OBJECTIVE
To describe the effect of indirect costs for patients with early rheumatoid arthritis (RA) within the COBRA trial (Combinatietherapie Bij Reumatoide Artritis) on the cost-effectiveness of both therapies. Analyses of the efficacy and direct costs of the treatments have already been reported.

METHODS
Patients with early RA selected for the 56-week trial were randomly assigned to prednisolone, methotrexate, and sulfasalazine (the COBRA combination) (n = 76, tapered after 28 weeks) or to sulfasalazine (SSZ; n = 79, of which 78 patients were evaluable) alone. The main efficacy outcomes were a pooled index and radiographic damage score in hands and feet, and utilities. Direct and indirect costs were measured (from a societal perspective) by means of cost diaries and interviews completed by patients during the intervention phase and the followup phase, each lasting 28 weeks. Differences in mean costs between groups and cost-utility ratios were evaluated by applying nonparametric bootstrapping techniques.

RESULTS
In the first 28 weeks, indirect costs per patient totaled US $2,578 and US $3,638 for COBRA and SSZ therapy, respectively (p = 0.09). The total costs were $5,931 and $7,853, respectively (p < 0.05). These differences were lost in the second 28 weeks. For the total period the mean total costs per patient were $10,262 and $12,788, respectively (p = 0.11). Sensitivity analyses showed robustness of the data. The point estimate of the cost per quality-adjusted life-year based on the rating scale was negative at $-385, suggesting dominance of COBRA (more effect at lower cost).

CONCLUSION
COBRA therapy adds additional disease control (improvements in disease activity, physical function, and rate of damage progression) at lower or equal cost compared to SSZ in early RA.


In 1972, the first major national study on body image was conducted under the auspices of Psychology Today. Body image was assessed with the Body Parts Satisfaction Scale, which examined the dissatisfaction people experienced with 24 aspects of their bodies. Despite the continued reliance on this scale and reference to the study, data on the factor structure of this measure in a sample of adults have never been published, and citations of the original scale have relied on an unpublished manuscript (Bohrnstedt, 1977). An exploratory factor analysis conducted on 2,013 adults revealed factors for men (Face, Sex Organ, Height, Lower Body, Mid Torso, Upper Torso, Height) and women (Face, Sex Organ, Height, Lower Torso, Mid Torso, Extremities, Breast). The factors were weakly to moderately intercorrelated, suggesting the scale can be analyzed by items, by subscales, or by total score. People who reported more dissatisfaction with their body also tended to report lower self-esteem and less comfort interacting with members of the other sex. The analyses provide a useful comparison point for researchers looking to examine gender differences in dissatisfaction with specific aspects of the body, as well as the factor structures linking these items.


We present simulations of atmospheric CO2 concentrations provided by two modeling systems, run at high spatial resolution: the Eulerian-based Weather Re- search Forecasting (WRF) model and the Lagrangian-based Stochastic Time-Inverted Lagrangian Transport (STILT) model, both of which are coupled to a diagnostic biospheric model, the Vegetation Photosynthesis and Respiration Model (VPRM). The consistency of the simulations is assessed with special attention paid to the details of horizontal as well as vertical transport and mixing of CO2 concentrations in the atmosphere. The dependence of model mismatch (Eulerian vs. Lagrangian) on models' spatial resolution is further in- vestigated. A case study using airborne measurements during which two models showed large deviations from each other is analyzed in detail as an extreme case. Using aircraft observa- tions and pulse release simulations, we identified differences in the representation of details in the interaction between tur- bulent mixing and advection through wind shear as the main cause of discrepancies between WRF and STILT transport at a spatial resolution such as 2 and 6 km. Based on observa- tions and inter-model comparisons of atmospheric CO2 con- centrations, we show that a refinement of the parameteriza- tion of turbulent velocity variance and Lagrangian time-scale in STILT is needed to achieve a better match between the Eulerian and the Lagrangian transport at such a high spatial resolution (e.g. 2 and 6 km). Nevertheless, the inter-model differences in simulated CO2 time series for a tall tower ob- servatory at Ochsenkopf in Germany are about a factor of two smaller than the model-data mismatch and about a fac- tor of three smaller than the mismatch between the current global model simulations and the data.


BACKGROUND
Little is known about trends in the timing of first nephrology consultation and associated outcomes among older patients initiating dialysis.

METHODS
Data from patients aged 67 years or older who initiated dialysis in the United States between January 1, 1996, and December 31, 2006, were stratified by timing of the earliest identifiable nephrology visit. Trends of earlier nephrology consultation were formally examined in light of concurrently changing case mix and juxtaposed with trends in 1-year mortality rates after initiation of dialysis.

RESULTS
Among 323,977 older patients initiating dialysis, the proportion of patients receiving nephrology care less than 3 months before initiation of dialysis decreased from 49.6% (in 1996) to 34.7% (in 2006). Patients initiated dialysis with increasingly preserved kidney function, from a mean estimated glomerular filtration rate of 8 mL/min/1.73 m(2) in 1996 to 12 mL/min/1.73 m(2) in 2006. Patients were less anemic in later years, which was partly attributable to increased use of erythropoiesis-stimulating agents, and fewer used peritoneal dialysis as the initial modality. During the same period, crude 1-year mortality rates remained unchanged (annual change in mortality rate, +0.2%; 95% confidence interval, 0% to +0.4%). Adjustment for changes in demographic and comorbidity patterns yielded estimated annual reductions in 1-year mortality rates of 0.9% (95% confidence interval, 0.7% to 1.1%), which were explained only partly by concurrent trends toward earlier nephrology consultation (annual mortality reduction after accounting for timing of nephrology care was attenuated to 0.4% [0.2% to 0.6%]).

CONCLUSIONS
Despite significant trends toward earlier use of nephrology consultation among older patients approaching maintenance dialysis, we observed no material improvement in 1-year survival rates after dialysis initiation during the same time period.


In this paper, we present a simple but effective method for multi-label classification (MLC), termed Correlated Logistic Models (Corrlog), which extends multiple Independent Logistic Regressions (ILRs) by modeling the pairwise correlation between labels. Algorithmically, we propose an efficient method for learning parameters of Corrlog, which is based on regularized maximum pseudolikelihood estimation and has a linear computational complexity with respect to the number of labels. Theoretically, we show that Corrlog enjoys a satisfying generalization bound which is independent of the number of labels. The effectiveness of Corrlog on modeling label correlations is illustrated by a toy example, and further experiments on real data show that Corrlog achieves competitive performance compared with popular MLC algorithms.


Proof Animation/sup TM/ is a family of products for animating discrete event simulations. Proof is available in a variety of versions, including an inexpensive, student version, mid-size and unlimited-size commercial versions, a run-time version, and a royalty-free, redistributable demo viewer. Proof is an ASCII-stream-driven, general-purpose animation system which runs on readily available PC hardware. Its vector-based geometry provides a large animation canvas and the ability to zoom in or out, while maintaining crisp, clear images. Proof includes built-in drawing tools and CAD import/export for ease in creating animation layouts. Proof's open architecture makes it ideally suited for serving as a concurrent or post-processed animation engine for models written in a wide variety of simulation and programming languages. Proof's superior power and performance assure smooth, realistic motion for animations, regardless of their size, complexity, or application. Proof uses Microsoft's DirectDraw/sup TM/ interface for accessing video hardware. DirectDraw is a built-in component of Windows 98 and Windows 2000, and it is available as an add-on for Windows 95. Proof is able to exploit high-performance MMX hardware.


Purpose: This study aims to report the preliminary clinical outcomes of a new procedure using open microwave ablation for the treatment of spinal metastases.
Materials and Methods: Fourteen patients with spinal metastases were treated by open microwave ablation between January 2006 and December 2008. Effectiveness was evaluated using Visual Analog Scale (VAS) and Frankel Classification of Neurological Deficit during the one-month postoperative follow-up.
Results: These procedures were technically successful in all bone lesions. Mean VAS scores during the one-month postoperative follow-up significantly improved compared to preoperative scores (2.3 ± 1.2 vs. 5.1 ± 1.5, P<0.05). Among the six patients who presented with preoperative neurological dysfunction, five patients recovered after surgery; while the remaining patients did not obtain any recovery. Among the eight patients without preoperative neurological dysfunction, one patient complained of loss of total sensory and motor function in the unilateral lower extremity after surgery. However, this was almost restored to normal after three weeks. Local recurrence was observed in three patients. Delayed wound healing occurred in one patient, but eventually healed after a secondary surgery. No wound infection or failure of fixation was observed in any patient. Six patients died after the operation, in which four cases died of primary diseases, and two cases died of cerebral bleeding and pneumonia, respectively.
Conclusions: Open microwave-induced in situ ablation is potentially a promising technique for the treatment of spinal metastases. Further studies with a larger number of samples and longer-term followups are warranted.


Abstract Context National statistical reports in Jordan indicate a decrease in the total fertility rate along with a parallel increase in contraceptive use. The folkloric use of medicinal herbs in gynecological disorders has been growing in Jordan, despite of deficient reports on the evidence-based safety and efficacy of these practices. Objective The aim of this comprehensive article is to review medicinal plants with claimed ethnonpharmacological usage in various gynecological and pregnancy-related issues in Jordan, and to assess their evidence-based pharmacological studies as well as their phytochemistry. Methods The published literature was surveyed using Google Scholar entering the terms "ethnopharmacology AND Jordan AND infertility AND gynecology OR gestation". We included ethnopharmacological surveys in Jordan with available full-text. Results Twelve articles were reviewed. Plant species which are commonly used for female gynecological issues such as Artemisia monosperma Del. and A. herba-alba Asso. (Asteraceae) have been found to exert an antifertility effect. Ricinus communis L. (Euphorbiaceae) and Citrullus colocynthis (L.) Schrad. (Cucurbitaceae) had antifertility effects in male rats, but Nigella sativa oil L. (Ranunculaceae) and Cinnamon zeylanicum J. Presl (Lauraceae) were found to enhance it. Conclusion Using plants for gynecological disorders is a common practice in Jordan. Many of them, whether utilised for gynecological or non-gynecological conditions equally, were found to have detrimental effects on female or male fertility. Thus, couples planning pregnancy should be discouraged from the consumption of these herbs. Further local studies are warranted to confirm the appreciable beneficial pharmacological effects and safety of these plants.


