bluuebunny/crossref_metadata_2025 huggingface dataset:
Primary testicular necrotizing vasculitis clinically presented as neoplasm of the testicle: a case report
Authors: Maričić Anton , Štifter Sanja , Valenčić Maksim , Ðorđević Gordana , Markić Dean , Španjol Josip , Sotošek Stanislav , Fučkar Željko
Published: June 2011

We present a case of necrotizing vasculitis with the testicle as the isolated affected organ. A 25-year-old man, pretreated for epididymo-orchitis, presented with a presumed testicular neoplasm. Radical orchiectomy was performed and diagnosis of necrotizing vasculitis was established. In the absence of any other sign of systemic disease, the diagnosis of isolated necrotizing vasculitis of the testis was confirmed. Two years after the operation, the patient showed no symptoms of systemic disease.
Use of 3D-computed tomography angiography for planning the surgical removal of pineal region meningiomas using Poppen's approach: a report of ten cases and a literature review
Authors: Li Yunqian , Zhao Gang , Wang Honglei , Zhu Wanan , Qu Limei , Li Ye , Yu Jinlu
Published: June 2011

Background

There are several treatment approaches for pineal region meningiomas, such as Poppen's approach, Krause's approach and combinations of the two approaches. We present our experience with the use of 3D-computed tomography angiography for planning the surgical removal of pineal region meningiomas using a suboccipital transtentorial approach (Poppen's approach) and evaluate the role of Poppen's approach.

Methods

During the period from January 2005 to June 2010, ten patients presented to us with pineal region meningioma. MRI was routinely used to define the tumor size, position, and its relevant complications while 3D-CTA was applied to define the blood supply of the tumor and the venous complex (VC) shift before operations. Most of the meningiomas had developed at both sides of the tentorial plane and extended laterally with typical characteristics of a pineal region tumor.

Results

All tumors were completely removed surgically without any injury to the VC. Postoperative intracranial infection occurred in one case who recovered after antibiotics were given. Postoperative intraventricular hemorrhage and pneumocephalus were found in one case, but fully recovered after conservative treatment. In the nine cases of concurrent hydrocephalus, this was gradually relieved in eight patients and the single case that became aggravated was successfully treated with ventriculoperitoneal shunt. Moreover, the follow-up MRI examinations did not indicate any recurrence of the meningiomas.

Conclusion

We found that the use of Poppen's approach is strongly supported for the successful removal of pineal region meningiomas without serious complications.
Falling behind: life expectancy in US counties from 2000 to 2007 in an international context
Authors: Kulkarni Sandeep C , Levin-Rector Alison , Ezzati Majid , Murray Christopher JL
Published: June 2011

Background

The United States health care debate has focused on the nation's uniquely high rates of lack of insurance and poor health outcomes relative to other high-income countries. Large disparities in health outcomes are well-documented in the US, but the most recent assessment of county disparities in mortality is from 1999. It is critical to tracking progress of health reform legislation to have an up-to-date assessment of disparities in life expectancy across counties. US disparities can be seen more clearly in the context of how progress in each county compares to international trends.

Methods

We use newly released mortality data by age, sex, and county for the US from 2000 to 2007 to compute life tables separately for each sex, for all races combined, for whites, and for blacks. We propose, validate, and apply novel methods to estimate recent life tables for small areas to generate up-to-date estimates. Life expectancy rates and changes in life expectancy for counties are compared to the life expectancies across nations in 2000 and 2007. We calculate the number of calendar years behind each county is in 2000 and 2007 compared to an international life expectancy time series.

Results

Across US counties, life expectancy in 2007 ranged from 65.9 to 81.1 years for men and 73.5 to 86.0 years for women. When compared against a time series of life expectancy in the 10 nations with the lowest mortality, US counties range from being 15 calendar years ahead to over 50 calendar years behind for men and 16 calendar years ahead to over 50 calendar years behind for women. County life expectancy for black men ranges from 59.4 to 77.2 years, with counties ranging from seven to over 50 calendar years behind the international frontier; for black women, the range is 69.6 to 82.6 years, with counties ranging from eight to over 50 calendar years behind. Between 2000 and 2007, 80% (men) and 91% (women) of American counties fell in standing against this international life expectancy standard.

Conclusions

The US has extremely large geographic and racial disparities, with some communities having life expectancies already well behind those of the best-performing nations. At the same time, relative performance for most communities continues to drop. Efforts to address these issues will need to tackle the leading preventable causes of death.
Two-round contributory group key exchange protocol for wireless network environments
Authors: Wu Tsu-Yang , Tseng Yuh-Min , Yu Ching-Wen
Published: June 2011

With the popularity of group-oriented applications, secure group communication has recently received much attention from cryptographic researchers. A group key exchange (GKE) protocol allows that participants cooperatively establish a group key that is used to encrypt and decrypt transmitted messages. Hence, GKE protocols can be used to provide secure group communication over a public network channel. However, most of the previously proposed GKE protocols deployed in wired networks are not fully suitable for wireless network environments with low-power computing devices. Subsequently, several GKE protocols suitable for mobile or wireless networks have been proposed. In this article, we will propose a more efficient group key exchange protocol with dynamic joining and leaving. Under the decision Diffie-Hellman (DDH), the computation Diffie-Hellman (CDH), and the hash function assumptions, we demonstrate that the proposed protocol is secure against passive attack and provides forward/backward secrecy for dynamic member joining/leaving. As compared with the recently proposed GKE protocols, our protocol provides better performance in terms of computational cost, round number, and communication cost.
A STAT-1 knockout mouse model for Machupo virus pathogenesis
Authors: Bradfute Steven B , Stuthman Kelly S , Shurtleff Amy C , Bavari Sina
Published: June 2011

Background

Machupo virus (MACV), a member of the Arenaviridae, causes Bolivian hemorrhagic fever, with ~20% lethality in humans. The pathogenesis of MACV infection is poorly understood, and there are no clinically proven treatments for disease. This is due, in part, to a paucity of small animal models for MACV infection in which to discover and explore candidate therapeutics.

