bluuebunny/crossref_metadata_2025 huggingface dataset:
Nocturnal emergency department visits, duration of symptoms and risk of hospitalisation among adults with asthma exacerbations: a multicentre observational study
Authors: Yasuda Hideto , Hagiwara Yusuke , Watase Hiroko , Hasegawa Kohei
Published: August 2016

Objectives

We sought to compare the characteristics of patients with asthma presenting to the emergency department (ED) during the night-time with those of patients presenting at other times of the day, and to determine whether the time of ED presentation is associated with the risk of hospitalisation.

Design and setting

A multicentre chart review study of 23 EDs across Japan.

Participants

Patients aged 18–54 years with a history of physician-diagnosed asthma, presented to the ED between January 2009 and December 2011

Outcome measures

The outcome of interest was hospitalisation, including admissions to an observation unit, inpatient unit and intensive care unit.

Results

Among the 1354 patients (30.1% in the night-time group vs 69.9% in the other time group) included in this study, the median age was 34 years and ∼40% were male. Overall 145 patients (10.7%) were hospitalised. Patients in the night-time group were more likely to have a shorter duration of symptoms (≤3 hours) before ED presentation than those in the other time group (25.9% in night-time vs 13.4% in other times; p<0.001). In contrast, there were no significant differences in respiratory rate, initial peak expiratory flow or ED asthma treatment between the two groups (p>0.05). Similarly, the risk of hospitalisation did not differ between the two groups (11.3% in night-time vs 10.5% in other times; p=0.65). In a multivariable model adjusting for potential confounders, the risk of hospitalisation in the night-time group was not statistically different from the other time group (OR, 1.10; 95% CI 0.74 to 1.61; p=0.63).

Conclusions

This multicentre study in Japan demonstrated no significant difference in the risk of hospitalisations according to the time of ED presentation.
New method of preoxygenation for orotracheal intubation in patients with hypoxaemic acute respiratory failure in the intensive care unit, non-invasive ventilation combined with apnoeic oxygenation by high flow nasal oxygen: the randomised OPTINIV study protocol
Authors: Jaber Samir , Molinari Nicolas , De Jong Audrey
Published: August 2016

Introduction

Tracheal intubation in the intensive care unit (ICU) is associated with severe life-threatening complications including severe hypoxaemia. Preoxygenation before intubation has been recommended in order to decrease such complications. Non-invasive ventilation (NIV)-assisted preoxygenation allows increased oxygen saturation during the intubation procedure, by applying a positive end-expiratory pressure (PEEP) to prevent alveolar derecruitment. However, the NIV mask has to be taken off after preoxygenation to allow the passage of the tube through the mouth. The patient with hypoxaemia does not receive oxygen during this period, at risk of major hypoxaemia. High-flow nasal cannula oxygen therapy (HFNC) has a potential for apnoeic oxygenation during the apnoea period following the preoxygenation with NIV. Whether application of HFNC combined with NIV is more effective at reducing oxygen desaturation during the intubation procedure compared with NIV alone for preoxygenation in patients with hypoxaemia in the ICU with acute respiratory failure remains to be established.

Methods and analysis

The HFNC combined to NIV for decreasing oxygen desaturation during the intubation procedure in patients with hypoxaemia in the ICU (OPTINIV) trial is an investigator-initiated monocentre randomised controlled two-arm trial with assessor-blinded outcome assessment. The OPTINIV trial randomises 50 patients with hypoxaemia requiring orotracheal intubation for acute respiratory failure to receive NIV (pressure support=10, PEEP=5, fractional inspired oxygen (FiO2)=100%) combined with HFNC (flow=60 L/min, FiO2=100%, interventional group) or NIV alone (reference group) for preoxygenation. The primary outcome is lowest oxygen saturation during the intubation procedure. Secondary outcomes are intubation-related complications, quality of preoxygenation and ICU mortality.

Ethics and dissemination

The study project has been approved by the appropriate ethics committee (CPP Sud-Méditerranée). Informed consent is required. If combined application of HFNC and NIV for preoxygenation of patients with hypoxaemia in the ICU proves superior to NIV preoxygenation, its use will become standard practice, thereby decreasing hypoxaemia during the intubation procedure and potential complications related to intubation.

Trial registration number

NCT02530957.
Pursuit of performance excellence: a population study of Norwegian adolescent female cross-country skiers and biathletes with disordered eating
Authors: Pettersen Ingvild , Hernæs Erik , Skårderud Finn
Published: August 2016

Aim

To examine the prevalence of disordered eating (DE) among the total population of Norwegian female cross-country skiers and biathletes at the junior level, and to determine whether sociodemographic characteristics predict DE among athletes.

Methods

A cross-sectional population study of Norwegian female junior cross-country skiers and biathletes (n=262), with a response rate of 86%. Descriptive statistics and logistic regression analyses explored the prevalence of DE and its relation to sports, competitive age groups, competitive status and education. DE was defined as meeting at least 1 of the following criteria from 2 subscales of the Eating Disorder Inventory-2: the Drive for Thinness score ≥15 and/or the Body Dissatisfaction score ≥14.

Results

18.7% of the athletes had DE. There was no significant difference in the occurrence of DE between the sports or the competitive age groups. Athletes who had dropped out of sports had a significantly higher occurrence of DE, while athletes who attended upper secondary schools of elite sports or general studies had a significantly higher occurrence of DE based on Drive for Thinness.

