bluuebunny/crossref_metadata_2025 huggingface dataset:
Abdominal neoplasia with sarcomatoid features as the presenting illness of a patient with a newly diagnosed HIV infection and no AIDS-related disorders. Case report, clinical and diagnostic features, and literature discussion
Authors: Manfredi Roberto , Sabbatani Sergio , Magistrelli Eleonora , Tardio Maria Lucia
Published: December 2014

We aim to describe a patient with an already advanced HIV infection disclosed for the first time during a complex diagnostic workup, which detected a gross abdominal mass attributable to a poorly differentiated mesenchymal cancer with sarcomatoid features which rapidly led our patient to death, in absence of other potential HIV-associated opportunistic diseases. Although extremely rare and rapidly lethal, our case report underscores the need of all caregivers who follow HIV-infected patients also in the cART era to maintain an elevated attention toward infrequent, unexpected, and clinically atypical solid tumors, in order to ensure a timely diagnosis and management when possible.
Teaching patients how to effectively solve medication-related problems in an acute inpatient psychiatric setting
Authors: Goldstone Lisa W. , Davis Erica , Norman Sarah , Warholak Terri L.
Published: December 2014

Patients with psychiatric disorders have high rates of medication nonadherence. Though there are many factors that contribute to medication nonadherence, lack of patient understanding about how to manage medication-related problems when they occur is associated with medication discontinuation. This article describes the importance of teaching patients to solve medication-related problems and discusses the scientific evaluation of such a practice.
Adherence through education: A call to clinicians to educate all patients on medication use
Authors: Allison Kristen
Published: December 2014

Medication nonadherence contributes to lack of achievement of desired therapeutic outcomes. This article reviews the evidence supporting patient education as a one of the tools to promote medication adherence. Patient education and provision of tools to help patients overcome adherence barriers are effective ways to improve medication adherence.
Clinical pearls for chronic use of antiepileptic drugs
Authors: Eudy Anne E. , Bainbridge Jacquelyn L.
Published: December 2014

Patients with various forms of epilepsy rely on antiepileptic medications to control and prevent seizures. This article describes some of the “clinical pearls” that should be considered when initiating, combining, or transitioning patients on epileptic medication therapy.
Citalopram-induced QTc prolongation: A brief review of the data
Authors: Tran Eric , Dishman Benjamin
Published: December 2014

Recently, Forest Laboratories warned about QTc prolongation associated with the use of citalopram. After these reports, the FDA warned that citalopram should no longer be used at doses greater than 40 mg/day for patients ≤ 60 years of age or greater than 20 mg/day in patients over 60 years of age. As a result, providers and formulary managers were advised to reevaluate the use of citalopram to conform to current FDA guidelines. Clinicians have the option to: (1) maintain the patient on the current dose (no change), document that the current EKG (with QTc) is within a normal range and inform the patient of the current recommendations or (2) change the therapy, which consists of either a dose reduction or change to an alternate agent. It may be appropriate to keep a patient on current therapy above the FDA recommended maximum if proper documentation is maintained (e.g., past history of severe depression, normal EKG). Citalopram should be discontinued in patients who have persistent QTc measurements greater than 500 ms.
The role of prepulse inhibition in medication management of PTSD: A case report
Authors: Gray Emily N. , Shuman Michael D. , McGrane Ian R.
Published: December 2014

Post traumatic stress disorder (PTSD) is defined as an anxiety disorder that can appear after exposure to a traumatic experience. This article will review a patient's history of PTSD, and course of treatment. A discussion on the available agents to properly treat this case will also be discussed.
The impact of technology on medication adherence
Authors: Heesch Chelsie
Published: December 2014

Medication nonadherence is a large contributor to inadequate therapeutic outcomes, especially among patients with mental illness and carries a high cost. Intervention strategies to increase adherence have incorporated technological advances, including electronic symptom monitoring and communication systems for patients and providers. This article presents a review of several studies demonstrating how technology may affect medication adherence.
Clinical implications and management of drug-drug interactions between antiretroviral agents and psychotropic medications
Authors: Jernigan Meredith G. , Kipp Gretchen M. , Rather Ashley , Jenkins Matthew T. , Chung Allison M.
Published: December 2014

Medications used in the treatment of human immunodeficiency virus (HIV) often have drug-drug interactions which complicate treatment of psychiatric illnesses in HIV-infected patients. Protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) are the two classes of HIV medications most likely to be involved with interactions, with the majority occurring via the cytochrome P450 (CYP450) system. These interactions can result in either increased or decreased exposure to psychotropic and antiretroviral medications, often requiring dosage adjustments and increased monitoring. This article reviews some of the major drug interactions with antiretroviral agents.
Advanced practice pharmacy experiences (APPE) in psychiatric pharmacy
Authors: Ott Carol A.
Published: December 2014

Advanced practice pharmacy experiences (APPEs) are the foundations upon which pharmacy students develop the skills to apply the knowledge gained from their didactic courses. This article describes the APPEs in psychiatric pharmacy that are offered at the Purdue University College of Pharmacy.
The use of second generation antipsychotics in children and adolescents with bipolar disorder and schizophrenia: A summary of the AHRQ comparative effectiveness review
Authors: Pulsipher Jeani , Levin Gary M.
Published: December 2014

