bluuebunny/crossref_metadata_2025 huggingface dataset:
Time-Series analysis of MODIS NDVI data along with ancillary data for Land use/Land cover mapping of Uttarakhand
Authors: Patakamuri S. K. , Agrawal S. , Krishnaveni M.
Published: December 2014

Abstract. Land use and land cover plays an important role in biogeochemical cycles, global climate and seasonal changes. Mapping land use and land cover at various spatial and temporal scales is thus required. Reliable and up to date land use/land cover data is of prime importance for Uttarakhand, which houses twelve national parks and wildlife sanctuaries and also has a vast potential in tourism sector. The research is aimed at mapping the land use/land cover for Uttarakhand state of India using Moderate Resolution Imaging Spectroradiometer (MODIS) data for the year 2010. The study also incorporated smoothening of time-series plots using filtering techniques, which helped in identifying phenological characteristics of various land cover types. Multi temporal Normalized Difference Vegetation Index (NDVI) data for the year 2010 was used for mapping the Land use/land cover at 250m coarse resolution. A total of 23 images covering a single year were layer stacked and 150 clusters were generated using unsupervised classification (ISODATA) on the yearly composite. To identify different types of land cover classes, the temporal pattern (or) phenological information observed from the MODIS (MOD13Q1) NDVI, elevation data from Shuttle Radar Topography Mission (SRTM), MODIS water mask (MOD44W), Nighttime Lights Time Series data from Defense Meteorological Satellite Program (DMSP) and Indian Remote Sensing (IRS) Advanced Wide Field Sensor (AWiFS) data were used. Final map product is generated by adopting hybrid classification approach, which resulted in detailed and accurate land use and land cover map.
Ice and AIS: ship speed data and sea ice forecasts in the Baltic Sea
Authors: Löptien U. , Axell L.
Published: December 2014

Abstract. The Baltic Sea is a seasonally ice-covered marginal sea located in a densely populated area in northern Europe. Severe sea ice conditions have the potential to hinder the intense ship traffic considerably. Thus, sea ice fore- and nowcasts are regularly provided by the national weather services. Typically, the forecast comprises several ice properties that are distributed as prognostic variables, but their actual usefulness is difficult to measure, and the ship captains must determine their relative importance and relevance for optimal ship speed and safety ad hoc. The present study provides a more objective approach by comparing the ship speeds, obtained by the automatic identification system (AIS), with the respective forecasted ice conditions. We find that, despite an unavoidable random component, this information is useful to constrain and rate fore- and nowcasts. More precisely, 62–67% of ship speed variations can be explained by the forecasted ice properties when fitting a mixed-effect model. This statistical fit is based on a test region in the Bothnian Sea during the severe winter 2011 and employs 15 to 25 min averages of ship speed.
Evaluate When and How to Use Piping Restraints
Authors: Riseden Doug
Published: December 2014

Piping restraints play an essential role in ensuring safe water and wastewater system operations. However, it's important to evaluate criteria such as local soil conditions, materials, existing infrastructure, deflection, seismic activity, and cost to determine the most appropriate restraint to use.
How Can We Ensure Water Mains Will Pass Bacteriological Tests?
Authors: Lauer William C.
Published: December 2014

Many factors in a pipeline installation can cause contamination and ineffective disinfection. However, carefully following all basic precautions will result in the highest possible passing percentage.
Comparative pharmacoeconomic assessment of apixaban vs. standard of care for the prevention of stroke in Italian atrial fibrillation patients
Authors: Pradelli Lorenzo , Calandriello Mario , Di Virgilio Roberto , Bellone Marco , Tubaro Marco
Published: December 2014

OBJECTIVES: The aim of this study was to evaluate the cost‑effectiveness of apixaban in the prevention of thromboembolic events in patients with non‑valvular atrial fibrillation (NVAF) relatively to standard of care (warfarin or aspirin) from the Italian National Health System (SSN) perspective.METHODS: A previously published lifetime Markov model was adapted for Italian context. Clinical effectiveness data were acquired from head‑to‑head randomized trials (ARISTOTLE and AVERROES); main events considered in the model were ischemic and hemorrhagic stroke, systemic thromboembolism, bleeds (both major and clinically relevant minor) and cardiovascular hospitalizations, besides treatment discontinuations. Expected survival was projected beyond trial duration using national mortality data adjusted for individual clinical risks and adjusted by utility weights for health states acquired from literature. Unit costs were collected from published Italian sources and actualized to 2013. Costs and health gains accruing after the first year were discounted at an annual 3.5% rate. The primary outcome measure of the economic evaluation was the incremental cost effectiveness ratio (ICER), where effectiveness is measured in terms of life‑years and quality adjusted life‑years gained. Deterministic and probabilistic sensitivity analyses (PSA) were carried out to assess the effect of input uncertainty.RESULTS: Apixaban is expected to reduce the incidence of ischemic events relative to aspirin and to improve bleeding safety profile when compared to warfarin. Incremental LYs (0.31/0.19), QALYs (0.28/0.20), and costs (1,932/1,104) are predicted with the use of apixaban relative to aspirin and warfarin, respectively. The ICERs of apixaban were € 6,794 and € 5,607 per QALY gained, respectively. In PSA, the probability of apixaban being cost effective relative to aspirin and warfarin was 95% and 93%, respectively, for a WTP threshold of € 20,000 per QALY gained. Univariate analyses indicate that results were most sensitive to variations of the absolute risk reduction for cardiovascular events with apixaban.CONCLUSIONS: Apixaban is expected to increase life expectancy and quality‑adjusted life expectancy, but also costs dedicated to Italian NVAF patients, as compared to standard of care. The resulting ICERs have high probabilities of being below the conventional thresholds of WTP for health benefits of the SSN, indicating efficient allocation of health care resources.
Cost-effectiveness of intravitreal therapy in Age-Related Macular Degeneration
Authors: Neri Piergiorgio , Arapi Ilir , Eandi Chiara Maria , Pirani Vittorio , Mariotti Cesare , Giovannini Alfonso
Published: December 2014

