bluuebunny/crossref_metadata_2025 huggingface dataset:
Cellular versus acellular matrix devices in treatment of diabetic foot ulcers: study protocol for a comparative efficacy randomized controlled trial
Authors: Lev-Tov Hadar , Li Chin-Shang , Dahle Sara , Isseroff Roslyn Rivkah
Published: January 2013

Background

Diabetic foot ulcers (DFUs) represent a significant source of morbidity and an enormous financial burden. Standard care for DFUs involves systemic glucose control, ensuring adequate perfusion, debridement of nonviable tissue, off-loading, control of infection, local wound care and patient education, all administered by a multidisciplinary team. Unfortunately, even with the best standard of care (SOC) available, only 24% or 30% of DFUs will heal at weeks 12 or 20, respectively.

The extracellular matrix (ECM) in DFUs is abnormal and its impairment has been proposed as a key target for new therapeutic devices. These devices intend to replace the aberrant ECM by implanting a matrix, either devoid of cells or enhanced with fibroblasts, keratinocytes or both as well as various growth factors. These new bioengineered skin substitutes are proposed to encourage angiogenesis and in-growth of new tissue, and to utilize living cells to generate cytokines needed for wound repair.

To date, the efficacy of bioengineered ECM containing live cellular elements for improving healing above that of a SOC control group has not been compared with the efficacy of an ECM devoid of cells relative to the same SOC. Our hypothesis is that there is no difference in the improved healing effected by either of these two product types relative to SOC.

Methods/Design

To test this hypothesis we propose a randomized, single-blind, clinical trial with three arms: SOC, SOC plus Dermagraft® (bioengineered ECM containing living fibroblasts) and SOC plus Oasis® (ECM devoid of living cells) in patients with nonhealing DFUs. The primary outcome is the percentage of subjects that achieved complete wound closure by week 12.

Discussion

If our hypothesis is correct, then immense cost savings could be realized by using the orders-of-magnitude less expensive acellular ECM device without compromising patient health outcomes. The article describes the protocol proposed to test our hypothesis.

Trial registration

ClinicalTrials.gov: NCT01450943. Registered: 7 October 2011
Dosimetric parameter predicting the deterioration of hepatic function after helical tomotherapy in patients with unresectable locally advanced hepatocellular carcinoma
Authors: Son Seok Hyun , Kay Chul Seung , Song Jin Ho , Lee Sea-Won , Choi Byung Ock , Kang Young Nam , Jang Jeong Won , Yoon Seung Kew , Jang Hong Seok
Published: January 2013

Background

The purpose of this study was to identify parameters capable of predicting the deterioration of hepatic function after helical tomotherapy in patients with unresectable locally advanced hepatocellular carcinoma.

Methods

Between March 2006 and February 2012, 72 patients were eligible for this study. All patients received hypofractionated radiotherapy using the TomoTherapy Hi-Art (TomoTherapy, Madison, WI, USA) at Seoul St. Mary's Hospital and Incheon St. Mary's Hospital, the Catholic University of Korea. The radiation dose was a median 50 Gy (range: 40–50 Gy) in 10 fractions to 95% of the planning target volume. Radiation-induced hepatic toxicity was defined as an increase of at least 2 points in the Child-Pugh (CP) score within 3 months after completion of helical tomotherapy.

Results

An increase of at least 2 points in the CP score occurred in 32 of the 72 patients (44.4%). Multivariate logistic regression analysis revealed that pretreatment CP class and V15Gy were significant parameters associated with an increase in CP score (p = 0.009 and p < 0.001, respectively). The area under receiver operating characteristic curve was 0.863 for V15Gy (p < 0.001). For V15Gy, with a cutoff value of 43.2%, the accuracy was 0.806 (58/72) with a sensitivity of 0.938 and a specificity of 0.725.

Conclusions

An increase of at least 2 points in the CP score is a radiation dose-limiting factor, and the non-target normal liver receiving a dose more than 15 Gy (V15Gy) should be <43.2% to reduce the risk of the deterioration of hepatic function.
Characterization and genomic analysis of kraft lignin biodegradation by the beta-proteobacterium Cupriavidus basilensis B-8
Authors: Shi Yan , Chai Liyuan , Tang Chongjian , Yang Zhihui , Zhang Huan , Chen Runhua , Chen Yuehui , Zheng Yu
Published: January 2013

Background

Lignin materials are abundant and among the most important potential sources for biofuel production. Development of an efficient lignin degradation process has considerable potential for the production of a variety of chemicals, including bioethanol. However, lignin degradation using current methods is inefficient. Given their immense environmental adaptability and biochemical versatility, bacterial could be used as a valuable tool for the rapid degradation of lignin. Kraft lignin (KL) is a polymer by-product of the pulp and paper industry resulting from alkaline sulfide treatment of lignocellulose, and it has been widely used for lignin-related studies.

Results

Beta-proteobacterium Cupriavidus basilensis B-8 isolated from erosive bamboo slips displayed substantial KL degradation capability. With initial concentrations of 0.5–6 g L-1, at least 31.3% KL could be degraded in 7 days. The maximum degradation rate was 44.4% at the initial concentration of 2 g L-1. The optimum pH and temperature for KL degradation were 7.0 and 30°C, respectively. Manganese peroxidase (MnP) and laccase (Lac) demonstrated their greatest level of activity, 1685.3 U L-1 and 815.6 U L-1, at the third and fourth days, respectively. Many small molecule intermediates were formed during the process of KL degradation, as determined using GC-MS analysis. In order to perform metabolic reconstruction of lignin degradation in this bacterium, a draft genome sequence for C. basilensis B-8 was generated. Genomic analysis focused on the catabolic potential of this bacterium against several lignin-derived compounds. These analyses together with sequence comparisons predicted the existence of three major metabolic pathways: β-ketoadipate, phenol degradation, and gentisate pathways.

