bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuropsychiatric symptoms in lupus
Authors: Lynall M
Published: November 2018

Patients with lupus experience a high burden of neuropsychiatric symptoms. While some patients have frank neurological complications, this represents a minority. Most neuropsychiatric symptoms are chronic and not associated with brain imaging abnormalities, for example, fatigue, ‘brain fog’ and altered mood. Factors which contribute to these symptoms may include medications, infections, the psychological burden of chronic unpredictable disease, and the direct effects of inflammation on the brain. This article summarizes our current understanding of psychological symptoms in lupus, and how this informs our approach to management.
The Protective Roles of Urinary Trypsin Inhibitor in Brain Injury Following Fat Embolism Syndrome in a Rat Model
Authors: Xiong Lili , Sun Linlin , Liu Shanshan , Zhu Xingyun , Teng Ze , Yan Junhao
Published: November 2018

Fat embolism syndrome (FES) is a common complication following long bone fracture; fat droplets are released into the blood circulation and form embolisms, mainly in lung and brain. However, the potential mechanisms involved remain to be clarified. In this study, the mechanism of brain injury following FES and the protective effects of urinary trypsin inhibitor (UTI)—a serine protease inhibitor—were investigated. Sixty male Sprague-Dawley rats were divided randomly into sham, FES and FES+UTI treatment groups. The FES model was established using tail vein injection of glycerol trioleate, and UTI was administered by intraperitoneal injection immediately following FES. Brain/lung water content evaluation, Evans blue content and magnetic resonance imaging examination were used to assess the effects of UTI. Furthermore, immunohistochemistry and western blot were also applied to explore the protective mechanism of UTI following FES. The results of oil red O staining indicated that the FES model was successfully established. UTI could significantly attenuate blood-brain-barrier (BBB) disruption, as seen through brain edema evaluation and Evans blue content examination. Immunofluorescence staining results indicated that the TLR4-JNK pathway was involved in brain injury after FES; this effect could be quenched by UTI treatment. Furthermore, UTI could decrease the levels of downstream target proteins of the TLR4-JNK pathway, phosphorylated-NF- κB (p65) and p53 in brain. Our results showed that UTI could alleviate BBB injury after FES through blocking activity of the TLR4-JNK pathway.
Evaluation of wood variation based on the eigenvalue distribution of near infrared spectral matrix
Authors: Fujimoto Takaaki
Published: November 2018

A method to evaluate the wood variation based on the eigenvalue analysis for the near infrared spectral matrix is presented. The set of eigenvalues calculated from the variance-covariance matrix is treated as the Hamiltonian, which represents the energy eigenstate of the wood, and the wood variation is discussed from the viewpoints of thermodynamics and statistical mechanics. To determine the validity of this idea, two sample groups, one having a high and the other having a low modulus of elasticity ( Efr), are prepared, because they obviously have different molecular configurations in the cell wall. The eigenvalues of the high Efr group are widely distributed compared with those of the low Efr group. The probability corresponding to each energy eigenstate of the low Efr group is flatly distributed compared with that of the high Efr group. These results indicate that the low Efr wood has a more disordered structure than the high Efr wood. The Helmholtz free energy is higher in the high Efr group; in contrast, the entropy is higher in the low Efr group. The results obtained in this study are consistent with the previous knowledge with regard to the relationship between the mechanical properties and the microscopic structure of wood. Hence, the eigenvalues obtained from the NIR spectral matrix provide useful information to assess the variation and stability of wood.
Financial Audit or Forensic Audit? Government Sector Panorama
Authors: Deb Rajat
Published: November 2018