Behavioral studies have shown that consistent practice of a cognitive task can increase the speed of performance and reduce variability of responses and error rate, reflecting a shift from controlled to automatic processing. This study examines how the shift from controlled to automatic processing changes brain activity. A verbal Sternberg task was used with continuously changing targets (novel task, NT) and with constant, practiced targets (practiced task, PT). NT and PT were presented in a blocked design and contrasted to a choice reaction time (RT) control task (CT) to isolate working memory (WM)-related activity. The three-dimensional (3-D) PRESTO functional magnetic resonance imaging (fMRI) sequence was used to measure hemodynamic responses. Behavioral data revealed that task processing became automated after practice, as responses were faster, less variable, and more accurate. This was accompanied specifically by a decrease in activation in regions related to WM (bilateral but predominantly left dorsolateral prefrontal cortex (DLPFC), right superior frontal cortex (SFC), and right frontopolar area) and the supplementary motor area. Results showed no evidence for a shift of foci of activity within or across regions of the brain. The findings have theoretical implications for understanding the functional anatomical substrates of automatic and controlled processing, indicating that these types of information processing have the same functional anatomical substrate, but differ in efficiency. In addition, there are practical implications for interpreting activity as a measure for task performance, such as in patient studies. Whereas reduced activity can reflect poor performance if a task is not sensitive to practice effects, it can reflect good performance if a task is sensitive to practice effects.


Abstract This study investigated whether hot pack treatment could provide prophylactic effects on muscle damage induced by eccentric exercise of the wrist extensors. Twenty-eight healthy men (age 21±1 years, weight 65±16 kg, height 171±6 cm) were randomly placed into hot pack (n = 14) and control (n = 14) groups. All participants performed an exercise consisting of 300 maximal eccentric contractions of the wrist extensors of the non-dominant arm using an isokinetic dynamometer. A hot pack was applied for 20 min to the wrist extensors of the exercised arm before the exercise for the hot pack group. The control group received no treatment before the exercise. Measured variables included pain intensity assessed by a visual analogue scale and a modified Likert's scale, cold thermal pain threshold, pressure pain threshold (PPT), range of motion in active wrist flexion (ROM-AF) and extension (ROM-AE), range of motion in passive wrist flexion (ROM-PF) and extension (ROM-PE), grip strength, and wrist extension strength. Changes in these variables before, immediately after, and 1 to 8 days following the exercise were compared between groups by a two-way repeated measures ANOVA. All outcome measures from both groups (except for the cold thermal pain threshold of the hot pack group) demonstrated a significant change within the first 2–3 days following exercise. Significant differences between groups were only found at a single point in time for PPT, ROM-PF, ROM-PE and ROM-AE, and the changes were smaller for the hot pack group in comparison to the control group. These results suggest that the prophylactic effects of hot pack treatment on eccentric exercise-induced muscle damage of the wrist extensors are limited.


"To Be Gifted & Talented & BLack (Arkology from the Last Angels of History" is an autobiomythography response to Rootwork Journal's call. It explores my journey through the educational system and that my greatest learning came after institutional schooling ended for me. Much of my process in this work uses etymology and wordplay, such as interplaying between the roots of ark/arch/archive. For me, wordplay is like speaking in tongues and is a form of remembering buried languages. Language is a form of coding and I want to imagine the possibilities of it beyond conventional ways. After reading works like Amiri Baraka's "Technology & Ethos" and Martin Heidegger's "The Question of Technology," the former thinking of technology through a black centric view and the latter from a white supremacist view, I wanted to write a poem reflecting on science and technology through the black body and earth and Afro-diasporic cultural mytho-history.


Choosing a textbook for a Women in Film or a Film and Gender course is never easy. Students are rarely prepared for the high theoretical pitch of much of the literature, and they often don't expect to work hard in a film course to begin with. My approach has always been to warn students that the course is hard work and then to maintain my high expectations. But I have to find a textbook to support this approach, which until recently was a real challenge. Two new anthologies-Thornham's 1999 Feminist Film Theory: A Reader and Kaplan's 2000 Feminism and Film-offer excellent choices. Prior to 1999, there were only a few viable classroom choices in print: Feminism and Film Theory, edited by Constance Penley (New York: Routledge; and London: BFI, 1988); Issues in Feminist Film Criticism, edited by Patricia Erens (Bloomington: Indiana University Press, 1990), and Multiple Voices in Feminist Film Criticism, edited by Diane Carson, Linda Dittmar, and Janice R. Welsch (Minneapolis: University of Minnesota Press, 1994). Erens and Penley offered collections of what has become the feminist film theoretical canon. Multiple Voices collected a wonderful range of voices, but can be too challenging if students have not read a collection like Erens's or Penley's first. I taught Penley's volume, once, and found that for my purposes, it did not engage psychoanalysis's critics enough, even though my own work is strongly influenced by psychoanalysis. Erens's Issues did noticeably better in that regard, but still didn't nearly suit my needs. I kept looking for some kind of combination, a book that would offer both canonical texts and challenges to them. The notion of a feminist film theory canon may seem anathema to some, as it does to me in some ways. But as a teacher, I feel an obligation to walk my students through the intellectual history of the topic at hand, and they therefore must read the major debate-generating contributions. To find them collected in one volume makes everyone's life easier. Except that-as we've all learned-there's no one version of a canon, theoretical or otherwise. What that means, in practice, is that any anthology will have strengths and weaknesses, and as an instructor one has to make peace with them. Enter the two volumes under consideration here. Amazingly, there are now two (!) volumes that I'm happy to teach from. What follows then, is a kind of kid-in-a-candy-shop discussion-all choices are good ones. Of the two, E. Ann Kaplan's is, not surprisingly, the more "classical." Given the surfeit of essays eligible for inclusion, Kaplan chose as an organizing principle Laura Mulvey's 1975 "Visual Pleasure and Narrative Cinema." In the preface, she says: Many of the major essays in the field responded in one way or another-including outright rejection-to Mulvey's theoretical positions, so I could produce a book of coherent essays by printing work that debated, argued against, or built out from "Visual Pleasure and Narrative Cinema." (v) By this logic, she compiled a collection that includes four large sections: "Pioneers and Classics: The Modernist Mode"; "Critiques of Phase I Theories: New Methods"; "Race, Sexuality, and Postmodernism in Feminist Film Theory"; and "Spectatorship, Ethnicity, and Melodrama." Each section begins with introductory notes, of about ten pages, which are enormously useful for scholars and students alike. Not only does she survey the essays she has included but also discusses some that she has not. This is a welcome way of combining the strengths of both textbooks and anthologies. There is also an ample "Further Reading" appendix, divided by section. The body of theory generated in response to Mulvey's widely read essay revolves around questions of textuality and reception. Is a masculine position built into film, as her article suggests? If so, is it built into all film? Can women only occupy masculine positions in our engagements with films? …


Single crystal X-ray diffraction (SC-XRD) is the principal method for determining the crystal structures of metal-organic frameworks (MOFs). This tutorial deals with the handling of MOF crystals and analysis of crystallographic data obtained from single-crystal X-ray diffraction, focusing on two features that are particularly important in MOF crystallography and have a large impact on the quality and reliability of the final crystal structures: (1) the treatment of pore-occupying entities (both in the physical crystals and in the crystallographic model) and (2) crystallographic twinning. Proper handling of samples and data will reduce the need for using solvent masking software (e.g. SQUEEZE) to obtain acceptable crystal structures. If SC-XRD is to retain its position as the definitive method of MOF structure determination, these issues must be addressed when a new MOF structure is determined and reported. The issues addressed in this review is also valid for other porous, crystalline solids such as porous organic cages, metal-organic polyhedra, covalent organic frameworks and zeotype materials.


Malaysia, as a former British colony, has inherited much of its trusts law from the English. One notoriously difficult area of law is constructive trusts. Precisely when and why constructive trusts arise are fundamental but imperfectly understood matters. This is unfortunate, because the lack of understanding might, in practice, be critically relevant for the determination of liability. To illustrate, consider the ongoing infamous '1MDB' saga. 1MDB was a government-run strategic development company (allegedly) utilized by the former Prime Minister of Malaysia, Najib Razak, and many others (including his aide, Jho Low) to siphon money to their personal and company accounts. The key events of the highly complex fraudulent scheme took place over a six-year period, leaving behind a long money trail which crossed multiple jurisdictional borders and involved numerous shell companies, international banks, investment companies, and even Hollywood celebrities. While the Malaysian government has focused its efforts on the criminal liability of those allegedly involved, little attention has thus far been paid to the potential private law liabilities, either of those directly breaching trusts or fiduciary duties, or those receiving proceeds of those breaches. These claims would likely be pursued as a matter of course, for example by the liquidators or new directors of 1MDB. At that stage the law of constructive trusts would be crucial for the determination of liability.

One of the first practical hurdles would be the question of limitation: are the constructive trust claims time-barred? As with the law of constructive trusts, the law of limitation in Malaysia is closely modelled on English law. Here, again, the interactions between Malaysian and English law throw up interest but difficult issues of law. This article considers those interactions in the particular context of the applicable limitation periods to constructive trusts claims in Malaysia, to evaluate and assess how English jurisprudence and local developments have shaped the law.