Second generation antipsychotics (SGAs) can be effective in treating mood disorders in pediatric patients; however, these medications also present with a risk of serious adverse effects. A recent review by the Agency for Healthcare Research and Quality (AHRQ) evaluated the use of SGAs in pediatric patients. This article summarizes the findings of the review, with a focus on bipolar disorder and schizophrenia.
Causes of death and comparative mortality in Texas public mental health clients, 2006–2008
Authors: Reynolds Robert J. , Becker Emilie A. , Shafer Alan B.
Published: December 2014

Seriously mentally ill patients are known to have rates of mortality much greater than those of the general population. Prior research in Texas has shown inpatient Public Mental Health Clients (PMHCs) treated in in-patient settings were subject to greatly increased mortality, but little is known about the mortality of PMHCs in an outpatient setting in Texas.

For this study outpatient service records for PMHCs treated in Texas were combined with death data from the Texas Department of State Health Services for 2006–2008. Frequencies of causes of death, age-adjusted death rates, standardized mortality ratios, and life expectancies were calculated from these data.

The most frequent causes of death were external causes, followed by circulatory disease, and then neoplasms. Examination of the outcomes suggests that substance abuse plays a major role in the mortality of PMHCs in Texas in the form of drug overdoses, tobacco-related cancers, and alcoholic liver disease. Prevention efforts should therefore aim at integrating mental health services, substance abuse services, and careful medical and pharmacological monitoring, including medication monitoring to prevent suicides and accidental overdoses.
Buprenorphine for opioid dependence
Authors: Berger Reisel
Published: December 2014

Opioid use disorder is a growing problem in the United States that can have devastating consequences on affected individuals. Buprenorphine is a partial mu-opioid agonist that can be used in the treatment of opioid dependence. In this article, the pharmacology of buprenorphine is discussed as is the dosing strategy. Formulations and product availability are mentioned and assessed. Several studies comparing the use of buprenorphine to methadone for opioid dependence are briefly reviewed.
Clinical psychiatric pharmacist involvement in an outpatient buprenorphine program
Authors: Grgas Marina
Published: December 2014

Background: Approximately nineteen million individuals in the United States are diagnosed with a substance use disorder (SUD), including many veterans enrolled in the Veterans Health Administration (VHA). The prevalence of SUD within the veteran population has been steadily increasing, resulting in increased utilization of substance abuse services, such as buprenorphine programs for opioid dependence. As this population grows, there is an increased need for multidisciplinary services. Clinical psychiatric pharmacists do not have prescriptive authority for buprenorphine, but can play a vital role in outpatient buprenorphine programs.

Description of Innovative Service: The clinical psychiatric pharmacist is involved in many aspects of the outpatient buprenorphine program. There are over 100 patients enrolled in the buprenorphine program at the White River Junction Veterans Affairs Medical Center (WRJVAMC). The clinical pharmacist devotes approximately ten hours per week to the program, which includes dispensing the medication, monitoring lab values, patient counseling and random medication counts. A spreadsheet is maintained and updated weekly to monitor doses, refill dates and urine toxicology results. The clinical pharmacist is also involved in the dispensing process in the outpatient pharmacy; this allows for open communication between the clinical pharmacist and patient.

Impact on Patient Care: The clinical psychiatric pharmacist has been involved in the outpatient buprenorphine program at the WRJVAMC for approximately two years. Prior to this, the program included less than 100 patients, pharmacy wait times were over sixty minutes and early refills were frequent. Since clinical pharmacy involvement, the pharmacy wait time is approximately 30 minutes or less and early refills are infrequent. Patient satisfaction has also significantly improved. The clinical pharmacist has helped open the lines of communication between the patient, the pharmacy and the prescriber.

Conclusion: Substance use disorder programs, such as buprenorphine programs, can benefit from clinical pharmacy involvement. Even with limited prescriptive authority, clinical psychiatric pharmacists can play an important and active role in outpatient buprenorphine programs.
Knowledge, attitudes, and professional practices versus personal beliefs of pharmacists regarding chemically dependent patients
Authors: Tomko John R. , Giannetti Vincent J.
Published: December 2014

Background: As pharmacists are increasingly involved in delivering services to chemically dependent populations, it is prudent to explore the perceptions community pharmacists have regarding such patients.

Methods: A random sample of one thousand pharmacists were sent a questionnaire

Results: Twenty-nine percent of responders report no formal education about chemical dependence in pharmacy school. Sixty-four percent of the sample believed that the pharmacist plays a vital role in the treatment of addiction; however slightly more than one third of the respondents admitted to being annoyed rather than sympathetic toward addicted patients.

