bluuebunny/crossref_metadata_2025 huggingface dataset:
Utilization of evidence-based treatment in elderly patients with chronic heart failure: using Korean Health Insurance claims database
Authors: Kim Ju-Young , Kim Hwa-Jung , Jung Sun-Young , Kim Kwang-Il , Song Hong Ji , Lee Joong-Yub , Seong Jong-Mi , Park Byung-Joo
Published: July 2012

Background

Chronic heart failure accounts for a great deal of the morbidity and mortality in the aging population. Evidence-based treatments include angiotensin-2 receptor blockers (ARBs), angiotensin-converting enzyme inhibitors (ACE-I), beta-blockers, and aldosterone antagonists. Underutilization of these treatments in heart failure patients were frequently reported, which could lead to increase morbidity and mortality. The aim of this study was to evaluate the utilization of evidence-based treatments and their related factors for elderly patients with chronic heart failure.

Methods

This is retrospective observational study using the Korean National Health Insurance claims database. We identified prescription of evidence based treatment to elderly patients who had been hospitalized for chronic heart failure between January 1, 2005, and June 30, 2006.

Results

Among the 28,922 elderly patients with chronic heart failure, beta-blockers were prescribed to 31.5%, and ACE-I or ARBs were prescribed to 54.7% of the total population. Multivariable logistic regression analyses revealed that the prescription from outpatient clinic (prevalent ratio, 4.02, 95% CI 3.31–4.72), specialty of the healthcare providers (prevalent ratio, 1.26, 95% CI, 1.12–1.54), residence in urban (prevalent ratio, 1.37, 95% CI, 1.23–1.52) and admission to tertiary hospital (prevalent ratio, 2.07, 95% CI, 1.85–2.31) were important factors associated with treatment underutilization. Patients not given evidence-based treatment were more likely to experience dementia, reside in rural areas, and have less-specialized healthcare providers and were less likely to have coexisting cardiovascular diseases or concomitant medications than patients in the evidence-based treatment group.

Conclusions

Healthcare system factors, such as hospital type, healthcare provider factors, such as specialty, and patient factors, such as comorbid cardiovascular disease, systemic disease with concomitant medications, together influence the underutilization of evidence-based pharmacologic treatment for patients with heart failure.
Does the effect of gender modify the relationship between deprivation and mortality?
Authors: Salcedo Natalia , Saez Marc , Bragulat Basili , Saurina Carme
Published: July 2012

Background

In this study we propose improvements to the method of elaborating deprivation indexes. First, in the selection of the variables, we incorporated a wider range of both objective and subjective measures. Second, in the statistical methodology, we used a distance indicator instead of the standard aggregating method principal component analysis. Third, we propose another methodological improvement, which consists in the use of a more robust statistical method to assess the relationship between deprivation and health responses in ecological regressions.

Methods

We conducted an ecological small-area analysis based on the residents of the Metropolitan region of Barcelona in the period 1994–2007. Standardized mortality rates, stratified by sex, were studied for four mortality causes: tumor of the bronquial, lung and trachea, diabetes mellitus type II, breast cancer, and prostate cancer. Socioeconomic conditions were summarized using a deprivation index. Sixteen socio-demographic variables available in the Spanish Census of Population and Housing were included. The deprivation index was constructed by aggregating the above-mentioned variables using the distance indicator, DP2. For the estimation of the ecological regression we used hierarchical Bayesian models with some improvements.

Results

At greater deprivation, there is an increased risk of dying from diabetes for both sexes and of dying from lung cancer for men. On the other hand, at greater deprivation, there is a decreased risk of dying from breast cancer and lung cancer for women. We did not find a clear relationship in the case of prostate cancer (presenting an increased risk but only in the second quintile of deprivation).

Conclusions

We believe our results were obtained using a more robust methodology. First off, we have built a better index that allows us to directly collect the variability of contextual variables without having to use arbitrary weights. Secondly, we have solved two major problems that are present in spatial ecological regressions, i.e. those that use spatial data and, consequently, perform a spatial adjustment in order to obtain consistent estimators.
Intratracheally administered titanium dioxide or carbon black nanoparticles do not aggravate elastase-induced pulmonary emphysema in rats
Authors: Roulet Agnès , Armand Lucie , Dagouassat Maylis , Rogerieux Françoise , Simon-Deckers Angélique , Belade Esther , Van Nhieu Jeanne Tran , Lanone Sophie , Pairon Jean-Claude , Lacroix Ghislaine , Boczkowski Jorge
Published: July 2012

Background

Titanium dioxide (TiO2) and carbon black (CB) nanoparticles (NPs) have biological effects that could aggravate pulmonary emphysema. The aim of this study was to evaluate whether pulmonary administration of TiO2 or CB NPs in rats could induce and/or aggravate elastase-induced emphysema, and to investigate the underlying molecular mechanisms.

Methods

On day 1, Sprague-Dawley rats were intratracheally instilled with 25 U kg−1 pancreatic porcine elastase or saline. On day 7, they received an intratracheal instillation of TiO2 or CB (at 100 and 500 μg) dispersed in bovine serum albumin or bovine serum albumin alone. Animals were sacrificed at days 8 or 21, and bronchoalveolar lavage (BAL) cellularity, histological analysis of inflammation and emphysema, and lung mRNA expression of heme oxygenase-1 (HO-1), interleukin-1β (IL-1β), macrophage inflammatory protein-2, monocyte chemotactic protein-1, and matrix metalloprotease (MMP)-1, and -12 were measured. In addition, pulmonary MMP-12 expression was also analyzed at the protein level by immunohistochemistry.