'The Machine to Be Another' is an embodiment system designed to address the relation between identity and empathy. The project merges performances with protocols of neuroscience experiments, in order to offer users an immersive experience of seeing themselves in the body of another person. The paper reports the methods and partial results of the interdisciplinary qualitative investigation that we are making on low budget approach to stimulate empathy through embodied interaction between individuals.


Endogenous retroviruses (ERVs) are present in the genome of all vertebrates and are remnants of ancient exogenous retroviral infections of the host germline transmitted vertically from generation to generation. Sheep betaretroviruses offer a unique model system to study the complex interaction between retroviruses and their host. The sheep genome contains 27 endogenous betaretroviruses (enJSRVs) related to the exogenous and pathogenic Jaagsiekte sheep retrovirus (JSRV), the causative agent of a transmissible lung cancer in sheep. The enJSRVs can protect their host against JSRV infection by blocking early and late steps of the JSRV replication cycle. In the female reproductive tract, enJSRVs are specifically expressed in the uterine luminal and glandular epithelia as well as in the conceptus (embryo and associated extraembryonic membranes) trophectoderm and in utero loss-of-function experiments found the enJSRVs envelope (env) to be essential for conceptus elongation and trophectoderm growth and development. Collectively, available evidence in sheep and other mammals indicate that ERVs coevolved with their hosts for millions of years and were positively selected for biological roles in genome plasticity and evolution, protection of the host against infection of related pathogenic and exogenous retroviruses, and placental development.


Purpose: The purpose of Juntos Y Saludables (Get Healthy Together [GHT]) is to reduce the prevalence of childhood obesity by focusing on physical activity and healthy eating. GHT is an ongoing project, with phase one of three completed in May 2010.The GHT program was implemented in the Edgewood Independent School District's Head Start centers located in San Antonio, TX. These centers were selected due to high prevalence of obesity (50%) and diabetes in children and adults living in the community. Methods: The gross motor intervention was implemented at two of the three centers. The intervention consisted of teacher training and supplemental gross motor resources (lesson plans and activity resources). The System for Observing Fitness Instruction Time (SOFIT) was used to assess the amount of time spent in moderate to vigorous physical activity (MVPA) and the Learning Accomplishment Profile – 3rd Editions (LAP-3) were used to evaluate the program's effects on gross motor development. Results: At the start of the project, the two intervention centers were spending eleven minutes (roughly 24%) of their gross motor class period engaged in MVPA while at the end of the program sixteen minutes (roughly 35%) of the time was spent engaged in MVPA. There was an overall increase in physical activity (P<0.001) and MVPA (P<0.019) levels in both intervention and control centers. A similar linear improvement was also observed in the LAP-3 results. At the conclusion of the project, all of the students either met or were above their gross motor developmental ages. Conclusions: Through the implementation of the GHT Gross Motor intervention a significant increase occurred in the student's gross motor skills and the percentage of time spent in MVPA.


A novel approach to calibrate a phase-shift formed in a long-period fiber grating (LPG) is firstly proposed and numerically demonstrated, which is based on the use of either intensity- or wavelength-interrogation technique to the main loss-peak of the phase-shift LPG in the spectrum. Moreover, by using a CO2 laser with high-repetition-rate pulses emission, an equivalent phase-shift is successfully created at middle of the LPG. As an application of the proposed calibration scheme, measurement for the temperature and the refractive index of the ambient solution has been proposed and successfully demonstrated by using a phase-shifted LPG.


The use of technology is believed to be a solution in overcoming the existing issues, including health issues. In health sector, an electronic documentation system referred to as the Electronic Health Record (EHR) has been introduced and started to be used widely in various countries, including Indonesia. In Indonesia, an innovation of EHR was introduced in 2018 under the name of nursBOX application. This study aimed to describe the perception of nurses towards the use of this application. This was a descriptive quantitative study using electronic survey data collection technique. A google form containing a questionnaire adapted from Galimany-Masclan et al. was sent via email to 322 respondents who were nursBOX users in Bandung District and City, who were obtained through the accidental sampling technique. This questionnaire consisted of 23 statements with a Likert scale. Data collected were then analyzed using the media value with 1 as the minimum value and 5 as the maximum value for each item. Interpretation was then made to classify the answers as positive or negative. Of the 322 respondents, 52 filled out the questionnaire with 53.8% of them expressed a positive perception towards the use of nurseBOX. This positive perception was found in continuity of care (53.8%), usability (50.0%), and record of information (53.8%) domains. Hence, the general perception of nurses towards the use of nursBOX application is positive. However, a review on this innovation should be done because the difference between the positive and negative perceptions is only 7.6%, which is quite insignificant. acting as the point-of-entry for any given scientific paper or patent application.


BACKGROUND
Patient involvement in the choice of antihyperglycemic agents could improve adherence and optimize glycemic control in patients with type 2 diabetes mellitus.

METHODS
We conducted a pilot, cluster randomized trial of Diabetes Medication Choice, a decision aid that describes 5 antihyperglycemic drugs, their treatment burden (adverse effects, administration, and self-monitoring demands), and impact on hemoglobin A(1c) (HbA(1c)) levels. Twenty-one clinicians were randomized to use the decision aid during the clinical encounter and 19 to dispense usual care and an educational pamphlet. We used surveys and video analysis to assess postvisit decisional outcomes, and medical and pharmacy records to assess 6-month medication adherence and HbA(1c) levels.

RESULTS
Compared with usual care patients (n = 37), patients receiving the decision aid (n = 48) found the tool more helpful (clustered-adjusted mean difference [AMD] in a 7-point scale, 0.38; 95% confidence interval [CI], 0.04-0.72); had improved knowledge (AMD, 1.10 of 10 questions; 95% CI, 0.11-2.09); and had more involvement in making decisions about diabetes medications (AMD, 21.8 of 100; 95% CI, 13.0-30.5). At 6-month follow-up, both groups had nearly perfect medication use (median, 100% of days covered), with better adherence (AMD, 9% more days covered; 95% CI, 4%-14%) and persistence (AMD, 12 more days covered; 95% CI, 3-21 days) in the usual care group, and no significant impact on HbA(1c) levels (AMD, 0.01; 95% CI, -0.49 to 0.50).

CONCLUSION
An innovative decision aid effectively involved patients with type 2 diabetes mellitus in decisions about their medications but did not improve adherence or HbA(1c) levels. Trial Registration clinicaltrials.gov Identifier: NCT00388050.


A fundamental pursuit of astronomy is to understand how galaxies form and evolve. What drives the decline in the cosmic star formation rate density? Why are high redshift galaxies clumpy and turbulent? How can we explain the emergence of the Hubble sequence? To answer these questions we must unravel a complex interplay of different processes, including gas accretion, star formation, feedback, and environmental effects. Studying the gas kinematics of galaxies can provide valuable insight. In this thesis we use integral field spectroscopy to probe the evolution of star-forming field and cluster galaxies over the past 8 billion years.

We first present a multi-wavelength analysis of 27 dusty starburst galaxies in a massive cluster at z~0.4. It is thought that starbursts represent an intermediate phase in the transition from spirals to S0s in dense environments. We combine H-alpha kinematics with far-infrared imaging and millimetre spectroscopy, and find that most galaxies are rotationally supported, with high angular momentum and large cold gas reservoirs. It appears that the starbursts have only recently been accreted to the cluster. To complete the transition to S0s, they must undergo a dynamical heating of the disk, increase in concentration, and reduce their angular momentum by ~40%. We conclude that the most likely way to achieve this is via multiple tidal interactions with other cluster members.

We next study the velocity dispersion properties of 472 galaxies observed as part of the KMOS Redshift One Spectroscopic Survey (KROSS). Most galaxies at this epoch are rotationally supported, but dynamically hot and highly turbulent. In order to make robust kinematic measurements, we model the effects of beam smearing using a series of mock KMOS data cubes. We then combine KROSS with data from the SAMI survey (z~0.05) and an intermediate redshift MUSE sample (z~0.5), and find that while there is a weak trend between velocity dispersion and stellar mass, at fixed mass there is a strong increase in velocity dispersion with redshift. At all redshifts, galaxies appear to follow the same weak trend of increasing velocity dispersion with star formation rate. We also test the predictions of two analytic models which suggest that turbulence in the ISM is driven by gravitational instabilities or stellar feedback. However we find that further observations are required to rule-out either model.

Finally, to understand the role of galaxy kinematics in "crystallising" the Hubble sequence, we study the HST images of 231 KROSS galaxies. We quantify differences in morphology using the asymmetry parameter. This metric correlates very well with our visual interpretation of "clumpiness", however there are no strong trends as a function of galaxy kinematics. On average, the velocity dispersion of clumps is consistent with the underlying disk, and there is no evidence to suggest that these star-forming regions are preferentially located towards the outskirts of the galaxy. We propose that adaptive optics assisted IFU observations would provide further insight, allowing us to test clump evolution theories and to study the radial distribution of angular momentum.


Some individuals actively appropriate and resist the impact of digital network technology while others passively accept. Understanding this complex process of human-technology engagement provides insights to its effect: amplifying or diminishing human behavior. Correlations between personality, decision-making style and engagement have been identified from in-depth interviews and self-reporting surveys, revealing two major groups; 'engaged-but-unaware' and 'engaged-and-aware'. The distinction was established by utilizing an ecological approach to 'digital networks' as a tool where the human-tool as a synthesized unit is evaluated within its environment. Engagement was found to involve a suite of behaviors 1) intensity and embededness, 2) responsiveness to feedback, 3) decision-management and 4) motivators. When taken together they form a conceptual model explaining why some individuals resist and appropriate digital network technology to their advantage while others passively accept and are managed by the technology. This paper is part of ongoing research into understanding digital network engagement.


