bluuebunny/crossref_metadata_2025 huggingface dataset:
Don’t call me a leader, but I am one: The Dutch mayor and the tradition of bridging-and-bonding leadership in consensus democracies
Authors: Karsten Niels , Hendriks Frank
Published: June 2016

In some democratic contexts, there is a strong aversion to the directive, individualistic and masculine expressions of leadership that have come to dominate the study of political leadership. Such leadership is antithetical to consensus democracies in parts of continental Europe, where the antipathy to leadership has linguistic, institutional as well as cultural dimensions. Political-administrative and socio-cultural contexts in these countries provide little room for heroic expressions of leadership. Consequently, alternative forms of leadership and associated vocabularies have developed that carry profound practical relevance but that have remained underexplored. Based on an in-depth mixed-methods study, this article presents the Dutch mayoralty as an insightful and exemplary case of what can be called ‘bridging-and-bonding leadership’; it provides a clear illustration of how understandings of democratic leadership can deviate from the dominant paradigm and of how leading in a consensus context brings about unique practical challenges for office holders. The analysis shows that the important leadership task of democratic guardianship that is performed by Dutch mayors is in danger of being overlooked by scholars of political leadership, as are consensus-oriented leadership roles in other parts of the world. For that reason, a recalibration of the leadership concept is needed, developing an increased theoretical sensitivity towards the non-decisive and process-oriented aspects of the leadership phenomenon. This article specifies how the future study of leadership, as a part of the change that is advocated, can benefit from adopting additional languages of leadership.
Variation in university research ethics review: Reflections following an inter-university study in England
Authors: Vadeboncoeur Claudia , Townsend Nick , Foster Charlie , Sheehan Mark
Published: June 2016

Conducting large multi-site research within universities highlights inconsistencies between universities in approaches, requirements and responses of research ethics committees. Within the context of a social science research study, we attempted to obtain ethical approval from 101 universities across England to recruit students for a short online survey. We received varied responses from research ethics committees of different universities with the steps to obtaining ethics approval ranging from those that only required proof of approval from our home institution, to universities that facilitated fast-track applications to those that required a full ethics review. Some universities also completely refused. After contacting all 101 universities in England, 60 universities gave clearance to our study. In this article, we present the different approaches universities adopted in response to our application to sample from students in their institution. We consider a number of conceptual and ethical issues pertinent to considering ethics approval for researchers from other universities in England and critically discuss three possible models of ethics governance that would cover all universities in England.
Improving scheduled maintenance by missing data reconstruction: A double-loop Monte Carlo approach
Authors: Compare Michele , Di Maio Francesco , Zio Enrico , Carlevaro Fausto , Mattafirri Sara
Published: June 2016

This article describes a Monte Carlo–based approach for reconstructing missing information in a dataset used by General Electric for reliability analysis, which contains data coming from field observations at inspection of gas turbine components. The approach is based on a combination of maximum likelihood estimation technique to estimate the failure model parameters, Fisher information matrix to estimate the confidence intervals on the estimated parameters, and a double-loop Monte Carlo approach to estimate the missing equivalent starts (i.e. data of turbine state without the relative equivalent starts). The proposed methodology reduces the uncertainty in the estimation of the parameters of the turbine. The results of the application of the novel approach to a real industrial dataset are discussed along with a sensitivity analysis for the quantification of the robustness of the methodology to deal with different sizes of datasets.
Violent women in Spanish TV ads: Stereotype reversal or the same old same old?
Authors: Pennock-Speck Barry
Published: June 2016

Why did different agencies, promoting diverse products, create three ads featuring violence perpetrated by women on their rather immature and submissive male partners in order to sell their products? I posit that the female viewers connect subconsciously with the image of the proactive female protagonists through the psychological mechanism in which we identify with ‘our like’ on the screen. This, in turn, allows for the projection of ‘common ground’, a positive politeness strategy, to favourably dispose the female audience towards the protagonists and, by extension, the products advertised. The success of these ads depends on women viewers identifying with the apparently dominant female protagonists – a case of ‘gender stereotype reversal’. However, I put forward that through the violent modification of their partners’ behaviour, the women become responsible for them, and so the ads convey the common gender stereotype of women as carers.
Performance Evaluations of Continuous Glucose Monitoring Systems: Precision Absolute Relative Deviation is Part of the Assessment
Authors: Obermaier Karin , Schmelzeisen-Redeker Günther , Schoemaker Michael , Klötzer Hans-Martin , Kirchsteiger Harald , Eikmeier Heino , del Re Luigi
Published: June 2016

Background:

Even though a Clinical and Laboratory Standards Institute proposal exists on the design of studies and performance criteria for continuous glucose monitoring (CGM) systems, it has not yet led to a consistent evaluation of different systems, as no consensus has been reached on the reference method to evaluate them or on acceptance levels. As a consequence, performance assessment of CGM systems tends to be inconclusive, and a comparison of the outcome of different studies is difficult.

Materials and Methods:

Published information and available data (as presented in this issue of Journal of Diabetes Science and Technology by Freckmann and coauthors) are used to assess the suitability of several frequently used methods [International Organization for Standardization, continuous glucose error grid analysis, mean absolute relative deviation (MARD), precision absolute relative deviation (PARD)] when assessing performance of CGM systems in terms of accuracy and precision.