Age-related macular degeneration (AMD) is still referred to as the leading cause of severe and irreversible visual loss world-wide. Advances in medical research have identified vascular endothelial growth factor (VEGF) as an important pathophysiological player in neovascular AMD and intraocular inhibition of VEGF as one of the most efficient therapies. Anti-VEGFs currently used to treat AMD included a monoclonal antibody (bevacizumab), an antibody fragments (ranibizumab), a fusion protein (aflibercept), and an aptamer (pegaptanib). The wide introduction of anti-VEGF therapy has led to an improvement in the prognosis of patients affected by AMD, with a consequent effects on the burden of care due to highly priced drugs, increasing patient numbers, and long-term disease chronicity. Aim of this review is to present an overview of available therapeutic strategies in AMD in term of clinical efficacy and economic sustainability.
Economic impact of the use of Hyalubrix® in the treatment of hip osteoarthritis in Italy
Authors: Migliore Alberto , Belisari Andrea , D'Angiolella Lucia S. , Bizzi Emanuele , Massafra Umberto , Piscitelli Prisco , Mantovani Lorenzo Giovanni
Published: December 2014

The present study aims at evaluating the economic impact of the use of hyaluronic acid (Hyalubrix®60/HyalOne) as an alternative to surgery in the treatment of hip osteoarthritis, consistently with the therapeutic protocol envisaged in the Ortobrix study. To quantify the cost and efficacy of the treatment options under evaluation, the perspective of both the Italian NHS and the Society was considered. To this end, a decision analysis model was created over a 4-year period, to quantify the cost of treatments, procedures and adverse events, as well as the benefits expressed as survival rates and reduced lost workdays. The results show that, since the treatment with Hyalubrix® enables to avoid or delay the need for Total Hip Replacement (THR) surgery, it is possible to reduce mortality, adverse events and total costs. Hyalubrix®, given in the hip by ultrasound-guided intra-articular injection as an alternative to surgery is the most favourable option, helping preserve the survival rate over a 4-year period, of approximately 1 in 100 patients considered candidates for THR, preserve work capacity for a total differential amount of 500 days, and achieve considerable savings in economic terms, of approximately 550,000 € and 600,000€ euros from the NHS and the Societal perspectives, respectively.
How do European patients feel about the listening skills of primary care physicians? Results from the EUprimecare Project
Authors: Sánchez Piedra Carlos Alberto , García-Pérez Sonia , Prado-Galbarro Francisco Javier , Sarría-Santamera Antonio
Published: December 2014

OBJECTIVE: EUprimecare is a study funded by the 7th Framework Programme of the European Union aimed at analyzing the quality of the different models of primary care (PC) in Europe. The objective of this study was to describe and analyze the determinants associated with patient satisfaction with the listening skills of their PC physicians.METHODS: Telephone population survey in each EUprimecare consortium countries (Germany, Spain, Estonia, Finland, Hungary, Italy and Lithuania) among PC users. The questionnaire included sociodemographic variables, health status, use and satisfaction with PC services. The survey was conducted in 3020 patients. It was developed descriptive analysis, bivariate correlations and ordinal regression model to study the direct relation between levels of satisfaction and the explanatory variables on demographics, state and health services for patients. We show the regression coefficients (β) with 95% confidence interval and statistical significance associated.RESULTS: We found significant relation between the level of satisfaction and age (β = 0.016), visits to specialist (β = ‑0.040), having a general practitioner (GP) (β = 0.619), having a chronic disease (β = 0.255), measuring weight, cholesterol and blood pressure (β = 0.650), countries (β1 Estonia= 0.938; β2 Germany = 0.469; β3 Lithuania = 0.483; β5 Italy = 0.544 and β6 Hungary = 1.010) and a better perception of health status (β = 0.388). Specialist visits have a negative influence with the higher degree of satisfaction.CONCLUSIONS: Overall, the results indicate some areas that may be related to greater doctor‑patient satisfaction. Different factors are converging to explain satisfaction with listening skills.
Management of phenytoin with enteral tube feeding
Authors: Phelps Nicole
Published: December 2014

Though the mechanism of the interaction is poorly understood, phenytoin absorption is reduced when given concomitantly with enteral tube feedings. This article reviews strategies that may help maintain phenytoin levels when enteral nutrition is required.
A review of eslicarbazepine acetate (Stedesa®)
Authors: Price Cristofer , Ryan Melody
Published: December 2014

Eslicarbazepine acetate is an anticonvulsant medication approved in Europe for adjunctive therapy in adults with partial-onset seizures. FDA approval is expected shortly for use in the United States. This article reviews the pharmacologic and pharmacokinetic profile of eslicarbazepine acetate, and factors that should be considered when using this medication.
A high-stakes decision: Generic substitution of antiepileptic drugs
Authors: Noel Jason
Published: December 2014

