bluuebunny/crossref_metadata_2025 huggingface dataset:
Legal Status of Telemedicine in the Internal Market
Authors: Glanowski Grzegorz
Published: June 2016

Health services enjoy freedom of movement within the European Union (eu). This freedom also applies to information society services (iss). This article presents a legal framework within which it is possible to provide qualifying health services with the help of information and telecommunications technology (ict) as iss. Due to the ambiguity of eu regulation, the problem regarding how to determine whether a particular medical service corresponds to favourable structural iss conditions is considered. Since telemedicine makes a wide application of electronic devices possible, a new element appears in the relationship between physicians and their patients. Therefore, using electronic devices may cause numerous doubts regarding the normative status of these devices, since they modify the physician’s responsibility and affect the scope of his duty with regard to information. At the same time, the complexity of functional elements (actions) necessary to provide health services using ict can, in some cases, prevent them from being recognised as iss.
A Substantial Change in the Approach to the Zoroastrian Long Liturgy
Authors: Cantera Alberto
Published: June 2016

Between 2006 and 2013 J. Kellens published in five volumes (the last one together with C. Redard) a corrected version of the text edited by K.F. Geldner of the longest and most important Zoroastrian ritual usually known by the name of one of its variants as the Yasna. The text accompanies an experimental translation and both are followed by a commentary. J. Kellens is pioneering in translating and studying, not only the standard daily variant of the liturgy, but also its more solemn version. Furthermore, his work is the first attempt to read the complete text of the liturgy as the coherent text (although produced at different times) of an old and meaningful liturgy, although it has been traditionally understood as a late composition. As it appears in the manuscripts and is celebrated still today in India, the liturgy is the result of a series of conscious interpretations, reinterpretations and rearrangements of older versions. Despite of this, it is a coherent text and ritual in which each section of the liturgy plays a concrete role that J. Kellens has tried to bring to light for the first time. In the present review, I try to highlight the extraordinary importance of Kellens’ new approach to the Zoroastrian Long Liturgy and to expose his main achievements. At the same time, I expose the main weaknesses of this monumental work: 1. its dependence on the text edited by Geldner, which hides part of the ritual variety of the Long Liturgy; 2. the conscious disregard of the meta-ritual information provided by the Zoroastrian tradition about the performance of the liturgy; 3. J. Kellens’s Yasna-centrism that prevents him to recognize the close connections between the Long Liturgy and other minor rituals and the participation within the Long Liturgy of many short rituals that can be celebrated independently.
The Rootless Faith of Ajātaśatru and Its Explanations in the *Abhidharma-mahāvibhāṣā
Authors: Wu Juan
Published: June 2016

A number of Indian Buddhist texts extant in Sanskrit, Chinese, and/or Tibetan speak of the rootless faith of the patricide Ajātaśatru. Some modern scholars interpret his rootless faith as the faith the Buddha has brought about in him despite the extirpation of his wholesome roots caused by his patricide. This paper argues that such an interpretation is inapplicable to the *Abhidharma-mahāvibhāṣā which claims the non-extirpation of Ajātaśatru’s wholesome roots and explains his rootless faith from five different perspectives. The Sarvāstivāda claim of the non-extirpation of Ajātaśatru’s wholesome roots is probably made in view of his acceptance of the existence of karmic cause and result. The five explanations of his rootless faith in the *Abhidharma-mahāvibhāṣā show the attempts of its compilers/redactors to recycle existing narrative material and to contextualize some of the material into their own doctrinal system.
“Journalists Discovered Łódź Like Columbus”
Authors: Marzec Wiktor , Zysiak Agata
Published: June 2016

This article examines Polish urban travelogue literature and reportage concerning the industrial city of Łódź in the late nineteenth and early twentieth centuries. Łódź, a rapidly growing textile production center, was one of the few places which paved the way to real industrial, capitalist modernization in the Russian-controlled Kingdom of Poland. It was inhabited by large non-Polish populations and came to be perceived as alien, hostile and even savage. We investigate the anti-urban discourse on Łódź from the background of the broader Polish debates and compare it with urban travel writing on England. Łódź, although located in Europe, was subjected to an almost touristic gaze and virtually orientalized. Drawing from concepts of orientalization and nesting orientalism and the strong program in cultural sociology, we argue that in this situation an unusual reversal occurred in the modernization debate. What was orientalized and excluded from the broader civic community, even denied civilization status, constituted precisely the components connected with industry, capitalism and modernization.
WOOD ANATOMY AND TRAIT-BASED ECOLOGY
Authors: Beeckman Hans
Published: June 2016

The largest part of forest biomass consists of wood. A global estimate of carbon stored in lignified tissues rises up to 400 Pg. Given these quantities, there is a growing interest of implementing wood research in diagnoses and evaluations of the carrying capacity of the global ecosystem and its forests. The question arises how disciplines like wood anatomy could respond to the increasing demands of a trait-based ecology, understood as a paradigmatic shift in addressing global changes. Dendrochronology and ecological wood anatomy, traditionally operating within the paradigm of species-based ecology, developed robust methods to address ecological questions. However, sampling strategies and database design will likely be different when wood traits are to be used to study individual tree performance, including responses to stress.