Results:

The combined use of MARD and PARD seems to allow for better characterization of sensor performance. The use of different quantities for calibration and evaluation, e.g., capillary blood using a blood glucose (BG) meter versus venous blood using a laboratory measurement, introduces an additional error source. Using BG values measured in more or less large intervals as the only reference leads to a significant loss of information in comparison with the continuous sensor signal and possibly to an erroneous estimation of sensor performance during swings. Both can be improved using data from two identical CGM sensors worn by the same patient in parallel.

Conclusions:

Evaluation of CGM performance studies should follow an identical study design, including sufficient swings in glycemia. At least a part of the study participants should wear two identical CGM sensors in parallel. All data available should be used for evaluation, both by MARD and PARD, a good PARD value being a precondition to trust a good MARD value. Results should be analyzed and presented separately for clinically different categories, e.g., hypoglycemia, exercise, or night and day.
Performance Evaluation of a Continuous Glucose Monitoring System under Conditions Similar to Daily Life
Authors: Pleus Stefan , Schmid Christina , Link Manuela , Zschornack Eva , Klötzer Hans-Martin , Haug Cornelia , Freckmann Guido
Published: June 2016

Background:

This study aimed at evaluating and comparing the performance of a new generation of continuous glucose monitoring (CGM) system versus other CGM systems, under daily lifelike conditions.

Methods:

A total of 10 subjects (7 female) were enrolled in this study. Each subject wore two Dexcom G4™ CGM systems in parallel for the sensor lifetime specified by the manufacturer (7 days) to allow assessment of sensor-to-sensor precision. Capillary blood glucose (BG) measurements were performed at least once per hour during daytime and once at night. Glucose excursions were induced on two occasions. Performance was assessed by calculating the mean absolute relative difference (MARD) between CGM readings and paired capillary BG readings and precision absolute relative difference (PARD), i.e., differences between paired CGM readings.

Results:

Overall aggregate MARD was 11.0% ( n = 2392). Aggregate MARD for BG >70 mg/dl was 13.7%; for BG between 70 and 180 mg/dl, MARD was 11.4%; and for BG >180 mg/dl, MARD was 8.5%. Aggregate PARD was 7.3%, improving from 11.6% on day 1 to 5.2% on day 7.

Conclusions:

The Dexcom G4 CGM system showed good overall MARD compared with results reported for other commercially available CGM systems. In the hypoglycemic range, where CGM performance is often reported to be low, the Dexcom G4 CGM system achieved better MARD than that reported for other CGM systems in the hypoglycemic range. In the hyperglycemic range, the MARD was comparable to that reported for other CGM systems, whereas during induced glucose excursions, the MARD was similar or slightly worse than that reported for other CGM systems. Overall PARD was 7.3%, improving markedly with sensor life time.
Performance Evaluation of Three Continuous Glucose Monitoring Systems: Comparison of Six Sensors Per Subject in Parallel
Authors: Freckmann Guido , Pleus Stefan , Link Manuela , Zschornack Eva , Klötzer Hans-Martin , Haug Cornelia
Published: June 2016

Background:

This study is aimed at comparing the performance of three continuous glucose monitoring (CGM) systems following the Clinical and Laboratory Standards Institute's POCT05-A guideline, which provides recommendations for performance evaluation of CGM systems.

Methods:

A total of 12 subjects with type 1 diabetes were enrolled in this study. Each subject wore six CGM systems in parallel, two sensors of each CGM system [FreeStyle Navigator™ (Navigator), MiniMed Guardian® REAL-Time with Enlite sensor (Guardian), DexCom™ Seven® Plus 3rd generation (Seven Plus)]. Each sensor was used for the lifetime specified by the manufacturer. To follow POCT05-A recommendations, glucose excursions were induced on two separate occasions, and venous and capillary blood glucose (BG) concentrations were obtained every 15 min for five consecutive hours. Capillary BG concentrations were measured at least once per hour during the day and once at night. Parameters investigated were CGM-to-BG differences [mean absolute relative difference (MARD)] and sensor-to-sensor differences [precision absolute relative difference (PARD)].

Results:

Compared with capillary BG reference readings, the Navigator showed the lowest MARD, with 12.1% overall and 24.6% in the hypoglycemic range; for the Guardian and the Seven Plus, MARD was 16.2%/34.9% and 16.3%/32.7%, respectively. PARD also was lowest for the Navigator (9.6%/9.8%), followed by the Seven Plus (16.7%/25.5%) and the Guardian (18.1%/20.2%). During induced glucose excursions, MARD between CGM and BG was, again, lowest for the Navigator (14.3%), followed by the Seven Plus (15.8%) and the Guardian (19.2%).

Conclusions:

In this study, two sensors of each of the three CGM systems were compared in a setting following POCT05-A recommendations. The Navigator CGM system achieved more accurate results than the Guardian or the Seven Plus with respect to MARD and PARD. Performance in the hypoglycemic range was markedly worse for all CGM systems when compared with BG results.
Higher Accuracy of Self-Monitoring of Blood Glucose in Insulin-Treated Patients in Germany: Clinical and Economical Aspects
Authors: Schnell Oliver , Erbach Michael , Wintergerst Eva
Published: June 2016

Background:

Accuracy standards of blood glucose (BG) meters are currently under review. Revised standards are expected to tighten accuracy requirements. Regarding clinical and financial impact of BG meter accuracy, very little data are available. The aim of this study was to analyze potential cost savings related to higher accuracy of glucose meters in Germany.

