bluuebunny/crossref_metadata_2025 huggingface dataset:
Paperwork and the decoupling of audit and animal welfare: The challenges of materiality for better regulation
Authors: Escobar Maria Paula , Demeritt David
Published: May 2016

This article uses the case of animal welfare to contribute to academic debates about audit and better regulation reforms designed to reduce administrative burdens and increase regulatory effectiveness. Combining desk-based policy document analysis, on-farm field visits, and 31 interviews with livestock farmers and animal health and welfare inspectors in England, it explores farmers' record-keeping practices and the contrasting role regulatory records are understood to play in assurance and good animal husbandry by farmers, regulatory inspectors, and veterinary experts. Farmers experience record-keeping as something they must do to satisfy external regulatory demands rather than anything that good farmers might themselves use in caring for their livestock. As a result they regard paperwork as burdensome and often fail to comply with record-keeping requirements. By contrast, inspectors and animal welfare experts frame record-keeping and analysis as central to good animal husbandry and to a properly anticipatory approach to managing animal health and welfare. Those veterinary-medical presumptions about farm practice inform both the design of specific animal welfare record-keeping requirements and their self-effacing conceit as being about peering over the farmer's shoulder to audit already existing records. Our findings highlight the dual tendency for the practice of regulatory record-keeping to become decoupled from both the formal requirements and from the quality of care that paperwork is meant to assure. Our analysis extends the critical literature on audit and regulation by drawing on the materialist tradition of science and technology studies to elucidate how this decoupling is shaped by the physical form and materiality of records themselves.
Social unionism and the framing of ‘fairness’ in the Wisconsin uprising
Authors: Chesters Graeme
Published: May 2016

The concept of ‘fairness’ has been used to frame political struggles by politicians and activists across the political spectrum. This article looks at its use in the US State of Wisconsin during the ‘Uprising’ – a series of occupations, protests, recall elections and militant direct action that began in 2011. These events were a response to a ‘budget repair bill’ that sought to strip public sector union members of their collective bargaining rights and to apply severe austerity measures within the State. This article suggests that although ‘fairness’ has a certain broad-based and intuitive appeal, its mutability means that it is unlikely to be successful in framing a structural critique that can build and sustain social action. Instead, it argues that framing this conflict as an uprising suggested a more explicit form of resistance that enabled a wider mobilization, and this can best be understood as an example of social (movement) unionism – the extension of traditional work place rights approaches to include broader agendas of social justice, civil rights, immigrant rights and economic justice for non-unionized workers.
Reducing the gap in perceptions of legitimacy of victims and non-victims
Authors: Aviv Gali , Weisburd David
Published: May 2016

Crime victims are a unique subgroup who evaluate the police and police legitimacy more harshly than those who have not been victimized. This could be explained by their victimization, and their special needs from and expectations of the police. Due to the importance of crime victims for the criminal justice system, the current study examines the mechanisms underlying differences in legitimacy evaluations of victims and non-victims. We focus on the two main antecedents of legitimacy: procedural justice and police performance. We find that procedural justice operates similarly for victims and non-victims, but that police performance plays a much more important role as an antecedent for victims. These findings suggest that managing perceptions of police performance may be key to closing the gap in legitimacy evaluations between victims and non-victims.
Age Weights for Health Services Derived from the Relative Social Willingness-to-Pay Instrument
Authors: Richardson Jeff , McKie John , Iezzi Angelo , Maxwell Aimee
Published: May 2016

The effect of a patient’s age on the social valuation of health services remains controversial, with empirical results varying in magnitude and implying a different age-value profile. This article employs a new methodology to re-examine these questions. Data were obtained from 2 independent Web-based surveys that administered the Relative Social Willingness to Pay instrument. In the first survey, the age of the patient receiving a life-saving service was varied. Patients were left with either poor mental or physical health. In the second survey, patient age was varied for a service that fully cured the patient’s poor mental or physical health. In total, therefore, 4 sets of age weights were obtained: weights for life-extending services with poor physical or mental health outcomes and weights for quality-of-life improvement for patients in poor mental or physical health. Results were consistent. Increasing age was associated in each case with a monotonic decrease in the social valuation of the services. The decrease in value was quantitatively small until age 60 years. By age 80 years, the social value of services had declined by about 50%. The decline commenced at an earlier age in the context of physical health, although the magnitude of the decrement by age 80 years was unrelated to the type of service. With 1 exception, there was little difference in the valuation of services by the age of the survey respondent. Respondents aged >60 years placed a lower, not higher, value on quality-of-life improvement for elderly individuals than other respondents. There was no difference in the valuation of life-extending services.
Fast probabilistic collision checking for sampling-based motion planning using locality-sensitive hashing
Authors: Pan Jia , Manocha Dinesh
Published: May 2016