Methods

Mice lacking signal transducer and activator of transcription 1 (STAT-1) were infected with MACV. Lethality, viral replication, metabolic changes, hematology, histopathology, and systemic cytokine expression were analyzed throughout the course of infection.

Results

We report here that STAT-1 knockout mice succumbed to MACV infection within 7-8 days, and presented some relevant clinical and histopathological manifestations of disease. Furthermore, the model was used to validate the efficacy of ribavirin in protection against infection.

Conclusions

The STAT-1 knockout mouse model can be a useful small animal model for drug testing and preliminary immunological analysis of lethal MACV infection.
Paramedic Initiated Lisinopril For Acute Stroke Treatment (PIL-FAST): study protocol for a pilot randomised controlled trial
Authors: Shaw Lisa , Price Christopher , McLure Sally , Howel Denise , McColl Elaine , Ford Gary A
Published: June 2011

Background

High blood pressure during acute stroke is associated with poorer stroke outcome. Previous trials have failed to show benefit from lowering blood pressure but treatment may have been commenced too late to be effective. The earliest that acute stroke treatments could be initiated is during contact with the emergency medical services (paramedics). However, experience of pre-hospital clinical trials is limited and logistical challenges are likely to be greater than for trials performed in other settings. We report the protocol for a pilot randomised controlled trial of paramedic initiated blood pressure lowering treatment for hypertension in acute stroke.

Methods

Trial Design: Double blind parallel group external pilot randomised controlled trial.

Setting: Participant recruitment and initial treatment by North East Ambulance Service research trained paramedics responding to the emergency call. Continued treatment in three study hospitals.

Participants: Target is recruitment of 60 adults with acute arm weakness due to suspected stroke (within 3 hours of symptom onset) and hypertension (systolic BP>160 mmHg).

Intervention: Lisinopril 5-10 mg (intervention group), matched placebo (control group), daily for 7 days.

Randomisation: Study medication contained within identical pre-randomised "trial packs" carried by research trained paramedics.

Outcomes: Study feasibility (recruitment rate, compliance with data collection) and clinical data to inform the design of a definitive randomised controlled trial (blood pressure monitoring, National Institute of Health Stroke Scale, Barthel ADL Index, Modified Rankin Scale, renal function).

Discussion

This pilot study is assessing the feasibility of a randomised controlled trial of paramedic initiated lisinopril for hypertension early after the onset of acute stroke. The results will inform the design of a definitive RCT to evaluate the effects of very early blood pressure lowering in acute stroke.

Trial Registration

EudraCT: 2010-019180-10

ClinicalTrials.gov: NCT01066572

ISRCTN: 54540667
Understanding and predicting synthetic lethal genetic interactions in Saccharomyces cerevisiae using domain genetic interactions
Authors: Li Bo , Cao Weiguo , Zhou Jizhong , Luo Feng
Published: June 2011

Background

Synthetic lethal genetic interactions among proteins have been widely used to define functional relationships between proteins and pathways. However, the molecular mechanism of synthetic lethal genetic interactions is still unclear.

Results

In this study, we demonstrated that yeast synthetic lethal genetic interactions can be explained by the genetic interactions between domains of those proteins. The domain genetic interactions rarely overlap with the domain physical interactions from iPfam database and provide a complementary view about domain relationships. Moreover, we found that domains in multidomain yeast proteins contribute to their genetic interactions differently. The domain genetic interactions help more precisely define the function related to the synthetic lethal genetic interactions, and then help understand how domains contribute to different functionalities of multidomain proteins. Using the probabilities of domain genetic interactions, we were able to predict novel yeast synthetic lethal genetic interactions. Furthermore, we had also identified novel compensatory pathways from the predicted synthetic lethal genetic interactions.

Conclusion

The identification of domain genetic interactions helps the understanding of originality of functional relationship in SLGIs at domain level. Our study significantly improved the understanding of yeast mulitdomain proteins, the synthetic lethal genetic interactions and the functional relationships between proteins and pathways.
Reliability of the Cerebral Performance Category to classify neurological status among survivors of ventricular fibrillation arrest: a cohort study
Authors: Ajam Kamal , Gold Laura S , Beck Stacey S , Damon Susan , Phelps Randi , Rea Thomas D
Published: June 2011

Background

The Cerebral Performance Category (CPC) score is widely used in research and quality assurance to assess neurologic outcome following cardiac arrest. However, little is known about the inter- and intra-reviewer reliability of the CPC.

