T63 to T319 using the distance of the maximum wind speed from the centre of the storm as a measure. The full three-dimensional structure of the storms becomes increasingly more realistic as the resolution is increased. For the T63 resolution, three ensemble runs are explored for the period 1860 until 2100 using the IPCC SRES scenario A1B and evaluated for three 30 yr periods at the end of the 19th, 20th and 21st century, respectively. While there is no significant change between the 19th and the 20th century, there is a considerable reduction in the number of the TC by some 20% in the 21st century, but no change in the number of the more intense storms. Reduction in the number of storms occurs in all regions. A single additional experiment at T213 resolution was run for the two latter 30-yr periods. The T213 is an atmospheric only experiment using the transient sea surface temperatures (SST) of the T63 resolution experiment. Also in this case, there is a reduction by some 10% in the number of simulated TC in the 21st century compared to the 20th century but a marked increase in the number of intense storms. The number of storms with maximum wind speeds greater than 50 m s−1 increases by a third. Most of the intensification takes place in the Eastern Pacific and in the Atlantic where also the number of storms more or less stays the same. We identify two competing processes effecting TC in a warmer climate. First, the increase in the static stability and the reduced vertical circulation is suggested to contribute to the reduction in the number of storms. Second, the increase in temperature and water vapour provide more energy for the storms so that when favourable conditions occur, the higher SST and higher specific humidity will contribute to more intense storms. As the maximum intensity depends crucially on resolution, this will require higher resolution to have its full effect. The distribution of storms between different regions does not, at first approximation, depend on the temperature itself but on the distribution of the SST anomalies and their influence on the atmospheric circulation. Two additional transient experiments at T319 resolution where run for 20 yr at the end of the 20th and 21st century, respectively, using the same conditions as in the T213 experiments. The results are consistent with the T213 study. The total number of TC were similar to the T213 experiment but were generally more intense. The change from the 20th to the 21st century was also similar with fewer TC in total but with more intense cyclones.


Networking is the practice of connecting several computing devices together in order to share resources.In real world, attacks via force and fraud are privacy (unauthorized release of information), Integrity (tampering with data), Service (denial of service).The goals are disallow unauthorized access, allow authorized access, resist DOS attacks .In recent years, many efficient AKE protocols have been proposed to achieve user privacy and integrity in the communications. A communication model is a representation where there are a large number of clients accessing multiple remote and distributed storage devices in parallel. Authenticated key exchange (AKE) protocol allows a user and a server to authenticate each other and generate a session key for the later communications. This paper focuses on how to exchange key materials and establish parallel secure sessions between the clients and the storage devices in the Network in an efficient and scalable manner.


Introduction Mobility, responsivity, autonomy, learning, and collaboration are characteristics commonly shared by biological and software agents. Our investigation into the physiological resources of communication suggested the possibility of using software rather than chemical agents in the treatment of disease. Assuming that the human body has adapting host platforms to agents presented in a form coherent with the biological conditions of receptivity, we developed a system that enables software agents to transport their state into the human body. A small-scale feasibility study was conducted to determine the value of this novel research path. Methods For a case-comparison, we studied 12 volunteers suffering from mild to moderate asthma and 15 healthy volunteers as controls. The subjects were teleconsulted over the Internet using a custom system (Biosign, Canada) that programs progressive analysis of Pulsewave and Oximetry Parameters (POP) acquired using a DAQ board (National Instruments, USA). POP patterns were identified and interpreted by an expert system integrated between the sensor and the effector units. Software agents were selected based on POP patterns and deployed over the Internet. Results All patients exhibited significant POP pattern divagation (P<0.001) compared with the controls. Four patients responded promptly to treatments using software agents, with no relapse during a six-week follow-up. The other patients did not respond at all. No side effects have been observed or reported. Discussion The results are discussed for each case. They suggest that digital therapy - namely, the therapeutic use of software agents, may be a viable and desirable alternative, especially when assessed according to the primary aims of telemedicine. Treating disease by means of software agents deployed over the Internet is, in our opinion, a goal attainable within the limits of current technology.