Methods:

As a model for calculation, a reduction of meter error from 20% to 5% was applied. The health economic analysis was based on four main pillars: (1) number of insulin-treated patients; (2) costs for glucose monitoring in Germany; (3) data of a modeling analysis on the impact on hypoglycemic episodes, glycosylated hemoglobin (HbA1c), and, subsequently, myocardial infarctions; and (4) costs of diabetes-related complications in Germany. A reduction of meter error from 20% to 5% was identified to be associated with a 10% reduction in severe hypoglycemic episodes and a 0.39% reduction in HbA1c, which translates into a 0.5% reduction of myocardial infarctions.

Results:

According to the health economic analysis, the reduction in severe hypoglycemic episodes and myocardial infarctions led to cost savings of €24.14 per patient per year. Considering 390,000 type 1 diabetes patients or 2.3 million insulin-treated patients in Germany, these savings could be equal to a reduction in health care expenditures of more than €9.4 million and €55.5 million, respectively.

Conclusions:

Potential cost savings and clinical effects due to higher accuracy of BG meters should provide an impetus to implementation of tighter accuracy standards and development of glucose meters that provide highest possible accuracy.
On the Problem of Patient-Specific Endogenous Glucose Production in Neonates on Stochastic Targeted Glycemic Control
Authors: Dickson Jennifer L. , Hewett James N. , Gunn Cameron A. , Lynn Adrienne , Shaw Geoffrey M. , Chase J. Geoffrey
Published: June 2016

Background:

Both stress and prematurity can induce hyperglycemia in the neonatal intensive care unit, which, in turn, is associated with worsened outcomes. Endogenous glucose production (EGP) is the formation of glucose by the body from substrates and contributes to blood glucose (BG) levels. Due to the inherent fragility of the extremely low birth weight (ELBW) neonates, true fasting EGP cannot be explicitly determined, introducing uncertainty into glycemic models that rely on quantifying glucose sources. Stochastic targeting, or STAR, is one such glycemic control framework.

Methods:

A literature review was carried out to gather metabolic and EGP values on preterm infants with a gestational age (GA) <32 weeks and a birth weight (BW) <2 kg. The data were analyzed for EGP trends with BW, GA, BG, plasma insulin, and glucose infusion (GI) rates. Trends were modeled and compared with a literature-derived range of population constant EGP models using clinically validated virtual trials on retrospective clinical data.

Results:

No clear relationship was found for EGP and BW, GA, or plasma insulin. Some evidence of suppression of EGP with increasing GI or BG was seen. Virtual trial results showed that population-constant EGP models fit clinical data best and gave tighter control performance to a target band in virtual trials.

Conclusions:

Variation in EGP cannot easily be quantified, and EGP is sufficiently modeled as a population constant in the neonatal intensive care insulin-nutrition-glucose model. Analysis of the clinical data and fitting error suggests that ELBW hyperglycemic preterm neonates have unsuppressed EGP in the higher range than that seen in literature.
Dynamic Insulin on Board: Incorporation of Circadian Insulin Sensitivity Variation
Authors: Toffanin Chiara , Zisser Howard , Doyle Francis J. , Dassau Eyal
Published: June 2016

Background:

Insulin-on-board (IOB) estimation is used in modern insulin therapy with continuous subcutaneous insulin infusion (CSII) as well as different automatic glucose-regulating strategies (i.e., artificial pancreas products) to prevent insulin stacking that may lead to hypoglycemia. However, most of the IOB calculations are static IOB (sIOB): They are based only on approximated insulin decay and do not take into account diurnal changes in insulin sensitivity.

Methods:

A dynamic IOB (dIOB) that takes into account diurnal insulin sensitivity variation is suggested in this work and used to adjust the sIOB estimations. The dIOB function is used to correct the dosage of insulin boluses in light of this circadian variation.

Results:

Basal-bolus as applied by pump users and model predictive control therapy with and without dIOB were evaluated using the University of Virginia/Padova metabolic simulator. Three protocols with four meals of 1 g carbohydrate/kg body weight were evaluated: A nominal scenario and two robustness scenarios, one in which insulin sensitivity was 15% greater than estimated and the other where the lunch is 30% less than announced. In the nominal and robustness scenarios, respectively, the dIOB led to 6% and 24% and 40% less hypoglycemia episodes than approaches without IOB. The new approach was also compared with the sIOB to evaluate the improvements with respect to the previous approach.