Results

TiO2 NPs per se did not modify the parameters investigated, but CB NPs increased perivascular/peribronchial infiltration, and macrophage MMP-12 expression, without inducing emphysema. Elastase administration increased BAL cellularity, histological inflammation, HO-1, IL-1β and macrophage MMP-12 expression and induced emphysema. Exposure to TiO2 NPs did not modify pulmonary responses to elastase, but exposure to CB NPs aggravated elastase-induced histological inflammation without aggravating emphysema.

Conclusions

TiO2 and CB NPs did not aggravate elastase-induced emphysema. However, CB NPs induced histological inflammation and MMP-12 mRNA and protein expression in macrophages.
Erratum to: Prospects of implant with locking plate in fixation of subtrochanteric fracture: experimental demonstration of its potential benefits on synthetic femur model with supportive hierarchical nonlinear hyperelastic finite element analysis
Authors: Latifi Mohammed Hadi , Ganthel Kunalan , Rukmanikanthan Shanmugam , Mansor Azura , Kamarul Tunku , Bilgen Mehmet
Published: July 2012

The first publication of the work [1] did not present one of the authors' names. Kunalan Ganthel has now been added to the author list. In addition, Habib Sherkat has been added to the Acknowledgements, with thanks for providing help with the use of hyperelastic module of Abaqus Software.
Directed migration of human neural progenitor cells to interleukin-1β is promoted by chemokines stromal cell-derived factor-1 and monocyte chemotactic factor-1 in mouse brains
Authors: Wu Yumei , Chen Qiang , Peng Hui , Dou Huanyu , Zhou You , Huang Yunlong , Zheng Jialin C
Published: July 2012

Background

Neurogenesis, including the proliferation, migration and differentiation of neural progenitor cells (NPCs), is impaired in HIV-1 associated dementia (HAD). We previously demonstrated HIV-1-infected macrophages (HIV-MDM) regulate stromal cell-derived factor 1 (SDF-1) production in astrocytes through Interleukin-1β (IL-1β). Chemokines are known to induce NPC migration; however, it remains unclear how chemokines produced in inflammation regulate NPC migration.

Methods

The secretion of SDF-1 and Monocyte chemotactic preotein-1 (MCP-1) in astrocytes upon IL-1β stimulation was measured by ELISA assay.Human NPCs were injected parallel along with IL-1β, SDF-1 or MCP-1 intracranially into basal ganglion 1 mm apart in SCID mice, and immunofluorescent staining was used to study the survival and migration of injected human NPCs.

Results

SDF-1 and MCP-1 are secreted by astrocytes upon IL-1β stimulation in a time-dependent manner. Injected human NPCs survived in SCID mice and migrated towards sites of IL-1β, SDF-1 and MCP-1 injection.

Conclusions

In conclusion, chemokines SDF-1 or MCP-1 secreted by astrocytes in the presence of IL-1β injection are attractive to NPCs injected into SCID mouse brains, suggesting that SDF-1 and MCP-1 play important roles in NPC migration during neuroinflammation.
Displacement-Based Fragility Curves for Seismic Assessment of Adobe Buildings in Cusco, Peru
Authors: Tarque Nicola , Crowley Helen , Pinho Rui , Varum Humberto
Published: July 2012

The seismic vulnerability of single-story adobe dwellings located in Cusco, Peru, is studied based on a mechanics-based procedure, which considers the analysis of in-plane and out-of-plane failure mechanisms of walls. The capacity of each dwelling is expressed as a function of its displacement capacity and period of vibration and is evaluated for different limit states to damage. The seismic demand has been obtained from several displacement response spectral shapes. From the comparison of the capacity with the demand, probabilities of limit state exceedance have been obtained for different PGA values. The results indicate that fragility curves in terms of PGA are strongly influenced by the response spectrum shape; however, this is not the case for the derivation of fragility curves in terms of limit state spectral displacement. Finally, fragility curves for dwellings located in Pisco, Peru, were computed and the probabilities of limit state exceedance were compared with the data obtained from the 2007 Peruvian earthquake.
Induction Chemotherapy and Conformal Radiation Therapy for Very Young Children With Nonmetastatic Medulloblastoma: Children's Oncology Group Study P9934
Authors: Ashley David M. , Merchant Thomas E. , Strother Douglas , Zhou Tianni , Duffner Patricia , Burger Peter C. , Miller Douglas C. , Lyon Nancy , Bonner Melanie J. , Msall Michael , Buxton Allen , Geyer Russell , Kun Larry E. , Coleman Lee , Pollack Ian F.
Published: July 2012

Purpose

P9934 was a prospective trial of systemic chemotherapy, second surgery, and conformal radiation therapy (CRT) limited to the posterior fossa and primary site for children between 8 months and 3 years old with nonmetastatic medulloblastoma. The study was open from June 2000 until June 2006.

Patients and Methods

After initial surgery, children received four cycles of induction chemotherapy, followed by age- and response-adjusted CRT to the posterior fossa (18 or 23.4 Gy) and tumor bed (cumulative 50.4 or 54 Gy) and maintenance chemotherapy. Neurodevelopmental outcomes were evaluated and event-free survival (EFS) results were directly compared with a previous study of multiagent chemotherapy without irradiation (Pediatric Oncology Group [POG] trial 9233).