Aiming at optimally involving wood research in trait-based ecology, some trait concepts are analysed. The value of the IAWA standard lists of wood anatomical features as starting points for trait databases is recognized. A summary of the functionality of wood is given to inform the trait-research community of basic aspects of tree performance. The time dimension is highlighted, as well as the foundations for understanding bio-hydraulics, bio-mechanics and metabolism of wood and relevant traits.

Guidelines are given for sampling strategies and database concepts. Prospects of time axis construction and system integration are discussed, as well as the importance of standardizing for size.
TREE-RING FEATURES: INDICATORS OF EXTREME EVENT IMPACTS
Authors: Bräuning Achim , De Ridder Maaike , Zafirov Nikolay , García-González Ignacio , Petrov Dimitrov Dimitar , Gärtner Holger
Published: June 2016

Wood anatomical features may be visible on the microscopic as well as on the macroscopic scale. While the former can often be quantified by detailed wood anatomical analyses, the latter are often treated as qualitative features or as binary variables (present/absent). Macroscopic tree-ring features can be quantified in terms of frequency, intensity, or classified according to their position within a tree ring, like intra-annual density variations (IADFs) in conifers or frost rings in earlywood or latewood. Although some of these tree-ring features, like e.g. missing rings or IADFs are often seen as anomalies, hampering dendrochronologists to perform proper crossdating of tree-ring series, many of these properties are formed under extreme environmental stress or heavy impact, and could mark these extreme events by the manifestation in the wood anatomical structures throughout the lifespan of trees. The described tree-ring features form discrete time-series of extreme events. For example, flood rings may be marked by lunar-shaped earlywood vessels or enlarged latewood vessels in ring-porous oaks. White earlywood rings and light rings indicate reduced cell wall thickness and lignification occurring in very cold years. Frost rings result from cambial cell death during abrupt cooling events in the growing season. Missing rings and IADFs are mainly caused by drought events. Characteristic variations in earlywood vessel size, shape, or number in ring-porous oak species are markers for flood events, defoliation, heat stress, or drought. Traumatic resin ducts may be triggered by a range of biotic or environmental stressors, including wounding, fires or mechanical factors. Reaction wood is indicative of mechanical stress, often related to geomorphic events. In many cases anatomical responses are unspecific and may be caused by different stressors or extreme events. Additionally, the sensitivity of trees to form such features may vary between species, or between life stages within one species. We critically evaluate the indicative value of different wood anatomical tree-ring features for environmental reconstructions.
GROWTH-RING DISTINCTNESS AND BOUNDARY ANATOMY VARIABILITY IN TROPICAL TREES
Authors: Tarelkin Yegor , Delvaux Claire , De Ridder Maaike , El Berkani Thomas , De Cannière Charles , Beeckman Hans
Published: June 2016

The phenomenon of distinct, absent or indistinct growth rings is a highly variable feature used for wood identification and a wide range of tree-ring studies. Causes for its variability are not yet fully understood. There is also a lack of consensus within the scientific community about how distinct and indistinct tree rings should be defined and classified. We use a selection of 103 Central African rainforest trees to analyse the anatomy of growth-ring boundaries of 103 Central African rainforest species and assessed the influence of the climate, tree organ and leaf shedding behaviour on growth-ring distinctness and anatomy. We observed a high variability of tree-ring boundaries anatomy and distinctness within and among individuals and species. Although, for some semi-deciduous species, higher incidence of distinct growth rings appears to be related with a more pronounced seasonal climate, no general trends are observed for the assembly of studied species. Growth rings are variable within individuals depending on the considered organ: trunks tend to show more distinct rings than branches. Growth-ring distinctness is difficult to implement as a trait to measure tree performance when only based on abrupt changes in fibre size and cell wall thickness. From the potential growth-ring markers identified in the IAWA list of hardwood features, those applying to vessel and parenchyma density and distended rays appear to be more useful in tropical trees than abruptly flattened latewood fibres or abrupt changes in vessel diameter.
EARLYWOOD VESSELS IN RING-POROUS TREES BECOME FUNCTIONAL FOR WATER TRANSPORT AFTER BUD BURST AND BEFORE THE MATURATION OF THE CURRENT-YEAR LEAVES
Authors: Kitin Peter , Funada Ryo
Published: June 2016

This paper reviews the development of xylem vessels in ring-porous dicots and the corresponding leaf phenology. Also included are our original observations on the time-course of vessel element growth, secondary wall deposition, and end wall perforation in the deciduous hardwood Kalopanax septemlobus. Different patterns of xylem growth and phenology serve different strategies of the species for adaptation to seasonal climates. Trees with ring-porous xylem form wide earlywood vessels (EWV) in spring and narrow latewood vessels in summer. The wide EWV become embolized or blocked with tyloses by the end of the growing season while the narrow vessels may remain functional for many years. The co-occurrence of wide and narrow vessels provides both efficiency and safety of the water transport as well as a potentially longer growing season. It has for a long time been assumed that EWV in ring-porous hardwoods are formed in early spring before bud burst in order to supply sap to growing leaves and shoots.