Conclusion

These results confirmed the capability of C. basilensis B-8 to promote KL degradation. Whole genomic sequencing and systematic analysis of the C. basilensis B-8 genome identified degradation steps and intermediates from this bacterial-mediated KL degradation method. Our findings provide a theoretical basis for research into the mechanisms of lignin degradation as well as a practical basis for biofuel production using lignin materials.
Mediator regulates non-coding RNA transcription at fission yeast centromeres
Authors: Thorsen Michael , Hansen Heidi , Venturi Michela , Holmberg Steen , Thon Genevieve
Published: January 2013

Background

In fission yeast, centromeric heterochromatin is necessary for the fidelity of chromosome segregation. Propagation of heterochromatin in dividing cells requires RNA interference (RNAi) and transcription of centromeric repeats by RNA polymerase II during the S phase of the cell cycle.

Results

We found that the Med8-Med18-Med20 submodule of the Mediator complex is required for the transcriptional regulation of native centromeric dh and dg repeats and for the silencing of reporter genes inserted in centromeric heterochromatin. Mutations in the Med8-Med18-Med20 submodule did not alter Mediator occupancy at centromeres; however, they led to an increased recruitment of RNA polymerase II to centromeres and reduced levels of centromeric H3K9 methylation accounting for the centromeric desilencing. Further, we observed that Med18 and Med20 were required for efficient processing of dh transcripts into siRNA. Consistent with defects in centromeric heterochromatin, cells lacking Med18 or Med20 displayed elevated rates of mitotic chromosome loss.

Conclusions

Our data demonstrate a role for the Med8-Med18-Med20 Mediator submodule in the regulation of non-coding RNA transcription at Schizosaccharomyces pombe centromeres. In wild-type cells this submodule limits RNA polymerase II access to the heterochromatic DNA of the centromeres. Additionally, the submodule may act as an assembly platform for the RNAi machinery or regulate the activity of the RNAi pathway. Consequently, Med8-Med18-Med20 is required for silencing of centromeres and proper mitotic chromosome segregation.
Neurologist practice patterns in treatment of muscle cramps in Canada
Authors: Fat Mary Jane Lim , Kokokyi Seint , Katzberg Hans Dieter
Published: January 2013

Recently an article provided patient perspectives on therapies and perceived effectiveness in preventing muscle cramps. However, there are few studies evaluating physicians' point of view in the management of this common symptom. In our study, we studied physician practice patterns in the treatment of muscle cramps by surveying a group of neurologists in Canada. We demonstrated that most physicians use a combination of pharmacological and non‐pharmacological methods in treating muscle cramps. The most commonly used medications are baclofen, quinine and gabapentin, of which baclofen and quinine were reported to be the most tolerated.
The effects of modified alternate-day fasting diet on weight loss and CAD risk factors in overweight and obese women
Authors: Eshghinia Samira , Mohammadzadeh Fatemeh
Published: January 2013

Background

Obesity is a worldwide health problem with increasing prevalence. Decrease in energy intake has been shown to lower the risk of coronary artery disease in obese subjects. The common form of dietary restriction is daily calorie restriction (CR). Another form is alternate-day fasting (ADF). This study examined the ability of modified ADF to facilitate weight loss and lower cardiovascular risk factors in overweight and obese women.

Methods

15 adult subjects completed an 8 weeks trial (2 weeks observed and 6 weeks ADF). All women consumed very low calorie diet on the fast day and usually diet in every other day. Body weight (BW), fat mass and blood pressure (BP) were measured. Fasting blood samples were collected at the first and 57th day of trial for biochemical analysis.

Results

During the course of the trial, BW of the subjects decreased (p < 0/0001) from 84/3 ± 11/44 kg to 78/3 ± 10/18 kg. Waist Circumference decreased from 87/87 ± 9/74 to 82/86 ± 9/68(p < 0/001). Reduction in systolic BP was seen from 114.8 ± 9.16 to 105.13 ± 10.19 mmHg (p < 0/001) and diastolic BP changed from 82.86 ± 10.6 to 74.5 ± 10.8 (P < 0.05). Total cholesterol decreased from 227/73 ± 49/96 to 214/67 ± 43/27, TG from 160/5 ± 46/18 to 143/9 ± 22/77, LDL from 149/46 ± 49/81 to 131/3 ± 50/97, and FBS from 102 ± 14/7 to 96 ± 11/79 mg/dl but were not significant. HDL increased from 42/32 ± 18/01 to 50/58 ± 19/46 and was not significant.

Conclusion

These finding suggest that short time ADF is a viable dietary option to help obese individuals lose weight and decrease some CAD risk factors. More and longer-term studies in human subjects are needed to support this important result.
Patient-level pooled analysis of adjudicated gastrointestinal outcomes in celecoxib clinical trials: meta-analysis of 51,000 patients enrolled in 52 randomized trials
Authors: Moore Andrew , Makinson Geoffrey , Li Chunming
Published: January 2013

Introduction

Although the safety of celecoxib has been investigated, limited data are available on complications affecting the entire (upper and lower) gastrointestinal (GI) tract, with no patient-level pooled analyses of upper and lower GI outcomes available. We therefore evaluated the upper and lower GI safety of celecoxib by using patient-level data from randomized controlled trials (RCTs).