Results

Seventy-four patients met eligibility requirements. The 4-year EFS and overall survival probabilities were 50% ± 6% and 69% ± 5.5%, respectively, which compared favorably to the results from POG 9233. Analysis showed that the desmoplastic/nodular subtype was a favorable factor in predicting survival. Our 4-year EFS rate was 58% ± 8% for patients with desmoplasia. Whereas seven of 10 patients who had disease progression before CRT had primary-site failure, 15 of 19 patients who progressed after CRT had distant-site failure. Neurodevelopmental assessments did not show a decline in cognitive or motor function after protocol-directed chemotherapy and CRT.

Conclusion

The addition of CRT to postoperative chemotherapy in young children with nonmetastatic medulloblastoma increased event-free survival compared with the use of postoperative chemotherapy alone. Future studies will use histopathologic typing (desmoplastic/nodular versus nondesmoplastic/nodular) to stratify patients for therapy by risk of relapse.
Concurrent Expression of MYC and BCL2 in Diffuse Large B-Cell Lymphoma Treated With Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone
Authors: Johnson Nathalie A. , Slack Graham W. , Savage Kerry J. , Connors Joseph M. , Ben-Neriah Susana , Rogic Sanja , Scott David W. , Tan King L. , Steidl Christian , Sehn Laurie H. , Chan Wing C. , Iqbal Javeed , Meyer Paul N. , Lenz Georg , Wright George , Rimsza Lisa M. , Valentino Carlo , Brunhoeber Patrick , Grogan Thomas M. , Braziel Rita M. , Cook James R. , Tubbs Raymond R. , Weisenburger Dennis D. , Campo Elias , Rosenwald Andreas , Ott German , Delabie Jan , Holcroft Christina , Jaffe Elaine S. , Staudt Louis M. , Gascoyne Randy D.
Published: July 2012

Purpose

Diffuse large B-cell lymphoma (DLBCL) is curable in 60% of patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). MYC translocations, with or without BCL2 translocations, have been associated with inferior survival in DLBCL. We investigated whether expression of MYC protein, with or without BCL2 protein expression, could risk-stratify patients at diagnosis.

Patients and Methods

We determined the correlation between presence of MYC and BCL2 proteins by immunohistochemistry (IHC) with survival in two independent cohorts of patients with DLBCL treated with R-CHOP. We further determined if MYC protein expression correlated with high MYC mRNA and/or presence of MYC translocation.

Results

In the training cohort (n = 167), MYC and BCL2 proteins were detected in 29% and 44% of patients, respectively. Concurrent expression (MYC positive/BCL2 positive) was present in 21% of patients. MYC protein correlated with presence of high MYC mRNA and MYC translocation (both P < .001), but the latter was less frequent (both 11%). MYC protein expression was only associated with inferior overall and progression-free survival when BCL2 protein was coexpressed (P < .001). Importantly, the poor prognostic effect of MYC positive/BCL2 positive was validated in an independent cohort of 140 patients with DLBCL and remained significant (P < .05) after adjusting for presence of high-risk features in a multivariable model that included elevated international prognostic index score, activated B-cell molecular subtype, and presence of concurrent MYC and BCL2 translocations.

Conclusion

Assessment of MYC and BCL2 expression by IHC represents a robust, rapid, and inexpensive approach to risk-stratify patients with DLBCL at diagnosis.
Phase II Study of Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone Immunochemotherapy Followed by Yttrium-90–Ibritumomab Tiuxetan in Untreated Mantle-Cell Lymphoma: Eastern Cooperative Oncology Group Study E1499
Authors: Smith Mitchell R. , Li Hailun , Gordon Leo , Gascoyne Randy D. , Paietta Elisabeth , Forero-Torres Andres , Kahl Brad S. , Advani Ranjana , Hong Fangxin , Horning Sandra J.
Published: July 2012

Purpose

To test the hypothesis that consolidation therapy with yttrium-90 (90Y) –ibritumomab tiuxetan after brief initial therapy with four cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with previously untreated mantle-cell lymphoma would be a well-tolerated regimen that would improve outcomes compared with historical R-CHOP data.

Patients and Methods

Patients ≥ 18 years old with histologically confirmed mantle-cell lymphoma expressing CD20 and cyclin D1 who had not received any previous therapy and had an Eastern Cooperative Oncology Group performance status of 0 to 2 and adequate organ function were eligible. The study enrolled and treated 57 patients, of whom 56 patients were eligible. Fifty-two patients (50 eligible patients) received90Y-ibritumomab tiuxetan. The study design required 52 eligible patients to detect a 50% improvement in the median time to treatment failure (TTF) compared with that reported for six cycles of R-CHOP.

Results

With 56 analyzed patients (median age, 60 years; men, 73%), the overall response rate was 82% (55% complete response/complete response–unconfirmed). With a median follow-up of 72 months, the median TTF was 34.2 months. The median overall survival (OS) has not been reached, with an estimated 5-year OS of 73% (79% for patients ≤ age 65 years v 62% for patients > age 65 years; P = .08 [log-rank test]). There were no unexpected toxicities.