This study was aimed at determining whether the digital volume pulse waveform using the Pulse Sensor can be used to extract features related to arterial compliance. The Pulse Sensor, a low-cost photoplethysmograph, measures green light reflection in the finger and generates output, which is indicative of blood flow and can be read by the low-cost Arduino UNO™. The Pulse Sensor code was modified to increase the sampling frequency and to capture the data in a file, which is subsequently used for waveform analysis using programs written in the R system. Waveforms were obtained using the Pulse Sensor during two 30-s periods of seated rest, in each of 44 participants, who were between the ages of 20 and 80 years. For each cardiac cycle, the first four derivatives of the waveform were calculated and low-pass filtered by convolution before every differentiation step. The program was written to extract 19 features from the pulse waveform and its derivatives. These features were selected from those that have been reported to relate to the physiopathology of hemodynamics. Results indicate that subtle features of the pulse waveform can be calculated from the fourth derivative. Feature misidentification occurred in cases of saturation or low voltage and resulted in outliers; therefore, trimmed means of the features were calculated by automatically discarding the outliers. There was a high efficiency of extraction for most features. Significant relationships were found between several of the features and age, and systolic, diastolic, and mean arterial blood pressure, suggesting that these features might be employed to predict arterial compliance. Further improvements in experimental design could lead to a more detailed evaluation of the Pulse Sensor with respect to its capability to predict factors related to arterial compliance.


Has the labor share declined? And what is the impact of international trade? These questions are not only relevant in an international context they also matter for understanding the regional distribution of incomes in a given country. In this paper, we study two regions with trade exposures that differ from the rest of the country, and which display distinct changes in the labor share. East German and Southern Italian regions have a degree of international openness which is below the countries' averages. At the same time, there has been a more pronounced decline in the labor share in East Germany than in West Germany. In Southern Italy, the labor share has increased in recent years. We show that increased trade openness is not the main culprit behind changing labor shares.


In this article, we describe the various types of banking services (payments, settlement and safekeeping) that the Bank of Canada provides to different types of clients (the Government of Canada, financial market infrastructures, financial institutions, foreign central banks and the Canada Deposit Insurance Corporation). We also explain the reasons the Bank provides these services and how this role supports its core mandates, in particular financial stability. Finally, we explore the factors driving the growth and evolution in the provision of these banking services.


The problem of stochastic (i.e. robust) water distribution system (WDS) design is formulated and solved here as an optimisation problem under uncertainty. The objective is to minimise total design costs subject to a target level of system robustness. System robustness is defined as the probability of simultaneously satisfying minimum pressure head constraints at all nodes in the network. The decision variables are the alternative design options available for each pipe in the WDS. The only source of uncertainty analysed is the future water consumption uncertainty. Uncertain nodal demands are assumed to be independent random variables following some pre-specified probability density function (PDF). Two new methods are developed to solve the aforementioned problem. In the Integration method, the stochastic problem formulation is replaced with a deterministic one. After some simplifications, a fast numerical integration method is used to quantify the uncertainties. The optimisation problem is solved using the standard genetic algorithm (GA). The Sampling method solves the stochastic optimisation problem directly by using the newly developed robust chance constrained GA. In this approach, a small number of Latin Hypercube (LH) samples are used to evaluate each solution's fitness. The fitness values obtained this way are then averaged over the chromosome age. Both robust design methods are applied to a New York Tunnels rehabilitation case study. The optimal solutions are identified for different levels of robustness. The best solutions obtained are also compared to the previously identified optimal deterministic solution. The results obtained lead to the following conclusions: (1) Neglecting demand uncertainty in WDS design may lead to serious under-design of such systems; (2) Both methods shown here are capable of identifying (near) optimal robust least cost designs achieving significant computational savings.


This peer-reviewed conference paper reports on a major Norwegian-funded research project 'Schooling and Cultural Values in Africa' (2001-2004 £180K) (RA5) led by Professor Stephens. The research investigated relationships between traditional and modern values and schooling in urban and rural communities in Western and Eastern Cape in South Africa. An original feature of the research is the employment of culture as a frame of reference and specifically the application of Bourdieu's concept of 'cultural capital' in a global South context. Research findings pose a number of important issues to be addressed by South African policy makers, notably around questions of language of instruction, curriculum content, and the extent to which South Africa can develop a quality education system for the most disadvantaged areas. The research has contributed significantly to Development discourses generally and specifically concerning the transfer of educational models from North to South.


The researched are rarely provided the opportunity to take a role in the collection, analysis, and interpretation of data they themselves provide to researchers. This article describes a novel indigenous research method, for a project in progress, which was developed to explore the relationships between intra-whānau (family) communication and whānau ora (family well-being) within eight whānau over a three year period. The relationships are explored through self-reflexive praxis where research participants are encouraged to think reflexively about their whānau conversations. Conversations that take place in the private world of whānau are audio-recorded by family members, without the imposition of an intrusive researcher. Whānau decide the extent to which their private lives are exposed to the researchers via the recordings and assist the researchers with an interpretation of their everyday conversations. This method offers an opportunity for both whānau and researchers to contribute to insights and understandings of the complex ecologies and realities of life for Māori families. This research methodology involves culturally-centred ethical practice drawn from both Western- and Māori-centred perspectives. Sensitive issues arising from the ways in which individuals perceived their role as active agents of research and the effects of self-reflection on the method are explored.


A firm's customers and suppliers make relationship-specific investments (RSI) whose value reduces if the firm undertakes risky investments. We hypothesize that the risk-taking incentives in the firm CEO's compensation will lower the RSI by firms up and down in the vertical channel. We provide significant evidence that customer/supplier RSI declines with the risk-taking incentives of the firm's CEO. Moreover, we find that RSI is more sensitive to the CEO's risktaking incentives when they are more likely to increase the firm's cash flow volatility. Our findings are robust to correcting for endogeneity and several measures for RSI and risk taking. JEL Classification G30


A technical reference guide and instruction text for the estimation of flood and drainage water levels in rivers, waterways and drainage channels. It is written as a user's manual for the openly available innovative Conveyance and Afflux Estimation System (CES-AES) software, with which water levels, flows and velocities in channels can be calculated. The impact of factors influencing these levels and the sensitivity of channels to extreme levels can also be assessed. Approaches and solutions are focused on addressing environmental, flood risk and land drainage objectives. Practical Channel Hydraulics is the first reference guide that focuses in detail on estimating roughness, conveyance and afflux in fluvial hydraulics. With its universal approach and the application of metric units, both book and software serve an international audience of consultants and engineers dealing with river modelling, flood risk assessment, maintenance of watercourses and the design of drainage systems. Suited as course material for training graduate Master's students in civil and environmental engineering or geomorphology who focus on river and flood engineering, as well as for professional training in flood risk management issues, open channel flow hydraulics and modelling. The CES-AES software development followed recommendations by practitioners and academics in the UK Network on Conveyance in River Flood Plain Systems, following the Autumn 2000 floods, that operating authorities should make better use of recent improved knowledge on conveyance and related flood (or drainage) level estimation. This led to a Targeted Programme of Research aimed at improving conveyance estimation and subsequent integration with other research on afflux at bridges and culverts at high flows. The CES-AES software tool aims to improve and assist with the estimation of: - hydraulic roughness - water levels (and corresponding channel and structure conveyance) - flow (given slope); section-average and spatial velocities - backwater profiles upstream of a known flow-head control e.g. weir (steady) - afflux upstream of bridges and culverts - uncertainty in water level


Infrared emission spectra of thin polymer layers on flat aluminum plate have been measured using Fourier transform infrared spectrometry. The detection limit of Fourier transform infrared emission spectrometry (FT-IR-EMS) was found to be comparable with that of Fourier transform infrared reflection absorption spectrometry (FT-IR-RAS) when an emission ray was collected at a viewing angle of 70°. The merits of FT-IR-EMS over FT-IR-RAS were demonstrated in the measurement of nonflat surfaces. The residual lubricant on steel tire cords could be detected efficiently by the FT-IR-EMS mode. The linear relationship found between the relative emission intensity and the thickness of film represents the possibility for a quantitative analysis of a thin overlayer on metal surface.


Large-scale genome sequencing is providing a comprehensive view of the complex evolutionary forces that have shaped the structure of eukaryotic chromosomes. Comparative sequence analyses reveal patterns of apparently random rearrangement interspersed with regions of extraordinarily rapid, localized genome evolution. Numerous subtle rearrangements near centromeres, telomeres, duplications, and interspersed repeats suggest hotspots for eukaryotic chromosome evolution. This localized chromosomal instability may play a role in rapidly evolving lineage-specific gene families and in fostering large-scale changes in gene order. Computational algorithms that take into account these dynamic forces along with traditional models of chromosomal rearrangement show promise for reconstructing the natural history of eukaryotic chromosomes.


A previously healthy, 16-year-old Hispanic boy initially presents to the clinic with a 5-day history of tactile fevers, achy malaise, congestion, and a dry cough. He was afebrile with negative rapid strep and monospot tests, but was prescribed fluticasone, benzonatate, and ibuprofen for a presumed upper respiratory infection. He was encouraged to return if symptoms did not improve.


In an open economy such as Canada's, exchange rate movements can have a material impact on consumer prices. This is particularly important in the current context, with the significant depreciation of the Canadian dollar vis-a-vis the U.S. dollar since late 2012. This paper provides a broad overview of the various mechanisms by which exchange rate movements pass through to consumer prices and discusses the implications of exchange rate pass-through (ERPT) for the conduct of monetary policy. It then describes some of the tools used at the Bank of Canada to help quantify ERPT. We conclude by taking a closer look at the current situation in Canada, presenting a range of evidence that suggests ERPT has played an important role in recent inflation dynamics.