Conclusions: This survey highlights the need for more extensive education in pharmacy school regarding chemical dependence.
Therapeutic drug monitoring with valproate–Why product selection is an important factor
Authors: McGraw Dan
Published: December 2014

There is a modest collection of literature describing the pharmacokinetic and clinical differences between the extended-release form of divalproex sodium (Depakote ER®) and the delayed-release form (Depakote®). Published articles are quick to espouse the extended-release formulation, especially in the setting of seizure control. Reasons commonly cited include a longer dosing interval, improved patient compliance, a more consistent pharmacokinetic profile, and fewer side effects. There are fewer articles discussing these differences in the context of treating mental illnesses, namely bipolar affective disorder. This article aims to compare these two formulations of divalproex with a special focus on their pharmacokinetic profiles, uses in psychiatric illness, and the role of therapeutic drug monitoring. The patient case that follows will describe a scenario in which a patient was prescribed each formulation during an acute hospitalization.
Key differences between Venlafaxine XR and Desvenlafaxine: An analysis of pharmacokinetic and clinical data
Authors: Colvard Michelle D.
Published: December 2014

Venlafaxine XR and its major active metabolite, desvenlafaxine, are serotonin-norepinephrine reuptake inhibitors. Both are FDA-approved for the treatment of major depressive disorder and have essentially the same pharmacologic and pharmacokinetic profiles; however, the recommended dosing is notably different. The FDA approved recommended starting and maintenance dose for desvenlafaxine is 50 mg daily, while venlafaxine XR requires titration from 37.5 mg daily to the maintenance dose of 150 - 225 mg daily. The dose recommendation for desvenlafaxine is based on results from 8-week acute-phase clinical trials, but complete therapeutic response is not always achieved in this short time period. Venlafaxine XR relies on CYP2D6 for conversion to desvenlafaxine while desvenlafaxine has no significant metabolism by CYP2D6 at recommended doses. Both venlafaxine XR and desvenlafaxine have limited clinically significant drug interactions. The most striking difference between the two products is cost.
Off-label use of atypical antipsychotic agents for treatment of insomnia
Authors: Morin Anna K
Published: December 2014

Despite limited supporting evidence, off-label uses of atypical or second generation antipsychotics (particularly olanzapine, quetiapine, and risperidone) are not uncommon. The off-label use of these agents for the treatment of insomnia is the focus of this review. While atypical antipsychotics are associated with a lower risk of tardive dyskinesia, extrapyramidal side effects, and more favorable effects on cognitive deficits and negative symptomatology in schizophrenic patients compared to typical or first generation antipsychotic agents, they are not without risks. Metabolic adverse effects are particularly problematic with atypical antipsychotics, even at doses lower than those used to treat FDA-approved indications. The receptor affinity profiles of most atypical antipsychotic agents promote sedation. The level of H1-histamine receptor blockade is believed to be most associated with somnolence and sedation. Several studies evaluating the safety and efficacy of the atypical antipsychotics quetiapine, olanzapine, and risperidone for the treatment of insomnia were identified and are summarized in this article.
Screening, diagnosis, and management of type II diabetes: A review of the 2014 American Diabetes Association guidelines
Authors: Patel Sweta , Thompson Amy N.
Published: December 2014

Individuals with schizophrenia and schizoaffective disorders are at higher risk than the general population for the development of chronic medical conditions, such as type II diabetes. This review article will focus on the 2014 recommendations from the American Diabetes Association for diagnosis, management, and assessment of glycemic control in patients with type II diabetes
Clearing the air: Chronic respiratory illnesses and smoking cessation in the adult psychiatric population
Authors: Palmer Emma C. , Frederick Emily K.
Published: December 2014

Objective: To review current practice guidelines in the treatment of asthma and chronic obstructive pulmonary disease (COPD), review therapeutic options for smoking cessation, and apply current evidence to management of these conditions in the psychiatric population.

Background: Chronic respiratory illnesses and nicotine dependence are frequently encountered conditions in the psychiatric population. Psychiatric illness itself may contribute to or be affected by these conditions; medication therapy may additionally be linked to alterations in mental status. However, it is well established that when left untreated or improperly managed, chronic respiratory illness and tobacco use can negatively affect patients' quality of life and lead to increased healthcare utilization.

Methods: Current practice guidelines, literature reviews, and primary data pertaining to management of patients with asthma, COPD, and nicotine dependence were examined. Additional data regarding patients with psychiatric illness was reviewed and commented upon.

Conclusions: Management of this particular population can pose significant clinical challenges. Regardless of what factors may contribute to the disease states and their treatment, it is important for clinicians to identify and take steps to manage both respiratory and psychiatric concerns as they are able. Identification, evidence-based treatment with appropriate medication therapy, and continuing patient education should be used together to help improve patient outcomes.
Community Care of North Carolina – A statewide initiative for innovative pharmacy practice with a behavioral health focus
Authors: Pikoulas Theodore , McKee Jerry , Jackson Carlos , Trygstad Troy , Mahan Amelia , Lancaster Michael
Published: December 2014

Community Care of North Carolina (CCNC) is a state-wide public/private partnership, primarily serving North Carolina (NC) Medicaid recipients, which focuses on the Primary Care Medical Home model of care. The CCNC Behavioral Health Pharmacy Coordinator has a leadership role for the direction and management of Behavioral Health Initiative (BHI) pharmacy projects, while other CCNC clinical pharmacists work in a variety of settings and help to implement and support those BHI projects. CCNC clinical pharmacists also perform medication management in all settings, help to implement the NC Medicaid Preferred Drug List (PDL), support the care managers, and are involved with the transitional care (TC) process. Transitional care medication management focuses on the identification of medication list discrepancies after discharge from an acute care facility. Patients receiving TC were 20% less likely to return to the hospital in the coming year. We observed the same trend even when looking specifically at those patients who were discharged from a psychiatric unit (Wilcoxon-Gehan statistic = 21.22, p<.0001). It is the goal of the CCNC behavioral health team to provide practicing pharmacists (those directly supported by CCNC and those collaborating with CCNC) with the tools to continue serving populations with behavioral health issues.
Targeting transitions of care-Role of the pharmacist in a federally qualified health center
Authors: Bradley Bridget , Deines Sarah
Published: December 2014