Conclusion

R-CHOP given for four cycles followed by90Y–ibritumomab tiuxetan compared favorably with historical results with six cycles of R-CHOP in patients with previously untreated mantle-cell lymphoma. This regimen was well tolerated and should be applicable to most patients with this disease.
Multidisciplinary Care and Pursuit of Active Surveillance in Low-Risk Prostate Cancer
Authors: Aizer Ayal A. , Paly Jonathan J. , Zietman Anthony L. , Nguyen Paul L. , Beard Clair J. , Rao Sandhya K. , Kaplan Irving D. , Niemierko Andrzej , Hirsch Michelle S. , Wu Chin-Lee , Olumi Aria F. , Michaelson M. Dror , D'Amico Anthony V. , Efstathiou Jason A.
Published: July 2012

Purpose

Multidisciplinary clinics offer a unique approach to the management of patients with cancer. Yet, limited data exist to show that such clinics affect management. The purpose of this study was to determine whether consultation at a multidisciplinary clinic is associated with selection of active surveillance in patients with low-risk prostate cancer.

Patients and Methods

The study comprised 701 men with low-risk prostate cancer managed at three tertiary care centers in Boston, MA in 2009. Patients either obtained consultation at a multidisciplinary prostate cancer clinic, at which they were seen by a combination of urologic, radiation, and medical oncologists in a concurrent setting, or they were seen by individual practitioners in sequential settings. The primary outcome was selection of active surveillance.

Results

Crude rates of selection of active surveillance in patients seen at a multidisciplinary clinic were double that of patients seen by individual practitioners (43% v 22%), whereas the proportion of men treated with prostatectomy or radiation decreased by approximately 30% (P < .001). On multivariate logistic regression, older age (odds ratio [OR], 1.09; 95% CI, 1.05 to 1.12; P < .001), unmarried status (OR, 1.66; 95% CI, 1.01 to 2.72; P = .04), increased Charlson comorbidity index (OR, 1.37; 95% CI, 1.06 to 1.77; P = .02), fewer positive cores (OR, 0.92; 95% CI, 0.90 to 0.94; P < .001), and consultation at a multidisciplinary clinic (OR, 2.15; 95% CI, 1.13 to 4.10; P = .02) were significantly associated with pursuit of active surveillance.

Conclusion

Multidisciplinary care is associated with increased selection of active surveillance in men with low-risk prostate cancer. This finding may have an important clinical, social, and economic impact.
“Who Is the Macho Who Wants to Kill Me?” Male Homosexuality, Revolutionary Masculinity, and the Brazilian Armed Struggle of the 1960s and 1970s
Authors: Green James N.
Published: July 2012

Several thousand students joined small clusters of soldiers, workers, and others in revolutionary opposition to the Brazilian civilian-military dictatorship that came to power in 1964 and controlled the government for two decades. Operating underground, these left-wing activists engaged in diverse efforts to organize an effective guerrilla opposition to the authoritarian regime. Within their ranks, some militants who had homosexual desires faced a hegemonic culture of the left that considered same-sex sexuality a reflection of “bourgeois decadence,” an immoral aberration, and an affront to proper revolutionary behavior. This article explores how leftist Brazilians with homoerotic desires negotiated norms of compulsory heterosexuality and constructions of revolutionary masculinity in the 1960s and 1970s as they lived in the underground, among members of different political organizations while imprisoned, or in political exile.
Photoreduced Deformylation of Zinc Chlorophyll-d Derivative
Authors: Tamiaki Hitoshi , Xu Meiyun , Machida Shinnosuke
Published: July 2012

Photochemical reaction of a zinc chlorophyll-d derivative possessing a formyl group at the 3-position with a reductant in a deaerated alcoholic solution gave the corresponding 3-unsubstituted chlorin in 43% yield based on consumed starting material. The novel deformylation was accompanied by expected 2,3- or 7,8-dihydrogenation to give minor products possessing a isobacteriochlorin or bacteriochlorin π-system, respectively, as stereochemical mixtures.
Synthesis and Properties of Ni–Cu Alloy Supported on Mg–Al Mixed Oxide Catalyst for Automotive Exhaust
Authors: Kang Chun Yong , Taniguchi Masashi , Uenishi Mari , Tanaka Hirohisa
Published: July 2012

A new Cu-based catalyst for automotive three way catalysts has been investigated. We succeeded in the synthesis of the Ni–Cu alloy supported on Mg–Al mixed oxide catalyst, Ni0.3Cu0.2/2MgO·1/2MgAl2O4. On the NO–CO reaction evaluation after pretreatment in oxidation atmosphere, the Ni0.3Cu0.2/2MgO·1/2MgAl2O4 showed higher activity than a Cu/Al2O3 catalyst. In the evaluation by using model gas simulated automotive exhaust, the Ni0.3Cu0.2/2MgO·1/2MgAl2O4 catalyst showed high catalytic activity, especially for hydrocarbon oxidation in reducing atmosphere.
Synthesis of a Dendrimer Reactor for Clusters with a Magic Number
Authors: Kitazawa Hirokazu , Albrecht Ken , Yamamoto Kimihisa
Published: July 2012

A new type of phenylazomethine dendrimer (DPA) that has one more coordination site compared to the tetraphenylmethane core DPA was synthesized for the “magic number 13” metal cluster template that has cubic or hexagonal densely packed structures. The stepwise complexation property was revealed, and this property is expected to be the “magic number 13” metal cluster template.
Anatomy of the foot venous pump: physiology and influence on chronic venous disease
Authors: Uhl J-F , Gillot C
Published: July 2012