However, the full time-course of development of EWV elements from initiation of growth until maturation for water transport has not been adequately studied until recently. Our observations clarify a crucial relationship between leaf maturation and the maturation of earlywood vessels for sap transport. Accumulated new evidence shows that EWV in branches and upper stem parts develop earlier than EWV lower in the stem. The first EWV elements are fully expanded with differentiated secondary walls by the time of bud burst. In lower stem parts, perforations in vessel end walls are formed after bud burst and before the new leaves have achieved full size. Therefore, the current-year EWV network becomes functional for water transport only by the time when the first new leaves are mature.
Conflict about Climate Change at the American Meteorological Society: Meteorologists’ Views on a Scientific and Organizational Controversy
Authors: Stenhouse Neil , Harper Allison , Cai Xiaomei , Cobb Sara , Nicotera Anne , Maibach Edward
Published: June 2016

This article analyzes open-ended survey responses to understand how members of the American Meteorological Society (AMS) perceive conflict within the AMS over global warming. Of all survey respondents, 53% agreed that there was conflict within the AMS; of these individuals who perceived conflict, 62% saw it as having at least some productive aspects, and 53% saw at least some unproductive aspects. Among members who saw a productive side to the conflict, most agreed as to why it was productive: debate and diverse perspectives enhance science. However, among members who saw an unproductive side, there was considerable disagreement as to why. Members who are convinced of largely human-caused climate change expressed that debate over global warming sends an unclear message to the public. Conversely, members who are unconvinced of human-caused climate change often felt that their peers were closed-minded and suppressing unpopular views. These two groups converged, however, on one point: politics was seen as an overwhelmingly negative influence on the debate. This suggests that scientific organizations faced with similar conflict should understand that there may be a contradiction between legitimizing all members’ views and sending a clear message to the public about the weight of the evidence. The findings also reinforce the conclusion that attempts by scientific societies to directly address differences in political views may be met with strong resistance by many scientists.
Evaluation of Variation in Surface Solar Irradiance and Clustering of Observation Stations in Japan
Authors: Watanabe Takeshi , Takamatsu Takahiro , Nakajima Takashi Y.
Published: June 2016

Variation in surface solar irradiance is investigated using ground-based observation data. The solar irradiance analyzed in this paper is scaled by the solar irradiance at the top of the atmosphere and is thus dimensionless. Three metrics are used to evaluate the variation in solar irradiance: the mean, standard deviation, and sample entropy. Sample entropy is a value representing the complexity of time series data, but it is not often used for investigation of solar irradiance. In analyses of solar irradiance, sample entropy represents the manner of its fluctuation; large sample entropy corresponds to rapid fluctuation and a high ramp rate, and small sample entropy suggests weak or slow fluctuations. The three metrics are used to cluster 47 ground-based observation stations in Japan into groups with similar features of variation in surface solar irradiance. This new approach clarifies regional features of variation in solar irradiance. The results of this study can be applied to renewable-energy engineering.
Atmospheric Response to a Midlatitude SST Front: Alongfront Winds
Authors: Kilpatrick Thomas , Schneider Niklas , Qiu Bo
Published: June 2016

Satellite observations and modeling studies show that midlatitude SST fronts influence the marine atmospheric boundary layer (MABL) and atmospheric circulation. Here, the Weather Research and Forecasting (WRF) mesoscale model is used to explore the atmospheric response to a midlatitude SST front in an idealized, dry, two-dimensional configuration, with a background wind oriented in the alongfront direction.

The SST front excites an alongfront wind anomaly in the free atmosphere, with peak intensity just above the MABL. This response is nearly quasigeostrophic, in contrast to the inertia–gravity wave response seen for cross-front background winds. The free-atmosphere response increases with the background wind , in contrast to previously proposed SST frontal MABL models.

The MABL winds are nearly in Ekman balance. However, a cross-front wind develops in the MABL as a result of friction and rotation such that the MABL cross-front Rossby number ε ≈ 0.2. The MABL vorticity balance and scaling arguments indicate that advection plays an important role in the MABL dynamics. Surface wind convergence shows poor agreement with MABL depth-integrated convergence, indicating that the MABL mixed-layer assumption may not be appropriate for SST frontal zones with moderate to strong surface winds.
Lower-Tropospheric Mixing as a Constraint on Cloud Feedback in a Multiparameter Multiphysics Ensemble
Authors: Kamae Youichi , Shiogama Hideo , Watanabe Masahiro , Ogura Tomoo , Yokohata Tokuta , Kimoto Masahide
Published: June 2016

Factors and possible constraints to extremely large spread of effective climate sensitivity (ECS) ranging about 2.1–10.4 K are examined by using a large-member ensemble of quadrupling CO2 experiments with an atmospheric general circulation model (AGCM). The ensemble, called the multiparameter multiphysics ensemble (MPMPE), consists of both parametric and structural uncertainties in parameterizations of cloud, cumulus convection, and turbulence based on two different versions of AGCM. The sum of the low- and middle-cloud shortwave feedback explains most of the ECS spread among the MPMPE members. For about half of the perturbed physics ensembles (PPEs) in the MPMPE, variation in lower-tropospheric mixing intensity (LTMI) corresponds well with the ECS variation, whereas it does not for the other half. In the latter PPEs, large spread in optically thick middle-cloud feedback over the equatorial ocean substantially affects the ECS, disrupting the LTMI–ECS relationship. Although observed LTMI can constrain uncertainty in the low-cloud feedback, total uncertainty of the ECS among the MPMPE cannot solely be explained by the LTMI, suggesting a limitation of single emergent constraint for the ECS.
Ancient Ethical Practices of Dualism and Ethical Implications for Future Paradigms in Nursing
Authors: Milton Constance L.
Published: June 2016