The study has been motivated to assay the selective stakeholders’ perceptions on whether the government financial audit has been converted into forensic audit. Adopting a cross-sectional study design with survey strategy through a self-administered interview schedule with a 50-item inventory, data has been collected from randomly chosen 120 sample respondents having equal representations from two groups—current and retired government employees and businessmen of Tripura. The significant statistical results have concluded that corruption and accounting slacks have important impacts on the government audits, and the latter if used in an appropriate manner are likely to detect frauds and catalyse in bringing accounting reforms.
Contextualizing Experiences of Diabetes-Related Stress in Rural Dominican Republic
Authors: Gonzalez Rodriguez Humberto , Wallace Deshira D. , Barrington Clare
Published: November 2018

Type 2 diabetes (T2D) is changing the burden of disease across Latin America. In this formative, qualitative study, we explored experiences of T2D diagnosis and management among adults in rural Dominican Republic. We conducted 28 in-depth interviews (12 men, 16 women) and used inductive analysis to explore the emotional burden of T2D and identify coping strategies. We found that stress relating to T2D began at diagnosis and persisted throughout management. Stress was produced by concerns about healthy food and medication access, fears about illness-induced injury, and the cyclical process of experiencing stress. Participants identified diabetes care and free medication services as external stress-reducers. Internally, participants’ mitigated stress by not thinking about diabetes (“ no dar mente”). Our study highlights the importance of a contextualized understanding of diabetes-related stress and the need for individual, clinic, and community-level interventions to reduce stressors and improve health outcomes among adults with T2D.
Nebivolol/Valsartan: A Novel Antihypertensive Fixed-Dose Combination Tablet
Authors: Battise Dawn , Boland Cassie L. , Nuzum Donald S.
Published: November 2018

Data Sources: A PubMed (1966 to October 2018) search was conducted using the following keywords: nebivolol, valsartan, and hypertension (HTN). Additional sources were identified by references. Study Selection and Data Extraction: Articles written in English were included if they evaluated the pharmacology, pharmacokinetics, efficacy, safety, or place in therapy of nebivolol/valsartan in human subjects. Data Synthesis: Most patients with HTN require combination therapy; however, β-adrenergic antagonists and AII type 1 receptor blockers have been considered less effective because of overlapping mechanisms of action. A phase III, randomized trial demonstrated that nebivolol/valsartan produced statistically significant blood pressure (BP) lowering as compared with monotherapy with the individual components or placebo. Substudy analyses confirmed this among subgroups and demonstrated that nebivolol/valsartan decreased plasma renin and aldosterone levels. One trial reported continued BP lowering at 52 weeks. Another study showed that nebivolol/valsartan had similar additivity scores as compared with other antihypertensive combinations. Relevance to Patient Care and Clinical Practice: This review discusses drug information, efficacy, and safety of nebivolol/valsartan and discusses its clinical relevance as a novel combination product in managing patients with HTN. Conclusion: Nebivolol/valsartan combination may offer a benefit to patients with an indication for both classes who desire to decrease pill burden. Although BP lowering was statistically significant in comparison to the individual components as monotherapy, the combination does not offer clinically significant benefits that would elevate its place in HTN management.
Higher Levels of Intelligence and Executive Functioning Protect Maltreated Children Against Adult Arrests: A Prospective Study
Authors: Nikulina Valentina , Widom Cathy Spatz
Published: November 2018

Research shows that maltreated children are at elevated risk of arrest as adults and that higher verbal intelligence, reading ability, and executive functioning (abstract reasoning and cognitive flexibility) may be protective against criminal behavior. The current study examines this hypothesis using data from court-substantiated cases of child abuse and neglect and demographically matched controls followed prospectively into middle adulthood ( N = 1,196). At age 29, verbal intelligence was assessed with the Quick Test and reading ability with the Wide Range Achievement Test–Revised. At age 41, abstract reasoning was assessed with the Matrix Reasoning Test and cognitive flexibility with the Trail Making Test-B. Arrest records were gathered from law enforcement agencies through mean age 51. Data were analyzed with binomial logistic regressions. The results indicated that maltreated children were at increased risk of arrest for nonviolent and violent crime. Higher verbal intelligence, reading ability, nonverbal reasoning, and cognitive flexibility were protective against arrest for violent crime. The protective effects of neuropsychological functions were more pronounced for violent than nonviolent crime, for the control than maltreated children, and differed by gender and race. These results suggest that interventions targeting improved cognitive and neuropsychological functions may serve an important role in reducing risk of crime.
Exploring the Role of Race and Gender on Perceived Bystander Ability and Intent: Findings Before and After Exposure to an Online Training Program to Prevent Sexual Assault on Campus
Authors: Burns Vicki L. , Eaton Asia A. , Long Haiying , Zapp Dan
Published: November 2018