The aim of this paper is to demonstrate the location of the venous foot pump using an anatomical study. Four hundred cadaveric feet were injected with green neoprene latex followed by a dissection. A coloured segmentation of the venous system was achieved. The Lejars’ concept of the venous sole of the foot is incorrect: the true blood venous reservoir of the foot is located deeply in the plantar veins, between the plantar muscles. The medial and mostly lateral plantar veins converge into the plexus shaped calcaneal crossroad, where the blood is ejected upwards into the two posterior tibial veins. In addition, the several medial perforators of the foot directly connect the deep system (medial plantar veins) to the superficial venous system (medial marginal vein). This forms a true ‘medial functional unit’ which is unique in the limb given its directional flow is from deep to superficial. In conclusion, the plantar veins play an important role in the physiology of the venous return since a venous reservoir of 25 mL of blood is mobilized upwards with each step during walking. Therefore, the impairment of the foot pump by a static foot disorder should be considered as an important risk factor for chronic venous disease, and should be evaluated and corrected in any patient with venous insufficiency.
Quality improvement programme, focusing on error reduction: a single center naturalistic study
Authors: Rosser David , Cowley Nicholas J , Ray Daniel , Nightingale Peter G , Jones Tim , Moore Julie , Coleman Jamie J
Published: July 2012

Objectives

Interventions to drive quality of care using strategies to empower clinical staff with personal and local performance indicators should lead to measurable improvements in outcome. The current evidence for the linkage of quality metrics and patient outcome usually relies on surrogate measures. There is a continuing need for the development of specific measurable indicators of quality of care, which have demonstrable links to patient outcome.

Design

A single centre naturalistic study to validate electronically collected drug administration and documentation measures of quality improvement, during the introduction of a quality improvement programme.

Setting

A large academic teaching hospital in the UK.

Participants

Staff involved in administration of prescribed medication using an in-house developed prescribing information and communication system (PICS).

Main outcome measures

Mortality data from nationally collected ‘hospital episode statistics’ and markers of the precision of medicines administration and documentation ‘uncharted’ and ‘missed’ drug doses.

Results

A 16.2% reduction in local mortality rate was demonstrated ( P=0.013) compared to static mortality rates throughout England. Similar temporal reductions were seen in the rates of missed and uncharted doses of medication at the hospital over the same period.

Conclusions

When monitored as part of a quality improvement strategy, ‘missed’ and ‘uncharted’ drug dose information may reflect wider institutional changes and act as a valid indicator of quality of healthcare more generally.
The development of one-stop wide-awake dupuytren's fasciectomy service: a retrospective review
Authors: Bismil Qmk , Bismil Msk , Bismil Annamma , Neathey Julia , Gadd Judith , Roberts Sue , Brewster Jennifer
Published: July 2012

Objectives

To detail the transition to a totally one-stop wide-awake (OSWA) Dupuytren's contracture surgical service.

Design

Retrospective review of Dupuytren's component of last 1000 OSWA cases.

Setting

The UK's first totally one-stop wide-awake orthopaedic service.

Participants

270 patients with Dupuytren's contracture out of the last 1000 OSWA cases.

Main outcome measures

Surgical outcomes, patient satisfaction and cost-effectiveness and efficiency.

Results

The OSWA Dupuytren's model is safe, efficient and effective; with a low complication rate, extremely high patient satisfaction; and cost-savings to the nhs of £2500 per case treated. The service saved the NHS approximately £675,000 for the 270 cases presented.

Conclusions

A totally one-stop wide-awake Dupuytren's Contracture service is practicable and feasible alternative to the conventional treatment pathway, with benefits in terms of efficiency and cost-effectiveness.
The interaction between the yeast telomerase RNA and the Est1 protein requires three structural elements
Authors: Lubin Johnathan W. , Tucey Timothy M. , Lundblad Victoria
Published: July 2012

In the budding yeast Saccharomyces cerevisiae, the telomerase enzyme is composed of a 1.3-kb TLC1 RNA that forms a complex with Est2 (the catalytic subunit) and two regulatory proteins, Est1 and Est3. Previous work has identified a conserved 5-nt bulge, present in a long helical arm of TLC1, which mediates binding of Est1 to TLC1. However, increased expression of Est1 can bypass the consequences of removal of this RNA bulge, indicating that there are additional binding site(s) for Est1 on TLC1. We report here that a conserved single-stranded internal loop immediately adjacent to the bulge is also required for the Est1–RNA interaction; furthermore, a TLC1 variant that lacks this internal loop but retains the bulge cannot be suppressed by Est1 overexpression, arguing that the internal loop may be a more critical element for Est1 binding. An additional structural feature consisting of a single-stranded region at the base of the helix containing the bulge and internal loop also contributes to recognition of TLC1 by Est1, potentially by providing flexibility to this helical arm. Association of Est1 with each of these TLC1 motifs was assessed using a highly sensitive biochemical assay that simultaneously monitors the relative levels of the Est1 and Est2 proteins in the telomerase complex. The identification of three elements of TLC1 that are required for Est1 association provides a detailed view of this particular protein–RNA interaction.
Selling to Conspicuous Consumers: Pricing, Production, and Sourcing Decisions
Authors: Tereyağoğlu Necati , Veeraraghavan Senthil
Published: July 2012

Consumers often purchase goods that are “hard to find” to conspicuously display their exclusivity and social status. Firms that produce such conspicuously consumed goods such as designer apparel, fashion goods, jewelry, etc., often face challenges in making optimal pricing and production decisions. Such firms are confronted with precipitous trade-off between high sales volume and high margins, because of the highly uncertain market demand, strategic consumer behavior, and the display of conspicuous consumption. In this paper, we propose a model that addresses pricing and production decisions for a firm, using the rational expectations framework. We show that, in equilibrium, firms may offer high availability of goods despite the presence of conspicuous consumption. We show that scarcity strategies are harder to adopt as demand variability increases, and we provide conditions under which scarcity strategies could be successfully adopted to improve profits. Finally, to credibly commit to scarcity strategy, we show that firms can adopt sourcing strategies, such as sourcing from an expensive production location/supplier or using expensive raw materials.