The paper asks whether the return of Borsa Istanbul100 index has long term relations with U.S. Dollar to Turkish Lira (TL) exchange rate, London Bullion Market Association (LMBA) gold fixing price, interest rate on TL saving deposit, and real house price index over the period of 2000:01-2014:07 in Turkey. We first test stationary of time series through Augmented Dickey Fuller, Phillips-Perron, Zivot-Andrews, and Lee-Strazicich unit root tests. Then, we perform Johansen cointegration test and multiple structural breaks cointegration test of Maki (2012). Johansen cointegration test suggests that there is a long term relationship among the variables, but Maki cointegration estimation do not provide evidence for the existence of cointegration. According to the latter result, we may argue that TL/FX saving deposits, gold, and housing markets in Turkey, having probably different investment dynamics and investor profile, may not integrate or compete with stock market under the impacts of structural breaks. This outcome may also imply that the policies on the development of stock market and contributions of stock market to the growth may have some structural limitations.


Complex fluorides of protactinium having a Pa/M ratio of one (where M = K, Rb, or NH4) have been prepared from concentrated solutions of HF. These MPaF6 compounds are isostructural with the corresponding compounds of pentavalent uranium but not with the tantalum analogs. The size of protactinium (V) is but slightly larger than that of uranium (V)


ABSTRACT Eolian sandstones occur interbedded with alluvial-fan and braided-river red beds in the Upper Triassic Wolfville Formation and at the base of the Lower Jurassic McCoy Brook Formation in Nova Scotia. Extensive semiaridity and aridity in the subtropical rift valley favored deposition of eolian sandstones, caliche paleosols, alluvial-fan conglomerates, braided-river alluvium, and playa mudstones. In postdrift configuration, paleowinds blew to the southwest, west, and northwest down the valley, reflecting the direction of trade winds at 25°N paleolatitude. A three-step hierarchy of surfaces truncates cross-beds. First-order bedding planes of low relief extend for at least hundreds of meters, truncating all eolian structures. These surfaces were sculptured by desert flash floods and then deflated to ventifact-bearing bimodal regs. Second-order surfaces bound cross-bed sets and are mostly concave-up and dip downwind, recording shifts in migration direction of individual dunes or dunes superimposed on larger dune structures. Third-order surfaces within cross-bed sets formed on the lee sides of dunes due to fluctuations in wind direction and strength. Barchans initially developed on the alluvial-fan and braided-river alluvium, later coalescing into barchanoid transverse ridges, as evidenced by the internal geometry of the eolian sandstones. /P>


A proper thermodynamic analysis of living-cell processes should elucidate the often-supposed sophistication of biochemical energy and material conversion, and it may provide valuable lessons on the design and operation of future technological processes. The difficulty however is to adequately account for the interaction of biochemical compounds with their complex intracellular environments, especially since available thermodynamic data typically only reflect highly idealised solution properties. To allow more meaningful analyses, this paper describes the various relevant contributions to the exergy of biochemical compounds at specific intracellular conditions. The resulting exergy-calculation procedure is illustrated for the well-known biochemical compound ATP, and it is shown how the potential of ATP to drive processes at intracellular conditions is almost twice the value suggested by biochemical standard Gibbs energy data. The paper discusses the relevance of the more accurate thermodynamic calculations, referring also to the performed exergy analyses of intracellular glucose degradation, fatty-acid degradation, and photosynthesis.


A new genus of Gesneriaceae, Bopopia Munzinger & J.R.Morel gen. nov., is described from New Caledonia. The genus is based on B. parviflora Munzinger & J.R.Morel gen. et sp. nov., a new species collected during an expedition on Mt Katalupaik, in the North Province of New Caledonia's main island. Originally considered as a species of Coronanthera, our phylogenetic analysis – including 19 species within Coronanthereae and two individuals of B. parviflora gen. et sp. nov., and using three molecular markers (nuclear rDNA ITS, and chloroplast regions trnL-trnF and trnE-trnT) – showed that the new species is not close to Coronanthera in subtribe Coronantherinae, but belongs to subtribe Negriinae where it is sister to Depanthus. From that genus Bopopia gen. nov. differs in floral symmetry (zygomorphic vs actinomorphic) and the number of stamens (4 vs 5). From the other genera of Negriinae the new genus differs in the white corolla and its indeterminate thyrse with 3 to 5 levels of branching. The morphological circumscription of the subtribe Negriinae is amended to include Bopopia gen. nov. Two keys are provided, one to the subtribes in the tribe Coronanthereae, and one to the genera in subtribe Negriinae. Following the IUCN Red List categories and criteria, the conservation status of B. parviflora gen. et sp. nov. is provisionally assessed as Endangered (EN).


Ros Kidd uses official correspondence to reveal the extraordinary extent of government controls over Aboriginal wages, savings, endowments and pensions in twentieth century Queensland. In a disturbing indictment of the government's $4000 reparations offer, Kidd unpicks official dealings on the huge trust funds compiled from private income and community endeavours, showing how governments used these finances to their advantage, while families and communities struggled in poverty. Casting the evidence in terms of national and international litigation, particularly cases relating to government accountability for Indigenous interests, Kidd makes a powerful case that the Queensland government should be held to the same standards of accountability and redress as any major financial institution. 'Trustees on Trial' is a timely warning for all other Australian jurisdictions to consider their liability for Aboriginal money taken in trust.


The unprecedented and growing amount of predictive information we can draw from an individual's genetic data poses serious threats to fundamental human rights for a number of reasons. Large-scale whole genome sequencing and data sharing, enabled by technological advancements, are ongoing internationally. The extent of data availability, and genetic data being the 'gold mines' of the 21st century, has led to large-scale data breaches being regular and unavoidable. The traditional protective measure – anonymisation of data – is ineffective in preventing re-identification of individuals. Moreover, genetic data are useful for more than a generation. Therefore, once information is extracted from genetic data and is in possession of potential misusers, even the discarding of sequenced genomes does not protect individuals from the numerous potential misuses of genetic information. Protection provided by the law is either non-existent or scattered across a number of legislations even in countries with recently updated laws, with fundamental rights being under threat. This threat is particularly imminent in developed economies, as genomic testing is becoming common and genomic medicine a reality. To protect individuals, societies must enact specific laws to regulate existing and anticipated uses of genetic information.


In order to find out the influence of gun bore structure on the performance of interior ballistic processes, a modified interior ballistic model is established. In the model, the energy conversion of an interior ballistic process is analyzed in detail, and many components of energy are absorbed into an item that is expressed in the form of work output from propellant gas system. With the combination of computational solid mechanics and fluid mechanics, the modified interior ballistic model can be solved without the use of a coefficient of energy losses. The relationship between the shot-base pressure and the mean pressure is derived under the hypothesis of Lagrange. And the projectile is directly pushed by the shot-base pressure and resisted by forces that source from the contact between a projectile and its barrel. In this paper, the classical interior ballistic model is modified firstly. Then the twist angle of the rifling and the forcing cone angle are selected as characteristic parameters of the gun bore structure, and their influences on the performance of interior ballistic processes is studied. In order to characterize the influences, a coefficient of energy losses is directly defined. Based on the simulated results, the coefficient is calculated and the influences are analyzed.


This research project began with the objective of obtaining a deeper understanding of the conduct of business on the Internet. Research regarding the overall performance of business on the Web has been limited due to several constraining factors. Firstly, the shear size, volume, and perceived complexity of business on the Web made it an imposing target for research. Secondly, the interdisciplinary nature of the field had an initial dampening effect on research activity. Kuhn (1962) describes this phenomenon as the insufficiency of methodological directives. He writes (p. 3) 'Instructed to examine electrical or chemical phenomena, the man who is ignorant of these fields but who knows what it is to be scientific may legitimately reach any one of a number of incompatible conclusions. Among those legitimate possibilities, the particular conclusions he does arrive at are probably determined by his prior experience in the other fields'. Thirdly, academic interest in Web businesses was somewhat diminished by the bursting of the dot com bubble during 2000-2001 as evidenced by the fact that many academic programs in electronic commerce have been discontinued or significantly reduced (Featherstone, Ellis & Borstorff 2004). Lastly, methodological issues arose which limited the application of previously available sampling methods. The impact of this meant that drawing representative samples of websites in order to examine business behaviour became a more complex endeavour. As a result, many fundamental questions regarding business on the Web have remained unanswered. For example, there has been no clear answer to the question of what new business models, if any, are evolving within the Web environment. What is the role of entrepreneurship employing the Web? What are the key elements or mechanisms driving business expansion in the Web? Some have suggested that Web use necessitates greater business cooperation than may be necessary in the non-virtual world. Is there evidence that this is so? This thesis addresses these questions. It accomplishes this by reducing the function of business on the Internet to its simplest element, the domain name, and by employing innovative methodologies to explore the business environment of the Web. Using Complexity and Network Theories as a contextual framework , and based upon a review of existing literature, this thesis develops a series of propositions regarding both the conduct and attributes of Web business, and proceeds to present evidence of confirmation or refutation of these propositions.


Although DNA transfection with calcium-phosphate/DNA precipitates for promoter analysis of genes has been previously applied to primary cultures of neuronal cells, it remains uncertain whether the expression of the introduced genes in glial cells, which are also in primary culture, affects the transcriptional signals obtained. Using plasmid DNA containing the brain-derived neurotrophic factor (BDNF) gene promoter I or c-fos promoter, we investigated the optimum conditions for calcium-phosphate-mediated DNA transfection in primary culture of rat cortical neuronal cells. Normalizing the firefly luciferase activity of the experimental reporter gene to the Renilla luciferase activity of the internal control increased experimental reliability. Maximum expression of firefly luciferase activity in the cells stimulated by membrane depolarization required 6-12 hrs of incubation after stimulation. Differences in the ratio of the experimental reporter gene to the internal control did not affect experimental gene expression. Under our optimal conditions, the activation of the BDNF gene promoter I was detected in neuronal but not in glial cells. Calcium-phosphate-mediated DNA transfection should be widely applicable for promoter analysis of inducible genes in neurons.