Methods

This patient-level pooled analysis included 52 prospective, randomized, double-blind parallel-group studies from the Celecoxib Clinical Database. Each study had a planned duration of continuous treatment with celecoxib or a nonselective nonsteroidal antiinflammatory drug (nsNSAID), rofecoxib, or the placebo comparator arm for at least 4 weeks. All studies with final reports completed by 1 October 2007 were included. The primary end point was the combined incidence of clinically significant upper and lower GI events (CSULGIEs). An independent blinded committee reviewed and adjudicated all end points by using predefined criteria and all available reported adverse events, laboratory data, and case narratives. All doses of celecoxib and all doses of all nsNSAIDs were pooled for analysis.

Results

The pooled analysis involved 51,048 patients; 28,614 were randomized to celecoxib; 15,278 to nsNSAIDs (including 3,248 patients taking naproxen, 2,640 taking ibuprofen, 8,066 taking diclofenac, 1,234 taking loxoprofen, and 90 taking ketoprofen); 5,827 to placebo and 1,329 to rofecoxib. The mean age was 60 years, and 65% were women. Data on 1,042 patients with potential GI events were reviewed for end-points adjudication; the adjudication committee confirmed 89 patients with CSULGIEs. The majority were in the celecoxib and nsNSAID groups (with raw incidence proportions of 37 (0.1%) and 40 (0.3%), respectively). The incidence rates were 0.3, 0.9 and 0.3 per 100 patient-years in the celecoxib, nsNSAID, and placebo groups, respectively. The time to incidence of CSULGIEs was significantly longer with celecoxib than with nsNSAIDs (P = 0.0004).

Conclusions

When compared with nsNSAIDs, celecoxib is associated with a significantly lower risk of all clinically significant GI events throughout the entire GI tract. This pooled analysis of 52 RCTs significantly advances the understanding of the upper and lower GI safety profile of celecoxib and its potential benefits to patients.
Atherosclerotic cardiovascular disease and dermatomyositis: an analysis of the Nationwide Inpatient Sample survey
Authors: Linos Eleni , Fiorentino David , Lingala Bharathi , Krishnan Eswar , Chung Lorinda
Published: January 2013

Introduction

Increased rates of cardiovascular disease are implicated in several rheumatologic diseases. Our aim was to characterize dermatomyositis hospitalizations and evaluate cardiovascular-associated mortality in this patient population.

Methods

We examined the frequency and mortality rates of several atherosclerotic cardiovascular diagnoses and procedures among hospitalized adult patients with dermatomyositis using data from the US Nationwide Inpatient Sample (NIS) from 1993 to 2007. We compared the odds of death among hospitalized dermatomyositis patients with each cardiovascular diagnosis or procedure to those without, as well as to controls with cardiovascular diagnoses, using logistic regression.

Results

A total of 50,322 hospitalizations of dermatomyositis patients occurred between 1993 and 2007 (mean age 58 years, and 73% female). Of all dermatomyositis hospitalizations, 20% were associated with a concurrent atherosclerotic cardiovascular diagnosis or procedure. The overall in-hospital mortality was 5.7%. Dermatomyositis patients with any associated atherosclerotic cardiovascular diagnosis or procedure were twice as likely to die during the inpatient stay compared to dermatomyositis patients who did not have atherosclerotic cardiovascular disease (OR = 2.0 95% CI 1.7-2.5, p < 0.0001). The odds ratio for death in patients with both dermatomyositis and cardiovascular disease compared to controls with cardiovascular disease alone was 1.98 (95% CI 1.57-2.48) in multivariate adjusted models.

Conclusions

Approximately one fifth of dermatomyositis hospitalizations in the US were associated with an atherosclerotic cardiovascular diagnosis or procedure. These patients have double the risk of in-hospital death in comparison with controls and dermatomyositis patients without a cardiovascular diagnosis, making identification of these groups important for both prognostic purposes and clinical care.
Predictors of Chikungunya rheumatism: a prognostic survey ancillary to the TELECHIK cohort study
Authors: Gérardin Patrick , Fianu Adrian , Michault Alain , Mussard Corinne , Boussaïd Karim , Rollot Olivier , Grivard Philippe , Kassab Somar , Bouquillard Eric , Borgherini Gianandrea , Gaüzère Bernard-Alex , Malvy Denis , Bréart Gérard , Favier François
Published: January 2013

Introduction

Long-lasting relapsing or lingering rheumatic musculoskeletal pain (RMSP) is the hallmark of Chikungunya virus (CHIKV) rheumatism (CHIK-R). Little is known on their prognostic factors. The aim of this prognostic study was to search the determinants of lingering or relapsing RMSP indicative of CHIK-R.

Methods

Three hundred and forty-six infected adults (age ≥ 15 years) having declared RMSP at disease onset were extracted from the TELECHIK cohort study, Reunion island, and analyzed using a multinomial logistic regression model. We also searched for the predictors of CHIKV-specific IgG titres, assessed at the time of a serosurvey, using multiple linear regression analysis.

Results

Of these, 111 (32.1%) reported relapsing RMSP, 150 (43.3%) lingering RMSP, and 85 (24.6%) had fully recovered (reference group) on average two years after acute infection. In the final model controlling for gender, the determinants of relapsing RMSP were the age 45-59 years (adjusted OR: 2.9, 95% CI: 1.0, 8.6) or greater or equal than 60 years (adjusted OR: 10.4, 95% CI: 3.5, 31.1), severe rheumatic involvement (fever, at least six joints plus four other symptoms) at presentation (adjusted OR: 3.6, 95% CI: 1.5, 8.2), and CHIKV-specific IgG titres (adjusted OR: 3.2, 95% CI: 1.8, 5.5, per one unit increase). Prognostic factors for lingering RMSP were age 45-59 years (adjusted OR: 6.4, 95% CI: 1.8, 22.1) or greater or equal than 60 years (adjusted OR: 22.3, 95% CI: 6.3, 78.1), severe initial rheumatic involvement (adjusted OR: 5.5, 95% CI: 2.2, 13.8) and CHIKV-specific IgG titres (adjusted OR: 6.2, 95% CI: 2.8, 13.2, per one unit increase). CHIKV specific IgG titres were positively correlated with age, female gender and the severity of initial rheumatic symptoms.