This paper was accepted by Preyas Desai and Pradeep Chintagunta, marketing.
You get what you Pay for: The Effect of Top Executives’ Compensation on Advertising and R&D Spending Decisions and Stock Market Return
Authors: Currim Imran S. , Lim Jooseop , Kim Joung W.
Published: July 2012

Although there is literature on how top executives’ compensation influences general management decisions, relatively little is known about whether and how compensation influences advertising and research-and-development (R&D) spending decisions. This study addresses two questions. First, is there an incentive effect of long- versus short-term compensation on advertising and R&D spending? Second, is there a mediation effect of advertising and R&D spending on the relationship between long- versus short-term compensation and stock market return? The authors address these questions using a combination of ExecuComp, Compustat, and Center for Research in Security Prices data on 842 firms during the 1993–2005 period. They find that an increase in the equity to bonus compensation ratio is positively associated with an increase in advertising and R&D spending as a share of sales. Advertising and R&D spending as a share of sales also mediates the effect of equity to bonus ratio on stock market return. The authors discuss implications for top management seeking to mitigate myopic management of resources by employing compensation to incentivize a longer-term orientation for advertising and R&D spending to improve stock return.
How to Organize Pricing? Vertical Delegation and Horizontal Dispersion of Pricing Authority
Authors: Homburg Christian , Jensen Ove , Hahn Alexander
Published: July 2012

Although pricing is one of the strongest drivers of profitability, little empirical research has examined how a firm should organize pricing internally. This research draws on the information-processing view of organizational design to conceptualize a framework of how firms organize their pricing authority both within the sales function and across the sales, marketing, and finance functions. The authors find a nonlinear, inverted U-shaped relationship between the vertical delegation of pricing authority and profitability as well as a positive relationship between the horizontal dispersion of pricing authority across sales, marketing, and finance and profitability. Another key finding is a positive interaction between vertical delegation and horizontal dispersion, indicating that firms need to jointly design vertical delegation and horizontal dispersion. In addition, the results identify price-related market dynamism as a moderator of the horizontal dispersion of the pricing authority–profitability relationship and emphasis on margin-based incentives as a moderator of vertical delegation of the pricing authority–profitability relationship. The authors also analyze the relationship between the organizational design of pricing authority and sales growth.
The Effect of Location on Price Estimation: Understanding Number–Location and Number–Order Associations
Authors: Cai Fengyan , Shen Hao , Hui Michael K.
Published: July 2012

The location in which a product is presented can influence consumers' numerical estimates of product attributes (e.g., price). This effect can be driven by two alternative processes. First, people may have acquired a learned association between numerical magnitude and location as a consequence of frequently viewing larger numbers to the right of smaller ones. In addition, they may have learned a procedure of reading or writing numbers from left to right in increasing order of magnitude. The authors present six experiments that demonstrate the effect of location on numerical estimates and provide evidence that both number–location associations and number–order associations could drive this effect.
Sham Surgery Trial Controls: Perspectives of Patients and Their Relatives
Authors: Swift Teresa L.
Published: July 2012

This study reports on qualitative research conducted in the UK with people with Parkinson's Disease and their relatives on the subject of “sham surgery.” It explores attitudes toward sham surgery and reasoning about hypothetical participation in a sham-controlled trial. Results showed that attitudes toward sham surgery may not necessarily predict trial participation behavior. A small majority of interviewees deemed sham surgery ethically acceptable with certain provisos, but hypothetical participation was driven primarily by disease severity and a lack of standard treatment options, with a preference for receiving the real surgery over sham. Ethical implications for patient equipoise and the autonomy of patients' research participation decisions are discussed.
Ethical Issues in a Stage 1 Cognitive-Behavioral Therapy Feasibility Study and Trial to Reduce Alcohol Use Among HIV-Infected Outpatients in Western Kenya
Authors: Papas Rebecca K. , Gakinya Benson N. , Baliddawa Joyce B. , Martino Steve , Bryant Kendall J. , Meslin Eric M. , Sidle John E.
Published: July 2012

Epidemics of both HIV/AIDS and alcohol abuse in sub-Saharan Africa have spurred the conduct of local behavioral therapy trials for these problems, but the ethical issues involved in these trials have not been fully examined. In this paper, we discuss ethical issues that emerged during the conduct of a behavioral intervention adaptation and trial using cognitive-behavioral therapy to reduce alcohol use among HIV-infected outpatients in Eldoret, Kenya. The study was performed within our multinational collaboration, the USAID-Academic Model Providing Access to Healthcare Partnership. We discuss relevant ethical considerations and how we addressed them.
Local IRBs vs. Federal Agencies: Shifting Dynamics, Systems, and Relationships
Authors: Klitzman Robert L.
Published: July 2012