Conclusions

The number of female cross-country skiers and biathletes with DE is higher than that found in previous similar studies using the same screening instruments. Type of education and competitive status are significant predictors of DE, indicating that DE in addition to having adverse effects on an athlete's health, may also lead to early dropout of sport. This indicates that health and achievement are not always compatible within sports.
Critical care in the Emergency Department: organ donation
Authors: Gardiner Dale C , Nee Matthew S , Wootten Andrea E , Andrews Francis J , Bonney Samantha C , Nee Patrick A
Published: August 2016

Organ transplantation is associated with improved outcomes for some patients with end-stage organ failure; however, the number of patients awaiting a transplant exceeds the available organs. Recently, an extended role has been proposed for EDs in the recognition and management of potential donors. The present review presents an illustrative case report and considers current transplantation practice in the UK. Ethical and legal considerations, the classification of deceased donors and future developments promising greater numbers of organs are discussed.
Psychological distress, neuroticism, and cause-specific mortality: early prospective evidence from UK Biobank
Authors: Batty G David , McIntosh Andrew M , Russ Tom C , Deary Ian J , Gale Catharine R
Published: August 2016

Background

It is well established that psychological distress (depression and anxiety) is related to an increased risk of mortality. The personality trait of neuroticism, reflecting a relatively stable tendency towards negative emotions, has also been associated with elevated rates of death in some studies. Accordingly, we tested the possibility that it is the neuroticism trait itself, rather than the distress state, that is generating an increased risk of mortality.

Methods

We used data from the UK Biobank study, a UK-wide prospective cohort study (2006–2010) in which distress was ascertained using the Patient Health Questionnaire and neuroticism using the Eysenck Personality Questionnaire-Revised Short Form.

Results

A mean of 6.2 years of follow-up of 308 721 study members gave rise to 4334 deaths. Higher neuroticism was weakly associated with total mortality (age-adjusted and sex-adjusted HR per SD increase; 95% CI 1.05; 1.02 to 1.09), and moderately strongly correlated with distress symptoms (r=0.55, p<0.0001). Distress symptoms were positively related to risk of total mortality (age-adjusted and sex-adjusted HR per SD increase in distress; 95% CI 1.23; 1.20 to 1.26). This gradient was, in fact, slightly strengthened after adding neuroticism to the multivariable model (1.30; 1.26 to 1.34) but markedly attenuated after taking into account other covariates which included health behaviours and somatic disease (1.16; 1.12 to 1.20). Similar results were apparent when cardiovascular disease, cancer and external cause of death were the end points of interest.

Conclusions

While there was good a priori reasons to anticipate the neuroticism would at least partially explain the relation between distress symptoms and cause-specific mortality, we found no such evidence in the present study.
Protective Effects of a Natural Product, Curcumin, against Amyloid β Induced Mitochondrial and Synaptic Toxicities in Alzheimer'S Disease
Authors: Reddy P Hemachandra , Manczak Maria , Yin Xiangling , Grady Mary Catharine , Mitchell Andrew , Kandimalla Ramesh , Kuruva Chandra Sekhar
Published: August 2016

The purpose of our study was to investigate the protective effects of a natural product—‘curcumin’— in Alzheimer's disease (AD)-like neurons. Although much research has been done in AD, very little has been reported on the effects of curcumin on mitochondrial biogenesis, dynamics, function and synaptic activities. Therefore, the present study investigated the protective effects against amyloid β (Aβ) induced mitochondrial and synaptic toxicities. Using human neuroblastoma (SHSY5Y) cells, curcumin and Aβ, we studied the protective effects of curcumin against Aβ. Further, we also studied preventive (curcumin+Aβ) and intervention (Aβ+curcumin) effects of curcumin against Aβ in SHSY5Y cells. Using real time RT-PCR, immunoblotting and immunofluorescence analysis, we measured mRNA and protein levels of mitochondrial dynamics, mitochondrial biogenesis and synaptic genes. We also assessed mitochondrial function by measuring hydrogen peroxide, lipid peroxidation, cytochrome oxidase activity and mitochondrial ATP. Cell viability was studied using the MTT assay. Aβ was found to impair mitochondrial dynamics, reduce mitochondrial biogenesis and decrease synaptic activity and mitochondrial function. In contrast, curcumin enhanced mitochondrial fusion activity and reduced fission machinery, and increased biogenesis and synaptic proteins. Mitochondrial function and cell viability were elevated in curcumin treated cells. Interestingly, curcumin pre- and post-treated cells incubated with Aβ showed reduced mitochondrial dysfunction, and maintained cell viability and mitochondrial dynamics, mitochondrial biogenesis and synaptic activity. Further, the protective effects of curcumin were stronger in pretreated SHSY5Y cells than in post-treated cells, indicating that curcumin works better in prevention than treatment in AD-like neurons. Our findings suggest that curcumin is a promising drug molecule to treat AD patients.
Whence ‘zoster’? The convoluted classical origins of a sometimes illogical term
Authors: Schott G D
Published: August 2016