Conclusions

Our data support the roles of age, severity at presentation and CHIKV specific IgG titres for predicting CHIK-R. By identifying the prognostic value of the humoral immune response of the host, this work also suggest a significant contribution of the adaptive immune response to the physiopathology of CHIK-R and should help to reconsider the paradigm of this chronic infection primarily shifted towards the involvement of the innate immune response.
Chronic Glucocorticoid Exposure Potentiates Placental Chorionic Plate Artery Constriction: Implications for Aberrant Fetoplacental Vascular Resistance in Fetal Growth Restriction
Authors: Nugent J. L. , Wareing M. , Palin V. , Sibley C. P. , Baker P. N. , Ray D. W. , Farrow S. N. , Jones R. L.
Published: January 2013

Fetal growth restriction (FGR) is a serious pregnancy complication, resulting in significant perinatal morbidity and mortality. Increased vascular resistance in the fetoplacental circulation is a hallmark of FGR and is associated with enhanced vasoconstriction of the resistance arteries in the placenta, the chorionic plate arteries (CPAs). Although the cause is unknown, FGR is associated with excess exposure to glucocorticoids (GCs), key mediators of vascular resistance in the systemic circulation. We hypothesized that GCs alter CPA reactivity, thereby contributing to the altered blood flow dynamics seen in FGR. We aimed to examine the acute and chronic effects of GCs on CPA reactivity and the operational mechanisms. Glucocorticoid receptors were highly expressed by CPA. 11β-Hydroxysteroid isoenzyme type 2 was detected within the endothelium, whereas 11β-hydroxysteroid isoenzyme type 1 was absent. Acute GC treatment significantly attenuated U46619-induced constriction. This effect was reversed by cotreatment with mifepristone or an endothelial NOS inhibitor. In contrast, chronic GC treatment potentiated U46619 constriction in a dose-dependent manner, which was partially abolished by mifepristone cotreatment. Similar effects were observed using a novel nonsteroidal glucocorticoid receptor-specific agonist. Chronic treatment with GCs altered the expression of several vasoactive factors, including thromboxane and bradykinin receptors, prokineticin-1, cyclooxygenase-2, and endothelial NOS. In summary, acute and chronic GC treatment exerts contrasting effects on CPA vasoreactivity. These opposing effects are consistent with temporal actions in other vascular beds and reflect activation of distinct nongenomic and genomic pathways. Chronic exposure to elevated GCs may contribute to the raised vascular resistance observed in the fetoplacental circulation in FGR.
Rapid Induction of Hypothalamic Iodothyronine Deiodinase Expression by Photoperiod and Melatonin in Juvenile Siberian Hamsters (Phodopus sungorus)
Authors: Prendergast Brian J. , Pyter Leah M. , Kampf-Lassin August , Patel Priyesh N. , Stevenson Tyler J.
Published: January 2013

Production of T3 in the mediobasal hypothalamus is critical for regulation of seasonal reproductive physiology. Type 2 iodothyronine deiodinase (DIO2) and DIO3 enzymes catalyze the prohormone T4 into biologically-active T3 and biologically-inactive rT3, respectively. In several seasonally-breeding vertebrates, DIO2 and DIO3 expression is implicated in photoperiod signal transduction in adulthood. These experiments tested the hypothesis that juvenile Siberian hamsters, which are highly responsive to photoperiod at weaning (postnatal day [PND]18), exhibit rapid and sustained changes in hypothalamic dio3 mRNA expression during photoperiod-induced and photoperiod-inhibited puberty. Hypothalamic dio2 and dio3 expression was measured via quantitative PCR in hamsters born and reared in a long-day photoperiod (15L:9D) and weaned on PND18 into short-day photoperiods (9L:15D). In SD males, hypothalamic dio3 mRNA was elevated 2.5-fold within 3 days (PND21) and continued to increase (>20-fold) through PND32; changes in dio3 mRNA preceded inhibition of gonadotropin (FSH) secretion and gonadal regression in SD. Females exhibited comparable dio3 responses to SD. In LD males, dio3 remained low and invariant from PND18–PND32. In contrast, dio2 mRNA rose conspicuously on PND21, independent of photoperiod, returning to basal levels thereafter. In LD, a single afternoon melatonin (MEL) injection on PND18 or PND20 was sufficient to increase hypothalamic dio3 mRNA, and dio3 increased in proportion to the number of successive days of MEL treatment. SD photoperiods and MEL exert rapid, sustained, and additive effects on hypothalamic dio3 mRNA, which may play a central role in inhibiting maturation of the peripubertal hypothalamo-pituitary-gonadal axis.
Economic Observation and Measurement in Russia Before 1917: Surveying Typicalities and Sampling Totalities
Authors: Barnett Vincent
Published: January 2013