There is growing interest in quantifying genetic population structure across the geographical ranges of species to understand why species might exhibit stable range limits and to assess the conservation value of peripheral populations. However, many assertions regarding peripheral populations rest on the long‐standing but poorly tested supposition that peripheral populations exhibit low genetic diversity and greater genetic differentiation as a consequence of smaller effective population size and greater geographical isolation relative to geographically central populations. We reviewed 134 studies representing 115 species that tested for declines in within‐population genetic diversity and/or increases in among‐population differentiation towards range margins using nuclear molecular genetic markers. On average, 64.2% of studies detected the expected decline in diversity, 70.2% of those that tested for it showed increased differentiation and there was a positive association between these trends. In most cases, however, the difference in genetic diversity between central and peripheral population was not large. Although these results were consistent across plants and animals, strong taxonomic and biogeographical biases in the available studies call for a cautious generalization of these results. Despite the large number of studies testing these simple predictions, very few attempted to test possible mechanisms causing reduced peripheral diversity or increased differentiation. Almost no study incorporated a phylogeographical framework to evaluate historical influences on contemporary genetic patterns. Finally, there has been little effort to test whether these geographical trends in putatively neutral variation at marker loci are reflected by quantitative genetic trait variation, which is likely to influence the adaptive potential of populations across the geographical range.


We model the price prediction in Sri Lankan stock market using Ising model and some recent developments in statistical physics techniques. In contrast to usual agent-models, the influence does not flow inward from the surrounding neighbors to the centre, but spreads outward from the center to the neighbors. Monte Carlo simulations were used to study this problem. The analysis was based on All share price index, Milanka price index in Colombo Stock Exchange and Simulated Price Process. The monthly and daily influences of the above indices to the Sri Lankan economy were also investigated. The model thus describes the spread of opinions traders.


Building on contemporary debates over the past several decades in Marxist and post-Marxist theory regarding the relationship between capitalism and postcapitalism, this essay will explore the enduring relevance of Marx's treatment of this issue in some of his most significant, though increasingly less contemporarily engaged with texts (as Capital [Vols. 1-3] and the Grundrisse take pride of place). Here, I look toward the middle and early period of Marx's oeuvre to pull out the most important statements and insights regarding the relationship between capitalism and postcapitalism, focusing on The German Ideology, The 18th Brumaire of Louis Bonaparte, Economic and Philosophic Manuscripts of 1844, and The Communist Manifesto in order to offer reflections on how Marx's work, 200 years since his birth, offer the contemporary and future left guidance on "minding the gap" between capitalism and postcapitalism as we live, work, and struggle still deeply ensconced within the confines of the decadent capitalist mode of production. Combing close-reading of key relevant texts in Marx's oeuvre with reflective commentary on how Marx's work can speak to the contemporary conjuncture, this paper offers a synthetic commentary on how leftists, both scholars and activists, should approach the question of the relationship between radical praxis within capitalism and the character of potential postcapitalisms that may emerge. This essay is loosely organised around three crucial questions: (1) What can we learn from Marx's discussions on the historical transition and the overall radical intellectual project of dialectical materialism that can assist us in understanding the transition from capitalism to a democratic, egalitarian postcapitalism (i.e., socialism/communism), specifically concerning complexity and time? (2) How does contemporary capitalism reproduce itself social-psychologically (i.e., ideologically) and what are the implications of that for a postcapitalist transformation? (3) What is/are the role(s) of revolutionaries in dealing with the first two questions?


This thesis offers a political history of PRC propaganda targeted at foreigners in the 20th and 21st century. It seeks to give an answer to the seeming contradiction that particularly over the last decade, China has repeatedly pledged to invest more resources into improving its image and influencing international public opinion, yet at the same time, there continue to be blunders of the most basic type, particularly in areas where China wants to influence foreigners' opinions most. The thesis examines how and to what extent China has been able to adapt its external propaganda apparatus, initially set up on the basis of the Soviet propaganda model that depended on the ability of the Party to regulate the flow of information into and out of China, to the current global media environment marked by porous national borders and fast-paced flows of information across the globe. Drawing on internal publications, archival documents, openly available materials, and interviews, it combines a bird's-eye perspective on the development of external propaganda in China over the course of the 20th and 21st century with in-depth reading and analysis of key texts.
Two propositions are tested: First, that external factors, including foreign models that China learns from, have had significant impact on how Chinese external propaganda policy has developed and second, that previous choices the PRC has made for its external propaganda sector substantially restrict the options available to the CPC today. Arguing that external propaganda has been path dependent at various levels, this study explains the difficulties China's external propaganda apparatus continues to face as well as what strategies people pushing for reforms have used to overcome historical, ideological, and bureaucratic baggage.


The rapid-pace development in mobile technology offers tremendous opportunities for both the public and private sector in healthcare domain. Unlike other forms of communications, e.g., the Internet, increasingly ubiquitous use of mobile technology and devices allow mobile health and wellness applications to have a greater impact on how care is delivered. Although, technology is an essential tool for healthcare provision, to fully leverage these opportunities other major issues on the emergence of more patient-centric healthcare solutions need to be addressed. A sustainable business model plays a significant role in exploration and exploitation of mobile health and wellness applications. Therefore, this paper presents a systematic literature review based on a business model ontology, in order to lay the basis for exploitation of these applications. The review shows that the extant literature mainly focuses on the service platforms components of business models and their underlying technological challenges, and that non-technological business model components such as value proposition, organizing and revenue models have not attracted the attention that is deemed necessary for exploitation of mobile health care solutions. This paper cautions that in a highly regulated yet often monopolistic industry such as healthcare, the regulatory and the legal issues must be considered as an external business factors.


Anti-Roma prejudice is characterized as a unique form of prejudice because of its blatant nature. News about Roma has been overlooked as a key explanation for anti-Roma prejudice. This study aims to offer insight into news messages about Roma in a systematic and longitudinal way. To this end, I conducted a content analysis of 15 years of all television news stories ( N = 181) about Roma in Flanders (2003–2017). Findings suggest a shift in patterns in news coverage of Roma. Although Roma are still underrepresented as a minority group on television and get a voice in only about one third of all news stories, uniformly negative news stories about Roma are on the decline in favor of more balanced news stories. Frames referring to blatant threats posed by Roma, such as criminal frames, are being replaced by more subtle frames. Journalists also more often portray Roma presence in society as a policy issue.


This thesis describes the synthesis and characterization of silicon and silicon germanium nanoparticles (NPs) in a dedicated plasma reactor. We investigate the oscillations found in the optical emission intensity and plasma current to estimate the time scales for dust formation. These measurements showed a specific periodic oscillation in the dusty regime. However these plasma properties showed no fluctuations in the non-dusty regime. We hypothesize that the fluctuations arise from periodic formation and ejection of a dust cloud from the plasma bulk when a critical dust size is reached. The proof of concept of the operation of the NP reactor is provided by demonstrating a fast and simple technique to synthesize non-embedded, non-agglomerated free standing Si NPs. Two ensembles of particles have been synthesized originating from two different locations, from the bulk of the plasma and from the locally enhanced plasma in the holes of the grounded electrode. They have significantly different characteristics in terms of size, shape, and crystallinity. We highlight that the locally enhanced plasma is beneficial as it contributes to the formation of, among other particles, free standing quantum sized crystalline nanoparticles due to the presence of excess energetic electrons. Precise size control of NPs can be obtained by pulsing the RF power with alternating ON (tON) and OFF times (tOFF). We study the time evolution of the formation of particles as a function of tON using high resolution electron microscopy and we identify three phases, ultimately leading to cauliflower structured particles. We hypothesize that these complex polycrystalline particles originate from a single nucleus and that gas phase species are subsequently added to this growing nucleus. The role of tOFF is studied to tailor the size of the silicon NPs. This study infers that when tOFF is less than the gas residence time, complex multi-sized nanostructures form because some NPs which are not pumped out of the reactor stay between the electrodes and their growth continues for various pulses. This situation is overcome for longer tOFF, which allows the source gas to be refreshed, making conditions beneficial for obtaining quantum sized monodisperse NPs. We investigate the relationship between the various plasma parameters such as power density (P), pressure (p) and inter-electrode distance (d) on the crystallinity of the Si NPs obtained in the gas phase. One of the less studied parameters for NP growth in PECVD reactors is the inter-electrode distance d. We studied the entire p and d process parameter space possible for our reactor and show that the optimum parameter space for the growth of NPs with improved morphology and crystallinity is the regime of higher p and larger d. We have successfully synthesized highly crystalline and homogeneously alloyed Si1-xGex NCs in continuous and pulsed plasmas. Agglomerated NCs have been produced with remarkable control over their composition by altering the precursor GeH4 gas flow in a continuous plasma. The presence of Si1-xGex alloy particles is confirmed with multiple techniques consistently yielding the same composition. In the pulsed plasma mode, quantum-sized free standing alloy NCs were obtained. The NCs synthesized here have potential applications in tandem solar cells with subcells of which the band gap can be tuned.


This dataset contains data on the Cohesion Policy projects managed by Local Managing Authorities in the selected case-studies of the PERCEIVE project over the 2007-2013 programming period.

The selected case-study regions are the following: Emilia-Romagna and Calabria (IT), Extremadura (ES), Burgenland (AT), Norra Mellansverige (SE), Sud-Est (RO), Essex (UK), Dolnośląskie and Warminsko-Mazurskie (PL). The framework for the data collection was built by UNIBO after the guidelines set by the European Commission for the monitoring of the Cohesion Policy projects. All partners from the PERCEIVE consortium have contributed to the construction of this dataset by gathering data referred to their own case-study region from the Managing Authorities, some of which are involved in the PERCEIVE project as third-parties: Regione Emilia-Romagna (IT), Ministerio de Economia y Hacienda - Direccion General de Fondos Comunitarios (ES) and Agentia pentru Dezvoltare Regionala Sud-Est (RO).