The term ‘zoster’ is nowadays associated with ‘herpes zoster’, the condition resulting from reactivation of the latent varicella-zoster virus which causes shingles. But in antiquity the meaning of ‘zoster’, a Latin word originating from the Greek for a belt or girdle, was variously associated in men with a form of body armour which could enclose just one half of the body; in women with a garment worn around the waist and sometimes called a ‘zona’; and with a place, Zoster, linked mythologically then with the goddess Leto and her zona. Around 48 AD, the Roman physician Scribonius Largus became the first to associate ‘zona’ with ‘herpes’, and to attribute a medical meaning to ‘zona’, here an abbreviation of ‘zona ignea’ (‘fiery girdle’). Although in the past the terms ‘zoster’ and ‘zona’ were sometimes used interchangeably, today only ‘zoster’ remains—even when etymologically illogical in those patients whose zoster rash occurs in body areas other than the trunk.
The clinical value of pathology tests and imaging study in the diagnosis of acute appendicitis
Authors: Chen Ko-Chin , Arad Alon , Chen Ko-Chien , Storrar Jonathan , Christy Andrew G
Published: August 2016

Objective

To explore the diagnostic accuracy of acute appendicitis among different patient groups and evaluate the statistical diagnostic values of common pathology and imaging tests for the diagnosis of acute appendicitis.

Main Measures

Proportions of histology-proven appendicitis in different patient groups. Statistical parameters including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (+LR), negative likelihood ratio (-LR) and diagnostic odds ratio (DOR) between the histology-proven appendicitis and abnormal results of U/S, CT, WCC, CRP, bilirubin, pancreatic, and combined test results of WCC and CRP.

Results

Our data showed that up to 25.7% of patients underwent appendectomy has normal appendix. Appendicitis is often accurately diagnosed among male patients, up to 90.3% of the time, while misdiagnosis of appendicitis among young females (<40 years old) is significantly high, up to 30.9%. CT has high diagnostic performance index for appendicitis, sensitivity > 90%, and no individual pathology test out of those examined can rival the sensitivity of CT. Nevertheless, by examining the combined results of WCC and CRP, we found that abnormal results in one or both these yields sensitivity similar to CT scans in detecting acute appendicitis, up to 95%.

Conclusion

Young female patients have highest risk of being falsely diagnosed with acute appendicitis and hence unnecessary surgery. Bilirubin and lipase exhibit no correlations with acute appendicitis. Combined interpretation of WCC or CRP abnormal results yields competitive sensitivity as CT. Hencewe would suggest that, under the appropriate clinical context, one can use both WCC and CRP as a simple tool to support the diagnosis of appendicitis. If both tests show normal results, we would highly recommend considering alternative diagnosis.
Compensation and exotic livestock disease management: the views of animal keepers and veterinarians in England
Authors: Hamilton‐Webb A. , Naylor R. , Little R. , Maye D.
Published: August 2016

Relatively little is known about the perceived influence of different compensation systems on animal keepers’ management of exotic livestock disease. This paper aims to address this research gap by drawing on interviews with 61 animal keepers and 21 veterinarians, as well as a series of nine animal keeper focus groups across five different livestock sectors in England. The perceived influence of current compensation systems on disease control behaviour was explored and alternative compensation systems that respectively reward positive practices and penalise poor practices were presented in the form of scenarios, alongside a third system that considered the option of a cost‐sharing levy system between industry and government. The results indicate that animal keepers consider themselves to be influenced by a range of non‐financial factors, for example, feelings of responsibility, reputation and animal welfare concerns, in the context of their exotic disease management practices. The majority of animal keepers were unaware of the current compensation systems in place for exotic diseases, and were therefore not consciously influenced by financial recompense. Concerns were raised about linking compensation to disease management behaviour due to auditing difficulties. A cost‐sharing levy system would likely raise awareness of exotic disease and compensation among animal keepers, but differentiation of payments based upon individual farm‐level risk assessments was called for by participants as a strategy to promote positive disease management practices.
Stratigraphic architecture of the Knarr Field, Norwegian North Sea: sedimentology and biostratigraphy of an evolving tide- to wave-dominated shoreline system
Authors: Churchill James M. , Poole Matthew T. , Skarpeid Silje S. , Wakefield Matthew I.
Published: August 2016

The Knarr Field is located on the Tampen Spur, Norwegian continental shelf and was discovered in 2008 by the Jordbær well (34/3-1S), with additional resources later added to the field by the Jordbær Vest well (34/3-3S) in 2011. Within the Knarr Field, the Cook Formation is informally divided into the Lower Cook and Upper Cook successions and appears to have prograded from east to west. The Lower Cook consists of Sands 1, 2 and 3 and the Upper Cook consists of Sands 4 and 5, with the sands separated by intraformational mudstones that are commonly chronostratigraphically constrained; the J15 maximum flooding surface separates the Lower and Upper Cook. The tide-dominated Lower Cook is notably heterolithic, with intricate intercalations of sandstone and mudrock lithologies representing tidal channel, tidal bar and intertidal bar facies. The Upper Cook represents a series of coarsening-upwards cycles that displays the systematic changes in facies and ichnology expected for a shoreface succession, consisting of offshore, offshore transition zone and shoreface facies. Palynomorphs confirm these observations and suggest that the Lower Cook was deposited in brackish-water conditions, whereas the presence of more marine fossils in the Upper Cook suggests an increase in marine influence. The integration of the sedimentology and biostratigraphy described herein enabled the establishment of a robust reservoir zonation that has been utilized during the development and ongoing exploitation of the Knarr Field.
Controls on the location of compressional deformation on the NW European margin
Authors: Kimbell G. S. , Stewart M. A. , Gradmann S. , Shannon P. M. , Funck T. , Haase C. , Stoker M. S. , Hopper J. R.
Published: August 2016