In recent years, generic versions of several antiepileptic drugs have been approved and released to the US market. This article reviews some of the concerns associated with generic substitution of antiepileptic drugs.
A review of human immunodeficiency virus (HIV) and postpartum depression
Authors: Owusu Kent , Patel Ravin , Chung Allison M.
Published: December 2014

Depression is common among HIV-infected women, predicts treatment non-adherence, and may impact mother to daughter (vertical) transmission of HIV. A majority of women who develop HIV are of child-bearing age, and are at risk for postpartum depression (PPD). A literature review was performed to analyze the literature regarding PPD in HIV-positive women. This review specifically looked at literature regarding the incidence, risk factors, outcomes, and treatment of PPD in HIV-positive women compared to the general population. While existing literature is limited, it seems to imply that there is no difference between HIV-positive women and unaffected women when it comes to PPD incidence or risk factors. A majority of studies did conclude that routine screenings are needed for depressive symptoms in HIV-positive women.
Occupational methamphetamine manufacturing toxin exposure: An exposure example
Authors: Pecina Carrie , Washington Nicole B. , Kelly-Rehm Merry C. , Brahm Nancy C.
Published: December 2014

Purpose

To illustrate opportunities for pharmacists as resources for community-based healthcare professionals that may be at-risk for occupational exposure to toxins of illicit methamphetamine (METH) manufacturing while providing case management services to community-based patients.

Summary

Pharmacists can serve as a resource with education and protocol development for minimizing the hazards of healthcare professionals, including pharmacists, at-risk for exposure to the toxins of METH manufacturing while providing community-based case management. The illicit production of METH requires solvents for extraction and purification and often results in the release of a number of harmful, and potentially deadly, chemicals and gases. For community-based healthcare professionals, risk factors include direct contact and inhalation. Community-based healthcare professionals providing case management services to patients involved in the production of METH are at-risk for exposure. Examples of an occupational exposure and how the pharmacist can serve as a resource to these providers are provided.

Conclusions

When conducting home- or community-based services, healthcare professionals may inadvertently experience health-related consequences and injuries because of exposure to hazardous wastes created by and used in the production of METH. The pharmacist can provide education and protocol development to help healthcare professionals identify hazards of exposure to the toxins of the manufacturing of METH, identify signs and symptoms of METH use, and identify signs and symptoms of toxin exposure.
Summary of 2012 Cochrane collaboration meta-analysis covering newer generation antidepressants for depressive disorders in children and adolescents
Authors: Trendler Ashley , Levin Gary M.
Published: December 2014

The Cochrane Collaboration recently published a meta-analysis on the use of newer generation antidepressants for the treatment of depressive disorders in children and adolescent patients. This article summarizes their findings.
Obsessive-compulsive disorder in pediatrics and adolescents: Review of treatment and future directions
Authors: Palmer Emma , Fuller Matthew
Published: December 2014

Obsessive-compulsive disorder (OCD) is an anxiety disorder associated with significant morbidity, and found at a relatively high overall prevalence in the pediatric and adolescent population. This article reviews the treatment of OCD in pediatrics and adolescents.
Management and prevention of agranulocytosis in patients receiving clozapine
Authors: Ojong Mebanga , Allen Shari N.
Published: December 2014

Clozapine is an antipsychotic associated with superior efficacy compared to other atypical antipsychotics in the treatment of schizophrenia. However, clozapine use is limited due to its association with a rare but potentially fatal adverse effect, agranulocytosis. Patients receiving clozapine therapy require frequent monitoring of white blood cell (WBC) and absolute neutrophil counts (ANC). This article reviews the monitoring parameters for patients receiving clozapine therapy, and the management and prevention of clozapine-associated agranulocytosis.
A case of tramadol dependence and successful treatment with buprenorphine/naloxone
Authors: Cupples Nicole , Moore Troy A.
Published: December 2014

Tramadol, a synthetic, centrally acting analgesic with weak mu-opioid agonist activity, is often prescribed as an alternative to opioids due to its negligible abuse potential. Although the potential for the abuse of tramadol appeared low when the medication first became available, findings have demonstrated increased rates of abuse with extended time on the market. This case report details the addiction to tramadol of a 39-year-old female serving in the United States Army. At the height of her addiction, she was consuming an average of 1400mg tramadol daily. Eventually the patient entered into residential inpatient treatment for 28 days at our facility. During this time she was successfully titrated to buprenorphine 8mg/naloxone 2mg daily while maintaining abstinence. Patient care transitioned to the outpatient treatment center during which she maintained sobriety with the continued use of buprenorphine/naloxone. This case adds to previous reports of the increasing abuse of tramadol and the need for quality evidence on successful treatments for this escalating concern.
Levomilnacipran (Fetzima™) for the treatment of major depressive disorder
Authors: Ross Clint
Published: December 2014

Levomilnacipran (Fetzima™) was approved by the United States Food and Drug Administration (FDA) in July 2013 for the treatment of Major Depressive Disorder (MDD) in adults. Levomilnacipran is the (1S,2R) enantiomer of racemic milnacipran and represents one of the newest medications designed and marketed as an enantiomer of an already approved medication with hopes of improving efficacy and limiting side effects. This article reviews the evidence supporting the use of milnacipran for MDD, examines the clinical studies behind levomilnacipran's approval, and discusses practical considerations regarding the use of this new antidepressant medication.
Antidepressant management of insomnia disorder in the absence of a mood disorder
Authors: Nazarian Pargol K. , Park Susie H.
Published: December 2014