Conclusions:

Improved glucose regulation was demonstrated using the dIOB where circadian insulin sensitivity is used to adjust IOB estimation. Use of diurnal variations of insulin sensitivity appears to promote effective and safe insulin therapy using CSII or artificial pancreas. Clinical trials are warranted to determine whether nocturnal hypoglycemia can be reduced using the dIOB approach.
Challenges and Future Directions of the T1D Exchange Clinic Network and Registry
Authors: Miller Kellee M. , Xing Dongyuan , Tamborlane William V. , Bergenstal Richard M. , Beck Roy W.
Published: June 2016

The T1D Exchange Clinic Network consists of 67 clinics throughout the United States. Among the more than 100,000 patients with type 1 diabetes mellitus (T1DM) who receive care at these centers, more than 26,000 have been enrolled in a registry. The registry includes participants over a wide age range, from age <1 to 93 years, and consists of both those newly diagnosed (more than 3000 diagnosed <1 year from the time of enrollment) and those with long-standing diabetes (more than 1000 with T1DM for at least 40 years). Data on diabetes history, insulin administration, diabetes management, monitoring, complications, medical conditions, medications, and laboratory results are collected at enrollment and annually through participant completion of Web-based questionnaires and data extraction from medical records. The clinic registry has provided a rich data set to address important clinical and public health issues, including important observations regarding the current state of treatment of T1DM in diabetes centers in the United States. Challenges encountered during the establishment of the clinic registry include establishment of criteria for a diagnosis of presumed autoimmune T1DM, standardization of data collected across clinics, data quality, and understanding of potential bias. Collecting the data and maximizing data quality has required considerable effort. Even with these efforts, certain data elements are difficult to capture in a meaningful way. A standard T1DM module used by all electronic health records could be developed based on the data collection instruments developed for the T1D Exchange clinic registry.
Penny Wise and Pound Foolish: Will Shortsighted Cost Reduction Measures Compromise Patient Access to Promising Self-Monitoring of Blood Glucose Technology >
Authors: Parkin Christopher G.
Published: June 2016

In this issue of Journal of Diabetes Science and Technology, Grady and coauthors enrolled 101 patients with type 1 and type 2 diabetes to evaluate new technology incorporated into the LifeScan VerioPro and VerioIQ blood glucose meters. The “pattern detection” software provides real-time, onscreen messages that alert users to patterns of high glucose (fasting and premeal) and low glucose as they are detected. The study showed that most participants possess a good understanding of the factors that can cause hyperglycemia; however, their understanding of the causes of hypoglycemia events was not as strong. Nevertheless, more than 70% of participants indicated they preferred to use a blood glucose meter that provides pattern detection capability. Although not designed to assess the impact of the pattern detection tool on clinical outcomes, the study highlights the value of continuous innovation in self-monitoring of blood glucose (SMBG) technology among manufacturers. Unfortunately, many patients may never have access to these systems due to reductions in Medicare reimbursement. Instead, they may be forced to use SMBG systems that are inaccurate and provide inadequate patient support. Stronger regulatory requirements are needed to ensure that all SMBG systems marketed to patients are accurate, reliable, and supported by adequate patient training, and current health care reimbursement policies should be restructured to encourage manufacturers to continue their efforts to develop innovative technology to further improve the utility and usability of their SMBG systems.
ASPIRE in-Home: Rationale, Design, and Methods of a Study to Evaluate the Safety and Efficacy of Automatic Insulin Suspension for Nocturnal Hypoglycemia
Authors: Klonoff David C. , Bergenstal Richard M. , Garg Satish K. , Bode Bruce W. , Meredith Melissa , Slover Robert H. , Ahmann Andrew , Welsh John B. , Lee Scott W.
Published: June 2016

Nocturnal hypoglycemia is a barrier to therapy intensification efforts in diabetes. The Paradigm® Veo™ system may mitigate nocturnal hypoglycemia by automatically suspending insulin when a prespecified sensor glucose threshold is reached. ASPIRE (Automation to Simulate Pancreatic Insulin REsponse) In-Home (NCT01497938) was a multicenter, randomized, parallel, adaptive study of subjects with type 1 diabetes. The control arm used sensor-augmented pump therapy. The treatment arm used sensor-augmented pump therapy with threshold suspend, which automatically suspends the insulin pump in response to a sensor glucose value at or below a prespecified threshold. To be randomized, subjects had to have demonstrated ≥2 episodes of nocturnal hypoglycemia, defined as >20 consecutive minutes of sensor glucose values ≤65 mg/dl starting between 10:00 PM and 8:00 AM in the 2-week run-in phase. The 3-month study phase evaluated safety by comparing changes in glycated hemoglobin (A1C) values and evaluated efficacy by comparing the mean area under the glucose concentration time curves for nocturnal hypoglycemia events in the two groups. Other outcomes included the rate of nocturnal hypoglycemia events and the distribution of sensor glucose values. Data from the ASPIRE In-Home study should provide evidence on the safety of the threshold suspend feature with respect to A1C and its efficacy with respect to severity and duration of nocturnal hypoglycemia when used at home over a 3-month period.
Comparative Dose Accuracy of Durable and Patch Insulin Infusion Pumps
Authors: Jahn Luis G. , Capurro Jorge J. , Levy Brian L.
Published: June 2016

Background:

As all major insulin pump manufacturers comply with the international infusion pump standard EN 60601–224:1998, there may be a general assumption that all pumps are equal in insulin-delivery accuracy. This research investigates single-dose and averaged-dose accuracy of incremental basal deliveries for one patch model and three durable models of insulin pumps.