The distribution of Cenozoic compressional structures along the NW European margin has been compared with maps of the thickness of the crystalline crust derived from a compilation of seismic refraction interpretations and gravity modelling, and with the distribution of high-velocity lower crust and/or partially serpentinized upper mantle detected by seismic experiments. Only a subset of the mapped compressional structures coincide with areas susceptible to lithospheric weakening as a result of crustal hyperextension and partial serpentinization of the upper mantle. Notably, partially serpentinized upper mantle is well documented beneath the central part of the southern Rockall Basin, but compressional features are sparse in that area. Where compressional structures have formed but the upper mantle is not serpentinized, simple rheological modelling suggests an alternative weakening mechanism involving ductile lower crust and lithospheric decoupling. The presence of pre-existing weak zones (associated with the properties of the gouge and overpressure in fault zones) and local stress magnitude and orientation are important contributing factors.
The Economics of Wind Power
Authors: van Kooten G. Cornelis
Published: August 2016

Many countries have incentivized wind power projects to reduce their reliance on fossil fuels for generating electricity. As shown in this review, the benefits and costs of integrating electricity from an intermittent wind source into a preexisting electricity grid depend on the operating protocols of the electricity system, the preexisting generation mix, wind profiles, and the nature of economic incentives. Electricity systems are discussed from generation through transmission and distribution to retail demand, including how wind energy impacts investment in marginal (peak time) generating assets. The discussion also examines issues that could limit the usefulness of wind power at the high penetration rates now envisioned: the inability to store electricity, the need for fast-responding backup-generating capacity, network instability, low-capacity factors, and inappropriate incentives. Overall, this review finds that the costs of wind power likely exceed the benefits and that there may be limits to the proportion of electricity that can be generated by wind.
Extracellular matrix fibronectin mediates an endothelial cell response to shear stress via the heparin-binding, matricryptic RWRPK sequence of FNIII1H
Authors: Okech William , Abberton Keren M. , Kuebel Julia M. , Hocking Denise C. , Sarelius Ingrid H.
Published: August 2016

Endothelial cells (EC) respond to mechanical forces such as shear stress in a variety of ways, one of which is cytoskeletal realignment in the direction of flow. Our earlier studies implicated the extracellular matrix protein fibronectin in mechanosensory signaling to ECs in intact arterioles, via a signaling pathway dependent on the heparin-binding region of the first type III repeat of fibrillar fibronectin (FNIII1H). Here we test the hypothesis that FNIII1H is required for EC stress fiber realignment under flow. Human umbilical vein ECs (HUVECs) exposed to defined flow conditions were used as a well-characterized model of this stress fiber alignment response. Our results directly implicate FNIII1H in realignment of stress fibers in HUVECs and, importantly, show that the matricryptic heparin-binding RWRPK sequence located in FNIII1 is required for the response. Furthermore, we show that flow-mediated stress fiber realignment in ECs adhered via α5β1-integrin-specific ligands does not occur in the absence of FHIII1H, whereas, in contrast, αvβ3-integrin-mediated stress fiber realignment under flow does not require FNIII1H. Our findings thus indicate that there are two separate mechanosignaling pathways mediating the alignment of stress fibers after exposure of ECs to flow, one dependent on αvβ3-integrins and one dependent on FNIII1H. This study strongly supports the conclusion that the RWRPK region of FNIII1H may have broad capability as a mechanosensory signaling site.
Dopamine induces lipid accumulation, NADPH oxidase-related oxidative stress, and a proinflammatory status of the plasma membrane in H9c2 cells
Authors: Begieneman Mark P. V. , ter Horst Ellis N. , Rijvers Liza , Meinster Elisa , Leen René , Pankras Jeannette E. , Fritz Jan , Kubat Bela , Musters René J. P. , van Kuilenburg André B. P. , Stap Jan , Niessen Hans W. M. , Krijnen Paul A. J.
Published: August 2016