Paradigms contain theoretical structures to guide scientific disciplines. Since ancient times, Cartesian dualism has been a prominent philosophy incorporated in the practice of medicine. The discipline of nursing has continued the body-mind emphasis with similar paradigmatic thinking and theories of nursing that separate body and mind. Future trends for paradigm and nursing theory development are harkening to former ways of thinking. In this article the author discusses the origins of Cartesian dualism and implications for its current usage. The author shall illuminate what it potentially means to engage in dualism in nursing and discuss possible ethical implications for future paradigm and theory development in nursing.
Power in Practice
Authors: Karnick Paula M.
Published: June 2016

Power in practice reveals itself in many ways. There are many definitions of power but in nursing care it could be said that the power is within the patient. Nurses facilitate patients power by engaging them in dialogical engagements. This helps patients to decide how to utilize the power of living their quality.
Effects of a Meditation Program on Nurses’ Power and Quality of Life
Authors: Chang Sun Ju , Kwak Eun Young , Hahm Bong-Jin , Seo Se Hee , Lee Da Woon , Jang Sun Joo
Published: June 2016

This study evaluated the effects of meditation programs on nurses’ power and quality of life. In this study, Barrett’s power theory derived from Rogers’ unitary human being science was used as a theoretical framework. A randomized controlled design with 50 recruited and randomly allocated participants was used. The results demonstrated that the eight-week meditation program significantly improved nurses’ power and quality of life. These results suggest that meditation has positive effects on power and quality of life.
The Two Nursing Disciplinary Scientific Revolutions
Authors: Koffi Kan , Fawcett Jacqueline
Published: June 2016

The purpose of this essay is to share Kan Koffi’s ideas about scientific revolutions in the discipline of nursing. Koffi has proposed that the works of Florence Nightingale and Martha E. Rogers represent two scientific revolutions in nursing as a learned discipline. The outcome of these two scientific revolutions is a catalyst for critical disciplinary and paradigmatic debate about the universal conceptualization of nursing’s distinctive professional and scientific knowledge.
Historic city, tourism performance and development: The balance of social behaviours in the city of Santiago de Compostela (Spain)
Authors: Fernández Belén Mª Castro , González Rubén Camilo Lois , Lopez Lucrezia
Published: June 2016

Santiago de Compostela is an iconic place. From the 9th century through to the present day the city has acted as the final destination of a major pilgrimage route named after it. In the article we ask ourselves how the contemporary reinvention of the pilgrimage and pilgrimages on the Way of St. James has boosted tourism development in the city. Development has been concentrated in the historic city centre and in the area around the cathedral. The importance of tourism has transformed the significance of the city itself, which acquires a magical component as a place of arrival and encounter for all kinds of visitors. The historic city has been set up in the 20th century as a destination for the Way and for cultural tourism. The buildings, particularly those connected with the pilgrimage route, become highly attractive and symbolic places and tourists carry out a number of rituals in them. They travel and enjoy Santiago as a unique experience. The study of tourism and of the tourist transformation of Santiago de Compostela is undertaken using a qualitative and quantitative method. The article analyses the heritage and symbolic value of the historic centre, together with the growth of its tourism activities. Numerical data are also provided on the perceptions and behaviour of visitors using surveys carried out by the city's Tourism Observatory.
Remembrance tourism in former multicultural Galicia: The revival of the Polish–Ukrainian borderlands
Authors: Bechtel Delphine
Published: June 2016

The historical region of Galicia was appropriated successively by the Habsburg Imperium, Independent Poland, the USSR, Hitler Germany, and Communist Poland and the USSR. It is presently divided in to two by the border between Poland and Ukraine, the EU and the belt of post-Soviet states. Its multicultural past has been eradicated through genocide, ethnic cleansing, and deportations by Hitler and Stalin as well as various interethnic conflicts between Polish and Ukrainian nationalists. From 1989 on, pilgrims, survivors, root tourists, and also religious, political, and community activists have started to rediscover it. Poles, Ukrainians, Jews, as well as Russian and Western travelers cross the borders to remember their childhood places, the locus of their deportation or survival, or the cradle of the family history, or just a province lost. Their expectations are partly met, or sometimes ignored, by municipal and regional authorities, travel agencies, private businesses, and locals, who all contribute to form a network of touristic infrastructures. The memory of WW2 and of the subsequent deportations looms large in the personal agendas of tourists and community activists. However, Poland and Ukraine envision local, historical, and identity tourism in the region variously. While Western Ukraine tries to convey a strongly nationalistic and monoethnic image of the region, Poland, under the influence of EU guidelines and subsidies, has opened to a more multicultural and postmodern concept. Transnational tourism across the border participates in the reassertion of conflicting national identities.
Developing a Canadian-Specific Version of the Fitness-to-Drive Screening Measure©
Authors: Classen Sherrilene , Alvarez Liliana , Ferreira Peter J. M. , Chen Chien H. , Meyer Carly K. , Nywening Amy G.
Published: June 2016

