bluuebunny/crossref_metadata_2025 huggingface dataset:
Interventions to Reduce Distress in Adult Victims of Rape and Sexual Violence
Authors: Regehr Cheryl , Alaggia Ramona , Dennis Jane , Pitts Annabel , Saini Michael
Published: February 2013

Objectives: This article presents a systematic evaluation of the effectiveness of interventions aimed at reducing distress in adult victims of rape and sexual violence. Method: Studies were eligible for the review if the assignment of study participants to experimental or control groups was by random allocation or parallel cohort design. Results: Six studies including 405 participants met eligibility criteria. Meta-analyses revealed that specific cognitive and behavioral interventions (cognitive-processing therapy, prolonged exposure therapy, and eye movement desensitization reprocessing) had a statistically significant effect on posttraumatic stress disorder and depression symptoms in comparison to the control groups. Other outcomes that had demonstrated improvement included anxiety, guilt, and dissociation. Conclusion: Many studies assessing the effectiveness of interventions for decreasing trauma symptoms combine victims of sexual violence in adulthood with other trauma-based samples despite the profound differences in these experiences. This review again points to the need for increased research that focuses specifically on the effectiveness of treatment models for adult victims of sexual violence.
Responding to “Issues in Differential Response”
Authors: Perry Robin Ernest
Published: February 2013

Hughes, Rycus, Saunders-Adams, Hughes, and Hughes’s article represents an important effort to critically examine the foundation of thought and empirical evidence associated with the rise in prominence of differential response (DR) within child welfare systems throughout the United States. The insights and criticisms offered are an important contribution to the professional literature. The arguments and perspective put forward can best be understood within the context of continuing conflict and debate (within child welfare) stemming from the countervailing influences of the principle of least intrusion and demands to ensure child safety. Although effective arguments are put forth that support many of the conclusions and interpretations, there are a few comments that require further discussion and reflection. More specifically, it is unclear if there is sufficient evidence to support their claim that children in DR alternative tracks may or are at a more heightened safety risk.
Development of the Career Indecision Profile
Authors: Hacker Jason , Carr Andrea , Abrams Matthew , Brown Steven D.
Published: February 2013

Prior research using a 167-item measure of career indecision (Career Indecision Profile-167 [CIP-167]) has suggested that career choice difficulties may be associated with four major sources of career indecision: neuroticism/negative affectivity, choice/commitment anxiety, lack of readiness, and interpersonal conflicts. The purpose of this study was to develop a shorter and more efficient measure of these four major sources of indecision for future use in research and counseling. The development of the measure (CIP-65) is described and the results of a confirmatory factor analytic study of its structure are presented along with initial reliability and validity data. We conclude by discussing implications for future research on the CIP-65 and its potential use in counseling individuals with choice-making difficulties.
Declines in Lower Extremity Amputation in the US Medicare Population, 2000-2010
Authors: Belatti Daniel A. , Phisitkul Phinit
Published: February 2013

Background:

Despite evidence that improved outcomes are associated with more distal lower extremity amputations (LEA), the impact of recent advances in the orthopedic approach to diabetic foot ulcer (DFU) on the use and anatomic level of LEAs is unknown.

Methods:

We queried the complete Medicare Part B claims database (2000-2010) for volume and reimbursement of all codes designating LEAs (hip and below) as well as a selection representing orthopedic treatments for DFU. Procedures were grouped for analysis; utilization rates per 100,000 Medicare enrollees and compound annual growth rates (CAGRs) of payments were calculated. Data are presented in the context of national health care spending trends.

Results:

LEA utilization rates declined from 282.5 to 201.0 per 105 enrollees (−28.8%) over the decade. In general, declines were greatest for the most proximal levels and smallest for the most distal sites. Use of orthopedic treatments for DFUs, including Achilles tendon release and total contact casting, rose from 26.0 to 63.3 per 105 enrollees (+143.3%). Payment trends mirrored utilization data. During this period, total health care spending in the United States increased at a CAGR of 6.5%, whereas total Medicare payments rose at a CAGR of 8.9%.

Conclusion:

The last decade saw a marked decline in the use of LEA in the Medicare population, despite unfavorable demographic changes. Furthermore, it became more likely for LEAs to occur at distal, limb-conserving locations. Over the same period, use of orthopedic treatments for DFU increased sharply.

Level of Evidence:

Level III, retrospective comparative database analysis.
Short-Term Radiographic Analysis of Operative Correction of Adult Acquired Flatfoot Deformity
Authors: Iossi Michael , Johnson Jeffrey E. , McCormick Jeremy J. , Klein Sandra E.
Published: February 2013

Background:

Multiple procedures have been described to treat stage II (flexible) deformities driven by the clinical presence of “mild” versus “severe” deformity. The purpose of this study was to identify the radiographic correction after bony realignment procedures and to compare preoperative measures with postoperative measures to better understand the clinical application of these procedures.

Methods:

Seventy-two feet in 68 patients treated for stage II deformity between January 1999 and December 2010 were available for retrospective chart review. The average age of the patients was 55 years, and final radiographs were evaluated at an average of 9 months postoperatively. All patients had a flexor digitorum longus transfer to the navicular and bony realignment. Radiographic parameters measured included lateral talus-first metatarsal angle, medial cuneiform-floor distance, calcaneal pitch, anteroposterior talus-second metatarsal angle, and talonavicular coverage angle. Differences in pre- and postoperative measurements and between group comparisons were analyzed.