Insomnia is the most common sleep disorder, and antidepressants are increasingly being used for its management. This article reviews the existing data concerning the use of antidepressants in the treatment of primary insomnia.
The long-term use of sedative hypnotics in chronic insomnia
Authors: Heesch Chelsie B.
Published: December 2014

Symptoms of insomnia are highly prevalent among adults and insomnia is often a chronic condition which may occur for years. Sedative hypnotics including benzodiazepines (BZDs), zolpidem, eszopiclone, and zaleplon (NBZDs) are commonly used to treat insomnia. The longest controlled studies evaluating the safety and efficacy of NBZDs were 12 months in duration and 2 months in duration for the BZD, temazepam. These studies suggest that NBZDs continue to be effective and safe when used for up to 12 months. The short-term adverse effects are more common and more severe for BZDs than for NBZDs. Despite the current practice of using sedative hypnotics for longer durations, studies have yet to evaluate the long-term adverse effect profile.
Potentially inappropriate medications in older adults: A review of the 2012 Beers Criteria and the implications in persons with dementia
Authors: Brandt Nicole J. , Turner Traci
Published: December 2014

In 2012, the American Geriatrics Society (AGS), along with a panel of 11 experts, updated the Beers Criteria which has evolved significantly since its inception in 1991. The Beers Criteria, in general, classifies medications/medication classes as: (1) potentially inappropriate for use in all older adults, (2) potentially inappropriate for older adults with certain diseases or symptoms and (3) requiring extra caution when used in older adults. Although each patient must be evaluated individually, the Beers Criteria is a useful clinical tool that can be used when initiating pharmacologic agents in both ambulatory and institutionalized patients. The concept behind use of the Beers Criteria is that it allows prescribers to readily identify, and avoid, medications associated with negative outcomes in older adults therefore decreasing the risk of adverse drug events (ADEs). Within this review article, there will be a highlight of potentially inappropriate medications (PIMs) commonly seen in clinical practice settings such as antipsychotics, benzodiazepines, non-benzodiazepine sedative-hypnotics, anticholinergics and sliding scale insulin. The focus will be to outline the risk-benefits of these drug classes within the context of persons with dementia. Furthermore, the use of PIMs has both clinical and financial implications in Medicare Star ratings and Healthcare Effectiveness Data and Information Set (HEDIS) measures.
Antipsychotic use in elderly patients with dementia: Efficacy and safety concerns
Authors: Marvanova Marketa
Published: December 2014

Behavioral and psychiatric symptoms of dementia (BPSD) refer to a heterogeneous group of symptoms that represent non-cognitive complications of Alzheimer's disease (AD) and other dementias. Currently, there are no FDA-approved antipsychotic medications for management of BPSD in the United States. Second generation antipsychotics (SGAs) should only be used for appropriate and justified BPSD targets including distressing and severe physical aggression and/or disturbing hallucinations or delusions that pose a risk of harm to self or others after non-pharmacologic interventions have failed. At best, SGAs provide only modest effects and are associated with increased risk for mortality and cerebrovascular complications in addition to other agent-specific side effects. Current evidence and recommendations support use of risperidone, aripiprazole or olanzapine for Alzheimer's disease (AD) and vascular dementia (VaD), and use of quetiapine or clozapine for Lewy body dementia (LBD) and Parkinson's disease dementia (PDD). Any SGA should be initiated at low dosages with slow titration; and the lowest effective dose should be used as a maintenance dose only for a short period of time. Patients should be monitored for clinical response and adverse effects and should be periodically evaluated for continued need for medication. Appropriate use of SGAs for management of BPSD is critical to increase safety for our growing elderly population with dementia.
Treatment options for sundowning in patients with dementia
Authors: Blais Joseph , Zolezzi Monica , Sadowski Cheryl A.
Published: December 2014

Objective. To review the evidence for the pharmacologic and non-pharmacologic management of sundowning in patients with dementia.

Methods. Databases were searched using the terms sundown, circadian, chronobiological, biological clock, elderly, aged, geriatric, and senior. Studies selected for inclusion assessed potential interventions for the treatment of sundowning or nocturnal agitation.

Results. A total of thirteen individual studies and two systematic reviews were evaluated. Study design and outcomes varied, but many measured sleep and nocturnal agitation. Non-pharmacologic interventions that may be of benefit include bright light therapy, music therapy, and aromatherapy. Pharmacologic therapies generally provided minimal benefit and were associated with safety concerns. Supportive evidence was found for the use of melatonin and antipsychotics. Evidence for antidepressants, donepezil, and dronabinol was weaker. Supportive evidence for the use of benzodiazepines was not found and thus cannot be recommended in elderly patients as they are more susceptible to their adverse effects.