Transitions of care in services within and between organizations are a potential source of medication-related problems. These include errors in medication reconciliation, which can lead to patient misunderstanding regarding their medication regimen. Health systems have increasingly focused on improving transitions of care to enhance patient outcomes and decrease the risk of adverse events and/or hospital readmissions. The clinical pharmacy team of the Virginia Garcia Memorial Health Center (VGMHC) collaborated with the pharmacy department and discharge planners of a local community hospital. The goal of this collaboration was to streamline the transition of care between the two organizations for new referrals of uninsured, complex patients that were recently hospitalized and needing to establish care with a primary care provider at a federally qualified health center. This article will further describe the process of collaboration between a local community hospital and a federally qualified health center targeting a specific population for transitions of care.
A retrospective analysis of inpatient utilization of paliperidone palmitate and readmission rates
Authors: Klug Mikayla J. , Smith April N. , Price Paul L.
Published: December 2014

Introduction: This study evaluated pharmacoeconomic considerations, specifically drug cost and patient readmission rates, of the non-formulary agent paliperidone palmitate, within the Alegent Creighton Health system. Pharmacy reimbursement rates for paliperidone palmitate are better on an outpatient versus inpatient basis. Given the low reimbursement rates for inpatient psychiatric care and the high cost of paliperidone palmitate, the drug cost could be justified if patients who received the injection demonstrated a subsequent reduction in readmission.

Methods: The electronic medical record was used to identify patients who received at least one inpatient injection of paliperidone palmitate within the Alegent Creighton Health system from January 2010 – April 2012. Indication, dose, administration date, concurrent antipsychotics, length of stay (LOS), discharge date, and time to readmission were also recorded. Finance reports determined hospital cost and reimbursement for each inpatient stay and pharmacy cost of each paliperidone palmitate injection.

Results: Thirty-two patients received paliperidone palmitate during the period specified. The average LOS was 18 days. The readmission rates for the paliperidone palmitate patients versus all patients at our institution with a diagnosis related group (DRG) of psychosis were as follows: within 30 days, 22% vs 12.5%; 60 days, 15% vs 15%; and 90 days, 25% vs 18%, respectively. The hospital experienced a net loss of roughly $5,610 per stay for the patients studied and paliperidone palmitate alone constituted approximately 16% of the total hospital cost per each patient stay.

Discussion: In this limited patient population, it appears inpatient administration of paliperidone palmitate increased hospital cost without significantly reducing readmission rates at 30, 60, or 90 days post-injection. If patients are due for their monthly maintenance dose while hospitalized, the injection should be deferred to outpatient care if discharge is anticipated within one week since product labeling states maintenance injections can be given seven days after the monthly due date and outpatient reimbursement for the drug is superior.
Pharmacogenomics of antidepressants for major depressive disorder
Authors: Martin Joel , Lee Kelly C.
Published: December 2014

Major depressive disorder (MDD) is a common disorder, affecting approximately 10% of adults in the United States each year. The primary treatment options for moderate to severe MDD are antidepressant medications, mainly selective serotonin reuptake inhibitors (SSRIs). Current guidelines recommend an initial trial of 4–8 weeks to determine if a medication is effective for a patient. Through the use of pharmacogenomics, it may be possible to predict whether patients will respond to and tolerate SSRIs. This article discusses several genes and alleles that may play a role in a patient's response to SSRIs.
Numerical analysis of stratification and destratification processes in a tidally energetic inlet with an ebb tidal delta
Authors: Purkiani Kaveh , Becherer Johannes , Flöser Götz , Gräwe Ulf , Mohrholz Volker , Schuttelaars Henk M. , Burchard Hans
Published: December 2014

Stratification and destratification processes in a tidally energetic, weakly stratified inlet in the Wadden Sea (south eastern North Sea) are investigated in this modeling study. Observations of current velocity and vertical density structure show strain‐induced periodic stratification for the southern shoal of the tidal channel. In contrast to this, in the nearby central region of the channel, increased stratification is already observed directly after full flood. To investigate the processes leading to this different behavior, a nested model system using GETM is set up and successfully validated against field data. The simulated density development along a cross section that includes both stations shows that cross‐channel stratification is strongly increasing during flood, such that available potential energy is released in the deeper part of the channel during flood. An analysis of the potential energy anomaly budget confirms that the early onset of vertical stratification during flood at the deeper station is mainly controlled by the stratifying cross‐channel straining of the density field. In contrast to this, in the shallow part of the channel, the relatively weak cross‐channel straining is balanced by along‐channel straining and vertical mixing. An idealized analytical model confirms the following hypothesis: The laterally convergent flood current advecting laterally stratified water masses from the shallow and wide ebb tidal delta to the deep and narrow tidal channel has the tendency to substantially increase cross‐channel density gradients in the tidal channel. This process leads to stratification during flood.
Thermodynamics versus Kinetics in Nanosynthesis
Authors: Wang Yawen , He Jiating , Liu Cuicui , Chong Wen Han , Chen Hongyu
Published: December 2014