Results:

Three patient groups were identified: medial displacement calcaneal osteotomy (group 1), lateral column lengthening (group 2), and both medial displacement calcaneal osteotomy and lateral column lengthening (group 3). The lateral talus-first metatarsal angle mean difference was 5.1 degrees in group 1, 16.2 degrees in group 2, and 16.5 degrees in group 3. The talonavicular coverage angle mean difference was 5.7 degrees in group 1, 24.2 degrees in group 2, and 19.4 degrees in group 3. Changes in pre- to postoperative measures were statistically significant for all groups for the parameters measured. The pairwise group comparison revealed a statistically significant difference in the correction obtained in group 3 compared with that of group 1.

Conclusion:

Clinical and radiographic parameters are a consideration when choosing bony realignment procedures to reconstruct a flexible flatfoot deformity. In the treatment of more severe deformities, lateral column lengthening resulted in a greater radiographic improvement in alignment. A medial displacement osteotomy alone is also a valuable tool to correct these deformities although it provided a different level of correction compared with the lateral column lengthening.

Level of Evidence:

Level III, comparative case series.
The Inefficiency of Knowledge and the Limits of Explanations; the Necessity of Critique
Authors: Reinertsen Anne Beate , Ryen Anne , Otterstad Ann Merete , Ben-Horin Oded
Published: February 2013

July 22nd 2011 Norway experienced the deadliest terror attack in the country since World War II. One man, Anders Behring Breivik, ABB (33), blew up the Governmental Headquarters in our capital Oslo, killing eight people. Later that day he shot and killed, one by one, 69 youths attending a summer camp at Utøya, and wounded many others. His target was the Norwegian Labour Party, its most prominent and influential members, and those who one day might be. His country is dying he says, because of multiculturalism. He is a commander and knight—future leader and even king. His actions were political, compulsory—necessary. . . he says. He regrets nothing.
Improving Program Results Through the Use of Predictive Operational Performance Indicators
Authors: Barrados Maria , Blain J. S.
Published: February 2013

In Canada, in-depth evaluations of federal programs are intended to occur every 5 years. As such, evaluation is a periodic retrospective (lag) indicator examining results achieved versus program objectives. In a Canadian context, stand-alone evaluations have proved challenging to implement, time consuming, and not well adapted to annual management accountability needs. Consequently, there are important benefits from developing parallel ongoing operational performance measurements, complementing periodic evaluations as an integrated system. With links to program evaluations, ongoing performance feedback can include predictive (lead) indicators of progress, through operational linkages to a program’s intended long-term outcomes. The present case study examines program efficiency concerns demonstrating lead indicators as an “early warning system”—targeting problem areas, producing speedier program adjustments (including accountability and efficiency improvements) and also demonstrating potential to increase quality, timeliness, and usefulness of longer term in-depth evaluations.
‘I wondered does this make me any less of a teacher …?’ Early childhood teachers in Aotearoa New Zealand claimed by and claiming authority within a dominant discourse
Authors: Warren Alison
Published: February 2013

Early childhood teachers in Aotearoa New Zealand negotiate their personal professional identities within the context of a nationally organised and regulated education sector. Early childhood teaching has become increasingly professionalised. Emphasis on qualifications and professional standards has constrained possible ways of being early childhood teachers. This article discusses two newly qualified teachers’ perceptions of claiming and being claimed by authority as they engaged in facilitated self-study. These teachers were participants in a post-structural qualitative collective case study that was a master’s thesis study. They had recently graduated from a field-based initial teacher education course, so they had been practitioners in early childhood settings while student teachers. The dominant authority discourse that emerged from data positioned these teachers as claimed by authority of qualification requirements and hierarchical professional relationships, and as claiming authority as knowledgeable and responsible teachers. I propose that these two participants’ ways of being teachers were constrained by disciplinary discursive practices within the authority discourse. They also actively negotiated their personal professional identities within the authority discourse through seeking pleasure, resistance to positioning and through negotiation of their subjectivities. I suggest that early childhood teachers and teacher educators should critically reflect on how the dominant authority discourse limits possible ways of being teachers in Aotearoa New Zealand, and consider whether this discourse unfairly excludes some people from the teaching profession to the detriment of practitioners, parents and families, and children.
Ruptured Hypogastric Artery Aneurysms
Authors: Morris Marvin E. , Huber Katherine M. , Maijub John G.
Published: February 2013

The ruptured hypogastric artery aneurysm (RHAA) is a rare clinical entity with an evolving and dynamic therapeutic armamentarium. The anatomical location and varied clinical presentation can pose a challenge for successful repair. Recently, endovascular and hybrid operative repairs have significantly improved the historically high-operative mortality rate. We present an illustrative case and contemporary review of the literature with respect to RHAA.
Inpatient Falls
Authors: Cumbler Ethan U. , Simpson Jennifer R. , Rosenthal Laura D. , Likosky David J.
Published: February 2013