Method:

For each pump model, discrete single doses delivered during 0.5 U/h basal rate infusion over a 20 h period were measured using a time-stamped microgravimetric system. Dose accuracy was analyzed by comparing single doses and time-averaged doses to specific accuracy thresholds (±5% to ±30%).

Results:

The percentage of single doses delivered outside accuracy thresholds of ±5%, ±10%, and ±20% were as follows: Animas OneTouch® Ping® (43.2%, 14.3%, and 1.8%, respectively), Roche Accu-Chek® Combo (50.6%, 24.4%, and 5.5%), Medtronic Paradigm® Revel™/Veo™ (54.2%, 26.7%, and 6.6%), and Insulet OmniPod® (79.1%, 60.5%, and 34.9%). For 30 min, 1 h, and 2 h averaging windows, the percentage of doses delivered outside a ±15% accuracy were as follows: OneTouch Ping (1.0%, 0.4%, and 0%, respectively), Accu-Chek Combo (4.2%, 3.5%, and 3.1%), Paradigm Revel/Veo (3.9%, 3.1%, and 2.2%), and OmniPod (33.9%, 19.9%, and 10.3%).

Conclusions:

This technical evaluation demonstrates significant differences in single-dose and averaged-dose accuracy among the insulin pumps tested. Differences in dose accuracy were most evident between the patch pump model and the group of durable pump models. Of the pumps studied, the Animas OneTouch Ping demonstrated the best single-dose and averaged-dose accuracy. Further research on the clinical relevance of these findings is warranted.
Do Currently Available Blood Glucose Monitors Meet Regulatory Standards? 1-Day Public Meeting in Arlington, Virginia
Authors: Klonoff David C. , Reyes Juliet S.
Published: June 2016

Blood glucose monitors (BGMs) are approved by regulatory agencies based on their performance during strict testing conducted by their manufacturers. However, after approval, there is uncertainty whether BGMs maintain the accuracy levels that were achieved in the initial data. The availability of inaccurate BGM systems pose a public health problem because their readings serve as a basis for treatment decisions that can be incorrect. Several articles have concluded that BGMs in the marketplace may not consistently provide accurate results in accordance with the regulatory standards that led to approval. To address this growing concern, Diabetes Technology Society organized and conducted a 1-day public meeting on May 21, 2013, in Arlington, VA, presided by its president, David Klonoff, M.D., FACP, Fellow AIMBE, to determine whether BGMs on the market meet regulatory standards. The meeting consisted of four sessions in which Food and Drug Administration diabetes experts as well as leading academic clinicians and clinical chemists participated: (1) How is BGM performance determined? (2) Do approved BGMs perform according to International Organization for Standardization standards? (3) How do approved BGMs perform when used by patients and health care professionals? (4) What could be the consequence of poor BGM performance?
Boluses in Insulin Therapy
Authors: Ziegler Ralph , Freckmann Guido , Heinemann Lutz
Published: June 2016

Giving a bolus is one major part in multiple dose insulin therapy (MDI) along with basal insulin substitution. To adjust the bolus optimally, different factors like carbohydrate content and composition of the meal, correction factors, and timing have to be considered. Advances in technologies like bolus advisors can assist the patients but still there a several open questions and technical challenges regarding boluses. This commentary provides an opportunity to address several of the above-mentioned factors influencing the result of bolusing. It shall draw attention to those factors and address the current opportunities, for example, continuous subcutaneous insulin infusion (CSII), as well as the need for further studies which can help to improve diabetes insulin therapy by means of the correct use of boluses.
β-cell replacement sources for type 1 diabetes: a focus on pancreatic ductal cells
Authors: Corritore Elisa , Lee Yong-Syu , Sokal Etienne M. , Lysy Philippe A.
Published: June 2016

Thorough research on the capacity of human islet transplantation to cure type 1 diabetes led to the achievement of 3- to 5-year-long insulin independence in nearly half of transplanted patients. Yet, translation of this technique to clinical routine is limited by organ shortage and the need for long-term immunosuppression, restricting its use to adults with unstable disease. The production of new bona fide β cells in vitro was thus investigated and finally achieved with human pluripotent stem cells (PSCs). Besides ethical concerns about the use of human embryos, studies are now evaluating the possibility of circumventing the spontaneous tumor formation associated with transplantation of PSCs. These issues fueled the search for cell candidates for β-cell engineering with safe profiles for clinical translation. In vivo studies revealed the regeneration capacity of the exocrine pancreas after injury that depends at least partially on facultative progenitors in the ductal compartment. These stimulated subpopulations of pancreatic ductal cells (PDCs) underwent β-cell transdifferentiation through reactivation of embryonic signaling pathways. In vitro models for expansion and differentiation of purified PDCs toward insulin-producing cells were described using cocktails of growth factors, extracellular-matrix proteins and transcription factor overexpression. In this review, we will describe the latest findings in pancreatic β-cell mass regeneration due to adult ductal progenitor cells. We will further describe recent advances in human PDC transdifferentiation to insulin-producing cells with potential for clinical translational studies.
Acute right atrial and pulmonary artery bone cement mass emboli following vertebroplasty
Authors: Diab Mohammad S , Diab Amr , Dihmis Walid , Diab Samir
Published: June 2016