Methods

We undertook an investigation to assess the inter-reviewer and source document reliability of the CPC among a cohort of survivors from out-of-hospital ventricular fibrillation cardiac arrest (n = 131) in a large metropolitan area between November 1, 2003 and December 31, 2005. Subjects with a CPC of 1 or 2 were classified as favorable outcome and those with CPC 3 or greater were classified as unfavorable outcome. One abstractor first used the discharge summary alone to determine the CPC. All 3 abstractors independently reviewed the entire hospital record. Reliability was assessed by determining the proportion of determinations that agreed between abstractors and the respective kappa statistics. We also evaluated the implications for determining survival with favorable neurological outcome when survival to hospital discharge was 20% and 30%.

Results

When the entire hospital record was used to determine CPC, favorable neurologic outcome (CPC 1 or 2) was recorded in 92% by abstractor 1, 89% by abstractor 2, and 74% by abstractor 3. Agreement was 96% (kappa = 0.78) between abstractors 1 and 2, 84% (kappa = 0.49) between abstractors 2 and 3, 82% (kappa = 0.38) between abstractors 1 and 3. The 3-way kappa was 0.50. Agreement was 90% (kappa = 0.71) between the discharge summary alone and the entire hospital record. If the results from review of the entire record are applied to a circumstance where survival to discharge is 20%, favorable neurologic status would occur in 18.4% for abstractor 1, 17.8% for abstractor 2, and 14.8% for abstractor 3. For survival to hospital discharge of 30%, favorable neurologic status would occur in 27.6% for abstractor 1, 26.7% for abstractor 2, and 22.2% for abstractor 3.

Conclusions

In this cohort study of survivors of out-of-hospital ventricular fibrillation cardiac arrest, the use of the CPC to classify favorable versus unfavorable neurological status at hospital discharge produced variable inter- and intra-reviewer agreement. The findings provide useful context to interpret outcome evaluations that report CPC.
Predictors for pathologically confirmed aortitis after resection of the ascending aorta: A 12-year Danish nationwide population-based cross-sectional study
Authors: Schmidt Jean , Sunesen Kaare , Kornum Jette B , Duhaut Pierre , Thomsen Reimar W
Published: June 2011

Introduction

Assessing the prevalence of, and predictors for, pathologically-confirmed inflammation of the aorta in Denmark, using a nationwide population-based study design.

Methods

We identified all adults with first-time surgery on the ascending aorta between January 1, 1997 and March 1, 2009 in Denmark. Presence of aortic inflammation was ascertained through linkage to a nationwide pathology registry. We used logistic regression to compute prevalence odds ratios (ORs) for sex, age at surgery, cardiovascular risk factors, cancer, connective tissue disease, and infectious diseases associated with the presence of aortitis.

Results

A total of 1,210 adults underwent resection of the ascending aorta, of who 610 (50.4%) had tissue submitted for pathological examination. Aortitis was found in 37 (6.1%) patients whose tissue was examined. Ten of the 37 patients were diagnosed with conditions known to be associated with aortitis or aortic aneurysm: five patients with temporal arteritis, one with Crohn's disease, one with rheumatoid arthritis, one with systemic lupus erythematosus, one with infectious aortitis, and one with Marfan's disease. Twenty-seven patients had idiopathic aortitis. Predictors of aortitis included history of connective tissue disease (adjusted OR 4.7, 95% confidence interval (CI) 1.6, 13.6), diabetes (OR 5.2, 95% CI 0.9, 29.7), advanced age (> 67 years OR 2.5, 95% CI 0.8, 7.6), and aortic valve pathology (OR 2.3, 95% CI 1.1, 4.9).

Conclusions

Aortitis was present in 6.1% of adults in Denmark who had pathological examination after resection of the ascending aorta. Predictors of inflammation included connective tissue disease, diabetes, advanced age, and aortic valve pathology.
The prognostic significance of tumour cell detection in the peripheral blood versus the bone marrow in 733 early-stage breast cancer patients
Authors: Molloy Timothy J , Bosma Astrid J , Baumbusch Lars O , Synnestvedt Marit , Borgen Elin , Russnes Hege Giercksky , Schlichting Ellen , van't Veer Laura J , Naume Bjørn
Published: June 2011

Introduction

The detection of circulating tumour cells (CTCs) in the peripheral blood and disseminated tumour cells (DTCs) in the bone marrow are promising prognostic tools for risk stratification in early breast cancer. There is, however, a need for further validation of these techniques in larger patient cohorts with adequate follow-up periods.

Methods

We assayed CTCs and DTCs at primary surgery in 733 stage I or II breast cancer patients with a median follow-up time of 7.6 years. CTCs were detected in samples of peripheral blood mononuclear cells previously stored in liquid-nitrogen using a previously-developed multi-marker quantitative PCR (QPCR)-based assay. DTCs were detected in bone marrow samples by immunocytochemical analysis using anti-cytokeratin antibodies.

Results

CTCs were detected in 7.9% of patients, while DTCs were found in 11.7%. Both CTC and DTC positivity predicted poor metastasis-free survival (MFS) and breast cancer-specific survival (BCSS); MFS hazard ratio (HR) = 2.4 (P < 0.001)/1.9 (P = 0.006), and BCSS HR = 2.5 (P < 0.001)/2.3 (P = 0.01), for CTC/DTC status, respectively). Multivariate analyses demonstrated that CTC status was an independent prognostic variable for both MFS and BCSS. CTC status also identified a subset of patients with significantly poorer outcome among low-risk node negative patients that did not receive adjuvant systemic therapy (MFS HR 2.3 (P = 0.039), BCSS HR 2.9 (P = 0.017)). Using both tests provided increased prognostic information and indicated different relevance within biologically dissimilar breast cancer subtypes.