The main aim of this work is to establish the capabilities of new green buildings to ascertain off-grid electricity generation based on the integration of wind turbines in the conceptual model of a rotating tower [2] in Dubai. An in depth performance analysis of the WinWind 3.0MW [3] wind turbine is performed. Data based on the Dubai Meteorological Services is collected and analyzed in conjunction with the performance analysis of this wind turbine. The mathematical model is compared with Computational Fluid Dynamics (CFD) results based on a conceptual rotating tower design model. The comparison results are further validated and verified for accuracy by conducting experiments on a scaled prototype of the tower design. The study concluded that integrating wind turbines inside a rotating tower can generate enough electricity to meet the required power consumption of the building, which equates to a wind farm containing 9 horizontal axis wind turbines located at an approximate area of 3,237,485 m [14]. Keywords—computational fluid dynamics, green building, horizontal axis wind turbine, rotating tower, velocity gradient.


Introduction In the last couple of years, students and lecturers in Nigerian tertiary institutions have increasingly demanded and preferred access to electronic sources delivery and networked information from their respective libraries (Covi and Cragin, 2004). Internet access is one of the greatest technological advancements being experienced in this 21st century. It revolves around advancements in Information and Communication Technology (ICT) which has gone a long way to influence the mode of information gathering, storage, retrieval and dissemination in these times. Internet access is used for electronic mailing services, electronic on-line chats, group activities among others (Akintunde, 2006). It has resulted in increased access to timely, accurate, relevant and current information in most ICT compliant libraries all over the world. Academic institutions play major roles in the manpower development of any nation since they provide the high as well as middle level manpower needed for the social, economic and political advancement of a nation. This is done through their programmes of teaching, learning, research and community services. The central place of academic libraries is called into play because it is the duty of these libraries to provide the necessary information to the lecturers and students to achieve their teaching learning and research needs in the easiest, fastest and most comprehensive way. This central place of the library in academics has resulted over the years in the necessity for academic libraries to continue to evolve and move with the times so that they can deliver on the requirements of academic libraries in meeting the academic needs of their clientele in the tertiary institutions. This need has resulted over the years in the libraries in higher institutions in Nigeria displaying different stages of development in the application of Information and Communication Technologies (ICT), to library services. The current trend in may library worldwide is the deployment of ICT facilities in rendering services of various kinds to their patrons thereby providing speedy and up-date information for their use. Furthermore, the globalization of the entire world in recent times has placed additional demands on academic libraries to conform in order to avoid the risk of obsolescence and irrelevance in the scheme of things. Teaching and research in tertiary institutions now demand the use of high caliber ICT infrastructure and facilities to keep abreast of current information in all fields. According to Omekwu, (2006), information growth has been exponential and the concept of information explosion is no longer new to information professionals. However, there are current developments in the professional horizon that impact on professional practice and the emerging roles of librarians in a global environment. Be that as it may, Akintunde, (2006) opines that "many libraries in Nigeria still operate in the traditional service pattern where librarians are in charge in main service points of circulation, reference, serials, acquisition, cataloguing and documents without any emphasis on academic disciplines" This is a sad affirmation of a similar complaint several years ago by Afullo (2000), that Nigeria was rated among the lowest in Africa in telecommunication infrastructure and so not much is expected of academic libraries in Nigeria. In the light of the foregoing, this papers will examine what globalization is, the benefits of globalization to library services, the problems inhibiting the deployment of ICT infrastructure and facilities in Academic libraries in Nigeria and the way forward. What Is Globalization? In the opinion of Guillen, (2000), globalization is a process leading to greater interdependence and mutual awareness among economic, political and social units of the world. It is the "accelerated compression of the contemporary world and the intensification of consciousness of the world as a singular entity" Wikipedia defines globalization in "literal sense as simply a means of international integration, that is a process by which the people of the world are unified into a single society and functioning together" This process is a combination of economic technological, socio-cultural and political forces, hence Akanni (008) asserts that globalization is a broad term with several dimensions such as economic globalization, globalization of education globalization sporting event, globalization of Library services, among others. …