The Fitness-to-Drive Screening Measure© (FTDS) is a valid and reliable screening tool that identifies at-risk older drivers. Although 12,300 Canadians have used the FTDS in the last 2 years, the resources/recommendations targeted the U.S. context. The objective of this article is to identify the FTDS resources/recommendations appropriate for Canadian users and the barriers that Canadian stakeholders experience when promoting older driver fitness. Twenty stakeholders from three provinces (eight occupational therapists, three certified driver rehabilitation specialists, four physicians, and five members of advocacy organizations) participated in semi-structured interviews. We conducted summative and thematic content analysis. A comprehensive set of resources/recommendations was identified. Barriers to older driver fitness decisions included fear of losing the license, compromising the physician–client relationship, insufficient training/resources for health care professionals, and inadequate alternative transportation. Canadian context-specific resources/recommendations were integrated into a Canadian version of the FTDS. This version may better serve Canadian older drivers, caregivers, and health care professionals.
DiAs User Interface: A Patient-Centric Interface for Mobile Artificial Pancreas Systems
Authors: Keith-Hynes Patrick , Guerlain Stephanie , Mize Benton , Hughes-Karvetski Colleen , Khan Momin , McElwee-Malloy Molly , Kovatchev Boris P.
Published: June 2016

Background:

Recent in-hospital studies of artificial pancreas (AP) systems have shown promising results in improving glycemic control in patients with type 1 diabetes mellitus. The next logical step in AP development is to conduct transitional outpatient clinical trials with a mobile system that is controlled by the patient. In this article, we present the user interface (UI) of the Diabetes Assistant (DiAs), an experimental smartphone-based mobile AP system, and describe the reactions of a round of focus groups to the UI. This work is an initial inquiry involving a relatively small number of potential users, many of whom had never seen an AP system before, and the results should be understood in that light.

Methods:

We began by considering how the UI of an AP system could be designed to make use of the familiar touch-based graphical UI of a consumer smartphone. After developing a working prototype UI, we enlisted a human factors specialist to perform a heuristic expert analysis. Next we conducted a formative evaluation of the UI through a series of three focus groups with N = 13 potential end users as participants. The UI was modified based upon the results of these studies, and the resulting DiAs system was used in transitional outpatient AP studies of adults in the United States and Europe.

Results:

The DiAs UI was modified based on focus group feedback from potential users. The DiAs was subsequently used in JDRF- and AP@Home-sponsored transitional outpatient AP studies in the United States and Europe by 40 subjects for 2400 h with no adverse events.

Conclusions:

Adult patients with type 1 diabetes mellitus are able to control an AP system successfully using a patient-centric UI on a commercial smartphone in a transitional outpatient environment.
DiAs Web Monitoring: A Real-Time Remote Monitoring System Designed for Artificial Pancreas Outpatient Trials
Authors: Place Jérôme , Robert Antoine , Ben Brahim Najib , Keith-Hynes Patrick , Farret Anne , Pelletier Marie-Josée , Buckingham Bruce , Breton Marc , Kovatchev Boris , Renard Eric
Published: June 2016

Background:

Developments in an artificial pancreas (AP) for patients with type 1 diabetes have allowed a move toward performing outpatient clinical trials. “Home-like” environment implies specific protocol and system adaptations among which the introduction of remote monitoring is meaningful. We present a novel tool allowing multiple patients to monitor AP use in home-like settings.

Methods:

We investigated existing systems, performed interviews of experienced clinical teams, listed required features, and drew several mockups of the user interface. The resulting application was tested on the bench before it was used in three outpatient studies representing 3480 h of remote monitoring.

Results:

Our tool, called DiAs Web Monitoring (DWM), is a web-based application that ensures reception, storage, and display of data sent by AP systems. Continuous glucose monitoring (CGM) and insulin delivery data are presented in a colored chart to facilitate reading and interpretation. Several subjects can be monitored simultaneously on the same screen, and alerts are triggered to help detect events such as hypoglycemia or CGM failures. In the third trial, DWM received approximately 460 data per subject per hour: 77% for log messages, 5% for CGM data. More than 97% of transmissions were achieved in less than 5 min.

Conclusions:

Transition from a hospital setting to home-like conditions requires specific AP supervision to which remote monitoring systems can contribute valuably. DiAs Web Monitoring worked properly when tested in our outpatient studies. It could facilitate subject monitoring and even accelerate medical and technical assessment of the AP. It should now be adapted for long-term studies with an enhanced notification feature.
In Silico Optimization of Basal Insulin Infusion Rate during Exercise: Implication for Artificial Pancreas
Authors: Schiavon Michele , Man Chiara Dalla , Kudva Yogish C. , Basu Ananda , Cobelli Claudio
Published: June 2016

Background:

Several clinical trials have been performed to assess safety and efficacy of closed-loop control. Some included physical activity (PA), with the goal of challenging the control algorithms with a rapid change in insulin sensitivity while reducing the risk of hypoglycemia. However, the question remains as to the necessity to inform the control algorithm on the imminent PA. The aim here is to assess in silico (i) if it is necessary to announce upcoming PA and (ii) if this is the case, what is the safest strategy of basal insulin reduction in the context of the closed-loop control.