This article provides a case study of the development of observational methodology and techniques in a non-Western country. It does so by first considering various institutions of observation that existed in Russia across the nineteenth century, such as government statistical departments, the Imperial Free Economic Society, and the zemstvo. This is then followed by an analysis of debates that occurred over observational methodology between various Russian economists such as A. I. Chuprov, A. A. Chuprov, D. I. Mendeleev, and A. V. Chayanov, and a consideration of the use such observations were put to by others such as S. N. Prokopovich. The political ramifications of different observational practices are outlined, for example, by Marxists such as V. I. Lenin and M. I. Tugan-Baranovsky, and the link considered to exist by some economists between social and natural scientific techniques of observation is scrutinized.
Observing Shocks
Authors: Duarte Pedro Garcia , Hoover Kevin D.
Published: January 2013

Macroeconomists have observed business cycle fluctuations over time by constructing and manipulating models in which shocks have increasingly played a greater role. Shock is a term of art that pervades modern economics appearing in nearly one-quarter of all journal articles in economics and in nearly half in macroeconomics. Surprisingly, its rise as an essential element in the vocabulary of economists can be dated only to the early 1970s. We trace the history of shocks in macroeconomics from Ragnar Frisch and Eugen Slutsky in the 1920s and 1930s through real business cycle and DSGE models and to the use of shocks as generators of impulse-response functions, which are in turn used as data in matching estimators. The history is organized around the observability of shocks. As well as documenting a critical conceptual development in economics, the history of shocks shows that James Bogen and James Woodward’s distinction between data and phenomena must be substantially relativized if it is to be at all plausible.
Active Dynamic Vibration Absorber for Broadband Control of a Multi-Mode System: Simulation and Experimental Verification
Authors: Ladipo Ismail L. , Muthalif Asan G.A.
Published: January 2013

The control of broadband steady state vibration amplitude of a multi-mode system is presented. This objective is achieved using an Active Dynamic Vibration Absorber (ADVA). The stiffness property of the ADVA is adaptively tuned to attenuate the vibration of the multi-mode system at resonance. The ADVA detects the excitation frequency of the multi-mode system and calibrates its stiffness property to give the required stiffness for that mode. To implement the ADVA, a prototype model with low modal frequencies is designed. The equations of the steady state response of the multi-mode system with the attached ADVA are derived. The behavior of the prototype model when the ADVA is attached to different locations is used to determine the optimal location of the ADVA. The simulation result shows a reduction in the broadband of the multi-mode system. The result of the implementation of the ADVA reveals a 46%, 73% and 97% vibration amplitude reduction at first, second and third mode of the multi-mode system respectively.
Helping Sufferers to Cope with Noise Using Distance Learning Cognitive Behaviour Therapy
Authors: Leventhall Geoff , Robertson Donald , Benton Steve , Leventhall Lyn
Published: January 2013

Unresolved noise complaints cause considerable distress to sufferers, and a deterioration in quality of life as a consequence of failure to cope with the noise stress. The environmental noise control structure is directed towards higher frequency noises, which can be assessed by use of A-weighted measurements and this results in some low frequency noise problems receiving an inadequate evaluation. A number of countries now have limits for low frequency noise, but these are not yet well known or widely used. (Leventhall, 2009). Is there a solution to the problem of what can be done to help the small number of people who are adversely affected by perception of a low frequency noise, which it has not been possible to control? This paper describes how Cognitive Behaviour Therapy can be a solution.
The Welfare Effects of Reversed Border Tax Adjustments as a Remedy under Unilateral Environmental Taxation
Authors: Seymore R. , Mabugu M. , van Heerden J. H.
Published: January 2013

Border Tax Adjustments (BTAs) resurfaced recently in national policy debates as a possible measure to counter the anti-competitiveness effect of unilateral environmental taxes. There seems to be no consensus in the literature on the effectiveness of BTAs under environmental taxes. This paper aims to provide a theoretical Heckscher-Ohlin analysis that not only challenges the effectiveness of BTAs, but also proposes an alternative approach to counter the anti-competitiveness effect of unilateral environmental taxes. Using conventional Heckscher-Ohlin methodology, in a small country, we show that policy makers should, instead of implementing BTAs, consider the opposite of BTAs to mitigate the anti-competitiveness effects of environmental taxes. We show that gains from trade, due to a reduction in import tariffs, could, under certain assumptions, offset the initial tax induced welfare loss.
Optimal Workflow Decisions for Investigators in Systems with Interruptions
Authors: Dobson Gregory , Tezcan Tolga , Tilson Vera
Published: January 2013

We model a system that consists of a stream of customers processed through three steps by two resources. The first resource, an investigator, handles the first step, in which she collects information from the customer and decides what work will be done in the second step by the second resource, the back office. In the third step, the investigator returns to the customer armed with the additional information or analysis done by the back office and provides the customer with a conclusion, solution, or diagnosis. The investigator has to prioritize either seeing a new customer or completing the work with a customer already in the system. While serving one customer, the investigator may be interrupted by requests from the other customers in the system. Our main objective is to understand the impact of the investigator's choices on system throughput. In addition, we are interested in the occupancy of the system (and thus the flow time of customers). We create a stylized queueing model to examine the investigator's decisions and show that, when interruptions are not an issue, the investigator should prioritize new customers to maximize throughput, keeping the system as full as possible. If customers who have been in the system for a long time generate interruptions and thus additional work for the investigator, we show that it is asymptotically optimal for the investigator to keep the system occupancy low and prioritize discharging customers. Our conclusions are based on a model of a re-entrant queue with dedicated servers serving multiple stations, with two novel features: a buffer that is shared between stations, and jobs in the system generating additional work for the servers.

This paper was accepted by Assaf Zeevi, stochastic models and simulation.
Nilotinib-Associated Acute Pancreatitis
Authors: Engel Tal , Justo Dan , Amitai Michal , Volchek Yulia , Mayan Haim
Published: January 2013

OBJECTIVE

To report a case of acute pancreatitis in a patient receiving nilotinib for chronic myelogenous leukemia (CML).