The Athens city-center building stock is in bad situation, due to the lack of appropriate urban policies for a very long time and the current long-lasting economic crisis. About 35% of the real properties are derelict. Due to the high renovation and modernization costs of the buildings, as well as the low rental values, they are gradually abandoned. Additionally, their very high degree of co-ownership renders buildings' renovation an extremely difficult task both for owners and developers.The building stock has been progressively excluded from the processes that could support the economic growth and the socio-economic development of the city. For the financial sector, buildings are no longer an object of interest, not because of their low market value, but because of the high risk in financing investments and the lack of interest for the mortgage market thereon. A vicious circle has been established: the buildings are depreciated due to the degradation of the urban environment and vice-versa.A model for the renovation of the buildings has been elaborated. This model is based on the property rights consolidation, in order to achieve the flexible use and management of the buildings as physical, legal and economic entities. It supports and promotes the mobilization and collaboration both of the private and public sectors, and PPP schemes.The main factors that have been taken into account are:Real estate development: The model supports the use of financial engineering schemes, following a deep analysis of the market and numerous feasibility studies.EU State Aid regulations: Under current financial conditions and local market failures, State aid and/or grants are required.Key legal issues: co-ownership decision making, tools for applying State policyregarding owners compliance to property obligations, institution of a legal framework permitting the compulsory purchase of abandoned properties to the benefit of private entities/developers and fast track investment.Finally, the whole administrative process and governance matters are regulated by the model, according to the existing European and national frameworks for urban projects.Research funded by the Onassis Foundation, following a MoU signed between the Foundation and the Greek Government.


Recent years have seen a proliferation of alternative reproductive technologies and the ready availability of reliable DNA testing. These developments have lead to enormous uncertainty concerning the meaning of a genetic tie between adult and child. On the one hand, reproductive technology has lead to a robust market where genetic material is readily bought and sold. This suggests it is not the root of parental status. On the other hand, DNA testing has allowed men to contest paternity of children, asserting that they are not genetically related to them. And their challenges have often been successful. Genetic linkage is particularly problematic for lesbians and gay men forming families. Their children are necessarily not related to one of the parents. At the same time genetic relationship has formed a strong basis on which lesbians in particular have asserted their maternity. This article calls for sustained critical analysis of the meaning of the genetic bond, particularly in lesbian families.


In the early 20th century, when the course of serious illness was first described, scientists offered little hope of recovery for people diagnosed with illnesses like schizophrenia. They were told to expect only continuing psychotic symptoms and progressive dementia and were given no hope of working and living independently. Since then, research has suggested more positive outcomes. In this volume, aimed at clinicians and advocates for the seriously mentally ill, Ruth O. Ralph and Patrick W. Corrigan bring together the available data on the phenomenon of recovery and suggest that various degrees of recovery are more realistic than commonly thought. Recovery in Mental Illness: Broadening our Understanding of Wellness explores what recovery means from various perspectives, including sociological models as well as qualitative studies that incorporate mental health consumers' subjective experiences. The mental health professional seeking to better understand the nature of recovery as well as what interventions and services might enhance well being and quality of life, will find a rich and nuanced discussion of recovery as process, outcome, and natural occurrence, and an examination of evidence-based services as well as consumer-endorsed practices that may not be measurable by traditional quantitative methodologies. Researchers will be challenged to develop innovative approaches to studying this complex and exciting phenomenon.


What are the effects on public support for the European Union (EU) when a member state exits? We examine this question in the context of Britain's momentous decision to leave the EU. Combining analyses of the European Election Study 2019 and a unique survey-embedded experiment conducted in all member states, we analyse the effect of Brexit on support for membership among citizens in the EU-27. The experimental evidence shows that while information about the negative economic consequences of Brexit had no significant effect, positive information about Britain's sovereignty significantly increased optimism about leaving the EU. Our findings suggest that Brexit acts as a benchmark for citizens' evaluations of EU membership across EU-27, and that it may not continue to act as a deterrent in the future.


Pesticide research has provided compounds of progressively increased activity, and recently discovered insecticides, fungicides and herbicides are outstandingly potent. Consideration of the practical use of such chemical agents suggests that greater attention should now be given to methods of application and to the physico-chemical properties that determine redistribution and biological availability following release. Effective economical control agents are not yet available for several categories of damaging organism including viruses, bacteria and certain soil-borne pests and diseases. Analysis of the reasons why these categories have proved so refractory suggests that alternative chemical approaches, such as treatments that modify the host plant, and additional properties such as mobility in plants should be investigated. Such analysis also emphasizes the need to consider chemical approaches together with other methods of control in relation to the life histories and population dynamics of the species concerned. Detailed consideration of this principle can not only yield information about the optimum deployment of chemical agents to ensure their continuing efficacy but also suggest the types of action that would be most appropriate. The potential for further improvements in the materials available and methods of use is substantial, but how far this potential is realized will depend as much on policy and economic considerations as scientific factors.