We present a novel approach to perform fast probabilistic collision checking in high-dimensional configuration spaces to accelerate the performance of sampling-based motion planning. Our formulation stores the results of prior collision queries, and then uses such information to predict the collision probability for a new configuration sample. In particular, we perform an approximate k-NN ( k-nearest neighbor) search to find prior query samples that are closest to the new query configuration. The new query sample’s collision status is then estimated according to the collision checking results of these prior query samples, based on the fact that nearby configurations are likely to have the same collision status. We use locality-sensitive hashing techniques with sub-linear time complexity for approximate k-NN queries. We evaluate the benefit of our probabilistic collision checking approach by integrating it with a wide variety of sampling-based motion planners, including PRM (Probabilistic roadmaps), lazyPRM, RRT Rapidly exploring random trees, and RRT*. Our method can improve these planners in various manners, such as accelerating the local path validation, or computing an efficient order for the graph search on the roadmap. Experiments on a set of benchmarks demonstrate the performance of our method, and we observe up to 2x speedup in the performance of planners on rigid and articulated robots.
“But they told me it was professional”: Extrinsic factors in the evaluation of musical performance
Authors: Kroger Carolyn , Margulis Elizabeth Hellmuth
Published: May 2016

This study investigated the performance preferences of listeners without formal training in music. Specifically, it asked whether the quality of the performance (as represented by the status of the performer), the order of presentation of the performances, and extrinsic information about the quality of the performance impacted preferences. In Experiment 1, participants heard pairs of performances of solo piano music and were informed that one was played by a conservatory student, and one by a world-renowned professional. After each pair, they selected the one they thought had been performed by the professional. Their responses seem to have been driven by a combination of a preference for the performance actually played by the professional and a preference for the second performance in the pair. In Experiment 2, they heard the same performance pairs, but this time were informed, correctly or incorrectly, before each performance whether it was played by a student or by a professional. After each pair, they selected the performance they preferred. This time, their responses were influenced not just by the actual performer identity and the order of presentation, but also by the priming condition. Listener preferences seem to be driven by a combination of factors intrinsic and extrinsic to the performance itself.
Determination of residual stress in a microtextured α titanium component using high-energy synchrotron X-rays
Authors: Park Jun-Sang , Ray Atish K , Dawson Paul R , Lienert Ulrich , Miller Matthew P
Published: May 2016

A shrink-fit sample is manufactured with a Ti-8Al-1Mo-1V alloy to introduce a multiaxial residual stress field in the disk of the sample. A set of strain and orientation pole figures are measured at various locations across the disk using synchrotron high-energy X-ray diffraction. Two approaches—the traditional [Formula: see text] method and the bi-scale optimization method—are taken to determine the stresses in the disk based on the measured strain and orientation pole figures, to explore the range of solutions that are possible for the stress field within the disk. While the stress components computed using the [Formula: see text] method and the bi-scale optimization method have similar trends, their magnitudes are significantly different. It is suspected that the local texture variation in the material is the cause of this discrepancy.
Impact of Obesity on Outcomes in a Multiethnic Cohort of Medical Intensive Care Unit Patients
Authors: Trivedi Vrinda , Jean Raymonde E. , Genese Frank , Fuhrmann Katherine A. , Saini Anjeet K. , Mangulabnan Van Derick , Bavishi Chirag
Published: May 2016

Purpose:

To examine the association of obesity with in-hospital mortality and complications during critical illness.

Methods:

We performed a retrospective analysis of a multiethnic cohort of 699 patients admitted to medical intensive care unit between January 2010 and May 2011 at Mount Sinai St. Luke’s and Mount Sinai West Hospitals, tertiary care centers in New York City. Multivariate logistic regression analysis was used to evaluate the association between obesity (body mass index [BMI] ≥ 30] and in-hospital mortality. Subgroup analysis was performed in elderly patients (age ≥65 years).

Results:

Compared to normal BMI, obese patients had lower in-hospital mortality (24.4% vs 17.6%, P = .04). On multivariate analysis, obesity was independently associated with lower in-hospital mortality (odds ratio [OR]: 0.49, 95% confidence interval [CI]: 0.27-0.89, P = .018). There was no significant difference in rates of mechanical ventilation, reintubation, and vasopressor requirement across BMI categories. In subgroup analysis, elderly obese patients did not display lower in-hospital mortality (adjusted OR: 0.85, 95% CI: 0.40-1.82, P = .68).

Conclusion:

Our study supports the hypothesis that obesity is associated with decreased mortality during critical illness. However, this finding was not observed among elderly obese patients. Further studies should explore the interaction between age, obesity, and outcomes in critical illness.
Resolution of a Mobile Right Atrial Thrombus Complicating Acute Pulmonary Embolism With Low-Dose Tissue Plasminogen Activator in a Patient With Recent Craniotomy
Authors: Patel Amisha K. , Kafi Aarya , Bonet Antonio , Shapiro Shelly M. , Oh Scott S. , Zeidler Michelle R. , Betancourt Jaime
Published: May 2016