CASE SUMMARY

A 69-year-old man recently diagnosed with chronic phase CML received nilotinib 300 mg twice daily and was admitted with acute pancreatitis that appeared the day after the first dose. The patient had normal levels of triglycerides and denied alcohol use. Serum pancreatic enzymes were within normal limits the day before nilotinib initiation. Abdominal computed tomography demonstrated a normal liver, bile duct without stones, and findings that were consistent with focal pancreatitis. The patient's history was significant for concomitant use of enalapril and simvastatin; both have been associated with pancreatitis, but the patient had been taking these medications for at least 5 years without adverse effects. Nilotinib was immediately discontinued. Abdominal pain resolved and serum pancreatic enzymes levels returned to normal 2 weeks later.

DISCUSSION

One of the adverse effects of some tyrosine kinase inhibitors is increased levels of serum pancreatic enzymes. Accordingly, nilotinib labeling includes “high lipase levels in serum” as an adverse event. There are few case reports of acute pancreatitis associated with nilotinib in the literature and some are incomplete. We present a well-documented case of nilotinib-associated acute pancreatitis. Consistent with Badalov's new classification system for drug-induced acute pancreatitis and with the Naranjo probability scale, this case represents a possible adverse reaction of pancreatitis associated with nilotinib therapy. As rechallenge is unethical, treatment with nilotinib has not been resumed.

CONCLUSIONS

This case demonstrates a possible association between acute pancreatitis and nilotinib use. Although a rare phenomenon, clinicians should be alert for signs and symptoms of pancreatitis, as treatment with nilotinib for CML is becoming more common.
Carfilzomib: A Second-Generation Proteasome Inhibitor for the Treatment of Relapsed and Refractory Multiple Myeloma
Authors: Thompson Jennifer L
Published: January 2013

OBJECTIVE

To review and summarize data on carfilzomib, which was approved by the Food and Drug Administration (FDA) in July 2012 for the treatment of patients with relapsed and refractory multiple myeloma (MM) who received prior bortezomib and thalidomide or lenalidomide.

DATA SOURCES

A literature search through PubMed was conducted through October 2012 using the terms carfilzomib, PR-171, proteasome inhibitor (PI), and MM. Data were also obtained through the American Society of Clinical Oncology and American Society of Hematology abstracts and FDA briefing documents.

STUDY SELECTION AND DATA EXTRACTION

The literature search was limited to human studies published in English. Priority was placed on trials of carfilzomib in relapsed and refractory MM.

DATA SYNTHESIS

Carfilzomib is a new PI that differs in pharmacology and pharmacokinetics from bortezomib, the first-in-class PI. The FDA approval was based on efficacy data from a Phase 2 study of carfilzomib in patients with relapsed and refractory MM (n = 266). All patients had received prior bortezomib and 80% were refractory or intolerant to both bortezomib and lenalidomide. Patients were treated with intravenous carfilzomib 20 mg/m2 (cycle 1) followed by 27 mg/m2 (cycles ≥2) on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle. The overall response rate was 23.7% (18.7–29.4), with a median duration of response of 7.8 (5.6–9.2) months. Safety data from an integrated analysis reported thrombocytopenia, anemia, fatigue, nausea, and diarrhea as the most common adverse events, with minimal dose-limiting neutropenia or peripheral neuropathy (PN) (n = 526). The incidence of grade 3 or higher thrombocytopenia was 24.9%, while that of neutropenia was 11.9%, and the incidence of all grades of treatment-emergent PN was 13%.

CONCLUSIONS

Carfilzomib is a safe and effective new treatment option for patients with relapsed MM refractory to bortezomib and thalidomide or lenalidomide. Randomized head-to-head trials with bortezomib will assist in formulary and treatment decisions in the context of PIs as a drug class.
Public History and Liberal Learning: Making the Case for the Undergraduate Practicum Experience
Authors: Belanger Elizabeth
Published: January 2013

This article explores a collaborative public history project between a small liberal arts undergraduate institution and a community social service agency. Drawing on evidence from student reflections and other course materials, it argues that undergraduate students gained important skills through the public history practicum including teamwork and problemsolving skills, intercultural awareness, and reflective practices, as well as discipline-specific learning outcomes. In documenting the student outcomes, it also demonstrates the potential of public history to contribute to undergraduate students' civic capabilities.
Exploring Identities: Public History in a Cross-Cultural Context
Authors: Lewis Catherine , Dickey Jennifer , Azhar Samir El , Brock Julia
Published: January 2013

The Museums Connect program, funded by the U.S. State Department's Bureau of Educational and Cultural Affairs and administered by the American Alliance of Museums, is a relatively new effort to connect international museums; the grant is set apart by its objective to sponsor projects that foster cross-cultural professional development and civic engagement in global communities. The following roundtable includes perspectives on the Museums Connect project Identities: Understanding Islam in a Cross-Cultural Context, undertaken by the Museum of History and Holocaust Education, Kennesaw State University (Georgia), and the Ben M'sik Community Museum, Université Hassan II Mohammedia, Ben M'sik (Casablanca, Morocco).
Bundle de prevenção da pneumonia associada à ventilação mecânica: uma construção coletiva
Authors: Silva Sabrina Guterres da , Nascimento Eliane Regina Pereira do , Salles Raquel Kuerten de
Published: January 2013