Conclusion. The number of studies on the management of sundowning is limited and the quality of evidence supporting its treatment is weak. Non-pharmacologic interventions are first line due to safety. Pharmacologic agents are recommended as second line treatment options, in particular antipsychotics and melatonin.
Utilization of vitamins, herbals, and over-the-counter products to delay progression of dementia
Authors: Butz Jami
Published: December 2014

Many consumers use alternative preparations such as herbals, vitamins, and over-the-counter products in an attempt to prevent or improve the outcome of dementia. Despite use by almost half of all patients, evidence supporting their utilization is either conflicting or lacking. Omega-3 fatty acids, vitamin B6, vitamin B12, vitamin C, and beta-carotene currently do not have clinical trials showing evidence impacting the progression or treatment of symptoms associated with dementia. In addition, conflicting data exist pertaining to the beneficial utilization of ginkgo biloba and nonsteroidal anti-inflammatory drugs associated with dementia treatment. While a link to the utility of folate associated with areas of improved cognitive functioning has been suggested, further studies are needed. Vitamin E may have some benefit in patients with Alzheimer's disease, however, may also have risks in patients with comorbid diseases such as cardiovascular disease or diabetes mellitus. With limited options still existing today in the treatment of dementia, the importance of further studies to quantify alternative therapies remains an important topic.
Use of second generation antipsychotics for treatment-resistant major depressive disorder
Authors: Waite Rebecca
Published: December 2014

Many of the second generation antipsychotics (SGAs) have been studied as adjunctive agents in the management of treatment-resistant major depressive disorder. Two have also been examined for use as monotherapy for depression. Currently, aripiprazole, olanzapine (in combination with fluoxetine), and quetiapine XR are approved by the FDA for use as adjunctive agents in the treatment of major depressive disorder, and no SGAs are FDA-approved as monotherapy for the disorder. This article reviews the available evidence regarding the use of SGAs in patients with treatment-resistant major depressive disorder and the subsequent role for these agents based on this evidence. There is evidence that aripiprazole, quetiapine, olanzapine, and risperidone can be effective in improving depressive symptoms when added to antidepressant therapy, but the benefits have to be weighed against their risk of producing serious adverse effects.
Enhancing patient outcomes globally by providing answers to clinical questions: Developing pharmacy information services and publishing tools and resources
Authors: Carls Katie A.
Published: December 2014

With the rapid growth of medication information and increased demands on healthcare practitioners, efficiently finding answers to clinical questions is of great importance. Working for a medical information services and publishing company is a unique pharmacy practice setting that aims to help improve global healthcare outcomes by efficiently delivering answers to clinical questions during a healthcare practitioner's normal work-flow. This practice setting is well-suited for pharmacists with strong interests in medical writing, research, evidence-based medicine, and informatics.
Case Based Clinical Pearls: A schizophrenic case study
Authors: Deardorff O. Greg , Burton Stephanie A.
Published: December 2014

Clinical pearls based on the treatment of a patient with schizophrenia who had stabbed a taxi cab driver are discussed in this case study. Areas explored include the pharmacokinetics of fluphenazine decanoate, strategies to manage clozapine-associated agranulocytosis, and approaches to addressing hyperprolactinemia.
Pharmacogenomics in psychiatry and neurology: Bridging research and clinical practice
Authors: Saldaña Shannon N. , Mascareñas Cynthia A.
Published: December 2014

The incorporation of pharmacogenomic information in clinical decisions is expected to lead to improved patient care and decreased health care costs. It is not always clear how and when to obtain pharmacogenomic information, due to a lack of guidelines on how to use this information. This article discusses some of the major groups which aim to address these barriers and several important drug-gene pairs relevant to the fields of neurology and psychiatry.
The basics of pharmacogenomics: Review the basics of genomics and available tests
Authors: Ehret Megan
Published: December 2014

Pharmacogenomics, which is the study of genes that determine drug behavior, is a field which has seen an increase in research and discoveries which impact the diagnosis and treatment of various disease states. This article reviews the basic concepts of pharmacogenomics and the genomic tests which are currently available.
Natural variability of CO2 and O2 fluxes: What can we learn from centuries‐long climate models simulations?
Authors: Resplandy L. , Séférian R. , Bopp L.
Published: December 2014

Ocean carbon uptake and oxygen content estimates over the past decades suggest that the anthropogenic carbon sink has changed and that the oxygen concentration in the ocean interior has decreased. Although these detected changes appear consistent with those expected from anthropogenic forced climate change, large uncertainties remain in the contribution of natural variability. Using century‐long simulations (500–1000 years) of unforced natural variability from six Earth System Models (ESMs), we examine the internally driven natural variability of carbon and oxygen fluxes from interannual to multidecadal time scales. The intensity of natural variability differs between the ESMs, in particular, decadal variability locally accounts for 10–50% of the total variance. Although the variability is higher in all regions with strong climate modes (North Atlantic, North Pacific, etc.), we find that only the Southern Ocean and the tropical Pacific significantly modulate the global fluxes. On (multi)decadal time scales, deep convective events along the Antarctic shelf drive the global fluxes variability by transporting deep carbon‐rich/oxygen‐depleted waters to the surface and by reducing the sea‐ice coverage. On interannual time scales, the global flux is modulated by (1) variations of the upwelling of circumpolar deep waters associated with the southern annular mode in the subpolar Southern Ocean and (2) variations of the equatorial/costal upwelling combined with changes in the solubility‐driven fluxes in response to El Niño Southern Oscillation (ENSO) in the tropical Pacific. We discuss the challenges of measuring and detecting long‐term trends from a few decade‐long records influenced by internal variability.
Oxidative Alkenylation/Annulation of Benzimidates via Ruthenium(II)‐Catalyzed CH Activation to Generate 3‐Methyleneisoindolin‐1‐ones
Authors: Li Xing Guang , Sun Min , Liu Kai , Liu Pei Nian
Published: December 2014

A novel ruthenium‐catalyzed oxidative alkenylation/annulation cascade reaction is described for synthesizing 3‐methyleneisoindolin‐1‐ones. In the protocol, the NH imidate is applied efficiently as a directing group in ruthenium‐catalyzed CH activation, generating various 3‐methyleneisoindolin‐1‐ones with high regio‐ and stereoselectivity in moderate to good yields.