Right heart thrombus in transit (RHTT) is a rare, severe form of venous thromboembolism that carries a high mortality rate. The optimal treatment for RHTT has not been well established. Thrombolysis is a therapeutic modality for RHTT but carries the risk of bleeding complications including intracranial hemorrhage. Low-dose thrombolysis has been shown to be effective in treating submassive pulmonary emboli without an increased risk in bleeding complications, but it has not been studied in patients with RHTT. Here, we discuss the case of a 74-year-old male with lung cancer and recent craniotomy with metastasectomy 30 days prior to admission presenting with RHTT and bilateral pulmonary emboli (PE). He was treated successfully with low-dose thrombolysis, despite his relative contraindication to thrombolytics. To our knowledge, this is the first reported case of low-dose alteplase (tissue plasminogen activator [tPA]) used to treat an in-transit PE in the setting of recent craniotomy with metastasectomy.
Metacommunication During Disaster Response
Authors: Castor Theresa , Bartesaghi Mariaelena
Published: May 2016

“To anticipate and forestall disasters is to understand regularities in the ways small events can combine to have disproportionately large effects.” Taking Weick’s observation to heart, we examine teleconference calls between Louisiana local and state officials and federal officials as Hurricane Katrina gathered momentum by applying action-implicative discourse analysis (AIDA). AIDA highlights the linkages between communication dilemmas and communication practices. We analyze “reporting” as a metacommunicative speech act that implicated pragmatic communication dilemmas of how to act in the face of emerging disaster. We explicate how, during the Hurricane Katrina teleconferences, “reporting” shaped and constrained the formulation of problems and responses by creating a structure that facilitated order while inhibiting the identification of and “talking through” of confusion points, and the communicative sharing of local resources. As such, we identify how sensemaking is interconnected with interactional framing. Reporting thus constituted a “small event” that occurred with “regularity” during the Hurricane Katrina disaster.
The Future of Intensive Care Unit Sedation: A Report of Continuous Infusion Ketamine as an Alternative Sedative Agent
Authors: Benken Scott T. , Goncharenko Alexandra
Published: May 2016

This report describes a patient case utilizing a nontraditional sedative, continuous infusion ketamine, as an alternative agent for intensive care unit (ICU) sedation. A 27-year-old female presented for neurosurgical management of a coup contrecoup injury, left temporal fracture, epidural hemorrhage (EDH), and temporal contusion leading to sustained mechanical ventilation. The patient experienced profound agitation during mechanical ventilation and developed adverse effects with all traditional sedatives: benzodiazepines, dexmedetomidine, opioids, and propofol. Ketamine was titrated to effect and eliminated the need for other agents. This led to successful ventilator weaning, extubation, and transition of care. Given the unique side effect profile of ketamine, it is imperative that information is disseminated on potential utilization of this agent. More information is needed regarding dosing, monitoring, and long-term effects of utilizing ketamine as a continuous ICU sedative, but given the analgesia, anesthesia, and cardiopulmonary stability, future utilization of this medication for this indication seems promising.
Investigation of the train driver injuries and the optimization design of driver workspace during a collision
Authors: Peng Yong , Hou Lin , Yang Mingzhi , Tian Hongqi
Published: May 2016

The purpose of this study was to analyze train driver injuries under secondary impact and to optimize the driver workspace to reduce the driver impact injury risk. The console–seat–dummy collision analysis model of train cab is established using MADYMO. The driver dynamic impact response and the driver injury results were obtained from the collision model. The optimization of driver workspace parameters was conducted to reduce the driver injury risk. Fifteen samples were chosen for numerical simulation based on the optimal Latin hypercube design; the polynomial response surface methodology was adopted to fit the relationship between the driver injury criteria and the workspace parameters. The driver injury results show that the driver injury is considerably severe. The optimization results indicate that the driver injury is minimal when factors A, B, C, and D are 356.6 mm, 404.6 mm, 145 mm, and 200 mm, respectively. Compared with the initial collision model, all six driver injury criteria after optimization decrease obviously and are well within the tolerance limits, respectively. The analysis of the optimization results and the results of computer simulation refined after the optimization confirm that the optimization results show good correlation with the injury results of the collision numerical model and the effectiveness of the optimization design in reducing the severity of the driver injury during a secondary impact.
Intersections of Race, Ethnicity, and Gender
Authors: O’Neal Eryn Nicole , Beckman Laura O.
Published: May 2016

Using an intersectional framework, this article discusses the barriers to social services that Latina victims of intimate partner violence encounter, a drastically underdeveloped area of theorizing. We argue that placing Latinas at the center of analysis will facilitate empirical knowledge, which is necessary because mainstream inquiry has historically ignored their interests. First, we discuss cultural barriers through the lenses of gender, race, and ethnicity. Second, we describe socioeconomic barriers in conjunction with gender, race, and ethnicity. Third, we examine legal barriers along with the representation of gender, race, and ethnicity. Finally, we suggest directions for research and recommendations for service providers.
The Clinical Utility of ASRS-v1.1 for Identifying ADHD in Alcoholics Using PRISM as the Reference Standard
Authors: Reyes Maria M. , Schneekloth Terry D. , Hitschfeld Mario J. , Geske Jennifer R. , Atkinson David L. , Karpyak Victor M.
Published: May 2016