One may discover a stone tool by chance but it takes more than luck to make a car or cell phone. With the advance of nanoscience, the synthesis of increasingly sophisticated nanostructures demands a rational design and a systems approach. In this Review, we advocate the distinction between thermodynamically and kinetically controlled scenarios, that is, whether a product forms because it is the most stable state or because the pathway leading to it has the lowest energy barrier. Great endeavours have been made to describe the multiple concurrent processes in typical nanosynthesis phenomena, so that the mechanistic proposals in the literature are brought into a common framework for easy contrast and comparison.
Insights into the Pamamycin Biosynthesis
Authors: Rebets Yuriy , Brötz Elke , Manderscheid Niko , Tokovenko Bogdan , Myronovskyi Maksym , Metz Peter , Petzke Lutz , Luzhetskyy Andriy
Published: December 2014

Pamamycins are macrodiolides of polyketide origin with antibacterial activities. Their biosynthesis has been proposed to utilize succinate as a building block. However, the mechanism of succinate incorporation into a polyketide was unclear. Here, we report identification of a pamamycin biosynthesis gene cluster by aligning genomes of two pamamycin‐producing strains. This unique cluster contains polyketide synthase (PKS) genes encoding seven discrete ketosynthase (KS) enzymes and one acyl‐carrier protein (ACP)‐encoding gene. A cosmid containing the entire set of genes required for pamamycin biosynthesis was successfully expressed in a heterologous host. Genetic and biochemical studies allowed complete delineation of pamamycin biosynthesis. The pathway proceeds through 3‐oxoadipyl‐CoA, a key intermediate in the primary metabolism of the degradation of aromatic compounds. 3‐Oxoadipyl‐CoA could be used as an extender unit in polyketide assembly to facilitate the incorporation of succinate.
Long jute fiber‐reinforced polypropylene composite: Effects of jute fiber bundle and glass fiber hybridization
Authors: Uawongsuwan Putinun , Yang Yuqiu , Hamada Hiroyuki
Published: December 2014

Two types of long jute fiber pellet consisting of twisted‐jute yarn (LFT‐JF/PP) and untwisted‐jute yarn (UT‐JF/PP) pellets are used to prepare jute fiber–reinforced polypropylene (JF/PP) composites. The mechanical properties of both long fiber composites are compared with that of re‐pelletized pellet (RP‐JF/PP) of LFT‐JF/PP pellet, which is re‐compounded by extrusion compounding. High stiffness and high impact strength of JF/PP composites are as a result of using long fiber. However, the longer fiber bundle consequently affects the distribution of jute fiber. The incorporation of 10 wt % glass fibers is found to improve mechanical properties of JF/PP composites. Increasing mechanical properties of hybrid composites is dependent on the type of JF/PP pellets, which directly affect the fiber length and fiber orientation of glass fiber within hybrid composites. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41819.
Differential diagnosis of liver tumours using intraoperative real-time tissue elastography
Authors: Omichi K , Inoue Y , Hasegawa K , Sakamoto Y , Okinaga H , Aoki T , Sugawara Y , Kurahashi I , Kokudo N
Published: December 2014

Background

Real-time tissue elastography is an innovative tool that informs the surgeon about tissue elasticity by applying the principle of ultrasonography. The aim of this study was to investigate the accuracy of intraoperative real-time tissue elastography (IORTE) for the detection and characterization of liver tumours.

Methods

Between October 2010 and November 2011, IORTE was performed for liver lesions after the completion of routine B-mode intraoperative ultrasonography (IOUS). The elasticity images of all tumours, except those of cysts, were classified into six categories according to modified criteria (types 1–6), according to the degree of strain contrast with the surrounding liver. The concordance of IORTE with pathological examination of the tumour, B-mode IOUS and clinical diagnosis after follow-up was assessed.

Results

Images were obtained from 92 hepatocellular carcinomas (HCCs), 92 adenocarcinomas, 19 other malignant tumours and 18 benign tumours in 158 patients. Using a minilinear probe, 73 of 88 HCCs were classified as having a ‘HCC pattern’ (type 3, 4 or 5), resulting in a sensitivity of 83·0 per cent, a specificity of 67·2 per cent and an accuracy of 73·7 per cent. Some 66 of 90 adenocarcinomas were classified as ‘adenocarcinoma pattern’ (type 6), resulting in a sensitivity of 73·3 per cent, specificity of 95·1 per cent and accuracy of 85·9 per cent. IORTE detected seven new lesions (8 per cent).