Methods:

We modified the University of Virginia/Padova type 1 diabetes simulator to incorporate the effect of PA based on a study in healthy subjects that demonstrated an almost doubling of insulin sensitivity during PA versus rest. Two in silico experiments, including a PA session, have been simulated on the virtual adult population: One in the absence of and one with different degrees of reductions and durations of basal insulin infusion rates.

Results:

Most in silico subjects experienced hypoglycemia in the absence of basal insulin adjustment. We show that, in the absence of patient-specific information, a safe and effective strategy is to reduce basal insulin by 50% starting 90 min before exercise and by 30% during exercise.

Conclusions:

Our results suggest that control algorithms could benefit by knowing an upcoming PA. Ideally, the control algorithm should be informed about the patient-specific basal insulin reduction pattern. An alternative strategy that has been proposed here has been deemed safe and effective in in silico experiments.
Artificial Pancreas: Model Predictive Control Design from Clinical Experience
Authors: Toffanin Chiara , Messori Mirko , Di Palma Federico , De Nicolao Giuseppe , Cobelli Claudio , Magni Lalo
Published: June 2016

Background:

The objective of this research is to develop a new artificial pancreas that takes into account the experience accumulated during more than 5000 h of closed-loop control in several clinical research centers. The main objective is to reduce the mean glucose value without exacerbating hypo phenomena. Controller design and in silico testing were performed on a new virtual population of the University of Virginia/Padova simulator.

Methods:

A new sensor model was developed based on the Comparison of Two Artificial Pancreas Systems for Closed-Loop Blood Glucose Control versus Open-Loop Control in Patients with Type 1 Diabetes trial AP@home data. The Kalman filter incorporated in the controller has been tuned using plasma and pump insulin as well as plasma and continuous glucose monitoring measures collected in clinical research centers. New constraints describing clinical knowledge not incorporated in the simulator but very critical in real patients (e.g., pump shutoff) have been introduced. The proposed model predictive control (MPC) is characterized by a low computational burden and memory requirements, and it is ready for an embedded implementation.

Results:

The new MPC was tested with an intensive simulation study on the University of Virginia/Padova simulator equipped with a new virtual population. It was also used in some preliminary outpatient pilot trials. The obtained results are very promising in terms of mean glucose and number of patients in the critical zone of the control variability grid analysis.

Conclusions:

The proposed MPC improves on the performance of a previous controller already tested in several experiments in the AP@home and JDRF projects. This algorithm complemented with a safety supervision module is a significant step toward deploying artificial pancreases into outpatient environments for extended periods of time.
Accuracy of a First-Generation Intravenous Blood Glucose Monitoring System in Subjects with Diabetes Mellitus: A Multicenter Study
Authors: Bailey Timothy , Gulino Angela , Higgins Michael J. , Leach Jacob , Kamath Apurv , Simpson Peter C.
Published: June 2016

Background:

Hyperglycemia and hypoglycemia in hospitalized patients have been associated with increased morbidity and mortality. Improvements in glucose monitoring technology may be helpful in the clinical management of critically ill patients with abnormal glucose levels. A first-generation intravenous blood glucose monitoring (IVBG) system was developed to facilitate glycemic control therapy in hospitalized patients. A nonrandomized, single-arm, multicenter study was performed to evaluate the safety and accuracy of the IVBG system in insulin-treated subjects with diabetes mellitus.

Methods:

The IVBG system is a bedside monitor that automatically measures venous blood glucose (BG) concentration. In this study, BG was measured every 7.5 min by the IVBG system. Reference samples [venous blood samples measured on the Yellow Springs Instruments (YSI) glucose analyzer] were drawn every 15 min during inpatient studies on days 1, 2, and 3. Fifty insulin-treated healthy volunteers with diabetes were studied, and a maximum of 72 reference samples were collected. Effectiveness was primarily evaluated by assessing the proportion of IVBG BG measurements within the 15 mg/dl or 20% criterion [15 mg/dl (for YSI <75 mg/dl) or 20% (for YSI ≥75 mg/dl)] compared with YSI. Adverse events and adverse device effects were evaluated.

Results:

A total of 95% of all IVBG values were within the 15 mg/dl or 20% criterion. The IVBG system BG measurement showed significant linear relationship with the laboratory YSI standard. Catheter insertion site irritation was mild and infrequent. No serious adverse events were reported. A total of 33% of the sensors were replaced during the 3-day use due to problematic IV lines or sensor/system errors.