The dataset is made up of 4 sheets:

"1. Categorisation" includes information on projects' scopes, locations, titles, as well as on the managing authorities and other bodies involved;
"2. Payments" contains information on the CP expenditure, broken down by source of the funding and year of payment, where available;
"3. Beneficiaries" contains information on the beneficiaries of the CP funding (name and location, if available) and the amount of funding received broken down by year, if available;
"4. Communication" reports the expenditure in Cohesion Policy-related communication and dissemination activities, broken down by type of activities and year, if available.
A codebook is included which provides information on the variables' content as well as details regards space and time coverage.
This dataset is also available on Zenodo (10.5281/zenodo.1035808).


The Internet and the digitalization of information have brought big changes in healthcare, but the arrival of smartphones and tablets represent a true revolution and a new paradigm is opened which completely changes our lives. In order to validate the impact of these new technologies in health care, it is essential to have enough clinical studies that validate their impact in wellbeing and healthcare of the patient. Traditional regulatory organisations are still looking for their role in this area. If they follow the classical path of medical devices, we get to a technical, administration and economic collapse. This contribution first presents the main indicators showing the potential of mHealth adoption. It then proposes a classification of mobile health care apps, and presents frameworks for mHealth evaluation. Regulation of mHealth as part of the evaluation process is discussed. Finally, the necessary steps and challenges that have to be taken into account by the industry to prepare the entrance of these technologies into the EU market is analysed.


Learning with noisy labels is a practically challenging problem in weakly supervised learning. In the existing literature, open-set noises are always considered to be poisonous for generalization, similar to closed-set noises. In this paper, we empirically show that open-set noisy labels can be non-toxic and even benefit the robustness against inherent noisy labels. Inspired by the observations, we propose a simple yet effective regularization by introducing Open-set samples with Dynamic Noisy Labels (ODNL) into training. With ODNL, the extra capacity of the neural network can be largely consumed in a way that does not interfere with learning patterns from clean data. Through the lens of SGD noise, we show that the noises induced by our method are random-direction, conflict-free and biased, which may help the model converge to a flat minimum with superior stability and enforce the model to produce conservative predictions on Out-of-Distribution instances. Extensive experimental results on benchmark datasets with various types of noisy labels demonstrate that the proposed method not only enhances the performance of many existing robust algorithms but also achieves significant improvement on Out-of-Distribution detection tasks even in the label noise setting.


It is well known that in the early stages of legal development in Commonwealth jurisdictions, when these countries were still colonies of the British Empire, there was uniformity in their laws as the English common law was received by these countries and applied by their judiciaries with little or no modifications. As time passed, with the shift towards independence in these former British colonies, some Commonwealth countries have diverged from the English common law by providing for judicial solutions that are perceived to best fit their individual circumstances, values and needs. In other words, there has been a break up of Commonwealth common law.
Whilst there has been much academic discussion on this phenomenon in relation to for example, tort and contract, hardly any has been written on private international law. Accordingly, it is the purpose of this thesis to address the paucity of academic writing on this subject matter by undertaking a comparative study of two areas of private international law, namely the doctrine of forum non conveniens and tort choice of law in Australia, Canada and Singapore, with the relevant English common law positions as the key reference point.
Specifically, this thesis began by establishing the existence as well as the nature and extent of the break up of forum non conveniens and tort choice of law in our selected Commonwealth jurisdictions. It is then argued that one reason for this phenomenon is that there are differences in the judicial treatment of policies, concepts and other wider considerations relevant to these areas of private international law in these countries. Subsequently, the issue of how these jurisdictions should respond to this phenomenon was examined and we concluded that the prospects for the harmonisation of jurisdictional and tort choice of law rules at the global, regional and Commonwealth level has been largely unpromising. Accordingly, it is argued that the way forward is for our selected Commonwealth jurisdictions to develop their own rules on these areas of private international law with their own social, economic and political circumstances in mind.


Mixed-media artist Carlos Betancourt and his influential studio, Imperfect Utopia, helped to launch the Miami art scene in the 1980 s. Betancourt s oeuvre is a lush explosion of radiant, eccentric colors in which he explores the kaleidoscope (multi-racial, multi-lingual, trans-cultural) of Caribbean and American culture. His work alludes to issues of memory, beauty, identity, and communication. He bends the lines between art, photography, and nature in his photographs, collages, painting, installations, and conceptual pieces. Carlos Betancourt s imagery reinterprets the past and present and offers it in a fresh context. He is inspired by Puerto Rico, Miami, and his extensive travels; also artist Ana Mendieta s interventions in nature, Robert Rauschenberg s assemblages, Andy Warhol s perceptions, Neo Rauch compositions, and a Federico Fellini-esque cast of characters for his photo assemblages. This exuberant volume explores Betancourt s body of work, with more than 250 images and texts by art critic Paul Laster, art history professor Robert Farris Thompson and United States Inaugural Poet, Richard Blanco. His artwork is included in the permanent collections of various museums, including The Metropolitan Museum of Art, The National Portrait Gallery, and The Smithsonian Institute."


Medulloblastoma is the most common type of malignant brain tumor in children, responsible for 25% of pediatric brain cancers. Conventional treatment methods, which include surgery, radiotherapy, and chemotherapy, have improved overall survival rates for patients with medulloblastoma to over 50%. A majority of survivors, however, suffer serious long-term side effects, including developmental, neurological, and psychoso‐ cial deficits. Now entering clinical trials for sonic hedgehog-driven medulloblastomas, Smoothened inhibitors have been FDA approved for the treatment of basal cell carcino‐ mas. However, treatment efficacy endures only for a few months before lesion relapses and drug resistance occurs. Therefore, there is an urgent need for new therapies to reduce the significant problems associated with current drug-resistant treatments. In this chapter, we will illustrate the clinical presentation and current treatment methods for medullo‐ blastoma and detail the molecular pathways within each of the four molecular sub‐ groups of medulloblastoma, with an eye for possible candidates for novel combination therapies.


The Ensemble Kalman filter (EnKF) has achieved great successes in data assimilation in atmospheric and oceanic sciences, but its failure in convergence to the right filtering distribution precludes its use for uncertainty quantification. Other existing methods, such as particle filter or sequential importance sampler, do not scale well to the dimension of the system and the sample size of the datasets. In this dissertation, we address these difficulties in a coherent way. In the first part of the dissertation, we reformulate the EnKF under the framework of Langevin dynamics, which leads to a new particle filtering algorithm, the so-called Langevinized EnKF (LEnKF). The LEnKF algorithm inherits the forecast-analysis procedure from the EnKF and the use of mini-batch data from the stochastic gradient Langevin-type algorithms, which make it scalable with respect to both the dimension and sample size. We prove that the LEnKF converges to the right filtering distribution in Wasserstein distance under the big data scenario that the dynamic system consists of a large number of stages and has a large number of samples observed at each stage, and thus it can be used for uncertainty quantification. We reformulate the Bayesian inverse problem as a dynamic state estimation problem based on the techniques of subsampling and Langevin diffusion process. We illustrate the performance of the LEnKF using a variety of examples, including the Lorenz-96 model, high-dimensional variable selection, Bayesian deep learning, and Long Short-Term Memory (LSTM) network learning with dynamic data. In the second part of the dissertation, we focus on two extensions of the LEnKF algorithm. Like the EnKF, the LEnKF algorithm was developed for Gaussian dynamic systems containing no unknown parameters. We propose the so-called stochastic approximation- LEnKF (SA-LEnKF) for simultaneously estimating the states and parameters of dynamic systems, where the parameters are estimated on the fly based on the state variables simulated by the LEnKF under the framework of stochastic approximation. Under mild conditions, we prove the consistency of resulting parameter estimator and the ergodicity of the SA-LEnKF. For non-Gaussian dynamic systems, we extend the LEnKF algorithm (Extended LEnKF) by introducing a latent Gaussian measurement variable to dynamic systems. Those two extensions inherit the scalability of the LEnKF algorithm with respect to the dimension and sample size. The numerical results indicate that they outperform other existing methods in both states/parameters estimation and uncertainty quantification.


This thesis investigates the role of the amygdala for the establishment of fear memories with a multidisciplinary approach, including behavioural, psychopharmacological, genetic, molecular, and electrophysiological techniques in rats or mice, under healthy or pathological conditions. This research program aims to shed light on the acquisition and storage of emotional memories in the amygdala and closely interconnected brain areas. In one line of experiments, the molecular mechanisms leading to the establishment of fear memory traces in the amygdala were investigated. For this purpose, the functional role of the polysialylated neural cell adhesion molecule PSA-NCAM, expressed in the synaptic junction, was assessed in the amygdala – and also prefrontal cortex and hippocampus – with psychopharmacological and genetic approaches and tasks that strongly rely on these brain areas. Two lines of studies were followed: 1) amygdala-targeted cleavage and enhancement of PSA-NCAM in rats and 2) general cleavage of PSA-NCAM throughout the brain using genetically modified mice. Taken together, both approaches show that amygdaloid PSA-NCAM plays no role in the acquisition and storage of fear memories, but is rather involved in their extinction. Furthermore, the results confirm the importance of PSA-NCAM in hippocampus mediated learning and for the first time show that prefrontal cortex mediated learning depends on PSA-NCAM. These results suggest that PSA-NCAM is selectively involved in some, but not all, synaptic plasticity processes in the brain. In another line of experiments, the valproic acid (VPA) animal model of autism was used to investigate a possible contribution of the amygdala towards the autistic pathology. VPA was injected once at a specific time point during gestation, the time of neural tube closure. The offspring of such treated rats were first characterized in a broad set of behavioural tasks. It was found that VPA-treated offspring exhibited very specific behavioural anomalies closely resembling autistic symptomotology, such as impaired social interaction, exploration and recognition, enhanced repetitive behaviours, impaired sensorimotor gating and increased anxiety, while other behavioural parameters were left unharmed. Once the validity of the model was established, amygdala functionality was assessed. The results demonstrated that VPA-treated offspring exhibited highly enhanced conditioned fear memories, which generalized to other stimuli and were resistant to extinction. Electrophysiological in vitro recordings in the amygdala revealed hyper-reactivity towards stimulation and enhanced activity-induced synaptic plasticity. These results imply that enhanced activity and plasticity in the amygdala may underlie the exaggerated fear memories. Furthermore it is suggested in this thesis that a hyper-reactive amygdala may underlie some of the most basic symptoms observed in autism: reduced social interactions and resistance to rehabilitation.