Trata-se de uma pesquisa qualitativa do tipo convergente-assistencial, que objetivou a construção coletiva de um bundle de prevenção da pneumonia associada à ventilação mecânica, por profissionais de enfermagem e fisioterapia da Unidade de Terapia Intensiva de um hospital público de Santa Catarina. A coleta dos dados ocorreu de maio a dezembro de 2011, por meio de entrevistas individuais e grupos de discussão, e contou com a participação de 25 e 14 profissionais, respectivamente. Para análise dos dados adotou-se o referencial de Morse e Field. A construção do bundle foi norteada pelos critérios da prática baseada em evidências e composto por quatro cuidados de prevenção: higiene oral com clorexidina 0,12%; cabeceira elevada (30-45°); pressão do cuff entre 20-30 cmH2O; e cuidados com aspiração das secreções. Acredita-se que a implementação dessas recomendações possa auxiliar a prática assistencial, contribuindo para redução das taxas de pneumonia associada à ventilação mecânica.
Conforto na perspectiva de familiares de pessoas internadas em Unidade de Terapia Intensiva
Authors: Freitas Kátia Santana , Menezes Igor Gomes , Mussi Fernanda Carneiro
Published: January 2013

O estudo objetivou compreender o significado de conforto para familiares de pessoas em Unidade de Terapia Intensiva. Trata-se de pesquisa qualitativa realizada na Unidade de Terapia Intensiva de um hospital, em Salvador-Bahia. Entrevistaram-se quatorze familiares. Recorreu-se aos pressupostos teóricos do Interacionismo Simbólico e à técnica de análise de dados qualitativos. Os resultados apontaram que as categorias Segurança, Acolhimento, Informação, Proximidade, Suporte social e espiritual, Comodidade e Integração consigo e o cotidiano expressaram o significado de conforto, que englobou confiança na competência técnico-científica e atitude solidária e sensível da equipe, chance de recuperação, acesso à informação e possibilidade de estar próximo do parente, apoio de pessoas do convívio social, de fontes espirituais e da estrutura ambiental do hospital e preservação do autocuidado e atividades habituais. Concluiu-se que a família é importante como objeto e sujeito das ações em saúde e deve ser enfocada nas políticas e programas de saúde pública no Brasil.
Saber popular sobre a utilização da planta Anredera cordifolia (folha gorda)
Authors: Heisler Elisa Vanessa , Badke Marcio Rossato , Andrade Andressa , Rodrigues Maria da Graça Soler
Published: January 2013

Este estudo buscou conhecer os saberes e práticas de moradores de um município localizado na região Noroeste do Estado do Rio Grande do Sul, sobre a utilização da planta Anredera cordifolia, no cuidado à saúde. Os procedimentos metodológicos adotados foram do tipo exploratório e descritivo, estruturados a partir de uma pesquisa qualitativa. A seleção dos sujeitos da pesquisa ocorreu por meio da rede de relações. Para a coleta dos dados, utilizou-se de entrevista semiestruturada e observação participante. Para a sustentação dos dados foi utilizada a análise de conteúdo. Os resultados da pesquisa foram divididos em dois grupos: origem do saber sobre a utilização da planta Anredera cordifolia e conhecimento popular sobre a utilização da planta Anredera cordifolia. Acredita-se que o estudo tenha relevância para as ciências da saúde e para a comunidade, apontando a necessidade de novas pesquisas, a fim de comprovar ou não a eficácia terapêutica da planta.
The Cost-Effectiveness of Initial Treatment of Multiple Myeloma in the U.S. With Bortezomib Plus Melphalan and Prednisone Versus Thalidomide Plus Melphalan and Prednisone or Lenalidomide Plus Melphalan and Prednisone With Continuous Lenalidomide Maintenance Treatment
Authors: Garrison Louis P. , Wang Si-Tien , Huang Hui , Ba-Mancini Abbie , Shi Hongliang , Chen Kristina , Korves Caroline , Dhawan Ravinder , Cakana Andrew , van de Velde Helgi , Corzo Deyanira , Duh Mei Sheng
Published: January 2013

The outlook for transplant-ineligible multiple myeloma patients has improved enormously over recent years with the incorporation of new agents into standard regimens. Novel regimens combine melphalan and prednisone (MP) with bortezomib (VMP), with thalidomide (MPT), and with lenalidomide with (MPR-R) and without (MPR) lenalidomide maintenance. The efficacy, safety, and cost-effectiveness of these regimens have not yet been compared; therefore, we conducted a pharmacoeconomic analysis using data from randomized controlled trials versus MP.

Using a Markov model developed from a U.S. payer's perspective, we compared VMP with MPT and MPR-R over a lifetime horizon. MPT and MPR-R were chosen because, like VMP, they are superior to MP in response and outcomes. Data from the Velcade as Initial Standard Therapy in Multiple Myeloma (VISTA; VMP), Intergroupe Francophone du Myelome (IFM) 99–06 (MPT), and MM-015 (MPR-R) trials were used. The IFM 99–06 study was selected because of the superior activity in this study compared with other MPT studies. Using patient-level (VMP) and published (MPT, MPR-R) data, we estimated the health-state transition and adverse event probabilities for each regimen, related costs, and state-specific utility estimates. Costs (in 2010 U.S. dollars) and health outcomes were discounted at 3%.

Discounted lifetime direct medical costs were lowest with VMP at $119,102. MPT cost $142,452 whereas MPR-R cost $248,358. Incremental cost-effectiveness ratio calculations projected that VMP would confer cost savings and better health outcomes relative to MPT and MPR-R. We conclude that VMP is highly likely to be cost-effective compared with MP, MPT, and MPR-R.
Health Care Costs and Resource Utilization, Including Patient Burden, Associated With Novel-Agent-Based Treatment Versus Other Therapies for Multiple Myeloma: Findings Using Real-World Claims Data
Authors: Teitelbaum April , Ba-Mancini Abbie , Huang Hui , Henk Henry J.
Published: January 2013

Background.