Conclusions

These results support the use of CTC analysis in early breast cancer to generate clinically useful prognostic information.
1,25(OH)2Vitamin D3 Stimulates Myogenic Differentiation by Inhibiting Cell Proliferation and Modulating the Expression of Promyogenic Growth Factors and Myostatin in C2C12 Skeletal Muscle Cells
Authors: Garcia Leah A. , King Keisha K. , Ferrini Monica G. , Norris Keith C. , Artaza Jorge N.
Published: June 2011

Skeletal muscle wasting is an important public health problem associated with aging, chronic disease, cancer, kidney dialysis, and HIV/AIDS. 1,25-Dihydroxyvitamin D (1,25-D3), the active form of vitamin D, is widely recognized for its regulation of calcium and phosphate homeostasis in relation to bone development and maintenance and for its calcemic effects on target organs, such as intestine, kidney, and parathyroid glands. Emerging evidence has shown that vitamin D administration improves muscle performance and reduces falls in vitamin D-deficient older adults. However, little is known of the underlying mechanism or the role 1,25-D3 plays in promoting myogenic differentiation at the cellular and/or molecular level. In this study, we examined the effect of 1,25-D3 on myoblast cell proliferation, progression, and differentiation into myotubes. C2C12 myoblasts were treated with 1,25-D3 or placebo for 1, 3, 4, 7, and 10 d. Vitamin D receptor expression was analyzed by quantitative RT-PCR, Western blottings and immunofluorescence. Expression of muscle lineage, pro- and antimyogenic, and proliferation markers was assessed by immunocytochemistry, PCR arrays, quantitative RT-PCR, and Western blottings. Addition of 1,25-D3 to C2C12 myoblasts 1) increased expression and nuclear translocation of the vitamin D receptor, 2) decreased cell proliferation, 3) decreased IGF-I expression, and 4) promoted myogenic differentiation by increasing IGF-II and follistatin expression and decreasing the expression of myostatin, the only known negative regulator of muscle mass, without changing growth differentiation factor 11 expression. This study identifies key vitamin D-related molecular pathways for muscle regulation and supports the rationale for vitamin D intervention studies in select muscle disorder conditions.
Placental-Specific Igf2 Deficiency Alters Developmental Adaptations to Undernutrition in Mice
Authors: Sferruzzi-Perri A. N. , Vaughan O. R. , Coan P. M. , Suciu M. C. , Darbyshire R. , Constancia M. , Burton G. J. , Fowden A. L.
Published: June 2011

The pattern of fetal growth is a major determinant of the subsequent health of the infant. We recently showed in undernourished (UN) mice that fetal growth is maintained until late pregnancy, despite reduced placental weight, through adaptive up-regulation of placental nutrient transfer. Here, we determine the role of the placental-specific transcript of IGF-II (Igf2P0), a major regulator of placental transport capacity in mice, in adapting placental phenotype to UN. We compared the morphological and functional responses of the wild-type (WT) and Igf2P0-deficient placenta in WT mice fed ad libitium or 80% of the ad libitium intake. We observed that deletion of Igf2P0 prevented up-regulation of amino acid transfer normally seen in UN WT placenta. This was associated with a reduction in the proportion of the placenta dedicated to nutrient transport, the labyrinthine zone, and its constituent volume of trophoblast in Igf2P0-deficient placentas exposed to UN on d 16 of pregnancy. Additionally, Igf2P0-deficient placentas failed to up-regulate their expression of the amino acid transporter gene, Slc38a2, and down-regulate phosphoinositide 3-kinase-protein kinase B signaling in response to nutrient restriction on d 19. Furthermore, deleting Igf2P0 altered maternal concentrations of hormones (insulin and corticosterone) and metabolites (glucose) in both nutritional states. Therefore, Igf2P0 plays important roles in adapting placental nutrient transfer capacity during UN, via actions directly on the placenta and/or indirectly through the mother.
Minireview: Vitamin D: Is There a Role in Extraskeletal Health?
Authors: Christakos Sylvia , DeLuca Hector F.
Published: June 2011

In recent years, vitamin D has received increased attention due to the resurgence of vitamin D deficiency and rickets in developed countries together with the identification of extraskeletal vitamin D receptor-mediated actions, suggesting unexpected benefits of vitamin D in health and diseases. Although there is increased awareness of the importance of vitamin D, the role of vitamin D in extraskeletal health has been a matter of debate. In this review, we will summarize what is known and indicate the questions that remain and need to be addressed.
Physiological and Pharmacological Mechanisms through which the DPP-4 Inhibitor Sitagliptin Regulates Glycemia in Mice
Authors: Waget Aurélie , Cabou Cendrine , Masseboeuf Myriam , Cattan Pierre , Armanet Mattieu , Karaca Mélis , Castel Julien , Garret Celine , Payros Gaëlle , Maida Adriano , Sulpice Thierry , Holst Jens J. , Drucker Daniel J. , Magnan Christophe , Burcelin Rémy
Published: June 2011