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Cutaneous B‐cell lymphomas: 2015 update on diagnosis, risk‐stratification, and management
Authors: Wilcox Ryan A.
Published: December 2014

Disease overview: Approximately one‐fourth of cutaneous lymphomas are B‐cell derived and are generally classified into three distinct subgroups: primary cutaneous follicle center lymphoma (PCFCL), primary cutaneous marginal zone lymphoma (PCMZL), and primary cutaneous diffuse large B‐cell lymphoma, leg type (PCDLBCL, LT).

Diagnosis: Diagnosis and disease classification is based on histologic review and immunohistochemical staining of an appropriate skin biopsy. Pathologic review and an appropriate staging evaluation are necessary to distinguish primary cutaneous B‐cell lymphomas from systemic B‐cell lymphomas with secondary skin involvement.

Risk‐stratification: Disease histology remains the most important prognostic determinant. Both PCFCL and PCMZL are indolent lymphomas that infrequently disseminate to extracutaneous sites and are associated with 5‐year survival rates that exceed 95%. In contrast, PCDLBCL, LT is an aggressive lymphoma with an inferior prognosis.

Risk‐adapted therapy: PCFCL and PCMZL patients with solitary or relatively few skin lesions may be affectively managed with local radiation therapy. While single‐agent rituximab may be employed for patients with more widespread skin involvement, multiagent chemotherapy is rarely appropriate. In contrast, management of patients with PCDLBCL, LT is comparable to the management of patients with systemic DLBCL. Am. J. Hematol. 90:74–76, 2015. © 2014 Wiley Periodicals, Inc.
Epiphyseal fusion in Pan troglodytes relative to dental age
Authors: Brimacombe Conrad S. , Kuykendall Kevin L. , Nystrom Pia
Published: December 2014

Previous studies on different aspects of chimpanzee growth and development have documented dental eruption and development, long bone and somatic growth, and to a lesser extent, skeletal fusion. Such data are useful in comparative and evolutionary studies of growth and some aspects of life history evolution in apes and early hominids. However, few studies have integrated dental development and other aspects of skeletal development, and none of these have been able to incorporate a large study sample. This study documents dental mineralization and skeletal epiphyseal fusion in a mixed‐sex sample of 155 Pan troglodytes skeletons, and aims to: a) document the pattern of dental and skeletal developmental in chimpanzees; b) compare male and female developmental patterns in chimpanzees; and c) compare these chimpanzee developmental patterns to general patterns of dental and skeletal development in published human studies. The analysis of both dental and skeletal development in this sample demonstrates clearly that dental development is complete before the fusion of the many skeletal epiphyses, in contrast to the pattern observed in humans. Age estimates for individuals were calculated using previously published regression equations for dental development and used to estimate fusion ages. These appear to be accurate in that our estimates are similar to published ranges. These data improve our understanding about chimpanzee dental and skeletal development and provide a basis for further comparison between extant apes and humans, as well as those extinct species represented by fossil partial skeletons. Am J Phys Anthropol 157:19–29, 2015. © 2014 Wiley Periodicals, Inc.
Highly Diastereoselective and Enantioselective Olefin Cyclopropanation Using Engineered Myoglobin‐Based Catalysts
Authors: Bordeaux Melanie , Tyagi Vikas , Fasan Rudi
Published: December 2014

Using rational design, an engineered myoglobin‐based catalyst capable of catalyzing the cyclopropanation of aryl‐substituted olefins with catalytic proficiency (up to 46 800 turnovers) and excellent diastereo‐ and enantioselectivity (98–99.9 %) was developed. This transformation could be carried out in the presence of up to 20 g L−1 olefin substrate with no loss in diastereo‐ and/or enantioselectivity. Mutagenesis and mechanistic studies support a cyclopropanation mechanism mediated by an electrophilic, heme‐bound carbene species and a model is provided to rationalize the stereopreference of the protein catalyst. This work shows that myoglobin constitutes a promising and robust scaffold for the development of biocatalysts with carbene‐transfer reactivity.
Effects of unsteady mountain‐gap winds on eddies in the Red Sea
Authors: Farley Nicholls J. , Toumi R. , Stenchikov G.
Published: December 2014

Atmosphere and ocean simulations capture the Tokar mountain‐gap wind jet and associated eddy dipole in the Red Sea. Results suggest that, once generated by a wind event, the anticyclonic eddy is further intensified through the summer by subsequent events. An asymmetry in magnitude of the two eddies is observed with the anticyclonic eddy attaining greater magnitude. A series of simulations with idealized wind forcing show that this asymmetry is not present under steady wind forcing. This effect depends on the intermittency of the wind forcing and the presence of a background northerly wind field.
Increase in surface albedo caused by agricultural plastic film
Authors: Fan X. , Chen H. , Xia X. , Yu Y.
Published: December 2014