Objective: The objective was to assess the clinical utility of the Adult ADHD Self-Report Scale (ASRS-v1.1) in identifying ADHD in alcoholics using the Psychiatric Research Interview for Substance and Mental Disorders (PRISM) as the diagnostic “gold standard.” Method: We performed a secondary analysis of data from 379 treatment-seeking alcoholics who completed the ASRS-v1.1 and the ADHD module of the PRISM. Data analysis included descriptive statistics. Results: The prevalence of ADHD was 7.7% (95% CI = [5.4, 10.8]). The positive predictive value (PPV) of the ASRS-v1.1 was 18.1% (95% CI = [12.4, 25.7]) and the negative predictive value (NPV) was 97.6% (95% CI = [94.9, 98.9]). The ASRS-v1.1 demonstrated a sensitivity of 79.3% (95% CI = [61.6, 90.2]) and a specificity of 70.3% (95% CI = [65.3, 74.8]). Conclusion: The ASRS-v1.1 demonstrated acceptable sensitivity and specificity in a sample of treatment-seeking alcoholics when compared with the PRISM as the reference standard for ADHD diagnosis.
Tavaborole, a Novel Boron-Containing Small Molecule Pharmaceutical Agent for Topical Treatment of Onychomycosis
Authors: Ciaravino Vic , Coronado Dina , Lanphear Cheryl , Hoberman Alan , Chanda Sanjay
Published: May 2016

Tavaborole is a topical antifungal agent approved by the US Food and Drug Administration for the treatment of toenail onychomycosis. The effects of tavaborole on gestation, parturition (delivery, labor), offspring development, and survival during the perinatal and postnatal periods were assessed in mated female rats. Females (F0 generation) were administered single daily oral (gavage) doses of 15, 60, or 100 mg/kg/d from gestation day 6 through lactation day 20. The females were allowed to deliver naturally and rear their offspring until lactation day 21, at which time the F0 females were euthanized. One male and female from each litter were selected (F1 generation) and retained for assessments, including growth, neurobehavior, fertility, and their ability to produce an F2 generation. Reproductive and offspring parameters were determined for the F1 and F2 generations, as applicable. F1 females and F2 pups were euthanized on postnatal day 7. In the F0 females, decreased activity was observed in the 100 mg/kg/d dose group. Excess salivation was observed in the 60 and 100 mg/kg/d dose groups (slight to moderate), however, this finding was not considered adverse. There were no tavaborole-related effects on the growth, viability, development, neurobehavioral assessments, or reproductive performance of the F1 generation. Survivability and mean body weight of the F2 pups were unaffected. The no observed adverse effect level (NOAEL) for maternal toxicity (F0 generation) was 60 mg/kg/d, based on the decreased activity observed in the 100 mg/kg/d dose group. The NOAEL for the offspring effects was ≥100 mg/kg/d, based on the lack of test article-related changes.
Behavior and modeling of fiber-reinforced polymer-confined concrete in elliptical columns
Authors: Teng JG , Wu JY , Casalboni S , Xiao QG , Zhao Y
Published: May 2016

Conversion of rectangular columns into elliptical columns (i.e. shape modification) followed by fiber-reinforced polymer jacketing provides an attractive alternative strengthening method than direct fiber-reinforced polymer jacketing of rectangular reinforced concrete columns (with corner rounding). For this method to be widely used in practice, a design method for the fiber-reinforced polymer jacket needs to be developed, and the key to such a design method is a reliable and yet relatively simple stress–strain model for fiber-reinforced polymer-confined concrete in elliptical reinforced concrete columns. This article presents a combined experimental and finite element study from which a stress–strain model for fiber-reinforced polymer-confined concrete in elliptical columns was derived. The article first presents the experimental program designed to examine the effects of key parameters. The accuracy of a finite element model for fiber-reinforced polymer-confined elliptical concrete columns is then demonstrated through comparisons with the test results. Finally, on the basis of the test data as well as the numerical results obtained with the verified finite element model, a simple and accurate stress–strain model for fiber-reinforced polymer-confined concrete in elliptical columns is formulated for use in design.
How the Web was told: Continuity and change in the founding fathers’ narratives on the origins of the World Wide Web
Authors: Bory Paolo , Benecchi Eleonora , Balbi Gabriele
Published: May 2016

The essay investigates the evolution of the “narratives of invention” used by the founding fathers of the World Wide Web in a selected corpus of papers written by Tim Berners-Lee and colleagues from 1989 up to 1993 and later in the books of James Gillies and Robert Cailliau and of Berners-Lee himself in 2000. Thanks to a textual analysis that cross these sources, we identify three main sets of common keywords that did not change and three couples of conflicting keywords that depict the evolution of the narratives over time. Change and continuity, intertwined with conservation and innovation, emerge as the key strategies of the Web’s founding fathers in narrating their idea.
Gold, power, protest: Digital and social media and protests against large-scale mining projects in Colombia
Authors: Specht Doug , Ros-Tonen Mirjam AF
Published: May 2016