Biological, atmospheric, and geochemical processes interact to shape how element cycles and nutrient losses develop within newly formed landscapes. We examined losses of nitrogen (N), phosphorus (P), and base cations across a four-million-year substrate age gradient of Hawaiian montane tropical forests, with the goal of understanding how losses depend on changes in biotic demand, weathering, and atmospheric sources. We were particularly interested in whether losses of nutrients that are not subject to traditional mechanisms of biotic availability could influence ecosystem fertility and nutrient limitation over time. Over a three-year period we sampled nutrient outputs in soil solutions below the active plant-soil system and small streams, gaseous N losses (NO, N2O, and N2), and pools and transformations of N in soils. Weathering was the major determinant of ecosystem losses of P, of base cations and Si, and of ecosystem acid-base status. Sharp reductions in weathering inputs after 20 000 years of forest development caused dramatically lower outputs of P (;65% reduction), Ca 2 1 (;99%), and Si (;94%), to rates that matched inputs from dilute sea-salt and dust aerosols. Internal production of organic acids, in combination with low weathering, caused highly acidic soil waters (pH , 5.0) with elevated Al (up to 300 mg/L) and Ca:Al ratios (,0.3) below values considered critical thresholds for many plant species. Long-term N and P interactions were more complex than predicted by the Walker and Syers model, with important influences of N and P loss pathways that were not subject to direct biotic availability. While losses of available forms of dissolved N and P, and N gases followed (as predicted) ecosystem nutrient availability, significant dissolved organic N (DON) and dissolved organic P (DOP) losses occurred independent of ecosystem N or P status. DON losses were not sufficient (relative to external inputs) to sustain N limitation beyond 20 000 years, while dissolved P losses remained large enough to maintain P lim- itation in older forests. Forests developed high N:P loss ratios over time ( .300 on mass weight basis) due to efficient P recycling and unexpectedly high N throughputs (4-9 kg N·ha 21 ·yr 21 ) by either N fixation and/or N deposition.


The decline in numbers of reef manta rays (Mobula alfredi) throughout their range has highlighted the need for improved information on their spatial ecology in order to design effective conservation strategies for vulnerable populations. To understand their patterns of movement in Seychelles, we used three techniques—archival pop-up satellite tags, acoustic tags, and photo-identification—and focussed on the aggregation at D'Arros Island and St. Joseph Atoll within the Amirantes Group. M. alfredi were photographed within six of the seven Island Groups of Seychelles, with 64% of individuals being resighted at least once between July 2006 and December 2019 over timeframes of 1–3,462 days (9.5 years; median = 1,018 days). Only three individuals from D'Arros Island were resighted at a second aggregation site located more than 200 km away at St. François Atoll during photo-identification surveys. Satellite-tracked M. alfredi (n = 5 tracks; maximum 180 days) remained within the boundary of the Seychelles Exclusive Economic Zone, where they spent the majority of their time (87%) in the upper 50 m of the water column in close proximity to the Amirantes Bank. The inclusion of acoustic tagging data in the models of estimated satellite-track paths significantly reduced the errors associated with the geolocation positions derived from archived light level data. The insights gained into the patterns of horizontal and vertical movements of M. alfredi using this multi-technique approach highlight the significance of D'Arros Island and St. Joseph Atoll, and the wider Amirantes Group, to M. alfredi in Seychelles, and will benefit future conservation efforts for this species within Seychelles and the broader Western Indian Ocean.


Copyright © 2016, MEJDS. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited. Abstract Background and objective: Family is one of the most important social institutions, which is based on marriage. As a human, sophisticated, elegant and dynamic relationship, marriage has been one of the fundamental issues of human life and human society throughout history. The first buds of relationships between human beings emerge in the privacy of the family. Relationships within the family are of paramount importance and sensitivity and the how of these relationships play an important role in shaping social attitudes and feedback, preparation and development of social skills of family members. In today's society, human life undergoes quick and dramatic changes in all aspects. Marriage is not an exception, disputes and misunderstandings are common in the family and no family is an exception. Sometimes these disputes lead to great problems. Therefore, the present study aims to determine the relationship between locus of control and self-efficacy beliefs with marital conflicts among university students. Methods: This study is a descriptive and correlational one. The population of this study includes all married male and female students of humanities faculty of Islamic Azad University of Sanandaj enrolling in 2015, i.e. 189 people. Random sampling was used to recruit 125 participants based on diagnostic criteria of DSM-V. The resarch instruments were Marital Conflict Questionnire developed by Sanaee and Barati, Locus of Control developed by Rotter Self-efficacy developed by Scherre. Of the 125 questionnaires distributed, 122 questionnaires were returned, of which 20 questionnaires were flawed. Finally, 102 questionnaires were used for statistical analysis. Pearson correlation coefficient and simple linear regression were used to analyze the data. Results: The results showed that there is no significant relationship between locus of control and marital conflict among students, indicating that the locus of control cannot predict marital conflicts among students. Although the mean of marital conflict among students with external locus of control was greater than the mean of marital conflict among students with internal locus of control, this difference is not significant. Therefore, marital conflicts of student with internal and external loci of control are similar. In addition, there is a negative significant relationship between self-efficacy of students and their marital conflicts (p<0.001, r=-0.369). This suggests that the higher the level of self-efficacy, the less marital conflict and vice versa. Conclusion: The findings can confirm the fact that people can control their life events, assume greater responsibility for their life, have more confidence in their capabilities to control their lives, as a result of having of certain beliefs about their lives. It can also be concluded that there is a significant relationship between self-efficacy and marital conflict, probably because self-efficacy is correlated with self-control and a sense of self-control plays an important role in coping with the stressors in life. Thus, it may be the case that people feel they can solve marital problems, through enhancing their self-efficacy beliefs.


Mechanisms of adaptation to environmental changes in osmolarity are fundamental for cellular and organismal survival. Here we identify a novel osmotic stress resistance pathway in Caenorhabditis elegans (C. elegans), which is dependent on the metabolic master regulator 5'-AMP-activated protein kinase (AMPK) and its negative regulator Folliculin (FLCN). FLCN-1 is the nematode ortholog of the tumor suppressor FLCN, responsible for the Birt-Hogg-Dubé (BHD) tumor syndrome. We show that flcn-1 mutants exhibit increased resistance to hyperosmotic stress via constitutive AMPK-dependent accumulation of glycogen reserves. Upon hyperosmotic stress exposure, glycogen stores are rapidly degraded, leading to a significant accumulation of the organic osmolyte glycerol through transcriptional upregulation of glycerol-3-phosphate dehydrogenase enzymes (gpdh-1 and gpdh-2). Importantly, the hyperosmotic stress resistance in flcn-1 mutant and wild-type animals is strongly suppressed by loss of AMPK, glycogen synthase, glycogen phosphorylase, or simultaneous loss of gpdh-1 and gpdh-2 enzymes. Our studies show for the first time that animals normally exhibit AMPK-dependent glycogen stores, which can be utilized for rapid adaptation to either energy stress or hyperosmotic stress. Importantly, we show that glycogen accumulates in kidneys from mice lacking FLCN and in renal tumors from a BHD patient. Our findings suggest a dual role for glycogen, acting as a reservoir for energy supply and osmolyte production, and both processes might be supporting tumorigenesis.


This very short paper (three pages) addresses a question raised by Chief Justice Roberts and later Justice Ginsburg in oral argument in MedImmune, Inc v. Genentech, Inc. The Justices asked whether a patentee, having granted a license that is still in force, could seek a declaratory judgment that the licensed patent is valid, in order to dispel legal uncertainty surrounding the patent and demand a higher royalty rate. The oral argument produced no clear answer, but there is an answer: based on two well-established legal doctrines, such a dispute would not be justifiable. The first well-established doctrine is Article III's requirement of resolvability - that the requested judgment resolve a dispute without further litigation. A declaratory judgment of patent validity would not have that effect because of the second well-established doctrine - a rule of black-letter contract law under which the validity of a contract depends only on the existence of consideration, not its value or amount. A patentee-licensor with a declaratory judgment of validity in her pocket would have to sue the licensee again, this time for a declaratory judgment that the contract was voidable for mutual mistake. That claim would be doubtful; and even if it succeeded the court would have no basis for redetermining the royalty rate but would have to remit the parties back to private bargaining. Thus the putative declaratory judgment of validity would not finally resolve the dispute. In contrast, a licensee with a declaratory judgment of invalidity would simply stop paying royalties, while continuing to manufacture products covered by the invalid patent's claims. The patentee would have no basis for suing, whether for patent infringement (because an invalid patent cannot be infringed) or for breach of contract (because of total failure of consideration). There is thus an asymmetry in the availability of declaratory judgments to patentee-licensors and licensees when a patent license is in force, but it follows from well-established principles of Article III and contract law.