Inhibition of dipeptidyl peptidase-4 (DPP-4) activity improves glucose homeostasis through a mode of action related to the stabilization of the active forms of DPP-4-sensitive hormones such as the incretins that enhance glucose-induced insulin secretion. However, the DPP-4 enzyme is highly expressed on the surface of intestinal epithelial cells; hence, the role of intestinal vs. systemic DPP-4 remains unclear. To analyze mechanisms through which the DPP-4 inhibitor sitagliptin regulates glycemia in mice, we administered low oral doses of the DPP-4 inhibitor sitagliptin that selectively reduced DPP-4 activity in the intestine. Glp1r−/− and Gipr−/− mice were studied and glucagon-like peptide (GLP)-1 receptor (GLP-1R) signaling was blocked by an iv infusion of the corresponding receptor antagonist exendin (9–39). The role of the dipeptides His-Ala and Tyr-Ala as DPP-4-generated GLP-1 and glucose-dependent insulinotropic peptide (GIP) degradation products was studied in vivo and in vitro on isolated islets. We demonstrate that very low doses of oral sitagliptin improve glucose tolerance and plasma insulin levels with selective reduction of intestinal but not systemic DPP-4 activity. The glucoregulatory action of sitagliptin was associated with increased vagus nerve activity and was diminished in wild-type mice treated with the GLP-1R antagonist exendin (9–39) and in Glp1r−/− and Gipr−/− mice. Furthermore, the dipeptides liberated from GLP-1 (His-Ala) and GIP (Tyr-Ala) deteriorated glucose tolerance, reduced insulin, and increased portal glucagon levels. The predominant mechanism through which DPP-4 inhibitors regulate glycemia involves local inhibition of intestinal DPP-4 activity, activation of incretin receptors, reduced liberation of bioactive dipeptides, and activation of the gut-to-pancreas neural axis.
Claiming Personality: Reassessing the Dangers of the “New Woman” in Early Taishō Japan
Authors: Reitan Richard
Published: June 2011

In early twentieth-century Japan, educators, journalists, and government bureaucrats debated the “proper” roles for women in society. They approached this “woman problem” as a struggle between two competing moral ideals for women: the “good wife/wise mother” and the “new woman.” Proponents of the former condemned the latter as a dangerous threat to “traditional” gender norms. Yet new women—few in number and with their publications closely regulated by government authorities—did not appear to present a threat commensurate with the attacks its critics launched. How should we assess the outcry against the “dangerous” new woman? I approach this question by analyzing the “woman problem” within the context of the broader moral discourse of the time. I show that the good wife/wise mother and the new woman positions were linked, respectively, to the national morality movement and the ethics of personalism. Moreover, as both the good wife/wise mother and the new woman were moral ideals grounded in ontological claims about women, I suggest that the woman problem be approached as both an ontological and a moral problem. Whoever controlled the ontological terrain so as to speak for what a woman “is” possessed the greater authority to legitimize a specific moral ideal for women, for how a woman “ought” to be. In short, the new woman movement was perceived as dangerous not merely because it questioned the good wife/wise mother ideal, but because it drew upon the subversive potential of personalism to destabilize the ontological foundation that grounded the good wife/wise mother ideal and, ultimately, ran counter to the state-sponsored national morality movement as well.
Black Market, Chinatown, and Kabukichō: Postwar Japanese Constructs of “Overseas Chinese”
Authors: Tsu Timothy Yun Hui
Published: June 2011

This paper examines postwar Japanese experiences of kakyō, or “overseas Chinese,” focusing on three “sites”: the black market, Chinatown, and Kabukichō. It argues that Japanese society assigns to the Chinese immigrant community stereotypical meanings that reflect first and foremost Japanese preoccupations in domestic and international affairs. Nonetheless, it also contends that the immigrants are not completely detached or passive, for they collaborate in the production of the stereotypes while trying to manipulate them to their advantage. By way of conclusion, it discusses some of the latest moves by host society and immigrant community to renegotiate the meaning of kakyō in the early twenty-first century.
Moving (realistically) from volume-based to value-based health care payment in the USA: Starting with Medicare payment policy
Authors: Mayes Rick
Published: June 2011

Employers and policy-makersintheUSAaredesperatetoslowtherateatwhich healthexpendituresgrow. Changing how most health care providers are reimbursed will be necessary to achieve this. Although both politically and practically daunting, massive restructuring or replacement of fee-for-service (FFS) reimbursement is what is most required. As the dominant reimbursement model in the USA, FFS payment to individual providers strongly encourages and financially rewards the quantity of care provided, regardless of its quality or necessity. Providing high quality, lower cost care with fewer complications and hospital re-admissions can even financial penalize providers. Unfortunately, physicians and other health providers respond rationally to existing financial incentives (translation: they do what they get paid to do and generally try to, or have to, minimize those activities and services for which they are not paid). Altering this reality and fostering the expansion of exemplary delivery models-such as the Mayo Clinic or Geisinger Health System-requires change in how providers behave. And changing behavior often starts with adjusting how providers are paid. Medicare is the programme and payer most capable of using payment reform to catalyze delivery system reform.
Intron cleavage affects processing of alternatively spliced transcripts
Authors: Pastor Tibor , Dal Mas Andrea , Talotti Gabriele , Bussani Erica , Pagani Franco
Published: June 2011