The area of agricultural greenhouses and cropland covered by plastic film has increased in China over the past three decades. Construction of large‐area plastic greenhouse potentially changes the physical and radiative properties of the surface and its albedo, thereby potentially affecting the surface energy budget and climate change. This study aims to investigate the effect of the plastic‐film cover on surface albedo based on computations with a simplified model and several field observation experiments. The results showed that surface albedo increased by ∼23.5 and ∼33.9% on clear and overcast days, respectively, if grassland was covered by plastic film. Surface albedo of bare soil covered by plastic film increased by ∼16.6% under clear sky conditions. A larger increase in surface albedo was derived for surface types with smaller surface albedo. Model calculations were in good agreement with field observations.
Efficacy of triplet regimen antiemetic therapy for chemotherapy‐induced nausea and vomiting (CINV) in bone and soft tissue sarcoma patients receiving highly emetogenic chemotherapy, and an efficacy comparison of single‐shot palonosetron and consecutive‐day granisetron for CINV in a randomized, single‐blinded crossover study
Authors: Kimura Hiroaki , Yamamoto Norio , Shirai Toshiharu , Nishida Hideji , Hayashi Katsuhiro , Tanzawa Yoshikazu , Takeuchi Akihiko , Igarashi Kentaro , Inatani Hiroyuki , Shimozaki Shingo , Kato Takashi , Aoki Yu , Higuchi Takashi , Tsuchiya Hiroyuki
Published: December 2014

The first aim of this study was to evaluate combination antiemetic therapy consisting of 5‐HT3 receptor antagonists, neurokinin‐1 receptor antagonists (NK‐1RAs), and dexamethasone for multiple high emetogenic risk (HER) anticancer agents in bone and soft tissue sarcoma. The second aim was to compare the effectiveness of single‐shot palonosetron and consecutive‐day granisetron in a randomized, single‐blinded crossover study. A single randomization method was used to assign eligible patients to the palonosetron or granisetron arm. Patients in the palonosetron arm received a palonosetron regimen during the first and third chemotherapy courses and a granisetron regimen during the second and fourth courses. All patients received NK‐1RA and dexamethasone. Patients receiving the palonosetron regimen were administered 0.75 mg palonosetron on day 1, and patients receiving the granisetron regimen were administered 3 mg granisetron twice daily on days 1 through 5. All 24 patients in this study received at least 4 chemotherapy courses. A total of 96 courses of antiemetic therapy were evaluated. Overall, the complete response CR rate (no emetic episodes and no rescue medication use) was 34%, while the total control rate (a CR plus no nausea) was 7%. No significant differences were observed between single‐shot palonosetron and consecutive‐day granisetron. Antiemetic therapy with a 3‐drug combination was not sufficient to control chemotherapy‐induced nausea and vomiting (CINV) during chemotherapy with multiple HER agents for bone and soft tissue sarcoma. This study also demonstrated that consecutive‐day granisetron was not inferior to single‐shot palonosetron for treating CINV.
Microwave Irradiation Coupled with Physically Mixed MeOx (Me=Mn, Ni) and Cu‐ZSM‐5 Catalysts for the Direct Decomposition of Nitric Oxide under Excess Oxygen
Authors: Xu Wentao , Zhou Jicheng , You Zhimin , Luo Yushang , Ou Yingpiao
Published: December 2014

The direct catalytic decomposition of NO into N2 and O2 with high activity and N2 selectivity at low temperature under excess oxygen is a challenge. Herein, we report a new approach for the direct decomposition of NO into N2 and O2 by microwave catalysis over MeOx‐Cu‐ZSM‐5 (Me=Mn, Ni) under excess oxygen. We observed that the microwave direct catalytic decomposition of NO over MeOx‐Cu‐ZSM‐5 under excess oxygen is highly efficient, and the NO conversions are 94.3 % over MnO2‐Cu‐ZSM‐5 at 300 °C and 92.3 % over Ni2O3‐Cu‐ZSM‐5 at 350 °C. Meanwhile, the N2 selectivity remains more than 98 %. Importantly, the apparent activation energies of MnO2‐Cu‐ZSM‐5 and Ni2O3‐Cu‐ZSM‐5 are as low as 15.5 and 25.7 kJ mol−1, which suggests a significant microwave catalytic effect. Furthermore, microwave irradiation exhibits a microwave selective effect. The oxygen concentration has almost no influence on the activity of catalytic decomposition of NO over MeOx‐Cu‐ZSM‐5 under microwave irradiation.
Porous Dual‐Layered MoOx Nanotube Arrays with Highly Conductive TiN Cores for Supercapacitors
Authors: Peng Xiang , Huo Kaifu , Fu Jijiang , Gao Biao , Wang Lei , Hu Liangsheng , Zhang Xuming , Chu Paul K.
Published: December 2014

Porous dual‐layered molybdenum oxide (MoOx) nanotube arrays (NTAs) with highly conductive titanium nitride (TiN) cores (MoOx/TiN/MoOx NTAs) are fabricated by depositing MoOx on porous TiN NTAs produced by nitriding as‐anodized TiO2 NTAs on Ti foils. The highly conductive TiN facilitates electron transfer and the porous MoOx wall allows the electrolyte to permeate the nanotubes readily, maximizing the active sites of the MoOx electroactive material to improve the specific capacitance and rate capability. The coaxial MoOx/TiN/MoOx NTA electrode shows a high specific capacitance of 97 mF cm−2 (323 F g−1) at a current density of 1 mA cm−2, and 60 % capacitance is retained when the current density is increased 20 times. A symmetrical device based on the MoOx/TiN/MoOx NTA electrode exhibits a capacitance as high as 24 F cm−3 (based on the volume of MoOx/TiN/MoOx NTAs) and no significant decay is observed after charging/discharging for 10 000 cycles.
Molecular Size and Electronic Structure Combined Effects on the Electrogenerated Chemiluminescence of Sulfurated Pyrene‐Cored Dendrimers
Authors: Valenti Giovanni , Fiorani Andrea , Di Motta Simone , Bergamini Giacomo , Gingras Marc , Ceroni Paola , Negri Fabrizia , Paolucci Francesco , Marcaccio Massimo
Published: December 2014