In this 2 part series, analysis of the risk stratification tools that are available, definition for the scope of the problem, and potential solutions through a review of the literature are presented. A systematic review was used to identify articles for risk stratification and interventions. Three risk stratification systems are discussed, St Thomas’s Risk Assessment Tool in Falling Elderly Inpatients, Morse Fall Scale, and the Hendrich Fall Risk Model. Of these scoring systems, the Hendrich Fall Risk Model is the easiest to use and score. Predominantly, multifactorial interventions are used to prevent patient falls. Education and rehabilitation are common themes in studies with statistically significant results. The second article presents a guide to implementing a quality improvement project around hospital falls. A 10-step approach to Plan-Do-Study-Act (PDSA) cycles is described. Specific examples of problems and analysis are easily applicable to any institution. Furthermore, the sustainability of interventions and targeting new areas for improvement is discussed. Although specific to falls in the hospitalized patient, the goal is to present a stepwise approach which is broadly applicable to other areas requiring quality improvement.
EGFL7 ligates αvβ3 integrin to enhance vessel formation
Authors: Nikolić Iva , Stanković Nevenka Dudvarski , Bicker Frank , Meister Jeannette , Braun Helene , Awwad Khader , Baumgart Jan , Simon Kirsten , Thal Serge C. , Patra Chinmoy , Harter Patrick N. , Plate Karl H. , Engel Felix B. , Dimmeler Stefanie , Eble Johannes A. , Mittelbronn Michel , Schäfer Michael K. , Jungblut Benno , Chavakis Emmanouil , Fleming Ingrid , Schmidt Mirko H. H.
Published: February 2013

Key Points

EGFL7 promotes angiogenesis via its interaction with integrin αvβ3. EGFL7 is involved in physiological and pathological angiogenesis.
Angiotensin 1-7 and Mas decrease thrombosis in Bdkrb2−/− mice by increasing NO and prostacyclin to reduce platelet spreading and glycoprotein VI activation
Authors: Fang Chao , Stavrou Evi , Schmaier Alec A. , Grobe Nadja , Morris Mariana , Chen Andrew , Nieman Marvin T. , Adams Gregory N. , LaRusch Gretchen , Zhou Yihua , Bilodeau Matthew L. , Mahdi Fakhri , Warnock Mark , Schmaier Alvin H.
Published: February 2013

Key Points

In Bdkrb2−/− mice, compensatory Mas and AT2R overexpression elevates NO and PGI2 to prolong bleeding times and delay arterial thrombosis. This NO and PGI2 elevation attenuates platelet integrin-dependent spreading and GPVI responses without altering thrombin or ADP activation.
Budesonide suppresses pulmonary antibacterial host defense by down-regulating cathelicidin-related antimicrobial peptide in allergic inflammation mice and in lung epithelial cells
Authors: Wang Peng , Wang Xiaoyun , Yang Xiaoqiong , Liu Zhigang , Wu Min , Li Guoping
Published: February 2013

Background

Glucocorticoids are widely regarded as the most effective treatment for asthma. However, the direct impact of glucocorticoids on the innate immune system and antibacterial host defense during asthma remain unclear. Understanding the mechanisms underlying this process is critical to the clinical application of glucocorticoids for asthma therapy. After sensitization and challenge with ovalbumin (OVA), BALB/c mice were treated with inhaled budesonide and infected with Pseudomonas aeruginosa (P. aeruginosa). The number of viable bacteria in enflamed lungs was evaluated, and levels of interleukin-4 (IL-4) and interferon-γ (IFN-γ) in serum were measured. A lung epithelial cell line was pretreated with budesonide. Levels of cathelicidin-related antimicrobial peptide (CRAMP) were measured by immunohistochemistry and western blot analysis. Intracellular bacteria were observed in lung epithelial cells.

Results

Inhaled budesonide enhanced lung infection in allergic mice exposed to P. aeruginosa and increased the number of viable bacteria in lung tissue. Higher levels of IL-4 and lower levels of IFN-γ were observed in the serum. Budesonide decreased the expression of CRAMP, increased the number of internalized P. aeruginosa in OVA-challenged mice and in lung epithelial cell lines. These data indicate that inhaled budesonide can suppress pulmonary antibacterial host defense by down-regulating CRAMP in allergic inflammation mice and in cells in vitro.

Conclusions

Inhaled budesonide suppressed pulmonary antibacterial host defense in an asthmatic mouse model and in lung epithelium cells in vitro. This effect was dependent on the down-regulation of CRAMP.
Studying the penetration of fatty acids into human skin by ex vivo TOF-SIMS imaging
Authors: Kezutyte Toma , Desbenoit Nicolas , Brunelle Alain , Briedis Vitalis
Published: February 2013

Fatty acids classified as chemical penetration enhancers (CPEs) might cause the fluidization and perturbation of stratum corneum (SC) lipid matrix. The penetration of oleic, linoleic, lauric and capric acids into human skin was studied by time-of-flight secondary ion mass spectrometry (TOF-SIMS) imaging and related to fatty acids enhancing effect on lipophilic model drug tolnaftate penetration into human epidermis and dermis ex vivo. Fatty acid enhancing effect on tolnaftate penetration into human skin was evaluated using Bronaugh-type flow-through diffusion cells. After in vitro penetration studies visualization and spatial localization of fatty acid molecules in human skin were performed using TOF-SIMS. Penetration of oleic, linoleic, lauric and capric acids into human skin was compared to the control skin sections by ion images and intensity profiles. Only oleic acid significantly (P<0.05) enhanced tolnaftate penetration into epidermis (enhancing ratio equal to 1.867). CPE might have no effect on model drug penetration enhancement, but might penetrate itself into the skin.
Common fixed point theorems for two hybrid pairs of mappings satisfying the common property (E.A) in Menger PM-spaces
Authors: Wu Zhaoqi , Zhu Chuanxi , Li Jin
Published: February 2013