We previously showed that the insertion of a hammerhead ribozyme (Rz) in a critical intronic position between the EDA exon and a downstream regulatory element affects alternative splicing. Here we evaluate the effect of other intronic cotranscriptional cleavage events on alternative pre-mRNA processing using different ribozymes (Rz) and Microprocessor target sequences (MTSs). In the context of the fibronectin EDA minigene, intronic MTSs were cleaved very inefficiently and did not affect alternative splicing or the level of mature transcripts. On the contrary, all hammerhead Rz derivatives and hepatitis δ Rz were completely cleaved before a splicing decision and able to affect alternative splicing. Despite the very efficient Rz-mediated cleavage, the levels of mature mRNA were only reduced to ∼40%. We show that this effect on mature transcripts occurs regardless of the type and intronic position of Rzs, or changes in alternative splicing and exon definition. Thus, we suggest that intron integrity is not strictly required for splicing but is necessary for efficient pre-mRNA biosynthesis.
Identifying Aspects of Pharmacists' Attitudes and Barriers toward Health Literacy: A Factor Analytic Study
Authors: Devraj Radhika , Gupchup Gireesh V
Published: June 2011

BACKGROUND:

Health literacy has gained prominence since the Institute of Medicine Report publicized the widespread prevalence of low health literacy. Pharmacists play an important role in enhancing health literacy as a result of their proximity to patients. Literature about pharmacists' perceptions and barriers in incorporating health literacy interventions is lacking.

OBJECTIVE:

To develop an instrument to measure pharmacists' attitudes and barriers toward health literacy.

METHODS:

A survey instrument assessing attitudes and barriers was designed based on a pharmacist focus group. The instrument was pretested among a sample of pharmacists from Illinois. The final instrument was administered to a systematic sample of 1500 pharmacists who were members of the Illinois Pharmacists Association. Dillman's 5-step total design method was followed to maximize survey responses. Exploratory principal components analysis with varimax rotation was performed on attitudes and barriers items to identify underlying components. Internal consistency of the components was determined using the Cronbach a and corrected item-total correlations.

RESULTS:

Overall, usable responses were received from 701 respondents, yielding a 48.1% response rate. Exploratory principal components analysis of the attitudes subscale produced a 5-factor solution that explained 55.87% of the variance. The 5 components included (1) low health literacy (LHL) situations, (2) LHL reasons, (3) LHL patient characteristics, (4) medication-related factors, and (5) LHL patient-interaction factors. The barriers subscale produced 3 components: (1) practice-related barriers, (2) knowledge and interaction-related barriers, and (3) process barriers, all of which explained 53.74% of the variance. Cronbach a values for the 5 attitudes subscales ranged from 0.33 to 0.78 and, for the 3 barriers, subscale values ranged from 0.56 to 0.71, offering evidence of internal consistency.

CONCLUSIONS:

Identification of components of pharmacists' attitudes and barriers toward health literacy will be useful to managers interested in incorporating health literacy interventions in their practice.
Dipyridamole-Associated Shock and Pulmonary Edema
Authors: Dioverti Maria , Fishman Robert , Moskowitz Robert , Arias Sixto A , Nair Sumi , Lall Priyanka , Schussheim Adam E , Zarich Stuart , Manthous Constantine
Published: June 2011

Objective:

To report a case of fulminant shock and noncardiogenic pulmonary edema induced by intravenously administered dipyridamole.

Case Summary:

A 73-year-old woman presented to the office of her cardiologist for dipyridamole myocardial scintigraphy. Several minutes after administration of intravenous dipyridamole 0.57 mg/kg over 4 minutes she developed wheezing, followed by cardiovascular collapse and pulmonary edema requiring 100% oxygen and endotracheal intubation. She had never received dipyridamole before this, and no other medications or exposures were documented proximate to the collapse. On transfer to the hospital, she developed shock refractory to multiple vasopressors, which responded to continuous infusions of epinephrine. She also had severe pulmonary edema requiring invasive ventilation, 100% inspired oxygen, and 24 cm H2O positive end-expiratory pressure. An echocardiogram did not show new left-ventricular dysfunction and there were signs of right-heart underfilling, supporting a diagnosis of noncardiogenic pulmonary edema. Both shock and pulmonary edema resolved within 12 hours.

Discussion:

Dipyridamole-associated hypotension has been reported in a number of case series and registries. Detailed case descriptions, however, are not available in the literature to permit understanding of the mechanism of shock following hypotension resulting from dipyridamole myocardial scintigraphy. Our case is exceptional in that echocardiography results support a diagnosis of hypovolemic (rather than cardiogenic) shock. To our knowledge, this is the first case of severe (most likely noncardiogenic) pulmonary edema associated with intravenous infusion of dipyridamole. An objective causality assessment suggested that this patient's cardiopulmonary collapse was probably related to dipyridamole.

Conclusions:

While hypotension has been previously associated with intravenous use of dipyridamole, ours is the first report to suggest a noncardiogenic mechanism for shock. To our knowledge, this is the first reported case of noncardiogenic pulmonary edema following dipyridamole infusion.
Vilazodone for the Treatment of Depression
Authors: Lindsey Wesley T
Published: June 2011

Objective:

To evaluate the clinical literature on and potential clinical role of vilazodone for the treatment of major depressive disorder.