Excess catecholamine levels are suggested to be cardiotoxic and to underlie stress-induced heart failure. The cardiotoxic effects of norepinephrine and epinephrine are well recognized. However, although cardiac and circulating dopamine levels are also increased in stress cardiomyopathy patients, knowledge regarding putative toxic effects of excess dopamine levels on cardiomyocytes is scarce. We now studied the effects of elevated dopamine levels in H9c2 cardiomyoblasts. H9c2 cells were cultured and treated with dopamine (200 μM) for 6, 24, and 48 h. Subsequently, the effects on lipid accumulation, cell viability, flippase activity, reactive oxygen species (ROS) production, subcellular NADPH oxidase (NOX) protein expression, and ATP/ADP and GTP/GDP levels were analyzed. Dopamine did not result in cytotoxic effects after 6 h. However, after 24 and 48 h dopamine treatment induced a significant increase in lipid accumulation, nitrotyrosine levels, indicative of ROS production, and cell death. In addition, dopamine significantly reduced flippase activity and ATP/GTP levels, coinciding with phosphatidylserine exposure on the outer plasma membrane. Furthermore, dopamine induced a transient increase in cytoplasmic and (peri)nucleus NOX1 and NOX4 expression after 24 h that subsided after 48 h. Moreover, while dopamine induced a similar transient increase in cytoplasmic NOX2 and p47phox expression, in the (peri)nucleus this increased expression persisted for 48 h where it colocalized with ROS. Exposure of H9c2 cells to elevated dopamine levels induced lipid accumulation, oxidative stress, and a proinflammatory status of the plasma membrane. This can, in part, explain the inflammatory response in patients with stress-induced heart failure.
Clinically relevant timing of antenatal sildenafil treatment reduces pulmonary vascular remodeling in congenital diaphragmatic hernia
Authors: Mous Daphne S. , Kool Heleen M. , Buscop-van Kempen Marjon J. , Koning Anton H. , Dzyubachyk Oleh , Wijnen Rene M. H. , Tibboel Dick , Rottier Robbert J.
Published: August 2016

Patients with congenital diaphragmatic hernia (CDH) suffer from severe pulmonary hypertension attributable to altered development of the pulmonary vasculature, which is often resistant to vasodilator therapy. Present treatment starts postnatally even though significant differences in the pulmonary vasculature are already present early during pregnancy. We examined the effects of prenatal treatment with the phosphodiesterase-5 inhibitor sildenafil on pulmonary vascular development in experimental CDH starting at a clinically relevant time. The well-established, nitrofen-induced CDH rodent model was treated daily with 100 mg/kg sildenafil from day 17.5 until day 20.5 of gestation (E17.5–20.5). Importantly, this timing perfectly corresponds to the developmental stage of the lung at 20 wk of human gestation, when CDH is detectable by 2D-ultrasonography and/or MRI. At E21.5 pups were delivered by caesarean section and euthanized by lethal injection of pentobarbital. The lungs were isolated and subsequently analyzed using immunostaining, real-time PCR, and volume measurements. Prenatal treatment with sildenafil improved lung morphology and attenuated vascular remodeling with reduced muscularization of the smaller vessels. Pulmonary vascular volume was not affected by sildenafil treatment. We show that prenatal treatment with sildenafil within a clinically relevant period improves pulmonary vascular development in an experimental CDH model. This may have important implications for the management of this disease and related pulmonary vascular diseases in human.
Somatic Engineering of Oncogenic Chromosomal Rearrangements: A Perspective
Authors: Maddalo Danilo , Ventura Andrea
Published: August 2016

The ability to engineer specific mutations in mice has proven essential to advancing our understanding of the molecular basis of cancer. Chromosomal rearrangements, a common and clinically relevant class of cancer-causing mutations, have however remained difficult to faithfully recapitulate in vivo. The development of genetic tools for in vivo somatic genome editing has recently overcome this limitation and led to the generation of more sophisticated and accurate preclinical models of human cancers. Here, we review the potential applications of these new technologies to the study of tumor biology and discuss their advantages over more conventional strategies, their limitations, and the remaining challenges. Cancer Res; 76(17); 4918–23. ©2016 AACR.
Challenging Roadblocks to Cancer Cure
Authors: Loda Massimo
Published: August 2016

The Pezcoller Symposium in Trento, Italy, June 2015, focused entirely on the question of why advanced cancer cure is so uncommon despite the extraordinarily rapid growth of invaluable therapeutic information. Participants were asked to define and to critically evaluate real and potential obstacles to permanent disease eradication. High-level concepts on potential road blocks to cures as well as opportunities for intervention in diverse areas of investigation ranging from genomic alterations to metabolism, microenvironment, immunity, and mechanotransduction were discussed. Provocative concepts and novel therapeutic avenues were proposed. What follows is a critical analysis of the highlights of this meeting. Cancer Res; 76(17); 4924–30. ©2016 AACR.
Impact of Blood–Brain Barrier Integrity on Tumor Growth and Therapy Response in Brain Metastases
Authors: Osswald Matthias , Blaes Jonas , Liao Yunxiang , Solecki Gergely , Gömmel Miriam , Berghoff Anna S. , Salphati Laurent , Wallin Jeffrey J. , Phillips Heidi S. , Wick Wolfgang , Winkler Frank
Published: August 2016

Purpose: The role of blood–brain barrier (BBB) integrity for brain tumor biology and therapy is a matter of debate.

Experimental Design: We developed a new experimental approach using in vivo two-photon imaging of mouse brain metastases originating from a melanoma cell line to investigate the growth kinetics of individual tumor cells in response to systemic delivery of two PI3K/mTOR inhibitors over time, and to study the impact of microregional vascular permeability. The two drugs are closely related but differ regarding a minor chemical modification that greatly increases brain penetration of one drug.

Results: Both inhibitors demonstrated a comparable inhibition of downstream targets and melanoma growth in vitro. In vivo, increased BBB permeability to sodium fluorescein was associated with accelerated growth of individual brain metastases. Melanoma metastases with permeable microvessels responded similarly to equivalent doses of both inhibitors. In contrast, metastases with an intact BBB showed an exclusive response to the brain-penetrating inhibitor. The latter was true for macro- and micrometastases, and even single dormant melanoma cells. Nuclear morphology changes and single-cell regression patterns implied that both inhibitors, if extravasated, target not only perivascular melanoma cells but also those distant to blood vessels.