Conclusions:

This clinical performance evaluation demonstrates that the IVBG system provides accurate and safe continuous BG measurements in healthy insulin-treated patients with diabetes.
Complexity of Continuous Glucose Monitoring Data in Critically Ill Patients: Continuous Glucose Monitoring Devices, Sensor Locations, and Detrended Fluctuation Analysis Methods
Authors: Signal Matthew , Thomas Felicity , Shaw Geoffrey M. , Chase J. Geoffrey
Published: June 2016

Background:

Critically ill patients often experience high levels of insulin resistance and stress-induced hyperglycemia, which may negatively impact outcomes. However, evidence surrounding the causes of negative outcomes remains inconclusive. Continuous glucose monitoring (CGM) devices allow researchers to investigate glucose complexity, using detrended fluctuation analysis (DFA), to determine whether it is associated with negative outcomes. The aim of this study was to investigate the effects of CGM device type/calibration and CGM sensor location on results from DFA.

Methods:

This study uses CGM data from critically ill patients who were each monitored concurrently using Medtronic iPro2s on the thigh and abdomen and a Medtronic Guardian REAL-Time on the abdomen. This allowed interdevice/calibration type and intersensor site variation to be assessed. Detrended fluctuation analysis is a technique that has previously been used to determine the complexity of CGM data in critically ill patients. Two variants of DFA, monofractal and multifractal, were used to assess the complexity of sensor glucose data as well as the precalibration raw sensor current. Monofractal DFA produces a scaling exponent ( H), where H is inversely related to complexity. The results of multifractal DFA are presented graphically by the multifractal spectrum.

Results:

From the 10 patients recruited, 26 CGM devices produced data suitable for analysis. The values of H from abdominal iPro2 data were 0.10 (0.03–0.20) higher than those from Guardian REAL-Time data, indicating consistently lower complexities in iPro2 data. However, repeating the analysis on the raw sensor current showed little or no difference in complexity. Sensor site had little effect on the scaling exponents in this data set. Finally, multifractal DFA revealed no significant associations between the multifractal spectrums and CGM device type/calibration or sensor location.

Conclusions:

Monofractal DFA results are dependent on the device/calibration used to obtain CGM data, but sensor location has little impact. Future studies of glucose complexity should consider the findings presented here when designing their investigations.
Blood Glucose Meters Employing Dynamic Electrochemistry are Stable against Hematocrit Interference in a Laboratory Setting
Authors: Pfützner Andreas , Musholt Petra B. , Schipper Christina , Demircik Filiz , Hengesbach Carina , Flacke Frank , Sieber Jochen , Forst Thomas
Published: June 2016

Background:

Hematocrit (HCT) is known to be a confounding factor that interferes with many blood glucose (BG) measurement technologies, resulting in wrong readings. Dynamic electrochemistry has been identified as one possible way to correct for these potential deviations. The purpose of this laboratory investigation was to assess the HCT stability of four BG meters known to employ dynamic electrochemistry (BGStar and iBGStar, Sanofi; Wavesense Jazz, AgaMatrix; Wellion Linus, MedTrust) in comparison with three other devices (GlucoDock, Medisana; OneTouch Verio Pro, LifeScan; FreeStyle Freedom InsuLinx, Abbott-Medisense).

Methods:

Venous heparinized blood was immediately aliquoted after draw and manipulated to contain three different BG concentrations (60–90, 130–160, and 280–320 mg/dl) and five different HCT levels (25%, 35%, 45%, 55%, and 60%). After careful oxygenation to normal blood oxygen pressure, each of the resulting 15 different samples was measured six times with three devices and three strip lots of each meter. The YSI Stat 2300 served as laboratory reference method. Stability to HCT influence was assumed when less than 10% difference occurred between the highest and lowest mean glucose deviations in relation to HCT concentrations [hematocrit interference factor (HIF)].

Results:

Five of the investigated self-test meters showed a stable performance with the different HCT levels tested in this investigation: BGStar (HIF 4.6%), iBGStar (6.6%), Wavesense Jazz (4.1%), Wellion Linus (8.5%), and OneTouch Verio Pro (6.2%). The two other meters were influenced by HCT (FreeStyle InsuLinx 17.8%; GlucoDock 46.5%).

Conclusions:

In this study, meters employing dynamic electrochemistry, as used in the BGStar and iBGStar devices, were shown to correct for potential HCT influence on the meter results. Dynamic electrochemistry appears to be an effective way to handle this interfering condition.
The Concomitant Relationship Shared by Sleep Disturbances and Type 2 Diabetes: Developing Telemedicine as a Viable Treatment Option
Authors: Seibert Pennie S. , Valerio Jennifer , DeHaas CodieAnn
Published: June 2016

Individually, sleep disturbances and type 2 diabetes pose pervasive challenges to health. In addition, the negative symptomology associated with each condition is exacerbated further when presenting concomitantly. This relationship formulates a destructive loop wherein those with diabetes experience decreased sleep quality, which, in turn, worsens a wide range of health threats experienced by those with diabetes, including obesity and glucose intolerance. Because major lifestyle changes and daily care are needed to effectively manage both diabetes and sleep disturbances, an efficient and timely modality of treatment is essential. Advanced technology incorporating telemedicine and telehealth has the potential to enhance treatment by delivering accepted standard of care, medical monitoring, and education quickly and seamlessly—even in rural locations. This type of intervention has the added potential benefit of fostering patient empowerment.
Algorithms for a Closed-Loop Artificial Pancreas: The Case for Model Predictive Control
Authors: Bequette B. Wayne
Published: June 2016