Conclusion

IORTE is useful for the detection and characterization of liver tumours.
Highly Enantioselective Catalytic Asymmetric [2+2] Cycloadditions of Cyclic α‐Alkylidene β‐Oxo Imides with Ynamides
Authors: Enomoto Kazuaki , Oyama Harufumi , Nakada Masahisa
Published: December 2014

Highly enantioselective catalytic asymmetric [2+2] cycloadditions of cyclic α‐alkylidene β‐oxo imides with ynamides are described. The high reactivity of the cyclic α‐alkylidene β‐oxo imide allows the [2+2] cycloadditions of a hindered substrate with unreactive ynamides at low temperature. The X‐ray crystallographic analysis of the product suggests that the enantioselectivity of the [2+2] cycloaddition can be well explained by the chelate model comprising the intramolecular hydrogen bond, wherein the cyclic α‐alkylidene β‐oxo imide coordinates with CuII through the two imide carbonyls. The imide group in the product can be transformed to amide, nitrile, and ester groups; moreover, it is removable.
Novel Tacrine‐Grafted Ugi Adducts as Multipotent Anti‐Alzheimer Drugs: A Synthetic Renewal in Tacrine–Ferulic Acid Hybrids
Authors: Benchekroun Mohamed , Bartolini Manuela , Egea Javier , Romero Alejandro , Soriano Elena , Pudlo Marc , Luzet Vincent , Andrisano Vincenza , Jimeno María‐Luisa , López Manuela G. , Wehle Sarah , Gharbi Tijani , Refouvelet Bernard , de Andrés Lucía , Herrera‐Arozamena Clara , Monti Barbara , Bolognesi Maria Laura , Rodríguez‐Franco María Isabel , Decker Michael , Marco‐Contelles José , Ismaili Lhassane
Published: December 2014

Herein we describe the design, multicomponent synthesis, and biological, molecular modeling and ADMET studies, as well as in vitro PAMPA‐blood–brain barrier (BBB) analysis of new tacrine–ferulic acid hybrids (TFAHs). We identified (E)‐3‐(hydroxy‐3‐methoxyphenyl)‐N‐{8[(7‐methoxy‐1,2,3,4‐tetrahydroacridin‐9‐yl)amino]octyl}‐N‐[2‐(naphthalen‐2‐ylamino)2‐oxoethyl]acrylamide (TFAH 10 n) as a particularly interesting multipotent compound that shows moderate and completely selective inhibition of human butyrylcholinesterase (IC50=68.2 nM), strong antioxidant activity (4.29 equiv trolox in an oxygen radical absorbance capacity (ORAC) assay), and good β‐amyloid (Aβ) anti‐aggregation properties (65.6 % at 1:1 ratio); moreover, it is able to permeate central nervous system (CNS) tissues, as determined by PAMPA‐BBB assay. Notably, even when tested at very high concentrations, TFAH 10 n easily surpasses the other TFAHs in hepatotoxicity profiling (59.4 % cell viability at 1000 μM), affording good neuroprotection against toxic insults such as Aβ1–40, Aβ1–42, H2O2, and oligomycin A/rotenone on SH‐SY5Y cells, at 1 μM. The results reported herein support the development of new multipotent TFAH derivatives as potential drugs for the treatment of Alzheimer′s disease.
The Use of Thermodynamic and Kinetic Data in Drug Discovery: Decisive Insight or Increasing the Puzzlement?
Authors: Klebe Gerhard
Published: December 2014

The prime property to rate the success of hit‐to‐lead‐to‐drug optimization in drug discovery is binding affinity. Rational approaches try to relate this property with structure. Affinity can be linked to the thermodynamic property, Gibbs free energy of binding, which itself factorizes into enthalpy and entropy. With respect to kinetic properties, affinity can be associated with the ratio of koff and kon of complex formation. Do these features help to obtain better insight into affinity? The present viewpoint assesses our current understanding of thermodynamics– or kinetics–structure relationships and questions the accuracy of data collected to learn about the thermodynamic and kinetic basis to comprehend affinity.
Histone deacetylase inhibitors in cancer: What have we learned?
Authors: Whittle James R. , Desai Jayesh
Published: December 2014

The authors outline the current stage in the development of histone deacetylase inhibitors in solid tumors. Despite single‐agent benefit in a small number of hematologic malignancies, evidence in solid organ cancers suggests that outcomes will be more promising with combination therapy and should be the focus of future studies.
Single‐cycle induction chemotherapy followed by chemoradiotherapy or surgery in patients with head and neck cancer: What are the best predictors of remission and prognosis?
Authors: Semrau Sabine , Haderlein Marlen , Schmidt Daniela , Lell Michael , Wolf Walburga , Waldfahrer Frank , Uder Michael , Iro Heinrich , Kuwert Torsten , Fietkau Rainer
Published: December 2014

BACKGROUND

There is controversy over the concept of function and organ preservation by chemotherapy/chemoradiation instead of surgery in locally advanced cancer of the larynx or pharynx. Tumor response to induction chemotherapy (ICT) can help in choosing between conservative and surgical treatment. This study compared 3 methods of assessing response to ICT: endoscopy, computed tomography, and 18F‐FDG‐PET/CT.

METHODS

Primary response to 1 cycle of ICT with docetaxel plus platinum was assessed by the aforementioned methods in 62 laryngopharyngeal cancer patients. Endoscopic response was the deciding factor for selecting further treatment: surgery for endoscopic nonresponders (<30% tumor response) versus chemoradiotherapy for endoscopic responders.