Colombia’s Internet connectivity has increased immensely. Colombia has also ‘opened for business’, leading to an influx of extractive projects to which social movements object heavily. Studies on the role of digital media in political mobilisation in developing countries are still scarce. Using surveys, interviews, and reviews of literature, policy papers, website and social media content, this study examines the role of digital and social media in social movement organisations and asks how increased digital connectivity can help spread knowledge and mobilise mining protests. Results show that the use of new media in Colombia is hindered by socioeconomic constraints, fear of oppression, the constraints of keyboard activism and strong hierarchical power structures within social movements. Hence, effects on political mobilisation are still limited. Social media do not spontaneously produce non-hierarchical knowledge structures. Attention to both internal and external knowledge sharing is therefore conditional to optimising digital and social media use.
Working together: Developing disaster risk reduction first aid training in a post-earthquake Chinese context
Authors: Sim Timothy , Liu Yang , Li Sijian
Published: May 2016

This brief review reports a current transdisciplinary practice by social work and nursing professionals working together with local stakeholders in a Chinese post-disaster context that is continually plagued by recurring secondary hazards. From a community psychosocial assessment in the village affected by recent landslides, the sense of insecurity posed by imminent landslides was apparent among the villagers. With the aim to reduce disaster risk, the collaboration focuses on providing first aid training using locally relevant knowledge and resources. Twenty relevant stakeholders were invited to help develop and attend the first-run of the program. This article explores the way social workers can apply transdisciplinary strategies to work with other professional practitioners and stakeholders in meeting disaster risk reduction needs in a Chinese remote village. One of the most apparent impacts of this approach is increasing the psychosocial well-being of the local residence as well as their preparedness in disasters.
Race and Retention in a Competitive Labor Market
Authors: LaFave Daniel , Nelson Randy , Doherty Michael
Published: May 2016

Between 1994 and 2013, Black head coaches of Division I National Collegiate Athletic Association basketball programs were more likely to be terminated than their White counterparts, adjusting for performance and characteristics of the coach. Controlling for employment at a historically Black college or university, which accounts for approximately a quarter of the Black coaches in our sample, overturns this result. The findings highlight the importance of understanding institutional environments when assessing discrimination in labor market outcomes.
In vitro selection technologies to enhance biomaterial functionality
Authors: Rosch Jonah C , Hollmann Emma K , Lippmann Ethan S
Published: May 2016

Cells make decisions and fate choices based in part on cues they receive from their external environment. Factors that affect the interpretation of these cues include the soluble proteins that are present at any given time, the cell surface receptors that are available to bind these proteins, and the relative affinities of the soluble proteins for their cognate receptors. Researchers have identified many of the biological motifs responsible for the high-affinity interactions between proteins and their receptors, and subsequently incorporated these motifs into biomaterials to elicit control over cell behavior. Common modes of control include localized sequestration of proteins to improve bioavailability and direct inhibition or activation of a receptor by an immobilized peptide or protein. However, naturally occurring biological motifs often possess promiscuous affinity for multiple proteins and receptors or lack programmable actuation in response to dynamic stimuli, thereby limiting the amount of control they can exert over cellular decisions. These natural motifs only represent a small fraction of the biological diversity that can be assayed by in vitro selection strategies, and the discovery of “artificial” motifs with varying affinity, specificity, and functionality could greatly expand the repertoire of engineered biomaterial properties. This minireview provides a brief summary of classical and emerging techniques in peptide phage display and nucleic acid aptamer selections and discusses prospective applications in the areas of cell adhesion, angiogenesis, neural regeneration, and immune modulation.
Assessing Metabolic Changes in Response to mTOR Inhibition in a Mantle Cell Lymphoma Xenograft Model Using AcidoCEST MRI
Authors: Akhenblit Paul J. , Hanke Neale T. , Gill Alexander , Persky Daniel O. , Howison Christine M. , Pagel Mark D. , Baker Amanda F.
Published: May 2016

AcidoCEST magnetic resonance imaging (MRI) has previously been shown to measure tumor extracellular pH (pHe) with excellent accuracy and precision. This study investigated the ability of acidoCEST MRI to monitor changes in tumor pHe in response to therapy. To perform this study, we used the Granta 519 human mantle cell lymphoma cell line, which is an aggressive B-cell malignancy that demonstrates activation of the phosphatidylinositol-3-kinase/Akt/mammalian target of rapamycin (mTOR) pathway. We performed in vitro and in vivo studies using the Granta 519 cell line to investigate the efficacy and associated changes induced by the mTOR inhibitor, everolimus (RAD001). AcidoCEST MRI studies showed a statistically significant increase in tumor pHe of 0.10 pH unit within 1 day of initiating treatment, which foreshadowed a decrease in tumor growth of the Granta 519 xenograft model. AcidoCEST MRI then measured a decrease in tumor pHe 7 days after initiating treatment, which foreshadowed a return to normal tumor growth rate. Therefore, this study is a strong example that acidoCEST MRI can be used to measure tumor pHe that may serve as a marker for therapeutic efficacy of anticancer therapies.
Portrait of a Consultant in Hard Times
Authors: Fulton William
Published: May 2016