In this paper, a new concept of the common property (E.A) for two hybrid pairs of mappings is introduced in Menger PM-spaces. Utilizing this concept, some common fixed point theorems, which shed some new light on the study of fixed point results for hybrid pairs in Menger PM-spaces, are obtained under strict contractive conditions. The corresponding results in metric spaces which generalize many known results are also obtained. Finally, an example is also given to exemplify our main results.
New oscillation results for second-order neutral delay dynamic equations
Authors: Zhang Chenghui , Agarwal Ravi P , Bohner Martin , Li Tongxing
Published: February 2013

This paper is concerned with oscillatory behavior of a certain class of second-order neutral delay dynamic equations

(
r
(
t
)

[
x
(
t
)
+
p
(
t
)
x

(
τ
(
t
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)

]

Δ

)

Δ

+
q
(
t
)
x

(
δ
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)

=
0
,

on a time scale

T

with

sup
T
=
∞

, where

0
≤
p
(
t
)
≤

p
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<
∞

. Some new results are presented that not only complement and improve those related results in the literature, but also improve some known results for a second-order delay dynamic equation without a neutral term. Further, the main results improve some related results for second-order neutral differential equations.

MSC:34K11, 34N05, 39A10.
Potency of a vaccine prepared from A/swine/Hokkaido/2/1981 (H1N1) against A/Narita/1/2009 (H1N1) pandemic influenza virus strain
Authors: Okamatsu Masatoshi , Sakoda Yoshihiro , Hiono Takahiro , Yamamoto Naoki , Kida Hiroshi
Published: February 2013

Background

The pandemic 2009 (H1N1) influenza virus has spread throughout the world and is now causing seasonal influenza. To prepare for the emergence of pandemic influenza, we have established a library of virus strains isolated from birds, pigs, and humans in global surveillance studies.

Methods

Inactivated whole virus particle (WV) and ether-split (ES) vaccines were prepared from an influenza virus strain, A/swine/Hokkaido/2/1981 (H1N1), from the library and from A/Narita/1/2009 (H1N1) pandemic strain. Each of the vaccines was injected subcutaneously into mice and their potencies were evaluated by challenge with A/Narita/1/2009 (H1N1) virus strain in mice.

Results

A/swine/Hokkaido/2/81 (H1N1), which was isolated from the lung of a diseased piglet, was selected on the basis of their antigenicity and growth capacity in embryonated chicken eggs. Two injections of the WV vaccine induced an immune response in mice, decreasing the impact of disease caused by the challenge with A/Narita/1/2009 (H1N1), as did the vaccine prepared from the homologous strain.

Conclusion

The WV vaccine prepared from an influenza virus in the library is useful as an emergency vaccine in the early phase of pandemic influenza.
A retrospective analysis of pegylated liposomal doxorubicin in ovarian cancer: do we still need it?
Authors: Staropoli Nicoletta , Ciliberto Domenico , Botta Cirino , Fiorillo Lucia , Gualtieri Simona , Salvino Angela , Tassone Pierfrancesco , Tagliaferri Pierosandro
Published: February 2013

Background

Ovarian cancer (OC) is the sixth most common cancer in women. Currently, carboplatin/paclitaxel ± bevacizumab is the cornerstone of front-line treatment. Conversely, the therapeutic options for recurrent or progressive disease are not well defined. For platinum-sensitive patients the best therapeutic approach is still a re-challenge with a platinum-based regimen. Pegylated liposomal doxorubicin (PLD), is considered one of the most active therapeutic options for recurrent or progressive OC. In this retrospective mono-institutional analysis, we evaluated the impact of PLD on the outcome of OC patients.

Patients and methods

We performed the retrospective study on a cohort of 108 patients with histologically confirmed serous papillary OC, followed at our Institution between 2001 and 2011. 80 patients were in stage III/IV and 55 of them received a second-line treatment. Thirty patients were treated with PLD. Both groups (PLD-treated versus PLD-untreated) underwent a median of 3 treatment lines and were prognostically balanced. The median follow-up was 60 months. Survival endpoints, toxicity and correlations between patients’ baseline characteristics and treatment efficacy were evaluated.

Results

Patients who had undergone PLD treatment (PLD group) showed a median overall survival (OS) of 45 months as compared to 65 months of patients not treated with PLD (PLD-free group) (HR 2.50 [0.95-6.67; p = 0.06]). Moreover, the median progression-free survival was 6 months in the PLD group versus 10 months in the PLD-free group (HR 1.75 [0.94-3.34; p = 0.07]). The overall objective response rate in II line treatment was 43% (13% in PLD group versus 57% in PLD-free group). Furthermore, we investigated survival endpoints in platinum-refractory patients who received PLD at least once during the course of disease. No OS advantage was achieved by PLD administration when compared to other therapeutic options (30 versus 32 months; HR 1.16 [0.31-4.34; p = 0.81]). No difference in term of toxicity was observed among different groups.