RESULTS

ICT achieved endoscopic response in 48 of 62 patients (77%). Individual relative residual tumor activity of standardized uptake value (resSUVmax) in 18F‐FDG‐PET/CT was a median 0.38 of baseline (0.09‐1.71), whereas residual tumor extent in CT (resCT) was 0.75 of baseline (0.32‐1.20). Endoscopic responders and nonresponders differed significantly in SUVmax after ICT (postSUVmax, 6.0 vs 14.5; P < .001), resSUVmax (0.34 vs 0.81, P < .001), and resCT (0.71 vs 0.87, P = .004), but not in maximum tumor diameter after ICT (14 vs 20 mm, P = .11). resSUVmax <0.8 and absolute postSUVmax <10 provided the best discriminatory power for long‐term success criteria (tumor‐free survival, overall survival).

CONCLUSIONS

Metabolic tumor response showed very good correlation with clinical tumor response to ICT. The value of metabolic response detected by 18F‐FDG‐PET/CT should be explored in a prospective clinical trial. Cancer 2015;121:1214–1222. © 2014 American Cancer Society.
High temperature electrical conductivity in undoped ceramic ZnO
Authors: Lott K. , Nirk T. , Gorokhova E. , Türn L. , Viljus M. , Öpik A. , Vishnjakov A.
Published: December 2014

The results of high temperature electrical conductivity (HTEC) measurements in undoped ceramic ZnO sample are presented. The ceramic sample under investigation was formed at high pressure and at high temperature in inert atmosphere. HTEC measurements data were obtained under the defined Zn component vapor pressure (up to 1 atm) and in temperature range (up to 1373 K). In these experiments the absolute value of HTEC in ZnO samples was several orders of magnitude higher than in undoped ZnS measured under the same conditions. Slow chemical diffusion was observed in ZnO. Slopes of HTEC isotherms in ZnO samples varied with component vapor pressure in the range from 0 to 0.2. Defect model for explanation of this experiment is discussed.
Challenging the paradigm of nitrogen cycling: no evidence of in situ resource partitioning by coexisting plant species in grasslands of contrasting fertility
Authors: Wilkinson Anna , Hill Paul W. , Vaieretti María V. , Farrar John F. , Jones Davey L. , Bardgett Richard D.
Published: December 2014

In monoculture, certain plant species are able to preferentially utilize different nitrogen (N) forms, both inorganic and organic, including amino acids and peptides, thus forming fundamental niches based on the chemical form of N. Results from field studies, however, are inconsistent: Some showing that coexisting plant species predominantly utilize inorganic N, while others reveal distinct interspecies preferences for different N forms. As a result, the extent to which hypothetical niches are realized in nature remains unclear. Here, we used in situ stable isotope tracer techniques to test the idea, in temperate grassland, that niche partitioning of N based on chemical form is related to plant productivity and the relative availability of organic and inorganic N. We also tested in situ whether grassland plants vary in their ability to compete for, and utilize peptides, which have recently been shown to act as an N source for plants in strongly N‐limited ecosystems. We hypothesized that plants would preferentially use NO3−‐N and NH4+‐N over dissolved organic N in high‐productivity grassland where inorganic N availability is high. On the other hand, in low‐productivity grasslands, where the availability of dissolved inorganic N is low, and soil availability of dissolved organic N is greater, we predicted that plants would preferentially use N from amino acids and peptides, prior to microbial mineralization. Turves from two well‐characterized grasslands of contrasting productivity and soil N availability were injected, in situ, with mixtures of 15N‐labeled inorganic N (NO3− and NH4+) and 13C15N labeled amino acid (l‐alanine) and peptide (l‐tri‐alanine). In order to measure rapid assimilation of these N forms by soil microbes and plants, the uptake of these substrates was traced within 2.5 hours into the shoots of the most abundant plant species, as well as roots and the soil microbial biomass. We found that, contrary to our hypothesis, the majority of plant species across both grasslands took up most N in the form of NH4+, suggesting that inorganic N is their predominant N source. However, we did find that organic N was a source of N which could be utilized by plant species at both sites, and in the low‐productivity grassland, plants were able to capture some tri‐alanine‐N directly. Although our findings did not support the hypothesis that differences in the availability of inorganic and organic N facilitate resource partitioning in grassland, they do support the emerging view that peptides represent a significant, but until now neglected, component of the terrestrial N cycle.
Demographic effects of extreme weather events: snow storms, breeding success, and population growth rate in a long‐livedAntarctic seabird
Authors: Descamps Sébastien , Tarroux Arnaud , Varpe Øystein , Yoccoz Nigel G. , Tveraa Torkild , Lorentsen Svein‐Håkon
Published: December 2014