Conclusions: Our study provides the first direct evidence that nonpermeable brain micro- and macrometastases can effectively be targeted by a drug designed to cross the BBB. Small-molecule inhibitors with these optimized properties are promising agents in preventing or treating brain metastases in patients. Clin Cancer Res; 22(24); 6078–87. ©2016 AACR.

See related commentary by Steeg et al., p. 5953
Multiple Expressed Endogenous Glioma Epitopes as Novel Vaccines for Gliomas
Authors: Lowenstein Pedro R. , Castro Maria G.
Published: August 2016

A novel approach to immunization against glioma tumors is described. Immunization against 11 antigens expressed in malignant brain tumors elicits responses to one or more antigens in a large percentage of patients. This novel approach suggests that it could be extended to a phase III trial. Clin Cancer Res; 22(19); 4760–2. ©2016 AACR.

See related article by Rampling et al., p. 4776
Multiparametric Genomic Assays for Breast Cancer: Time for the Next Generation?
Authors: Brufsky Adam M. , Davidson Nancy E.
Published: August 2016

The Breast Cancer Index appears to perform better than the 21-gene recurrence score in predicting 10-year disease-free survival in postmenopausal women with hormone receptor–positive lymph node–negative early-stage breast cancer. This may have implications for clinical use of first-generation versus second-generation multiparametric genomic assays. Clin Cancer Res; 22(20); 4963–5. ©2016 AACR.

See related article by Sestak et al., p. 5043
O empoderamento de mulheres para o enfrentamento da violência doméstica e familiar – reflexões sobre o projeto Maria, Marias
Authors: Angotti Bruna , Perrone Tatiana Santos
Published: August 2016

O presente artigo tem por objetivo expor algumas reflexões sobre educação popular em direitos como instrumento para o enfrentamento da violência doméstica e familiar contra as mulheres. As reflexões partem da experiência do projeto Maria, Marias que busca organizar e mobilizar mulheres para aplicação integral da Lei 11.340/2006, mais conhecida como Lei Maria da Penha. O Maria, Marias tem como principal atividade um curso anual que visa capacitar sobre a lei, serviços e ONGs que trabalham no enfrentamento da violência contra as mulheres. Após apresentar o projeto e seu funcionamento, são trabalhados os depoimentos sobre o impacto do curso na perspectiva das alunas da 7ª e 8ª edição, que em suas avaliações escritas do curso trazem as palavras “empoderamento”, “conhecimento”, “luta” e “rede” para traduzir o que significou para essas mulheres participar do Maria, Marias. Para finalizar, apresentamos algumas breves considerações refletindo sobre as potencialidades da educação popular em direitos.
Butterflies (Lepidoptera) of the Kameng Protected Area Complex, western Arunachal Pradesh, India
Authors: Sondhi Sanjay , Kunte Krushnamegh
Published: August 2016

The butterflies of the Kameng Protected Area Complex in western Arunachal Pradesh, India, covering the protected areas of Eaglenest Wildlife Sanctuary, Pakke Tiger Reserve and Sessa Orchid Wildlife Sanctuary were surveyed over a 5-year period (2009–2014).  A total of 421 butterfly species were recorded during the survey, including two species new to India (Gonepteryx amintha thibetana and Bhutanitis ludlowi) and several species rediscoveries and range extensions in the Eastern Himalaya, most notably Arhopala belphoebe, Sovia separata magna, Aulocera saraswati vishnu, Calinaga aborica, Callerebia annada annada, and Callerebria scanda opima.  Here we provide an annotated checklist of butterflies of the Kameng Protected Area Complex, including historical records, distributions, abundance, habitats and other notes on these 421 species. An additional 42 species recorded in older literature or by other authors in recent times are also listed, taking the total number of species recorded in the landscape to 463.
Elucidating the Association Between Depressive Symptoms, Coronary Heart Disease, and Stroke in Black and White Adults: The REasons for Geographic And Racial Differences in Stroke (REGARDS) Study
Authors: Moise Nathalie , Khodneva Yulia , Richman Joshua , Shimbo Daichi , Kronish Ian , Safford Monika M.
Published: August 2016

Background

Depression is a relapsing and remitting disease. Prior studies on the association between depressive symptoms and incident cardiovascular disease (
CVD
) have been limited by single measurements, and few if any have examined both incident coronary heart disease and stroke in a large biracial national cohort. We aimed to assess whether time‐dependent depressive symptoms conferred increased risk of incident
CVD
.

Methods and Results

Between 2003 to 2007, 22 666 black and white participants (aged ≥45 years) without baseline CVD in the
RE
asons for Geographic And Racial Differences in Stroke (
REGARDS
) study were recruited. Cox proportional hazards regression analyses assessed the association between up to 3 measurements of elevated depressive symptoms (4‐item Center for Epidemiologic Studies Depression Scale score ≥4) and incident coronary heart disease, stroke, and
CVD
death adjusting for age, sex, region, income, health insurance, education, blood pressure, cholesterol, medication, obesity, diabetes mellitus, kidney disease, C‐reactive protein, corrected
QT
interval, atrial fibrillation, left ventricular hypertrophy, smoking, alcohol, physical inactivity, medication adherence, and antidepressant use. The participants’ average age was 63.4 years, 58.8% were female, and 41.7% black. Time‐varying depressive symptoms were significantly associated with
CVD
death (adjusted hazard ratio 1.30, 95%
CI
1.04–1.63), with a trend toward significance for fatal and nonfatal stroke (adjusted hazard ratio 1.26, 95%
CI
0.99–1.60) but not fatal and nonfatal coronary heart disease (adjusted hazard ratio 1.11, 95%
CI
0.89–1.38). Race did not moderate the association between depressive symptoms and CVD.