The electrochemistry, photophysics, and electrochemically generated chemiluminescence (ECL) of a family of polysulfurated dendrimers with a pyrene core have been thoroughly investigated and complemented by theoretical calculations. The redox and luminescence properties of dendrimers are dependent on the generation number. From low to higher generation it is both easier to reduce and oxidize them and the emission efficiency increases along the family, with respect to the polysulfurated pyrene core. The analysis of such data evidences that the formation of the singlet excited state by cation–anion annihilation is an energy‐deficient process and, thus, the ECL has been justified through the triplet–triplet annihilation pathway. The study of the dynamics of the ECL emission was achieved both experimentally and theoretically by molecular mechanics and quantum chemical calculations. It has allowed rationalization of a possible mechanism and the experimental dependence of the transient ECL on the dendrimer generation. The theoretically calculated Marcus electron‐transfer rate constant compares very well with that obtained by the finite element simulation of the whole ECL mechanism. This highlights the role played by the thioether dendrons in modulating the redox and photophysical properties, responsible for the occurrence and dynamics of the electron transfer involved in the ECL. Thus, the combination of experimental and computational results allows understanding of the dendrimer size dependence of the ECL transient signal as a result of factors affecting the annihilation electron transfer.
Supramolecular Control of Spin Exchange in a Spin‐Labelled [2]Rotaxane Incorporating a Tetrathiafulvalene Unit
Authors: Romano Francesco , Manoni Roberta , Franchi Paola , Mezzina Elisabetta , Lucarini Marco
Published: December 2014

The EPR properties of a novel triradical obtained by single‐electron oxidation of a nitroxide‐spin‐labelled rotaxane containing a tetrathiafulvalene unit and cyclobis(paraquat‐p‐phenylene) ring is reported. Rotaxanation is proved to have a dramatic effect on through‐space magnetic interactions between radical fragments. Analysis of the EPR spectra by a three‐jump model, allowed us to obtain structural information on the interlocked structure.
The next generation of epidermal growth factor receptor tyrosine kinase inhibitors in the treatment of lung cancer
Authors: Steuer Conor E. , Khuri Fadlo R. , Ramalingam Suresh S.
Published: December 2014

The discovery of “driver” genomic alterations in patients with non‐small cell lung cancer (NSCLC) has dramatically changed the field of thoracic oncology in recent years. The best understood of these molecular drivers are those involving the epidermal growth factor receptor (EGFR), which when aberrantly activated are integral to the development of a subset of NSCLC tumors. First‐generation and second‐generation tyrosine kinase inhibitors (TKIs) specific to the activated EGFR have shown significant efficacy and have brought about the era of targeted therapy for NSCLC. The most common resistance mechanism is a threonine‐to‐methionine substitution (T790M) in exon 20 of the EGFR gene. Although the previous standard of care in patients with EGFR‐mutated NSCLC that progressed on initial TKI therapy was chemotherapy, third‐generation EGFR TKIs have now been developed and have yielded promising results for this population of patients with NSCLC. This article reviews the emerging data regarding third‐generation agents in the treatment of patients with advanced NSCLC. Cancer 2015;121:E1–E6. © 2014 American Cancer Society.
Remarkable Selectivity and Photo‐Cytotoxicity of an Oxidovanadium(IV) Complex of Curcumin in Visible Light
Authors: Banerjee Samya , Dixit Akanksha , Karande Anjali A. , Chakravarty Akhil R.
Published: December 2014

Oxidovanadium(IV) complexes of 2‐(2′‐pyridyl)‐1,10‐phenanthroline (pyphen), viz. [VO(pyphen)(acac)](ClO4) (1), [VO(pyphen)(anacac)](ClO4) (2) and [VO(pyphen)(cur)](ClO4) (3), where acac is acetylacetonate (in 1), anacac is anthracenylacetylacetonate (in 2) and cur is curcumin monoanion (in 3) were synthesized, characterized and their photo‐induced DNA cleavage activities and photo‐cytotoxicities studied. The complexes are 1:1 electrolytes in DMF. The one‐electron paramagnetic complexes show a d‐d band near 760 nm in DMF. Complexes 2 and 3 are blue and green emissive, respectively, in DMSO. The complexes exhibit irreversible VIV/VIII reductive responses near –1.1 V and VV/VIV oxidative responses near 0.85 V vs. SCE in DMF–0.1 M TBAP. Complexes 2 and 3 display significant and selective photo‐cytotoxicity upon irradiation with visible light giving an IC50 value of about 5 μM against HeLa and MCF‐7 cancer cells; they are significantly less‐toxic against normal 3T3 control cells and in the absence of light. Complex 1 was used as a control. Both cytosolic and nuclear localization of the complexes were observed on the basis of fluorescence imaging. The complexes, avid binders to calf thymus (ct) DNA, were found to photocleave supercoiled pUC19 DNA upon irradiation with near‐IR light (785 nm) by generating hydroxyl radical (·OH) as the reactive oxygen species (ROS). Cell death events noted with HeLa and MCF‐7 cell lines likely are attributable to apoptotic pathways involving light‐assisted generation of intracellular ROS.