How IRBs relate to federal agencies, and the implications of these relationships, have received little, if any, systematic study. I interviewed 46 IRB chairs, directors, administrators, and members, contacting the leadership of 60 U.S. IRBs (every fourth one in the list of the top 240 institutions by NIH funding), interviewing IRB leaders from 34 (response rate=55%). IRBs describe complex direct and indirect relationships with federal agencies that affect IRBs through audits, guidance documents, and other communications, and can generate problems and challenges. Researchers often blame IRBs for frustrations, but IRBs often serve as the “local face” of federal regulations and agencies and are “stuck in the middle.” These data have critical implications for policy, practice, and research.
Similarities and differences in interactions of thyroid stimulating and blocking autoantibodies with the TSH receptor
Authors: Núñez Miguel Ricardo , Sanders Jane , Sanders Paul , Young Stuart , Clark Jill , Kabelis Katarzyna , Wilmot Jane , Evans Michele , Roberts Emma , Hu Xiaoling , Furmaniak Jadwiga , Rees Smith Bernard
Published: July 2012

Binding of a new thyroid-stimulating human monoclonal autoantibody (MAb) K1–18 to the TSH receptor (TSHR) leucine-rich domain (LRD) was predicted using charge–charge interaction mapping based on unique complementarities between the TSHR in interactions with the thyroid-stimulating human MAb M22 or the thyroid-blocking human MAb K1–70. The interactions of K1–18 with the TSHR LRD were compared with the interactions in the crystal structures of the M22–TSHR LRD and K1–70–TSHR LRD complexes. Furthermore, the predicted position of K1–18 on the TSHR was validated by the effects of TSHR mutations on the stimulating activity of K1–18. A similar approach was adopted for predicting binding of a mouse thyroid-blocking MAb RSR-B2 to the TSHR. K1–18 is predicted to bind to the TSHR LRD in a similar way as TSH and M22. The binding analysis suggests that K1–18 light chain (LC) mimics binding of the TSH-α chain and the heavy chain (HC) mimics binding of the TSH-β chain. By contrast, M22 HC mimics the interactions of TSH-α while M22 LC mimics TSH-β in interactions with the TSHR. The observed interactions in the M22–TSHR LRD and K1–70–TSHR LRD complexes (crystal structures) with TSH–TSHR LRD (comparative model) and K1–18–TSHR LRD (predictive binding) suggest that K1–18 and M22 interactions with the receptor may reflect interaction of thyroid-stimulating autoantibodies in general. Furthermore, K1–70 and RSR-B2 interactions with the TSHR LRD may reflect binding of TSHR-blocking autoantibodies in general. Interactions involving the C-terminal part of the TSHR LRD may be important for receptor activation by autoantibodies.
Iodothyronine deiodinase structure and function: from ascidians to humans
Authors: Darras Veerle M , Van Herck Stijn L J
Published: July 2012

Iodothyronine deiodinases are important mediators of thyroid hormone (TH) action. They are present in tissues throughout the body where they catalyse 3,5,3′-triiodothyronine (T3) production and degradation via, respectively, outer and inner ring deiodination. Three different types of iodothyronine deiodinases (D1, D2 and D3) have been identified in vertebrates from fish to mammals. They share several common characteristics, including a selenocysteine residue in their catalytic centre, but show also some type-specific differences. These specific characteristics seem very well conserved for D2 and D3, while D1 shows more evolutionary diversity related to itsKm, 6-n-propyl-2-thiouracil sensitivity and dependence on dithiothreitol as a cofactorin vitro. The three deiodinase types have an impact on systemic T3levels and they all contribute directly or indirectly to intracellular T3availability in different tissues. The relative contribution of each of them, however, varies amongst species, developmental stages and tissues. This is especially true for amphibians, where the impact of D1 may be minimal. D2 and D3 expression and activity respond to thyroid status in an opposite and conserved way, while the response of D1 is variable, especially in fish. Recently, a number of deiodinases have been cloned from lower chordates. Both urochordates and cephalochordates possess selenodeiodinases, although they cannot be classified in one of the three vertebrate types. In addition, the cephalochordate amphioxus also expresses a non-selenodeiodinase. Finally, deiodinase-like sequences have been identified in the genome of non-deuterostome organisms, suggesting that deiodination of externally derived THs may even be functionally relevant in a wide variety of invertebrates.
Histological and endocrine characterisation of the annual luteal activity in Eurasian lynx (Lynx lynx)
Authors: Carnaby Kim , Painer Johanna , Söderberg Arne , Gavier-Widèn Dolores , Göritz Frank , Dehnhard Martin , Jewgenow Katarina
Published: July 2012

Lynx presents a unique sexual cycle with persistentcorpora lutea(CLs) and elevated serum progesterone (P4) throughout parturition and lactation. In other mammals, CLs normally disintegrate after parturition, therefore the aim of our study was to characterise the annual life cycle of lynx CLs. Ovaries from Eurasian lynxes were obtained from the National Veterinary Institute in Sweden, where tissues from killed lynx were stored at −20 °C. Ovaries from 66 animals were weighed; eachcorpus luteumwas segmented for histology and hormone analysis. Ovary and CLs weights were constant throughout the year, peaking during pregnancy. In non-pregnant lynxes, the seasonal level of intraluteal steroids was steady for P4(3.2±1.9 s.d. μg/g,n=53) and total oestrogens (18.3±15.5 s.d. ng/g,n=53). Within histology slides, structurally intact luteal cells were found throughout the year with the highest incidence in March/April; evidence of luteal regression was predominantly found in post-breeding season. Ovaries from pregnant animals contained two types of CLs. Group A was bigger in size with large luteal cells (P4, 72.3±65.4 s.d. μg/g; oestrogen, 454.0±52.4 s.d. ng/g). In contrast, group B were smaller, with greater luteal regression and lower steroid concentrations (P4, 8.3±2.9 s.d. μg/g; oestrogen, 31.5±20.4 s.d. ng/g). Our results suggest that structural luteolysis proceeds throughout the year and into next breeding cycle, resulting in two CLs types on the same ovary.
Estimating Allele Age and Selection Coefficient from Time-Serial Data
Authors: Malaspinas Anna-Sapfo , Malaspinas Orestis , Evans Steven N , Slatkin Montgomery
Published: July 2012