Conclusions

Proximal depressive symptoms were associated with incident fatal and nonfatal stroke and
CVD
death even after controlling for multiple explanatory factors, further supporting the urgent need for timely management of depressive symptoms.
The relationship between work and family preferences and behaviors
Authors: Nilsson Karina , Hammarström Anne , Strandh Mattias
Published: August 2016

Proposed theories to explain gender inequality in the labor market and family, such as gender specialization within families and gender segregation in the labor markets, lack consideration for individual preferences. Preference theory accounts for individual choice and gendered preferences but has been substantially criticized, indicating a need for further research. This study uses Swedish longitudinal data to explore how preferences for work and family relate to behavior. We explore three critical issues raised in previous research: gender differences in preferences; the relationship between work and family changes and subsequent preferences; how preferences relate to work and family behaviors. Our results showed small general gender differences in preferences, although women had a stronger preference for both children and work than men. Changes in work status were further related to changes in work preferences, while changes in family status were related to changes in family preferences. Moreover, preferences had poor predictive power in relation to work and family behaviors. Our results indicate that preferences do not explain gender inequality in Sweden. The relationship between preferences and behaviors seems bidirectional and preferences and behavior within the family sphere has little to do with preferences and behavior within the work sphere.
The effects of mechanical milling on the structural, mechanical, and electromagnetic properties of Cu-8 wt% NdFeB composite alloys
Authors: López Marta , Jiménez José , Mangalaraja RV
Published: August 2016

In an attempt to develop new materials that combine structural (mechanical) and functional (electrical and magnetic) properties, a copper composite alloy reinforced through the dispersion of fine Nd2Fe14B intermetallic particles has been synthesized by the powder metallurgy route. Composite master alloy was prepared by blending copper and 8 wt% of intermetallic NdFeB in a planetary ball mill working at 250 r/min under argon atmosphere for 10 h. Resulting composite powders were encapsulated in Cu cans and then consolidated by extrusion at 1023 K. Microstructure features of blended powders and consolidated materials were characterized by means of X-ray diffraction, scanning electron microscopy, and electron probe micro analysis. Fitting of the X-ray diffraction patterns with the Rietveld method revealed that during processing, some NdFeB particles reacted with copper and oxygen to form Nd2CuO4. The lower Nb content on the Nd2Fe14B intermetallic phase due to this oxidation causes the dispersion of Fe and Fe2B particles, which also have soft magnetic properties but a higher moment compared to Nd2Fe14B. The extruded alloys showed enhanced mechanical properties (with yield strength ≥ 600 MPa, ultimate tensile strength ≥700 MPa, and 5% elongation to failure) with satisfactory electrical conductivity (46% IACS) and high values of the coercive field (≥30,000 A/m).
University-Based Teacher Preparation and Middle Grades Teacher Effectiveness
Authors: Preston Courtney
Published: August 2016

For over two decades, there have been calls to assess the relationship of the features of teacher preparation programs to teacher effectiveness, to provide guidance for program improvement. At the middle grades level, theory suggests that coursework in educational psychology is particularly important for teacher effectiveness. Using 4 years of data from 15 middle grades teacher preparation programs, this study estimates the relationship of their structural features, that is required elements of coursework and fieldwork, to student achievement gains in math and English/Language Arts. Findings suggest that few requirements are positively associated with achievement gains.
Image database of printed fabric with repeating dot patterns part (I) – image archiving
Authors: Kuo Chung-Feng Jeffrey , Lee Cheng-Lin , Shih Chung-Yang
Published: August 2016

An image database of printed fabrics with repeating dot patterns was created to alleviate issues associated with management of and searches for numerous dot printed fabrics in the printing industry. The function of the database is to archive and allow retrieval of images. First, we discuss image archiving of repeating pattern-based dot printed fabrics. The color image was scanned by resolution of 200 dpi. The wavelet transformation was used to preprocess the image to obtain a scanned image 1/16 of the size of the original to be the stored image. To acquire images with repeating pattern color and repeating pattern template, the binary image of each pattern was obtained using the Sobel edge detection method and a morphological operation. Then pattern elements identical to the target pattern element were screened out. Afterwards, the centroid positions of these identical pattern elements were used to subdivide the repeating pattern color image and repeating pattern template image using a vertical vector method. Finally, the RGB 512-color histogram was used as the color feature of the dot printed fabrics, and the geometric and moment invariant feature values of the repeating pattern template image were used as the pattern feature of the dot printed fabrics. Our experimental results show that images can be acquired that are suitable for use in a dot printed fabric image database. The color and template images of the repeating patterns, which represent the image content of the printed fabrics, were obtained to create an image database of repeating pattern-based dot printed fabrics. This image database contains data on 300 printed fabrics which can be used for subsequent research on database image retrieval.
Happy Hosts? International Tourist Arrivals and Residents’ Subjective Well-being in Europe
Authors: Ivlevs Artjoms
Published: August 2016