Cardiac and pulmonary artery emboli are lethal complications following vertebroplasty. Clinicians should recognise these fatal complications immediately and surgical extraction is mandatory and provides the best outcome.
Stevens–Johnson syndrome/toxic epidermal necrolysis caused by cefadroxil in a cat
Authors: Sartori Roberta , Colombo Silvia
Published: June 2016

Case summary

A 5-year-old, spayed female, indoor-only domestic shorthair cat was referred with an acute history of multifocal cutaneous and mucocutaneous erosive-ulcerative lesions and skin detachment. The lesions occurred on the seventh day of therapy with cefadroxil. Erosive-ulcerative and occasionally crusted lesions were apparent on the medial and lateral canthus of both eyes, ventral neck, abdomen, perivulvar region, periungual skin and medial aspect of the front and hindlimbs. Diffuse and severe exfoliation was present on the dorsum and tail base and in both external ear canals. The cat was also dehydrated, tachycardic and febrile. Histopathological examination revealed extensive epidermal ulceration, interface dermatitis with vacuolar degeneration, apoptosis at multiple epidermal levels and basal, suprabasal and spinous dermoepidermal detachment. The histopathological diagnosis was consistent with Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). The recently reported Algorithm of Drug Causality in Epidermal Necrolysis (ALDEN), currently used in human medicine, was applied and a score of +6 was calculated; this supported the view that SJS/TEN in this cat was very likely to be associated with cefadroxil administration.

Relevance and novel information

This clinical communication reports cefadroxil as a very probable cause of SJS/TEN in a cat; the ALDEN was applied in this case and supported diagnosis.
Tibial Plateau Fractures in Elderly Patients
Authors: Rozell Joshua C. , Vemulapalli Krishna C. , Gary Joshua L. , Donegan Derek J.
Published: June 2016

Tibial plateau fractures are common in the elderly population following a low-energy mechanism. Initial evaluation includes an assessment of the soft tissues and surrounding ligaments. Most fractures involve articular depression leading to joint incongruity. Treatment of these fractures may be complicated by osteoporosis, osteoarthritis, and medical comorbidities. Optimal reconstruction should restore the mechanical axis, provide a stable construct for mobilization, and reestablish articular congruity. This is accomplished through a variety of internal or external fixation techniques or with acute arthroplasty. Regardless of the treatment modality, particular focus on preservation and maintenance of the soft tissue envelope is paramount.
Expectancy Effect in Three Mind-Body Clinical Trials
Authors: Hicks Matthew , Hanes Douglas , Wahbeh Helané
Published: June 2016

Expectancy, arguably the prime component of the placebo effect, has been shown to significantly modify the effects of many treatments. Furthermore, various forms of mind-body interventions have demonstrated effective improvements in outcomes. The aim of this study was to examine the relationship between pretreatment expectations and symptom reduction in a secondary analysis of 3 mind-body intervention programs. An adjusted correlation and regression analysis compared data from a 6-question expectancy questionnaire to a self-reported clinical impression of change score. Only 1 of the 6 expectancy questions in 1 of the 3 studies reached significance ( B = 0.087; P = .025). The combined data from all 3 studies did not reveal significant expectancy effects. The positive effects of mindfulness meditation appear to be independent of an expectancy effect.
Measuring Energy Intensity and Elasticity in India: A Dummy Variable Approach for Unit Level Household Data
Authors: Pandey Alok Kumar
Published: June 2016

In the present article an attempt has been made to estimate the responsiveness of prices and household expenditure on consumption of energy for cooking and lighting at household level in rural and urban areas in India. Household level energy elasticities are estimated for the rural and urban areas with the help of dummy variable regression approach by using National Sample Survey Organization (NSSO) 66th quinquennial rounds of unit level data for the year 2009–2010. The results reveal the fact that energy intensity for rural areas is higher than urban areas while average expenditure recorded on energy for cooking and lighting in urban areas is higher than in rural areas at all India level. Majority of the households are using dirty fuel for cooking in rural areas while in urban areas clean fuel, that is, LPG is used for cooking. The expenditure on energy for cooking and lighting at household level is inelastic. The marginal budget share in rural and urban areas is the same. Results reveal the fact that 100 percent increase in the prices of energy for cooking and lighting will increase the expenditure of households in rural region more than in urban region.
Opening- and Closing-Wedge Distal Femoral Osteotomy
Authors: Chahla Jorge , Mitchell Justin J. , Liechti Daniel J. , Moatshe Gilbert , Menge Travis J. , Dean Chase S. , LaPrade Robert F.
Published: June 2016

Background:

Lateral compartment osteoarthritis of the knee can be a challenging pathology in the younger, active population due to limited treatment options and high patient expectations. Distal femoral osteotomy (DFO) has been reported to be a potential treatment option.

Purpose:

To perform a systematic review on the survival, outcomes, and complications of DFO for treatment of genu valgum with concomitant lateral compartment osteoarthritis of the knee.

Study Design:

Systematic review; Level of evidence, 4.

Methods:

A systematic review of the literature was performed using the Cochrane Database of Systematic Reviews, the Cochrane Central Registry of Controlled Trials, PubMed, and MEDLINE from 1980 to present. Inclusion criteria were as follows: outcomes of opening- and closing-wedge DFOs performed for treatment of genu valgum with concomitant lateral compartment osteoarthritis of the knee, English language, minimum 2-year follow-up, and human studies. Data abstracted from the selected studies included type of osteotomy (opening vs closing), survival rate, patient-reported and radiographic outcomes, and complications.