Weather extremes are one important element of ongoing climate change, but their impacts are poorly understood because they are, by definition, rare events. If the frequency and severity of extreme weather events increase, there is an urgent need to understand and predict the ecological consequences of such events. In this study, we aimed to quantify the effects of snow storms on nest survival in Antarctic petrels and assess whether snow storms are an important driver of annual breeding success and population growth rate. We used detailed data on daily individual nest survival in a year with frequent and heavy snow storms, and long term data on petrel productivity (i.e., number of chicks produced) at the colony level. Our results indicated that snow storms are an important determinant of nest survival and overall productivity. Snow storm events explained 30% of the daily nest survival within the 2011/2012 season and nearly 30% of the interannual variation in colony productivity in period 1985–2014. Snow storms are a key driver of Antarctic petrel breeding success, and potentially population dynamics. We also found state‐dependent effects of snow storms and chicks in poor condition were more likely to die during a snow storm than chicks in good condition. This stresses the importance of considering interactions between individual heterogeneity and extreme weather events to understand both individual and population responses to climate change.
Genome‐wide methylation analysis in vestibular schwannomas shows putative mechanisms of gene expression modulation and global hypomethylation at the HOX gene cluster
Authors: Torres‐Martín Miguel , Lassaletta Luis , de Campos Jose M , Isla Alberto , Pinto Giovanny R. , Burbano Rommel R. , Melendez Bárbara , Castresana Javier S. , Rey Juan A.
Published: December 2014

Schwannomas are tumors that develop from Schwann cells in the peripheral nerves and commonly arise from the vestibular nerve. Vestibular schwannomas can present unilaterally and sporadically or bilaterally when the tumor is associated with neurofibromatosis Type 2 (NF2) syndrome. The molecular hallmark of the disease is biallelic inactivation of the NF2 gene. The epigenetic signature of schwannomas remains poorly understood and is mostly limited to DNA methylation of the NF2 gene, whose altered expression due to epigenetic factors in this tumor is controversial. In this study, we tested the genomewide DNA methylation pattern of schwannomas to shed light on this epigenetic alteration in these particular tumors. The methodology used includes Infinium Human Methylation 450K BeadChip microarrays in a series of 36 vestibular schwannomas, 4 nonvestibular schwannomas, and 5 healthy nerves. Our results show a trend toward hypomethylation in schwannomas. Furthermore, homeobox (HOX) genes, located at four clusters in the genome, displayed hypomethylation in several CpG sites in the vestibular schwannomas but not in the nonvestibular schwannomas. Several microRNA (miRNA) and protein‐coding genes were also found to be hypomethylated at promoter regions and were confirmed as upregulated by expression analysis; including miRNA‐21, Met Proto‐Oncogene (MET), and PMEPA1. We also detected methylation patterns that might be involved in alternative transcripts of several genes such as NRXN1 or MBP, which would increase the complexity of the methylation and expression patterns. Overall, our results show specific epigenetic signatures in several coding genes and miRNAs that could potentially be used as therapeutic targets. © 2014 Wiley Periodicals, Inc.
Intensity‐modulated radiotherapy for early‐stage glottic cancer
Authors: Berwouts Dieter , Swimberghe Martijn , Duprez Fréderic , Boterberg Tom , Bonte Katrien , Deron Philippe , De Gersem Werner , De Neve Wilfried , Madani Indira
Published: December 2014

Background

The purpose of this study was to report on treatment outcome of intensity‐modulated radiotherapy (IMRT) for early‐stage (cT1–2 cN0 M0) squamous cell carcinoma of the glottis, as compared with patients treated with conventional radiotherapy.

Methods

Between November 2007 and December 2011, 40 consecutive patients were treated with IMRT with daily cone‐beam CT position verification. The median prescription to the planning target volume (PTV) was 63 Gy/28 fractions and 67.5 Gy/30 fractions for T1 and T2 tumors, respectively. The historical control comprised 81 consecutive patients treated with conventional radiotherapy to total doses of 66 Gy/33 fractions (66 patients) and 70 Gy/35 fractions (15 patients) for T1 and T2 tumors, respectively.

Results

The median follow‐up of living patients was 3.8 years (range, 1.0–5.0 years) in the IMRT group and 9.0 years, (range, 5.2–12.7 years) in the conventional group. Five‐year actuarial local control was equal compared to the conventional group: 83% versus 74% (p = .64). Five‐year actuarial ultimate local control was 100% in the IMRT group and 95% in the conventional group (p = .17). Five‐year actuarial overall and disease‐specific survival was 85% after IMRT versus 65% after conventional radiotherapy (p = .15) and 97% versus 89% (p = .31), respectively. Incidence and severity of acute dermatitis was significantly less during IMRT than in the control group (p < .001). Two patients receiving IMRT had late grade 3 hoarseness.

Conclusion

IMRT is as efficient as conventional radiotherapy in terms of disease control and overall survival. It has the potential to reduce toxicity as compared to conventional radiotherapy. © 2015 Wiley Periodicals, Inc. Head Neck 38: E179–E184, 2016
Performance Management: Perceiving Goals as Invariable and Implications for Perceived Job Autonomy and Work Performance
Authors: Kuvaas Bård , Buch Robert , Dysvik Anders
Published: December 2014

In this study, we investigated whether perceiving goals as invariable is negatively related to work performance and whether this relationship is mediated by perceived job autonomy. Perceiving goals as invariable refers to the extent to which employees believe that the goals in a performance management system represent absolute standards that they must meet without exception, even if they think other factors are more important (e.g., situational factors or factors that are not associated with goals). In support of our hypotheses, we found a negative relationship between perceiving goals as invariable and work performance and that perceived job autonomy mediated this relationship. Theoretical and practical implications and directions for future research are discussed. © 2014 Wiley Periodicals, Inc.