Objective: ABO blood type is associated with cardiovascular diseases. Several studies have suggested sex-related differences in both hypertrophic cardiomyopathy (HCM) clinical features and ABO blood type. However, few data are available regarding the relationship between ABO blood type and HCM clinical features. We aimed to analyze the relationship between ABO blood type and HCM clinical features, and the potential effects of sex on these relationship. Methods: A total of 549 patients with HCM were enrolled consecutively. Left ventricular outflow tract gradients at rest (LOVTG-R) were measured by echocardiography. Left ventricular end-diastolic dimension, interventricular septum, left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), and left ventricular mass (LVM) were assessed using cardiovascular magnetic resonance imaging. Results: Compared with the non-B antigen group, patients with B antigen had significantly higher LOVTG-R and LVEF values, worse New York Heart Association (NYHA) classification, lower left ventricular volume index values, as well as no difference in LVM index values. After adjustments for sex, male patients with B antigen still had higher LOVTG-R values and frequency of NYHA classification III/IV as well as lower LVEDV and LVESV index values. These differences were not present in female patients. Additionally, patients with NYHA classification III/IV had lower LVEDV index values. Conclusion: In males, not females, patients with HCM with blood type B antigens exhibited worse cardiac functional capacity, higher LOVTG-R values, and lower left ventricular volume index values. These relationships are a potential indicator for clinical prevention. We speculate that rehydration is more efficient in relieving symptoms in male patients with HCM with B antigens.


Introduction Is difficult to conceive of a more legally and ethically challenging circumstance than a dispute between family members and a health care team regarding the withdrawal or withholding of treatment at the end of life. On one hand are families who are emotionally devastated and trying to come to terms with the condition of their loved one. On the other is a health care team struggling to balance the wishes of family members with their ethical and legal obligations to do no harm and to act in the best interests of their patient. While the patient's family in these situations is clearly suffering, health care providers also experience distress when they are pressured to provide treatment they deem to be futile, harmful or otherwise not clinically indicated. This paper will briefly summarize the main aspects of the recent Supreme Court of Canada decision in Cuthbertson v Rasouli (1) ( " Rasouli " ) and will consider the impact of the decision both inside and outside of Ontario. The Rasouli Decision In October 2010, Hassan Rasouli was admitted to the Sunnybrook Health Science Centre in Toronto, Ontario for the removal of a benign brain tumor. He subsequently developed an infection causing severe brain damage and was placed on life support. Rasouli's health care team, understanding him to he in a persistent vegetative state with no real chance of recovering, sought to remove artificial life support and implement palliative care. The care team believed that further artificial life support provided no medical benefit and advised Rasouli's wife, Ms. Salasel, that discontinuing life support and providing palliative care was the best option available. Ms. Salasel, as Mr. Rasouli's substitute decision maker ( "SDM" ), disagreed with this assessment and applied to the Ontario Supreme Court for an order preventing the physicians from withdrawing life sustaining treatment without her consent, citing the provisions of Ontario's Health Care Consent Act ("HCCA" ). (2) Rasouli's health team cross-applied seeking a ruling that consent was not required to withdraw life support when the treatment being provided was futile. The trial judge granted Ms. Salasel's application holding that her consent was required for the withdrawal of care and if she refused, the physicians were required to apply to the Consent and Capacity Board ( " CCB " ). The Ontario Court of Appeal subsequently upheld this decision. (3) Two questions were at issue at the Supreme Court of Canada. The first was whether withdrawal of an intervention no longer providing a medical benefit was considered "treatment" under s. 10(1) of the HCCA. Key to this issue is the HCCA's definition of "treatment" which reads in part: Treatment means anything that is done for a therapeutic, preventive, palliative, diagnostic, cosmetic or other health-related purpose, and includes a course of treatment, plan of treatment or community treatment plan. (4) lithe HCCA was found not to apply, the second question was whether the common law permitted the removal of life support without Ms. Salasel's consent. Given the breadth of the definition of "treatment" under the HCCA, and how close the administration of palliative care was linked to the withdrawal of life support, it was found that for the purposes of the HCCA, the withdrawal of treatment did constitute "treatment" and consent was required. The Court held that in this case, with Ms. Salasel's refusal to consent, the physicians were required to apply to the CCB. As the Court stated, " it will be for the Board to determine whether Ms. Salasel's refusal to provide consent to the withdrawal of life support was in Mr. Rasouli's best interests, within the meaning of s. 21(2) of the HCCA" . (5) According to the Court, while questions involving end of life care may indeed place physicians in difficult ethical situations, this does not alter the burdens placed on them by the HCCA. …