Data Sources:

Searches were conducted on MEDLINE (1948-February 2011), Iowa Drug Information Service (1988-February 2011), EBSCO Academic Search Premier (1975-February 2011), Google Scholar (1992-February 2011), PsycINFO (1980-February 2011), and PsycARTICLES (1985-February 2011), and on general Internet search engines including Google and Bing (no lower limit-February 2011). Search terms were vilazodone, EMD 68843, depression, and major depressive disorder. Potential prior marketers of vilazodone, including Merck KGaA in Germany and Genaissance Pharmaceuticals, were contacted for any available unpublished Phase 1, Phase 2, Phase 3 studies, or preclinical information.

Study Selection and Data Extraction:

All applicable full-text English-language articles, abstracts, and professional poster presentations found were evaluated and included in the review, as well as marketing and Securities and Exchange Commission filings available from the patent holders.

Data Synthesis:

Vilazodone is an antidepressant recently approved by the Food and Drug Administration (FDA) that is first in a new class regarding mechanism of action. It has demonstrated efficacy in the primary outcome of the Montgomery-Asberg Depression Rating Scale (MADRS) response in an 8-week pivotal Phase 3 trial. Phase 2 trials did not demonstrate efficacy for primary outcomes of the 17-item Hamilton Rating Scale for Depression but showed statistically significant improvements in select secondary outcomes such as Clinical Global Impressions severity and MADRS. Long-term efficacy data are still forthcoming. An emerging aspect to vilazodone's development has been the identification and assessment of potential genetic biomarkers associated with both therapeutic response and more serious adverse effects. Initial studies into biomarkers have been inconclusive.

Conclusions:

Vilazodone is a new agent recently approved by the FDA for treating major depressive disorder. Response rates seen with vilazodone are similar to those of currently available antidepressants.
Accurate Single-Nucleotide Polymorphism Allele Assignment in Trisomic or Duplicated Regions by Using a Single Base–Extension Assay with MALDI-TOF Mass Spectrometry
Authors: Trewick Anne L , Moustafa Julia S El-Sayed , de Smith Adam J , Froguel Philippe , Greve Gottfried , Njølstad Pål R , Coin Lachlan JM , Blakemore Alexandra IF
Published: June 2011

BACKGROUND

The accurate assignment of alleles embedded within trisomic or duplicated regions is an essential prerequisite for assessing the combined effects of single-nucleotide polymorphisms (SNPs) and genomic copy number. Such an integrated analysis is challenging because heterozygotes for such a SNP may be one of 2 genotypes—AAB or ABB. Established methods for SNP genotyping, however, can have difficulty discriminating between the 2 heterozygous trisomic genotypes. We developed a method for assigning heterozygous trisomic genotypes that uses the ratio of the height of the 2 allele peaks obtained by mass spectrometry after a single-base extension assay.

METHODS

Eighteen COL6A2 (collagen, type VI, alpha 2) SNPs were analyzed in euploid and trisomic individuals by means of a multiplexed single-base extension assay that generated allele-specific oligonucleotides of differing Mr values for detection by MALDI-TOF mass spectrometry. Reference data (mean and SD) for the allele peak height ratios were determined from heterozygous euploid samples. The heterozygous trisomic genotypes were assigned by calculating the z score for each trisomic allele peak height ratio and by considering the sign (+/−) of the z score.

RESULTS

Heterozygous trisomic genotypes were assigned in 96.1% (range, 89.9%–100%) of the samples for each SNP analyzed. The genotypes obtained were reproduced in 95 (97.5%) of 97 loci retested in a second assay. Subsequently, the origin of nondisjunction was determined in 108 (82%) of 132 family trios with a Down syndrome child.

CONCLUSIONS

This approach enabled reliable genotyping of heterozygous trisomic samples and the determination of the origin of nondisjunction in Down syndrome family trios.
Oral Fluid Cannabinoids in Chronic, Daily Cannabis Smokers during Sustained, Monitored Abstinence
Authors: Lee Dayong , Milman Garry , Barnes Allan J , Goodwin Robert S , Hirvonen Jussi , Huestis Marilyn A
Published: June 2011

BACKGROUND

Oral fluid (OF) is an accepted alternative biological matrix for drug treatment, workplace, and DUID (driving under the influence of drugs) investigations, but establishing the cannabinoid OF detection window and concentration cutoff criteria are important.

METHODS

Cannabinoid concentrations were quantified in OF from chronic, daily cannabis smokers during monitored abstinence. Δ9-tetrahydrocannabinol (THC)3, cannabidiol (CBD), cannabinol (CBN), and 11-nor-9-carboxy-THC (THCCOOH) were determined in daily OF samples collected with the Quantisal™ device. GC-MS limits of quantification (LOQ) were 0.5 μg/L for THC and CBD, 1 μg/L for CBN, and 7.5 ng/L for THCCOOH.

RESULTS

After providing written informed consent for this institutional review board–approved study, 28 participants resided from 4 to 33 days on the secure research unit and provided 577 OF specimens. At the LOQ, THC was generally quantifiable for 48 h, whereas CBD and CBN were detected only at admission. Median THCCOOH detection time was 13 days (CI 6.4–19.6 days). Mean THC detection rates decreased from 89.3% at admission to 17.9% after 48 h, whereas THCCOOH gradually decreased from 89.3% to 64.3% within 4 days. Criteria of THC ≥2 μg/L and THCCOOH ≥20 ng/L reduced detection to <48 h in chronic cannabis smokers. An OF THCCOOH/THC ratio ≤4 ng/μg or presence of CBD or CBN may indicate more recent smoking.