Results:

Fourteen studies met the inclusion criteria and were considered for the review. A total of 9 closing-wedge and 5 opening-wedge DFO studies were included. All were retrospective studies and reported good to excellent patient-reported outcomes after DFO. Survival decreased with increasing time from surgery, with 1 study reporting a 100% survival rate at 6.5 years, compared with 21.5% at 20 years in another study. A low rate of complications was reported throughout the review.

Conclusion:

Highly heterogeneous literature exists for both opening- and closing-wedge DFOs for the treatment of isolated lateral compartment osteoarthritis with valgus malalignment. A mean survival rate of 80% at 10-year follow-up was reported, supporting that this procedure can be a viable treatment option to delay or reduce the need for joint arthroplasty. A low complication rate was observed, with symptomatic hardware being the most prevalent postoperative complication.
Who Should Define the “Social” in “Social Enterprise”
Authors: André Rae
Published: June 2016

During the past decade, new legal forms termed social enterprises have been introduced in the United States, purportedly to create opportunities for altruistic companies to be more socially responsible than traditional companies. This development has sparked significant controversy, however, with many legal scholars arguing that the forms introduce new types of corporate greenwashing. This exercise literally brings students into this debate, helping them clarify their values about the roles of government and business in a capitalist democracy. Such clarification can help all students navigate their roles in business and society, and it can help new entrepreneurs choose an appropriate legal form of incorporation. The exercise focuses on the most widely implemented social enterprise, the benefit corporation, inviting students to debate whether this form improves corporate social responsibility. It is appropriate for courses in business and society, business ethics and law, and social entrepreneurship.
Comprehensive characterization of programmed death ligand structural rearrangements in B-cell non-Hodgkin lymphomas
Authors: Chong Lauren C. , Twa David D. W. , Mottok Anja , Ben-Neriah Susana , Woolcock Bruce W. , Zhao Yongjun , Savage Kerry J. , Marra Marco A. , Scott David W. , Gascoyne Randy D. , Morin Ryan D. , Mungall Andrew J. , Steidl Christian
Published: June 2016

Key Points

Capture sequencing reveals that PDL SRs cluster into 2 discrete breakpoint regions. PDL SRs are significantly associated with increased protein expression and limit T-cell activation.
Atg7 suppression enhances chemotherapeutic agent sensitivity and overcomes stroma-mediated chemoresistance in acute myeloid leukemia
Authors: Piya Sujan , Kornblau Steven M. , Ruvolo Vivian R. , Mu Hong , Ruvolo Peter P. , McQueen Teresa , Davis R. Eric , Hail Numsen , Kantarjian Hagop , Andreeff Michael , Borthakur Gautam
Published: June 2016

Key Points

Atg7 expression is associated with shorter remission duration in AML. Atg7 inhibition is a proapoptotic phenotype and enhances sensitivity to chemotherapy.
Therapeutic targeting of IL-7Rα signaling pathways in ALL treatment
Authors: Cramer Sarah D. , Aplan Peter D. , Durum Scott K.
Published: June 2016

Increased understanding of pediatric acute lymphoblastic leukemia (ALL) pathobiology has led to dramatic improvements in patient survival. However, there is still a need to develop targeted therapies to enable reduced chemotherapy intensity and to treat relapsed patients. The interleukin-7 receptor α (IL-7Rα) signaling pathways are prime therapeutic targets because these pathways harbor genetic aberrations in both T-cell ALL and B-cell precursor ALL. Therapeutic targeting of the IL-7Rα signaling pathways may lead to improved outcomes in a subset of patients.
Exploring the psychological morbidity of waiting for sinus surgery using a mixed methods approach
Authors: Tsang Gordon Fung-Zak , McKnight Carmen L. , Kim Laura Minhui , Lee John M.
Published: June 2016

Background

Patients with chronic rhinosinusitis (CRS) often have to endure significant wait times for endoscopic sinus surgery (ESS). The pyschiatric impact of placement on a waitlist for ESS has not been explored.

Methods

Questionnaires measuring CRS symptom severity and health-related anxiety and stress (SNOT-22, HADS, WPAI-GH) were sent to patients diagnosed with CRS and currently on a waitlist for ESS. Fifteen representative waitlisted patients participated in one-on-one semi-structured interviews discussing their experience with their wait for ESS. A deductive thematic analysis was used to interpret the interview data using a quantitative driven mixed methods analysis.

Results

Participants waiting for ESS reported worsening clinical symptomatology during their waiting period. Participants reported waitlist and CRS impact on both work and social aspects of their lives. The HADS scale showed no overall significant level of depression or anxiety in the HADS screening questionnaire. The qualitative data describe the effects of the symptom burden of CRS.