The purpose of this paper is to briefly review theory and applications of RASC and CASC. The latest versions of these computer programmes employ user-friendly graphic modules. Since 1978, these methods have been widely applied by major oil companies to correlate over long distances between wells drilled for hydrocarbon exploration. The purpose of ranking is to construct an optimum sequence of fossil events for a sedimentary basin. It is an average of the sequences of events in a number of individual sequences. During the scaling, distances are being estimated between the average fossil event positions. In CASC, either the optimum sequence or the scaled optimum sequence is used to construct lines of correlation of probable event positions in different wells. The probable event positions are accompanied by 95% confidence intervals (error bars). Special attention is paid to integration of RASC and CASC with seismic events and the numerical geological timescale.


Purpose Research on the longitudinal association of workplace social capital and mental health is limited. The purpose of the present study was to investigate the prospective association of social capital in the workplace with mental distress, measured by K6, adjusting for individuals factors as well as workplace-related factors among employees in Japan. Methods The participants included 6387 men and 1825 women from 12 private companies in Japan. Questionnaires, inquiring about workplace social capital, K6, job strain and effort-reward imbalance were administered at the baseline survey between October 2010 and December 2011 (response rate=77.4%). At 1-year follow-up, social capital and K6 were assessed again (follow-up rate=79.5%), and a generalised linear model was used to estimate the association between changes in workplace social capital and change in K6. Results After adjusting for baseline demographic characteristics and workplace-related factors (Job Content Questionnaire (JCQ), Effort-Reward Imbalance Questionnaire (ERIQ)), increased workplace social capital between waves was associated with improved psychological distress (β=−0.2327, p<0.0001). An inverse association was found in both men and women, all age groups, and among employees with high or low baseline mental health. The association was stronger among those who reported higher stress at baseline. Conclusions Boosting workplace social capital may promote mental health in the workplace.


Some preliminary results from a normative study on spontaneous speech from children between four and eight years are presented. The study is part of a project to develop a standardized and normalized method of analysis of spontaneous speech samples to be used in the assessment of developmental language disorders.From four groups of 30 4-, 5-, 6-, and 7-year olds respectively, spontaneous speech samples have been collected from adult-child conversations. The groups are heterogeneous but comparable to each other with respect to social background. The samples have been segmented into -units. To reduce interviewer-effects, a distinction was made between elliptical answers (answers to previous questions, without finite verb) and free utterances (all other utterances). 50 consecutive free utterances per child have been analyzed on several variables with regard to length (9), fluency (22), grammatical, semantic and pragmatic accept-ability (18) , and syntactic and semantic complexity (43) . The resulting frequency curves (mean frequencies per 50 free utterances per age group) have been analyzed with respect to the following questions:(1) do the groups differ in the relative frequencies for these variables?(2) if so, can these differences be fitted into a model of gradual increase or decrease?(3) or, if there are sudden decreases and/or increases in frequency, how can they be explained?Differences between the age groups were found on many of the variables, and several of these differences indeed do not fit the gradual model. Sudden dips and jumps in the frequency curves do occur. Examples of non-monotonic frequency curves are given for fluency (fig.3 and 4.), prono-minalization (fig.5), coordination and past tense (fig.7), and for adverbial phrases of time (fig.8). Some explanations are suggested for these non-gradual developments.The stability of these frequency patterns is now being tested on a second group of 120 children. If developmental frequency curves prove to be fairly stable, intensive frequency pattern analysis on both cross-sectional and longitudinal data, taking into account situational variability, might be a way to trace the more subtle developments in the later stages of language acquisition.