Conclusions

No evidence of superiority if PLD was compared to alternative agents was found in this analysis, particularly in the platinum-refractory setting. Our findings indicate a modest therapeutic activity of PLD in OC. Analysis of cost/benefit of PLD in OC is eagerly awaited.
The regulation of cellular metabolism by tumor suppressor p53
Authors: Liang Yingjian , Liu Juan , Feng Zhaohui
Published: February 2013

As a hallmark of tumor cells, metabolic alterations play a critical role in tumor development and could be targeted for tumor therapy. Tumor suppressor p53 plays a central role in tumor prevention. As a transcription factor, p53 mainly exerts its function in tumor suppression through its transcriptional regulation of its target genes to initiate various cellular responses. Cell cycle arrest, apoptosis and senescence are most well-understood functions of p53, and are traditionally accepted as the major mechanisms for p53 in tumor suppression. Recent studies have revealed a novel function of p53 in regulation of cellular metabolism. p53 regulates mitochondrial oxidative phosphorylation, glycolysis, glutamine metabolism, lipid metabolism, and antioxidant defense. Through the regulation of these metabolic processes, p53 maintains the homeostasis of cellular metabolism and redox balance in cells, which contributes significantly to the role of p53 as a tumor suppressor. Further understanding of the role and molecular mechanism of p53 in cellular metabolism could lead to the identification of novel targets and development of novel strategies for tumor therapy.
Glucocorticoid-Induced Suppression of β-Cell Proliferation Is Mediated by Mig6
Authors: Colvin E. Scott , Ma Hong-Yun , Chen Yi-Chun , Hernandez Angelina M. , Fueger Patrick T.
Published: February 2013

Glucocorticoids can cause steroid-induced diabetes or accelerate the progression to diabetes by creating systemic insulin resistance and decreasing functional β-cell mass, which is influenced by changes in β-cell function, growth, and death. The synthetic glucocorticoid agonist dexamethasone (Dex) is deleterious to functional β-cell mass by decreasing β-cell function, survival, and proliferation. However, the mechanism by which Dex decreases β-cell proliferation is unknown. Interestingly, Dex induces the transcription of an antiproliferative factor and negative regulator of epidermal growth factor receptor signaling, Mig6 (also known as gene 33, RALT, and Errfi1). We, therefore, hypothesized that Dex impairs β-cell proliferation by increasing the expression of Mig6 and thereby decreasing downstream signaling of epidermal growth factor receptor. We found that Dex induced Mig6 and decreased [3H]thymidine incorporation, an index of cellular replication, in mouse, rat, and human islets. Using adenovirally delivered small interfering RNA targeted to Mig6 in rat islets, we were able to limit the induction of Mig6 upon exposure to Dex, compared with islets treated with a control virus, and completely rescued the Dex-mediated impairment in replication. We demonstrated that both Dex and overexpression of Mig6 attenuated the phosphorylation of ERK1/2 and blocked the G1/S transition of the cell cycle. In conclusion, Mig6 functions as a molecular brake for β-cell proliferation during glucocorticoid treatment in β-cells, and thus, Mig6 may be a novel target for preventing glucocorticoid-induced impairments in functional β-cell mass.
New Insights into the Anti-inflammatory Mechanisms of Glucocorticoids: An Emerging Role for Glucocorticoid-Receptor-Mediated Transactivation
Authors: Vandevyver Sofie , Dejager Lien , Tuckermann Jan , Libert Claude
Published: February 2013

Glucocorticoids are anti-inflammatory drugs that are widely used for the treatment of numerous (autoimmune) inflammatory diseases. They exert their actions by binding to the glucocorticoid receptor (GR), a member of the nuclear receptor family of transcription factors. Upon ligand binding, the GR translocates to the nucleus, where it acts either as a homodimeric transcription factor that binds glucocorticoid response elements (GREs) in promoter regions of glucocorticoid (GC)-inducible genes, or as a monomeric protein that cooperates with other transcription factors to affect transcription. For decades, it has generally been believed that the undesirable side effects of GC therapy are induced by dimer-mediated transactivation, whereas its beneficial anti-inflammatory effects are mainly due to the monomer-mediated transrepressive actions of GR. Therefore, current research is focused on the development of dissociated compounds that exert only the GR monomer-dependent actions. However, many recent reports undermine this dogma by clearly showing that GR dimer-dependent transactivation is essential in the anti-inflammatory activities of GR. Many of these studies used GRdim/dim mutant mice, which show reduced GR dimerization and hence cannot control inflammation in several disease models. Here, we review the importance of GR dimers in the anti-inflammatory actions of GCs/GR, and hence we question the central dogma. We summarize the contribution of various GR dimer-inducible anti-inflammatory genes and question the use of selective GR agonists as therapeutic agents.
Weight Restrictions and Free Production in Data Envelopment Analysis
Authors: Podinovski Victor V. , Bouzdine-Chameeva Tatiana
Published: February 2013

It is known that the incorporation of weight restrictions in models of data envelopment analysis may result in their infeasibility. In our paper we investigate this effect in detail. We show that the infeasibility is only one of several possible outcomes that point to a particular problem with weight restrictions. For example, the use of weight restrictions may also lead to zero or negative efficiency scores of some units. Removing problematic units from the data set does not necessarily remove the underlying problem caused by the weight restrictions and only makes it undetected. We prove that all such problems arise when weight restrictions induce free or unlimited production of outputs in the underlying technology. This is unacceptable from the production theory point of view and indicates that the weight restrictions need reassessing. We develop analytical criteria and computational methods that allow us to identify the above problematic situations.
Technical Note—Managing a Secret Project
Authors: Pinker Edieal , Szmerekovsky Joseph , Tilson Vera
Published: February 2013