Conclusions

Patients waitlisted for ESS did not demonstrate any significant level of psychiatric distress, however variability exists. The qualitative arm of this study elucidates how patients cope with their wait.
Multiple myeloma cells promote migration of bone marrow mesenchymal stem cells by altering their translation initiation
Authors: Dabbah Mahmoud , Attar-Schneider Oshrat , Zismanov Victoria , Tartakover Matalon Shelly , Lishner Michael , Drucker Liat
Published: June 2016

The role of the bone marrow microenvironment in multiple myeloma pathogenesis and progression is well recognized. Indeed, we have shown that coculture of bone marrow mesenchymal stem cells from normal donors and multiple myeloma cells comodulated translation initiation. Here, we characterized the timeline of mesenchymal stem cells conditioning by multiple myeloma cells, the persistence of this effect, and the consequences on cell phenotype. Normal donor mesenchymal stem cells were cocultured with multiple myeloma cell lines (U266, ARP1) (multiple myeloma–conditioned mesenchymal stem cells) (1.5 h,12 h, 24 h, 48 h, and 3 d) and were assayed for translation initiation status (eukaryotic translation initiation factor 4E; eukaryotic translation initiation factor 4G; regulators: mechanistic target of rapamycin, MNK, 4EBP; targets: SMAD family 5, nuclear factor κB, cyclin D1, hypoxia inducible factor 1, c-Myc) (immunoblotting) and migration (scratch assay, inhibitors). Involvement of mitogen-activated protein kinases in mesenchymal stem cell conditioning and altered migration was also tested (immunoblotting, inhibitors). Multiple myeloma–conditioned mesenchymal stem cells were recultured alone (1–7 d) and were assayed for translation initiation (immunoblotting). Quantitative polymerase chain reaction of extracted ribonucleic acid was tested for microRNAs levels. Mitogen-activated protein kinases were activated within 1.5 h of coculture and were responsible for multiple myeloma–conditioned mesenchymal stem cell translation initiation status (an increase of >200%, P < 0.05) and elevated migration (16 h, an increase of >400%, P < 0.05). The bone marrow mesenchymal stem cells conditioned by multiple myeloma cells were reversible after only 1 d of multiple myeloma–conditioned mesenchymal stem cell culture alone. Decreased expression of microRNA-199b and microRNA-125a (an increase of <140%, P < 0.05) in multiple myeloma–conditioned mesenchymal stem cells supported elevated migration. The time- and proximity-dependent conditioning of normal donor mesenchymal stem cells in our model points to a dynamic interaction between multiple myeloma cells and the bone marrow niche, which causes profound changes in the nonmalignant bone marrow constituents. Future studies are warranted to identify clinically relevant means of blocking this crosstalk and improving multiple myeloma therapy.
Cellular metabolism of myeloid cells in sepsis
Authors: Arts Rob J W , Gresnigt Mark S , Joosten Leo A B , Netea Mihai G
Published: June 2016

In recent years, it has become appreciated that immune cells have different metabolic profiles depending on their activation status. During sepsis, circulating leukocytes go through a hyperinflammatory state, which can be accompanied or followed by defective antimicrobial defenses (also described as immune tolerance or paralysis). In this review, the modulation of different cellular metabolic pathways during sepsis in monocytes and macrophages will be discussed. Glycolysis is studied extensively in sepsis and is up-regulated in hyperinflammatory cells, whereas in immune tolerance, it is often down-regulated. Few data are available on other metabolic pathways in immune cells from patients with sepsis. The pentose phosphate pathway is up-regulated during acute hyperinflammatory responses, whereas fatty acid β-oxidation is increased later during sepsis and is associated with an anti-inflammatory (M2) phenotype of macrophages. Within the amino acid metabolism we will discuss the most studied metabolites. Collectively, these data argue that exploration of the immunometabolic pathways in sepsis is an important area of research, and the targeting of metabolic pathways may represent a promising novel strategy as a therapy of sepsis.
A new parameter set for anisotropic multiparameter full-waveform inversion and application to a North Sea data set
Authors: da Silva Nuno V. , Ratcliffe Andrew , Vinje Vetle , Conroy Graham
Published: June 2016

Parameterization lies at the center of anisotropic full-waveform inversion (FWI) with multiparameter updates. This is because FWI aims to update the long and short wavelengths of the perturbations. Thus, it is important that the parameterization accommodates this. Recently, there has been an intensive effort to determine the optimal parameterization, centering the fundamental discussion mainly on the analysis of radiation patterns for each one of these parameterizations, and aiming to determine which is best suited for multiparameter inversion. We have developed a new parameterization in the scope of FWI, based on the concept of kinematically equivalent media, as originally proposed in other areas of seismic data analysis. Our analysis is also based on radiation patterns, as well as the relation between the perturbation of this set of parameters and perturbation in traveltime. The radiation pattern reveals that this parameterization combines some of the characteristics of parameterizations with one velocity and two Thomsen’s parameters and parameterizations using two velocities and one Thomsen’s parameter. The study of perturbation of traveltime with perturbation of model parameters shows that the new parameterization is less ambiguous when relating these quantities in comparison with other more commonly used parameterizations. We have concluded that our new parameterization is well-suited for inverting diving waves, which are of paramount importance to carry out practical FWI successfully. We have demonstrated that the new parameterization produces good inversion results with synthetic and real data examples. In the latter case of the real data example from the Central North Sea, the inverted models show good agreement with the geologic structures, leading to an improvement of the seismic image and flatness of the common image gathers.