The relative merits of model predictive control (MPC) and proportional-integral-derivative (PID) control are discussed, with the end goal of a closed-loop artificial pancreas (AP). It is stressed that neither MPC nor PID are single algorithms, but rather are approaches or strategies that may be implemented very differently by different engineers. The primary advantages to MPC are that (i) constraints on the insulin delivery rate (and/or insulin on board) can be explicitly included in the control calculation; (ii) it is a general framework that makes it relatively easy to include the effect of meals, exercise, and other events that are a function of the time of day; and (iii) it is flexible enough to include many different objectives, from set-point tracking (target) to zone (control to range). In the end, however, it is recognized that the control algorithm, while important, represents only a portion of the effort required to develop a closed-loop AP. Thus, any number of algorithms/approaches can be successful—the engineers involved in the design must have experience with the particular technique, including the important experience of implementing the algorithm in human studies and not simply through simulation studies.
Dependence on glutamine uptake and glutamine addiction characterize myeloma cells: a new attractive target
Authors: Bolzoni Marina , Chiu Martina , Accardi Fabrizio , Vescovini Rosanna , Airoldi Irma , Storti Paola , Todoerti Katia , Agnelli Luca , Missale Gabriele , Andreoli Roberta , Bianchi Massimiliano G. , Allegri Manfredi , Barilli Amelia , Nicolini Francesco , Cavalli Albertina , Costa Federica , Marchica Valentina , Toscani Denise , Mancini Cristina , Martella Eugenia , Dall’Asta Valeria , Donofrio Gaetano , Aversa Franco , Bussolati Ovidio , Giuliani Nicola
Published: June 2016

Key Points

Myeloma cells produce ammonium in the presence of glutamine, showing high glutaminase and low glutamine synthetase expression. Myeloma cells show high expression of glutamine transporters and inhibition of ASCT2 transporter hinders myeloma growth.
Adult human megakaryocyte-erythroid progenitors are in the CD34+CD38mid fraction
Authors: Sanada Chad , Xavier-Ferrucio Juliana , Lu Yi-Chien , Min Elizabeth , Zhang Ping-Xia , Zou Siying , Kang Elaine , Zhang Meng , Zerafati Gazelle , Gallagher Patrick G. , Krause Diane S.
Published: June 2016

Key Points

Purification strategies developed for human Mk-E progenitors, as well as committed Mk and E progenitors. MYB regulates the biphenotypic fate decision of human MEPs.
Dimethyl fumarate restores apoptosis sensitivity and inhibits tumor growth and metastasis in CTCL by targeting NF-κB
Authors: Nicolay Jan P. , Müller-Decker Karin , Schroeder Anne , Brechmann Markus , Möbs Markus , Géraud Cyrill , Assaf Chalid , Goerdt Sergij , Krammer Peter H. , Gülow Karsten
Published: June 2016

Key Points

DMF induces specific cell death in CTCL cells and inhibits CTCL tumor growth and metastasis in vivo via inhibition of NF-κB. DMF therefore represents a promising, nontoxic novel therapeutic approach to treating CTCL.
Asperger syndrome in childhood – personality dimensions in adult life: temperament, character and outcome trajectories
Authors: Helles Adam , Gillberg I. Carina , Gillberg Christopher , Billstedt Eva , Wallinius Märta
Published: June 2016

Background

Temperament and character have been shown to be important factors in understanding psychiatric and neurodevelopmental disorder. Adults with autism spectrum disorder (ASD) have repeatedly been shown to have a distinct temperament and character, but this has not been evaluated in relation to psychiatric comorbidity and ASD diagnostic stability.

Aims

To examine temperament and character in males that were diagnosed with ASD in childhood and followed prospectively over almost two decades.

Method

Temperament and character were assessed in 40 adult males with a childhood diagnosis of ASD. Results were analysed by the stability of ASD diagnosis over time and current psychiatric comorbidity.

Results

Three distinct temperament and character profiles emerged from the data. Those no longer meeting criteria for ASD had high reward dependence while those with a stable ASD diagnosis and psychiatric comorbidity showed elevated harm avoidance and low self-directedness and cooperativeness. Finally, those with a stable ASD and no comorbidity showed low novelty seeking and somewhat elevated harm avoidance.

Conclusions

Temperament and character are important factors correlated with long-term diagnostic stability and psychiatric comorbidity in males diagnosed with ASD in childhood.
Review Essay on British Economic Growth, 1270–1870 by Stephen Broadberry, Bruce M. S. Campbell, Alexander Klein, Mark Overton, and Bas van Leeuwen
Authors: Williamson Jeffrey G.
Published: June 2016

British Economic Growth, 1270–1870 makes a big leap forward in our understanding of the long-run performance of what became the leading nineteenth-century economy and the workshop of the world. It does so by implementing a giant quantitative enterprise, one that will make it the standard data source for studying the evolution of the British economy for decades to come. (JEL C82, D31, E23, I31, I32, N13, N33)