CONCLUSIONS

THC, THCCOOH, CBD, and CBN quantification in confirmatory OF cannabinoid testing is recommended. Inclusion of multiple cannabinoid cutoffs accounted for residual cannabinoid excretion in OF from chronic, daily cannabis smokers and could reduce the potential for positive test results from passive cannabis smoke exposure and lead to greatly improved test interpretation.
The Alignment of Contract Terms for Knowledge-Creating and Knowledge-Appropriating Relationship Portfolios
Authors: Lee Jongkuk
Published: June 2011

Interfirm collaborative relationships for developing new products involve the two fundamental tasks of creating new knowledge and appropriating the newly created or current stocks of knowledge. This study examines the alignment of two contract terms—form of resource integration (how partners integrate their resources) and form of equity sharing (whether partners are engaged in equity investment)—for knowledge-creating and knowledge-appropriating relationship portfolios. By analyzing interfirm relationship agreements initiated in the pharmaceutical industry between 1990 and 2006, the author shows that knowledge-creating and knowledge-appropriating relationship portfolios benefit from different alignments of contract terms to address their unique concerns. The author also shows that the appropriate alignments of contract terms are more critical for small firms than for large firms. The results provide specific insights into the management of knowledge-creating and knowledge-appropriating relationship portfolios for developing a greater number of radical and incremental new products.
Closing the Marketing Capabilities Gap
Authors: Day George S.
Published: June 2011

Marketers are being challenged by a deluge of data that is well beyond the capacity of their organizations to comprehend and use. Their strategies are not keeping up with the disruptive effects of technology-empowered customers; the proliferation of media, channel, and customer contact points; or the possibilities for microsegmentation. Closing the widening gap between the accelerating complexity of their markets and the limited ability of their organizations to respond demands new thinking about marketing capabilities. Three adaptive capabilities are needed: (1) Vigilant market learning that enhances deep market insights with an advance warning system to anticipate market changes and unmet needs, (2) adaptive market experimentation that continuously learns from experiments, and (3) open marketing that forges relationships with those at the forefront of new media and social networking technologies and mobilizes the skills of current partners. The benefits of these adaptive capabilities will only be realized in organizations that are more resilient and free-flowing, with vigilant leadership and more adaptive business models.
Bridging the Academic–Practitioner Divide in Marketing Decision Models
Authors: Lilien Gary L.
Published: June 2011

The marketing decision models field has produced many striking developments that have had a dramatic impact on practice. However, the field has produced orders of magnitude more developments that have received minimal use. In this article, the author notes the many successful marketing model developments but then considers the relatively low level of practical use (trial or adoption) and questions why that is the case. He then suggests how changes in the incentive and reward systems for marketing academics, marketing practitioners, and marketing intermediaries can bring about adoption and implementation improvements that would be mutually beneficial, bridging the academic–practitioner divide. The author also outlines a program of research in the area of the adoption and use of marketing decision models that will provide guidance on what to develop and how to get those developments adopted.
Marketing Scholarship 2.0
Authors: Lutz Richard J.
Published: June 2011

The system for the design, production, and dissemination of marketing scholarship aimed at contributing to marketing practice is under increasing strain due to pressures exerted by globalization, digitization, and environmentalism. Scholarly research in marketing adheres largely to a twentieth-century manufacturing model. Change is needed now. Marketing scholarship can benefit from embracing a twenty-first-century, collaborative approach to the conception, design, and dissemination of research. “Crowdsourcing” is becoming a frequently employed strategy in industry. Marketing academe should adopt some of the same techniques and technologies to make stronger research contributions that will benefit marketing practice. In particular, more collaboration is needed, both among academic researchers and between academe and industry, to be sure important problems are being investigated using sound theories and methods. An open, collaborative model will allow the field to evolve from Marketing Scholarship 1.0 to Marketing Scholarship 2.0.
The Asymmetric Effects of Extending Brands to Lower and Higher Quality
Authors: Heath Timothy B. , DelVecchio Devon , McCarthy Michael S.
Published: June 2011

Managers often extend brands to different quality levels (e.g., Charmin's lower-quality Charmin Basic), which may increase sales but risks diluting brand image. This study examines such line extensions by testing middle-quality brands (e.g., Giovanni's pasta sauce [fictitious], Foster's beer [real]) that offer higher-quality (e.g., Giovanni's Magnifico) or lower-quality line extensions (e.g., Foster's Grog). A robust asymmetry emerges in which higher-quality extensions improve brand evaluation far more than lower-quality extensions damage it. The asymmetry prevails across various perceptual and evaluative dimensions, multiple product classes, numerous fictitious and real brands that differ on various dimensions (familiarity, liking, personality, and prestige), and consumer regulatory focus. Group and individual-level tests show that the standard asymmetry is the modal pattern (though not universal) and that it is associated with two primary underlying processes: (1) opponent processes produced by lower-quality extensions whose negative quality-association effects are tempered by positive variety effects (in general, consumers prefer broader product lines) and (2) best-of-brand processing, in which consumers consider higher-quality extensions more relevant to brand evaluation than lower-quality extensions.