While there has been a growing interest in the relationship between perceived tourism impacts and residents’ quality of life, little is known about how residents’ well-being is affected by actual tourist arrivals. This article studies the effect of international tourist arrivals on the subjective well-being—happiness and life satisfaction—of residents in European countries. Data come from the six waves of the European Social Survey, conducted in 32 countries in 2002-2013. The results of the OLS fixed-effects and instrumental-variable estimations suggest that tourist arrivals reduce residents’ life satisfaction. This negative relationship tends to be more pronounced in countries where tourism intensity is relatively high, as well as among people living in rural areas. In addition, tourist arrivals have a greater negative relationship with the evaluative component of subjective well-being (life satisfaction) than its affective component (happiness).
Unexpected Fees and the Prediction of Material Weaknesses in Internal Control Over Financial Reporting
Authors: Albring Susan M. , Elder Randal J. , Xu Xiaolu
Published: August 2016

We investigate whether prior year unexpected audit fees help predict new material weaknesses in internal control over financial reporting reported under Section 404 of the Sarbanes–Oxley Act (SOX). Predicting material weaknesses may be useful to investors and other financial statement users because these disclosures have adverse economic impacts on disclosing firms. Unexpected fees are significantly associated with material weaknesses reported under Section 404, even after controlling for Section 302 disclosures and other factors associated with internal control weaknesses. Unexpected fees are associated with company-level weaknesses but are not significantly associated with account-specific weaknesses, consistent with differences in the nature and severity of the two types of material weaknesses. Our results are consistent with unexpected audit fees containing information on unobserved audit costs and client control risks, which help predict future internal control weaknesses.
Acute Alpha-Naphthylisothiocyanate-induced Liver Toxicity in Germfree and Conventional Male Rats
Authors: Cullen John M. , Faiola Brenda , Melich David H. , Peterson Richard A. , Jordan Holly L. , Kimbrough Carie L. , Miller Richard T.
Published: August 2016

Differences in the responses of conventional and germfree male Sprague-Dawley rats to acute injury induced by alpha-naphthylisothiocyanate (ANIT), a well-characterized biliary epithelial toxicant, were evaluated. Conventional and germfree rats were dosed once orally with 50 mg/kg of ANIT or corn oil alone and serially sacrificed daily for the next 3 days. Germfree rats treated with ANIT tended to have greater increases in virtually all liver and biliary-related analytes compared with conventional rats treated with ANIT; however, significant differences were found only in a few of these analytes including increased bile acids on day 3, total bilirubin on day 4, glutamate dehydrogenase (GLDH) on day 3, and reduced paraoxonase 1 (PON1) on days 2 and 3. Histologic differences between the conventional and germfree rats were modest, but most pronounced on day 2 (24-hr post dosing). Based on subjective scoring, biliary necrosis, neutrophilic cholangitis, and portal tract edema were more severe in germfree rats at 24 hr post dosing compared with conventional rats. Biliary epithelial replication did not differ between treated groups, however. Overall, germfree rats had a modestly greater level of biliary tract injury based on subjective histologic scoring and clinical chemistry measurements following an acute exposure to the well-characterized biliary toxin, ANIT; however, the difference between the ANIT-treated germfree and conventional groups was modest and most evident only within the first day following exposure. These findings suggest that the microbiome did not significantly affect ANIT-induced acute biliary tract injury in the conditions of this study.
Solving Complex Problems
Authors: Hamby Anne , Pierce Meghan , Brinberg David
Published: August 2016

Three distinct literatures address social change: social entrepreneurship, community action research, and social marketing. While these activities have a shared goal to create social change, each orientation approaches their activities from a different perspective. The current work explores how macro-social marketing efforts can benefit from alternative orientations to enhance enduring social change. Social entrepreneurship highlights the importance of enduring resources and considering scalability. Community action highlights the importance of obtaining legitimacy and buy-in from multiple entities in the social change system. Social marketing highlights the importance of an end-user perspective and the application of behavioral theories to create systematic change. This work describes a case study in the Kenyan education context to highlight the value of this approach.
Surgical treatment for an uncommon headache: A gap of 4800 years
Authors: Isidro Albert , Burdeus Joan Manel , Loscos Sergi , Bara Javier , Bosch Josep , Gallart Anna
Published: August 2016

Background

Surgical management of headache due to anomalies in the cervical spine is uncommon, as most cases improve with drugs and/or physical therapy.

Case

We report two instances of a very uncommon congenital upper cervical spine anomaly due to the presence of a pseudoarthrosis between a unilateral paracondylar process in the base of the skull and an epitransverse process arising from the transverse apophysis (PCP/ETA). The first one corresponds to a male on whom an endoscopic guided puncture was performed, and the second to an adult male from the Neolithic period who showed two cranial trepanations together with the presence of morphine metabolites in both bones and dental calculus.

Discussion

We draw a parallel between the treatment of two individuals separated by a gap of more than 4800 years: contemporary direct vision of the false joint through a small endoscope, which provides an accurate puncture, and ancient double trepanation with clear signs of bone eburnation.