We study project scheduling in a competitive setting taking the perspective of a project manager with an adversary, using a Stackelberg game format. The project manager seeks to limit the adversary's opportunity to react to the project and therefore wants to manage the project in a way that keeps the adversary “in the dark” as long as possible while completing the project on time. We formulate and illustrate a new form of project management problem for secret projects where the project manager uses a combination of deception, task scheduling, and crashing to minimize the time between when the adversary initiates a response to the project to when the project is completed. We propose a novel mixed-integer linear programming formulation for the problem and determine characteristics of optimal schedules in this context. Using a detailed example of nuclear weapons development, we illustrate the interconnectedness of the deception, task scheduling, and crashing, and how these influence adversary behavior.
The Robust Capacitated Vehicle Routing Problem Under Demand Uncertainty
Authors: Gounaris Chrysanthos E. , Wiesemann Wolfram , Floudas Christodoulos A.
Published: February 2013

The robust capacitated vehicle routing problem (CVRP) under demand uncertainty is studied to address the minimum cost delivery of a product to geographically dispersed customers using capacity-constrained vehicles. Contrary to the deterministic CVRP, which postulates that the customer demands for the product are deterministic and known, the robust CVRP models the customer demands as random variables, and it determines a minimum cost delivery plan that is feasible for all anticipated demand realizations. Robust optimization counterparts of several deterministic CVRP formulations are derived and compared numerically. Robust rounded capacity inequalities are developed, and it is shown how they can be separated efficiently for two broad classes of demand supports. Finally, it is analyzed how the robust CVRP relates to the chance-constrained CVRP, which allows a controlled degree of supply shortfall to decrease delivery costs.
Aspirin/Clopidogrel-Induced Spontaneous Liver Hematoma; Adenosine-Induced Severe Bronchospasm in a Patient without Pulmonary Disease; Paclitaxel-Induced Acral Erythema; Acute Laryngeal Dystonia Associated with Aripiprazole; Incidence of Thrombocytopenia during Heparin Prophylaxis; Oral Fluoroquinolones and the Risk of Retinal Detachment; Prenatal Exposure to Antidepressants: How Safe Are They? Proton Pump Inhibitors: The Good, the Bad, and the Unwanted
Authors: Shuster Joel
Published: February 2013

The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA's) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers.
Enzalutamide and Ruxolitinib
Authors: Hobson Susan A. , Waddell J. Aubrey , Solimando Dominic A.
Published: February 2013

The complexity of cancer chemotherapy requires pharmacists be familiar with the complicated regimens and highly toxic agents used. This column reviews various issues related to preparation, dispensing, and administration of antineoplastic therapy, and the agents, both commercially available and investigational, used to treat malignant diseases.
Consider Creating a Channel Management Strategy with Both Colleagues and Patients
Authors: Felkey Bill G. , Fox Brent I.
Published: February 2013

Patient engagement is poised to provide considerable opportunities for reaching patients. The range of connectivity options should be considered to include the best option for each specific patient. In this article, we address this area of growing importance, telecommunication channel management.
Antipsychotic Prescribing Patterns, and the Factors and Outcomes Associated with Their Use, among Patients Requiring Prolonged Mechanical Ventilation in the Long-Term Acute Care Hospital Setting
Authors: Al-Qadheeb Nada S , O'Connor Heidi H , White Alexander C , Neidhardt Aura , Albizati Mark , Joseph Bernard , Roberts Russel J , Ruthazer Robin R , Devlin John W
Published: February 2013

BACKGROUND:

Administration of scheduled antipsychotic therapy to mechanically ventilated patients to prevent or treat delirium is common, despite the lack of evidence to support its use. Among long-term acute care hospital (LTACH) patients requiring prolonged mechanical ventilation (PMV), the frequency of scheduled antipsychotic therapy use, and the factors and outcomes associated with it, have not been described.

OBJECTIVE:

To identify scheduled antipsychotic therapy prescribing practices, and the factors and outcomes associated with the use of antipsychotics, among LTACH patients requiring PMV.

METHODS:

Consecutive patients without major psychiatric disorders or dementia who were admitted to an LTACH for PMV over 1 year were categorized as those receiving scheduled antipsychotic therapy (≥24 hours of use) and those not receiving scheduled antipsychotic therapy. Presence of delirium, use of psychiatric evaluation, nonscheduled antipsychotic therapy, and scheduled antipsychotic therapy—related adverse effects were extracted and compared between the 2 groups and when significant (p ≤ 0.05), were entered into a regression analysis using generalized estimating equation techniques.

RESULTS:

Among 80 patients included, 39% (31) received scheduled antipsychotic therapy and 61% (49) did not. Baseline characteristics, including age, sex, illness severity, and medical history, were similar between the 2 groups. Scheduled antipsychotic therapy was administered on 52% of LTACH days for a median (interquartile range [IQR]) of 25 (6–38) days and, in the antipsychotic group, was initiated at an outside hospital (45%) or on day 2 (1–6; median [IQR]) of the LTACH stay (55%). Quetiapine was the most frequently administered scheduled antipsychotic (77%; median dose 50 [37–72] mg/day). Use of scheduled antipsychotic therapy was associated with a greater incidence of psychiatric evaluation (OR 5.7; p = 0.01), delirium (OR 2.4; p = 0.05), as-needed antipsychotic use (OR 4.1; p = 0.005) and 1:1 sitter use (OR 7.3; p = 0.001), but not benzodiazepine use (p = 0.19).