John Nolen was one of the first planners to build a national consulting practice focused on new towns. However, his office began to struggle financially in the late 1920s. Despite a thirty-year record, Nolen had no paying private-sector clients after 1931 and finally had to downsize his office. He survived on New Deal contracts for a while. But eventually he could not obtain work even from the Resettlement Administration, where his former protégés were implementing his ideas. Modern new town ideas from Clarence Stein were ascendant. Seen as a relic, Nolen died without a single project pending in his portfolio.
Assisting the Novice in Lifestyle Change
Authors: Silveira Stephanie L. , LaVoy Emily C. , Johnston Craig A.
Published: May 2016

The beginning of a lifestyle intervention is a sensitive time, as doing “too much too quickly” may stress the immune system, resulting in an increase in upper respiratory symptoms and, consequently, attrition. However, “too little too slowly” may not align with patients’ motivation to change and may also result in attrition. There is also evidence that early weight loss is predictive of long-term maintenance of goal weight. Health care providers are frequently presented with contradictory information on the best model to promote enduring lifestyle change. Best practice dictates that health care provider acknowledge their patients’ motivation to change and incorporate each individual’s goals in designing the lifestyle change intervention. Additional support and advice may be warranted at the beginning of an intervention to promote the patient’s health and avoid attrition.
Information time scales for interim analyses of randomized clinical trials
Authors: Freidlin Boris , Othus Megan , Korn Edward L
Published: May 2016

Background:

Interim monitoring is a key component of randomized clinical trial design from both ethical and efficiency perspectives. In studies with time-to-event endpoints, timing of interim analyses is typically based on observing a pre-specified proportion of the total number of events required for the final analysis. While most randomized clinical trial designs pool events over the experimental and control arms in determining the analysis times, some designs use only the control-arm events for scheduling interim looks.

Purpose:

To evaluate the performance of the pooled and control-arm-based interim monitoring approaches and to propose a new procedure, the earliest information time procedure, that combines the benefits of the two approaches.

Methods:

The analytical and logistical considerations for the procedures are presented. The methodology is illustrated on data from three published randomized clinical trials. The procedures are compared in a simulation study.

Results:

The control-arm approach results in a slight inflation of the study type I error in one-sided randomized clinical trial designs. When the new treatment is no better than the control treatment, the pooled-arm approach results in, on average, earlier stopping times than the control-arm approach. When the new treatment works exceptionally well, the average stopping times under the control-arm approach are earlier than those under the pooled approach. The proposed earliest information time procedure is shown to result in stopping times corresponding to the best (earliest) of the two approaches over the entire range of alternatives.

Limitations:

The earliest information time procedure may result in a slight inflation of the type I error (especially in small trials); when exact control of the type I error is required, it is necessary to use a simulation-based method to correct the inflation.

Conclusion:

In time-to-event settings, the earliest information time procedure is an attractive alternative to the pooled and control-arm approaches. Improving the timing of interim analyses helps to minimize patient exposure to inferior treatments and to accelerate dissemination of the study results.
Epigenetic therapy in gastrointestinal cancer: the right combination
Authors: Abdelfatah Eihab , Kerner Zachary , Nanda Nainika , Ahuja Nita
Published: May 2016

Epigenetics is a relatively recent field of molecular biology that has arisen over the past 25 years. Cancer is now understood to be a disease of widespread epigenetic dysregulation that interacts extensively with underlying genetic mutations. The development of drugs targeting these processes has rapidly progressed; with several drugs already FDA approved as first-line therapy in hematological malignancies. Gastrointestinal (GI) cancers possess high degrees of epigenetic dysregulation, exemplified by subtypes such as CpG island methylator phenotype (CIMP), and the potential benefit of epigenetic therapy in these cancers is evident. The application of epigenetic drugs in solid tumors, including GI cancers, is just emerging, with increased understanding of the cancer epigenome. In this review, we provide a brief overview of cancer epigenetics and the epigenetic targets of therapy including deoxyribonucleic acid (DNA) methylation, histone modifications, and chromatin remodeling. We discuss the epigenetic drugs currently in use, with a focus on DNA methyltransferase (DNMT) and histone deacetylase (HDAC) inhibitors, and explain the pharmacokinetic and mechanistic challenges in their application. We present the strategies employed in incorporating these drugs into the treatment of GI cancers, and explain the concept of the cancer stem cell in epigenetic reprogramming and reversal of chemo resistance. We discuss the most promising combination strategies in GI cancers including: (1) epigenetic sensitization to radiotherapy, (2) epigenetic sensitization to cytotoxic chemotherapy, and (3) epigenetic immune modulation and priming for immune therapy. Finally, we present preclinical and clinical trial data employing these strategies thus far in various GI cancers including colorectal, esophageal, gastric, and pancreatic cancer.
Cost-effectiveness analysis of rifaximin-α administration for the reduction of episodes of overt hepatic encephalopathy in recurrence compared with standard treatment in France
Authors: Kabeshova Anastasiia , Ben Hariz Soumaia , Tsakeu Elyonore , Benamouzig Robert , Launois Robert
Published: May 2016

Background:

Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome that occurs most often in a context of acute or chronic liver disease. Despite the seriousness of the pathology, only a few treatments have been developed for improving its management. Rifaximin-α is the first treatment that has been clinically developed for overt HE (OHE) episodes. Recent results of clinical studies demonstrated its significant improvement in the health-related quality of life. The objective of the current study was to estimate the long-term cost-effectiveness of rifaximin-α used in combination with lactulose compared with lactulose monotherapy in cirrhotic patients, who have experienced at least two prior OHE events.