Treatment of multiple myeloma has dramatically improved with the introduction of bortezomib (BOR), thalidomide (THAL), and lenalidomide (LEN). Studies assessing health care costs, particularly economic burden on patients, are limited. We conducted a claims-based, retrospective analysis of total health care costs as well as patient burden (patient out-of-pocket costs and number of ambulatory/hospital visits) associated with BOR/THAL/LEN treatment versus other therapies (OTHER).

Methods.

Treatment episodes starting between January 1, 2005 and September 30, 2010 were identified from the claims database of a large U.S. health plan. Health care costs and utilization were measured during 1 year after initiation and analyzed per treatment episode. Multivariate analyses were used to adjust for patient characteristics, comorbidities, and line of treatment.

Results.

A total of 4,836 treatment episodes were identified. Mean adjusted total costs were similar between BOR ($112,889) and OTHER ($111,820), but higher with THAL ($129,412) and LEN ($158,428). Mean adjusted patient out-of-pocket costs were also similar for BOR ($3,846) and OTHER ($3,900) but remained higher with THAL ($4,666) and LEN ($4,483). Mean adjusted rates of ambulatory visits were similar across therapies (BOR: 69.67; THAL: 66.31; LEN: 65.60; OTHER: 69.42).

Conclusions.

Adjusted analyses of real-world claims data show that total health care costs, as well as patient out-of-pocket costs, are higher with THAL/LEN treatment episodes than with BOR/OTHER therapies. Additionally, similar rates of ambulatory visits suggest that any perceived advantage in patient convenience of the orally administered drugs THAL/LEN is not supported by these data.
Nutrient Restriction and Radiation Therapy for Cancer Treatment: When Less Is More
Authors: Champ Colin E. , Baserga Renato , Mishra Mark V. , Jin Lianjin , Sotgia Federica , Lisanti Michael P. , Pestell Richard G. , Dicker Adam P. , Simone Nicole L.
Published: January 2013

abstract

CME Learning Objectives

Identify molecular pathways that are potential targets of calorie restriction combined with radiation therapy. Identify cancer patients for whom calorie restriction would be contraindicated.

Calorie restriction (CR), or a diet modification aiming to reduce the total intake of calories by 20%–40%, has been shown to increase longevity across multiple species. Recently, there has been growing interest in investigating the potential role of CR as a treatment intervention for age-related diseases, such as cancer, because an increasing body of literature has demonstrated a metabolic component to both carcinogenesis and tumor progression. In fact, many of the molecular pathways that are altered with CR are also known to be altered in cancer. Therefore, manipulation of these pathways using CR can render cancer cells, and most notably breast cancer cells, more susceptible to standard cytotoxic treatment with radiation and chemotherapy. In this review article we demonstrate the laboratory and clinical evidence that exists for CR and show compelling evidence through the molecular pathways CR induces about how it may be used as a treatment in tandem with radiation therapy to improve our rates of disease control.
Interleukin-10 Gene Polymorphisms are Associated With Freedom From Treatment Failure for Patients With Hodgkin Lymphoma
Authors: Schoof Nils , Franklin Jeremy , Fürst Robert , Zander Thomas , von Bonin Frederike , Peyrade Frederic , Trümper Lorenz , Diehl Volker , Engert Andreas , Kube Dieter , Re Daniel
Published: January 2013

CME Learning Objectives

Discuss whether and how genetic variations influence clinical outcomes of Hodgkin lymphoma patients. Evaluate evidence that proximal IL10 promoter gene variations are associated with clinical courses of Hodgkin lymphoma patients. Compare host genetic variations from different cytokine/cytokine receptor gene variations.

Background.

Hodgkin lymphoma (HL) is a lymphoid malignancy characterized by the production of various cytokines possibly involved in immune deregulation. Interleukin-10 (IL-10) serum levels have been associated with clinical outcome in patients with HL. Because host genetic variations are known to alter the expression and function of cytokines and their receptors, we investigated whether genetic variations influence clinical outcome of patients with HL.

Methods.

A total of 301 patients with HL who were treated within randomized trials by the German Hodgkin Study Group were included in this exploratory retrospective study. Gene variations of IL-10 (IL-10-597AC, rs1800872; IL-10-824CT, rs1800871; IL-10-1087AG, rs1800896; IL-10-3538AT, rs1800890; IL-10-6208CG, rs10494879; IL-10-6752AT, rs6676671; IL-10-7400InDel), IL-13 (IL-13-1069CT, rs1800925; IL-13Q144R, rs20541), and IL-4R (IL-4RI75V, rs1805010; IL-4RQ576R, rs1801275) were genotyped.

Results.

Inferior freedom from treatment failure (FFTF) was found in patients harboring the IL-10-597AA, IL-10-824TT, or the IL-10-1087AA genotype. In contrast, the IL-10-1087G-824C-597C haplotype present in about 48% of analyzed HL patients is nominally significant for a better FFTF in a Cox-Regression model accounting for stage and treatment. No associations were observed between the other IL-10 gene variations, IL-13-1069CT, IL-13Q144R, IL-4RI75V, IL-4RQ576R and the clinical outcome of patients with HL.

Conclusions.

Our study provides further evidence that proximal IL-10 promoter gene variations are associated with clinical course of patients with HL. However, treatment success and survival rates are already at a very high rate, supporting the need to design studies focusing on identification of predictors to reduce the side effects of therapy.