Recent advances in sequencing technologies have made available an ever-increasing amount of ancient genomic data. In particular, it is now possible to target specific single nucleotide polymorphisms in several samples at different time points. Such time-series data are also available in the context of experimental or viral evolution. Time-series data should allow for a more precise inference of population genetic parameters and to test hypotheses about the recent action of natural selection. In this manuscript, we develop a likelihood method to jointly estimate the selection coefficient and the age of an allele from time-serial data. Our method can be used for allele frequencies sampled from a single diallelic locus. The transition probabilities are calculated by approximating the standard diffusion equation of the Wright–Fisher model with a one-step process. We show that our method produces unbiased estimates. The accuracy of the method is tested via simulations. Finally, the utility of the method is illustrated with an application to several loci encoding coat color in horses, a pattern that has previously been linked with domestication. Importantly, given our ability to estimate the age of the allele, it is possible to gain traction on the important problem of distinguishing selection on new mutations from selection on standing variation. In this coat color example for instance, we estimate the age of this allele, which is found to predate domestication.
Cellular Memory of Acquired Stress Resistance inSaccharomyces cerevisiae
Authors: Guan Qiaoning , Haroon Suraiya , Bravo Diego González , Will Jessica L , Gasch Audrey P
Published: July 2012

Cellular memory of past experiences has been observed in several organisms and across a variety of experiences, including bacteria “remembering” prior nutritional status and amoeba “learning” to anticipate future environmental conditions. Here, we show that Saccharomyces cerevisiae maintains a multifaceted memory of prior stress exposure. We previously demonstrated that yeast cells exposed to a mild dose of salt acquire subsequent tolerance to severe doses of H2O2. We set out to characterize the retention of acquired tolerance and in the process uncovered two distinct aspects of cellular memory. First, we found that H2O2 resistance persisted for four to five generations after cells were removed from the prior salt treatment and was transmitted to daughter cells that never directly experienced the pretreatment. Maintenance of this memory did not require nascent protein synthesis after the initial salt pretreatment, but rather required long-lived cytosolic catalase Ctt1p that was synthesized during salt exposure and then distributed to daughter cells during subsequent cell divisions. In addition to and separable from the memory of H2O2 resistance, these cells also displayed a faster gene-expression response to subsequent stress at >1000 genes, representing transcriptional memory. The faster gene-expression response requires the nuclear pore component Nup42p and serves an important function by facilitating faster reacquisition of H2O2 tolerance after a second cycle of salt exposure. Memory of prior stress exposure likely provides a significant advantage to microbial populations living in ever-changing environments.
Antiphospholipid syndrome and pregnancy
Authors: Gadó Klára , Domján Gyula
Published: July 2012

Antiphospholipid syndrome is characterized by arterial and venous thromboembolic events and persistent laboratory evidence of antiphospholipid antibodies. Obstetric complications such as recurrent miscarriage, early delivery, oligohydramnios, prematurity, intrauterine growth restriction, fetal distress, fetal or neonatal thrombosis, pre-eclampsia/eclampsia, and HELLP syndrome are also hallmarks of antiphospholipid syndrome. This syndrome is one of the diseases associated with the most severe thrombotic risk. Changes in the hemostatic system during normal pregnancy also result in a hypercoagulable state resulting in elevated thrombotic risk. Thromboembolic events are responsible of the vast majority of maternal and fetal deaths. Administration of appropriate thromboprophylaxis helps prevent thromboembolic complications during pregnancy in women with antiphospholipid syndrome and also give birth to healthy children. It is important to centralize the medication and management of these patients. It helps in the thoughtful care of these pregnant women encountering serious problems. Orv. Hetil., 2012, 153, 1207–1218.
Financial Reporting Outcomes under Rules-Based and Principles-Based Accounting Standards
Authors: Collins Denton L. , Pasewark William R. , Riley Mark E.
Published: July 2012

SYNOPSIS:

This archival study addresses whether the presence or absence of “bright lines” in a lease accounting standard influences the classification of leases as capital or operating. To the best of our knowledge, our study is the first archival research to address the association between lease classification decisions and the use of U.S. GAAP and IFRS lease accounting standards. We examine firms' lease classification decisions using 2007–2009 data from a matched sample of members of the Fortune Global 500 that report under U.S. GAAP and IFRS. Consistent with experimental work by Agoglia et al. (2011), we find strong evidence that U.S. GAAP firms using a lease standard containing bright-line guidance (i.e., ASC 840) are more likely to classify leases as operating than IFRS firms adhering to a lease accounting standard that lacks the bright lines of the U.S. standard (i.e., IAS 17). Also consistent with Agoglia et al. (2011), we find little evidence of increased dispersion accompanying financial reporting under IFRS. In fact, we find some evidence suggesting the use of IFRS may actually lead to lower dispersion in reporting outcomes.