Methods:

A Markov model was used to estimate rifaximin-α cost-effectiveness, evaluating it from the perspective of all contributors as recommended by French health technology assessment guidelines. Costs were based on current French treatment practices. The transition between health states was based on the reanalysis of the rifaximin-α pivotal clinical trials RFHE3001 and RFHE3002. The main outcome of the model was cost per quality adjusted life year (QALY).

Results:

The results indicate that rifaximin-α is a cost-effective treatment option with an incremental cost per QALY gained of €19,187 and €18,517 over two different time horizons (2 and 5 years). The robustness of the model was studied using probabilistic sensitivity analysis.

Conclusion:

For the societal willingness to pay threshold of €27,000 per QALY gained, rifaximin-α in combination with lactulose is a cost-effective and affordable treatment for patients who have experienced at least two prior overt HE episodes.
Probiotics modify tight-junction proteins in an animal model of nonalcoholic fatty liver disease
Authors: Briskey David , Heritage Mandy , Jaskowski Lesley-Anne , Peake Jonathan , Gobe Glenda , Subramaniam V. Nathan , Crawford Darrell , Campbell Catherine , Vitetta Luis
Published: May 2016

Background:

We have investigated the effects of a multispecies probiotic preparation containing a combination of probiotic bacterial genera that included Bifidobacteria, Lactobacilli and a Streptococcus in a mouse model of high-fat diet or obesity-induced liver steatosis.

Methods:

Three groups of C57B1/6J mice were fed either a standard chow or a high-fat diet for 20 weeks, while a third group was fed a high-fat diet for 10 weeks and then concomitantly administered probiotics for a further 10 weeks. Serum, liver and large bowel samples were collected for analysis.

Results:

The expression of the tight-junction proteins ZO-1 and ZO-2 was reduced ( p < 0.05) in high-fat diet-fed mice compared to chow-fed mice. Probiotic supplementation helped to maintain tight ZO-1 and ZO-2 expression compared with the high-fat diet group ( p < 0.05), but did not restore ZO-1 or ZO-2 expression compared with chow-fed mice. Mice fed a high-fat diet ± probiotics had significant steatosis development compared with chow-fed mice ( p < 0.05); steatosis was less severe in the probiotics group compared with the high-fat diet group. Hepatic triglyceride concentration was higher in mice fed a high-fat diet ± probiotics compared with the chow group ( p < 0.05), and was lower in the probiotics group compared with the high-fat diet group ( p < 0.05). Compared with chow-fed mice, serum glucose, cholesterol concentration and the activity of alanine transaminase were higher ( p < 0.05), whereas serum triglyceride concentration was lower ( p < 0.05) in mice fed a high-fat diet ± probiotics.

Conclusions:

Supplementation with a multispecies probiotic formulation helped to maintain tight-junction proteins ZO-1 and ZO-2, and reduced hepatic triglyceride concentration compared with a high-fat diet alone.
Treatment of hyperuricemia in gout: current therapeutic options, latest developments and clinical implications
Authors: Sattui Sebastian E. , Gaffo Angelo L.
Published: May 2016

Despite being the most common type of inflammatory arthritis, gout is often poorly managed. Except for febuxostat and pegloticase, research in new therapeutic agents for the management of hyperuricemia in gout remained insufficient for several decades. With emerging evidence of possible roles of hyperuricemia in cardiometabolic comorbidities, as well as more convincing evidence regarding poor outcomes (e.g. disability, recurrent hospital admissions) in patients with uncontrolled gout, several agents are current under development. Increasing knowledge regarding renal urate transporters has resulted in the development of new generation uricosurics such as lesinurad and arhalofenate. This review aims at discussing current therapeutic strategies for gout, as well as their limitations and the possible role of emerging agents in the chronic management of hyperuricemia in gout. Drugs in phases I and II of development will be discussed, along with new agents and therapeutic classes, such as purine nucleoside phosphorylase inhibitors and dual-action drugs. These new developments are encouraging, and will hopefully contribute to a more adequate management of hyperuricemia in gout.
Evaluation of the Effect of Carbohydrate Intake on Postprandial Glucose in Patients With Type 1 Diabetes Treated With Insulin Pumps
Authors: James Mariel L. , Green Louisa , Amiel Stephanie A. , Choudhary Pratik
Published: May 2016

Background:

It has been suggested that dietary freedom in functional insulin therapy may be detrimental to glycemic control in type 1 diabetes. This study evaluates the effect of carbohydrate intake on glycemic control and postprandial blood glucose concentrations.