CONCLUSIONS:

Among LTACH patients requiring PMV, scheduled antipsychotic therapy is used frequently and is associated with a greater incidence of psychiatric evaluation, delirium, as-needed psychotic use, and sitter use. Although scheduled antipsychotic therapy—related adverse effects are uncommon, these effects are infrequently monitored.
Role of Phosphodiesterase Type 5 Inhibitors for Lower Urinary Tract Symptoms
Authors: Miller Mindi S
Published: February 2013

OBJECTIVE:

To determine the efficacy of phosphodiesterase inhibitors for the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia (BPH).

DATA SOURCES:

MEDLINE and PubMed were searched from January 1, 2000, to October 31, 2012, using the MeSH terms phosphodiesterase inhibitor, lower urinary tract symptoms, benign prostatic hyperplasia, sildenafil, vardenafil, and tadalafil. Additional articles were obtained from references identified in the original search.

STUDY SELECTION AND DATA EXTRACTION:

English-language randomized controlled trials and review articles were evaluated.

DATA SYNTHESIS:

Men with BPH commonly experience lower urinary tract symptoms (LUTS) such as urgency, frequency, nocturia, and dribbling. α-Adrenergic antagonists have been the mainstay of medical treatment of LUTS but are associated with adverse effects such as orthostatic hypotension, dizziness, and sexual dysfunction. The 5-α reductase inhibitors are associated with sexual dysfunction, and treatment effects may be delayed for 6–12 months. Phosphodiesterase type 5 (PDE-5) inhibitors are effective for the treatment of erectile dysfunction (ED), and large-scale epidemiologic studies suggest a strong link between LUTS and ED. The available PDE-5 inhibitors (sildenafil, tadalafil, and vardenafil) have shown efficacy in the treatment of LUTS in several randomized controlled trials in men with and without concomitant ED.

CONCLUSIONS:

PDE-5 inhibitors consistently reduce LUTS associated with BPH. These medications may offer advantages over conventional therapies such as rapid onset of action, fewer adverse effects, and enhanced sexual function. Quality of life improvements have also been realized in men with BPH who receive PDE-5 inhibitors.
Distinct Claudin Expression Profiles of Hepatocellular Carcinoma and Metastatic Colorectal and Pancreatic Carcinomas
Authors: Holczbauer Ágnes , Gyöngyösi Benedek , Lotz Gábor , Szijártó Attila , Kupcsulik Péter , Schaff Zsuzsa , Kiss András
Published: February 2013

Tight junction proteins, including claudins, are often dysregulated during carcinogenesis and tumor progression. Moreover, the claudin expression pattern usually varies between different tumor entities. We aimed to investigate claudin expression profiles of primary and metastatic liver malignancies. We analyzed claudin-1, -2, -3, -4, and -7 expression by quantitative immunohistochemistry and real-time RT-PCR, respectively. Twenty hepatocellular carcinomas (HCCs) and liver metastases of 20 colorectal adenocarcinomas (CRLMs) and 15 pancreatic adenocarcinomas (PLMs) were studied together with paired surrounding non-tumorous liver samples and 5 normal liver samples. Strong claudin-3 and -7 immunohistochemical positivities were detected in CRLM samples, each with significantly stronger staining when compared with HCC and PLM groups. Claudin-1 protein was found highly expressed in CRLM, in contrast to lower expression in PLM and HCC. CRLMs and PLMs also were strongly positive for claudin-4, while being virtually undetectable in HCC. Claudin-2 showed strong positivity in non-tumorous liver tissue, whereas significantly weaker positivity was observed in all tumors. Differences in mRNA expression were mostly similar to those found by immunohistochemistry. In conclusion, HCC and both CRLM and PLM display distinct claudin expression profiles, which might provide better understanding of the pathobiology of these lesions and might be used for differential diagnosis.
Increased use of antimicrobial agents and hospital admission for infections in patients with primary adrenal insufficiency: a cohort study
Authors: Smans Lisanne C C J , Souverein Patrick C , Leufkens Hubert G M , Hoepelman Andy I M , Zelissen Pierre M J
Published: February 2013

Background

Previous studies have suggested that infections are an important cause of death in patients with Addison's disease, but epidemiological studies on the frequency of infections in this population are lacking.

Objective

To assess and compare the incidence risk of infections in patients with primary adrenal insufficiency with controls.

Design and setting

We conducted a cohort study, using data from the Dutch PHARMO record linkage system, that links patients' demographics and medication histories to hospital admissions.

Patients

From a cohort of oral glucocorticoid users, 390 patients with primary adrenal insufficiency were identified by assessing concurrent use of glucocorticoids and mineralocorticoids using pharmacy dispensing records. A reference cohort (n=1933) with the same age and sex distribution was sampled from patients not using glucocorticoids.

Outcome measure

Incidence rates and incidence rate ratios (IRR) were calculated of infections, defined by use of antimicrobial agents, as well as hospital admissions for infection.