Methods:

Insulin pump data from 148 adults with type 1 diabetes, trained in functional insulin therapy, using pumps for ≥6 months, with ≥2 weeks of consecutive downloaded data, ≥80% use of a bolus calculator, ≥3 capillary blood glucose tests/day, and a concurrent HbA1C, were analyzed. More detailed periprandial data (pre- and postmeal glucose, carbohydrate intake, insulin bolus) were collected from a subset of 105 downloads (3495 meals).

Results:

Mean (± SD) age of contributors was 43 ± 13 years, HbA1C 7.84% ± 0.93 (62.19 mmol/mol); daily carbohydrate intake 166 ± 71 g. HbA1C reduced with increased meals/day ( r = –.370, P < .0005) and increased with mean carbohydrate content/meal ( r = .198, P = .043). However, total daily carbohydrate intake had a weak but significant negative association with HbA1C ( r = –.181, P = .027). There was no association between standard deviation of carbohydrate intake and HbA1C ( r = .021, P = .802) or between meal carbohydrate content and postprandial change in blood glucose ( r = –.004, P = .939) for meals with early postprandial (1-3 hours; n = 390) readings. There was a weak positive correlation ( r = .184, P = .008) between meal carbohydrate content and late (4-7 hours; n = 390) postprandial readings.

Discussion:

With appropriate training, patients using insulin pumps can accommodate a flexible diet with variable carbohydrate intake, without detriment to glycemic control. However, large carbohydrate meals may contribute to poorer outcomes, through impact on late postprandial glycemia.
New avenues for treating emotional memory disorders: towards a reconsolidation intervention for posttraumatic stress disorder
Authors: Kindt Merel , van Emmerik Arnold
Published: May 2016

The discovery that fear memories may change upon retrieval, a process referred to as memory reconsolidation, opened avenues to develop a revolutionary new treatment for emotional memory disorders. Reconsolidation is a two-phase process in which retrieval of a memory initiates a transient period of memory destabilization, followed by a protein synthesis-dependent restabilization phase. This reconsolidation window offers unique opportunities for amnesic agents to interfere with the process of memory restabilization, thereby weakening or even erasing the emotional expression from specific fear memories. Here we present four uncontrolled case descriptions of patients with symptoms of posttraumatic stress disorder (PTSD) who received a reconsolidation intervention. The intervention basically involves a brief reactivation of the trauma memory aimed to trigger memory destabilization, followed by the intake of one pill of 40 mg propranolol HCl (i.e. a noradrenergic beta-blocker) that should disrupt the process of memory restabilization. We present three cases who showed a steep decline of fear symptoms after only one or two intervention sessions. To illustrate that the translation from basic science to clinical practice is not self-evident, we also present a description of a noneffective intervention in a relatively complex case. Even though the reconsolidation intervention is very promising, the success of the treatment depends on whether the memory reactivation actually triggers memory reconsolidation. Obviously the uncontrolled observations described here warrant further study in placebo-controlled designs.
Contemporary Hospitalization Rate Among Adults With Complex Congenital Heart Disease
Authors: Cedars Ari , Benjamin Lawrence , Vyhmeister Ross , Harris Kathryn , Bradley Elisa A. , Wadia Subeer , Awad Ahmed J. , Novak Eric
Published: May 2016

Background:

Adults with congenital heart disease are hospitalized at increasing rates in the Western world. Identification of rates of and risk factors for hospitalization is essential for research and improving patient outcomes.

Methods:

We conducted a single-center retrospective analysis of patients with a primary diagnosis of tetralogy of Fallot (TOF), transposition of the great arteries (both d- and l-transposition of the great arteries [TGAs]), or single ventricle (SV). We investigated the rates of mortality, annual hospitalization, and patient-specific risk factors for unplanned cardiac hospitalization.

Results:

Adult patients with complex congenital heart disease are hospitalized at a rate four to eight times greater than the general US population ( P < .001). In addition, there are significant differences between the rates of hospitalization in TOF and TGA (0.39 and 0.41 hospitalizations per patient-year, respectively) and SV (0.72 hospitalizations per patient-year). The majority of excess hospitalizations in the study group were due to cardiac disease ( P < .001 for all three groups). Risk factors for unplanned cardiac hospitalization in TOF included pulmonary atresia, depressed left ventricular and right ventricular ejection fraction, and smoking; in TGA, they included Ebstein malformation, surgeries other than primary repair, noncardiac diagnoses, atrial arrhythmias, atrioventricular nodal block, left ventricular ejection fraction, and smoking; and in SV, they included atrial arrhythmias and cyanosis.

Conclusions:

Patients born with complex congenital heart disease are hospitalized far more frequently than the general US population, primarily for cardiac-related illness. Future research should focus on confirming the present findings and on identification of strategies to improve outcomes in this growing group of patients.