Results

The incidence of infectious episodes, defined by usage of antimicrobial agents, among patients with primary adrenal insufficiency (incidence rate 59.2/100 person-years) was 1.5 times higher compared with controls, yielding a crude IRR of 1.61 (95% CI 1.51–1.72). The IRR decreased slightly to 1.58 (95% CI 1.47–1.70) after adjustment for co-medication and co-morbidity also associated with infection risk. Also with respect to hospital admissions for infection, the incidence rates observed for patients with primary adrenal insufficiency was higher compared with controls (3.8/100 vs 0.8/100 person-years): crude IRR 5.02 (3.66–6.87) and adjusted IRR 4.34 (95% CI 3.04–6.22).

Conclusion

Patients with primary adrenal insufficiency had an increased use of antimicrobial agents and hospital admissions related to infection.
Effect of Substrate Elasticity onIn VitroAging of Human Mesenchymal Stem Cells
Authors: LeBlon Courtney E. , Fodor Caitlin R. , Zhang Tony , Zhang Xiaohui , Jedlicka Sabrina S.
Published: February 2013

Human mesenchymal stem cells (hMSCs) were routinely cultured on tissue-culture polystyrene (TCPS) to investigate thein vitroaging and cell stiffening. hMSCs were also cultured on thermoplastic polyurethane (TPU), which is a biocompatible polymer with an elastic modulus of approximately 12.9MPa, to investigate the impact of substrate elastic modulus on cell stiffening and differentiation potential. Cells were passaged over several generations on each material. At each passage, cells were subjected to osteogenic and myogenic differentiation. Local cell elastic modulus was measured at every passage using atomic force microscopy (AFM) indentation. Gene and protein expression was examined using qRT-PCR and immunofluorescent staining, respectively, for osteogenic and myogenic markers. Results show that the success of myogenic differentiation is highly reliant on the elastic modulus of the undifferentiated cells. The success of osteogenic differentiations is most likely somewhat dependent on the cell elastic modulus, as differentiations were more successful in earlier passages, when cells were softer.
The Role of Disorder and the Elastic Robustness of Bulk Metallic Glasses
Authors: Derlet P. M. , Maaß R.
Published: February 2013

Despite significant atomic-scale heterogeneity, bulk metallic glasses well below their glass transition temperature exhibit a surprisingly robust elastic regime and a sharp elastic-to-plastic transition with a yield stress that depends approximately linearly on temperature. The present work attempts to understand these features within the framework of thermally activated plasticity. The presented statistical thermal activation model, in which the number of available structural transformations scales exponentially with system size, results in two distinct temperature regimes of deformation. At temperatures close to the glass transition temperature thermally activated Newtonian plastic flow emerges, whilst at lower temperatures the deformation properties fundamentally change due to the eventual kinetic freezing of the available structural transformations. In this regime, a linear temperature dependence emerges for the stress which characterises the elastic to plastic transition. For both regimes the transition to macroscopic plastic flow corresponds to a transition from a barrier energy dominated to a barrier entropy dominated statistics. The work concludes by discussing the possible influence that kinetic freezing might have on the low temperature heterogeneous and high temperature homogeneous plasticity of bulk metallic glasses.
Transmission Fourier Transform Infra-red Spectroscopy Investigation of Structure Property Relationships in Low-k SiOxCy:H Dielectric Thin Films
Authors: King Sean W. , Mays Ebony , Ege Canay , Hellgren Niklas , Xu Jessica , Li Han , Boyanov Boyan
Published: February 2013

In order to understand the structure property relationships for inorganic low dielectric constant (i.e. low-k) materials, transmission Fourier Transform-Infrared (FTIR) spectroscopy has been utilized to study the local bonding structure in various plasma enhanced chemically vapor deposited low-k materials in the SiOxCy:H phase diagram. The FTIR measurements were combined with additional mechanical, electrical, and optical property measurements to elucidate the structure property relationships for these materials. The combined measurements show that increased incorporation of terminal methyl bonding results in a decrease in network bonding that manifests itself in a reduction in mass density, dielectric constant, refractive index, Young’s modulus and many other important material properties.
Synthesis and Characterization of Cu-doped ZnO Film in Nanowire like Morphology Using Low Temperature Self-Catalytic Vapor-Liquid-Solid (VLS) Method
Authors: Thankalekshmi Ratheesh R. , Dixit Samwad , Bae In-Tae , VanHart Daniel , Rastogi A.C.
Published: February 2013

Cu-doped ZnO film in nanowire structure is synthesized by a closed space flux sublimation and periodic oxidation method at ∼300°C over Si substrate. Oxidative process controlled selfcatalytic VLS mechanism is proposed for the film growth. X-ray diffraction pattern establishes that Cu-doped ZnO nanowires retain the crystallite structure of the wurtzite ZnO. TEM studies indicate single crystal character of the Cu-doped ZnO nanowires. Optical absorption analysis of Cu-doped ZnO nanowires defines two direct energy band gaps. The low energy band gap at 3.2eV is intrinsic to the Cu-doped ZnO material. The higher energy band gap at 3.5eV is attributed to the nanosize, mediated by strong forward scattering of light from the nanowires. Sharp photoluminescence in Cu-doped ZnO corresponding to near bandgap free exciton emission is observed and a redshift of ∼0.07 eV is consistent with the effect of Cu-doping. The visible emission band in both ZnO and Cu-doped ZnO shows a broad green emission band with Cu-substitution shifting the maximum visible luminescence towards the higher energy side.