The current study explores the significance of race and gender on bystander attitudes before and after an online bystander intervention program to prevent sexual assault. A diverse sample of 750 college students participated in an online intervention and participants’ perceived bystander intervention ability and intent were assessed. The interaction of participant race and gender had a marginally significant impact on bystander ability and intent baseline scores. Furthermore, when analyzing gain scores from pre- to posttest, there was a significant race by gender interaction. Specifically, Latinx and Black men had higher preintervention scores, and White men had higher gains postintervention. Relevant cultural and social factors and directions for future research are discussed.
Fetal Anthropometric Features: A Postmortem Study of Fetuses After the Termination of Pregnancy for Psychosocial Reasons Between 12 and 20 Gestational Weeks
Authors: Muller Brochut Anne-Claude , Taffe Patrick , Piaget-Rossel Romain , de Leval Laurence , Rougemont Anne-Laure
Published: November 2018

Introduction

Reference ranges in fetal postmortem anthropometric data derive from heterogeneous studies and rely on data obtained after intrauterine fetal death and abortion, which may introduce bias in the reported fetal growth parameters. We report anthropometric findings in fetuses with the least variation due to cause of death or developmental anomalies.

Methods

We analyzed fetuses after the termination of pregnancy for psychosocial reasons. The external measurements, X-ray dimensions, and body and organ weights were recorded as well as the placenta weight. A thorough and standardized postmortem analysis allowed the design of 2 different groups. Group 1 was composed of fetuses (1) born to mothers with no relevant obstetrical history, (2) no X-ray anomaly, (3) no abnormal autopsy findings, and (4) unremarkable placenta histology. An anomaly in any of these 4 entities moved the fetuses to Group 2. For reference ranges and graph construction, a well-designed statistical methodology was applied.

Results

A total of 335 fetuses were analyzed during an 11-year period. Group 1 comprised 232 fetuses aged 12 to 20 gestational weeks, whereas 103 fetuses were considered in Group 2. Comparison between the 2 groups showed almost no differences. Only the Group 1 results were submitted to statistical analysis, and reference ranges and graphs were constructed.

Conclusions

To the best of our knowledge, we provide in this study the first anthropometric references established from almost normal fetuses, albeit for a limited fetal timeframe.
Seismic performance evaluation of coupled wall system with novel replaceable steel truss coupling beams
Authors: Li Yong , Liu Ye , Meng Shaoping
Published: November 2018

Coupled wall systems are often used in high-rise buildings in zone of high seismic risk to provide lateral resistance to earthquake loading. Once damaged, reinforced concrete coupling beams are costly and time-consuming to repair post-earthquake. To enhance the seismic resilience for coupled wall structures, a novel replaceable steel truss coupling beam is first introduced. The proposed replaceable steel truss coupling beam consists of chord members at the top and bottom, respectively, and two buckling-restrained energy dissipaters are employed in the diagonal direction. The energy dissipaters can yield first before the wall piers and dissipate large amounts of energy to protect the main structure under seismic loadings. In addition, the energy dissipaters can be easily installed and post-earthquake repaired through pin connection with the chord members. This article mainly focused on the numerical and theoretical analyses of the proposed replaceable steel truss coupling beam, and nonlinear analytical models were developed in PERFORM-3D. An 11-story prototype structure was designed per Chinese code. The seismic response of hybrid coupled wall system with replaceable steel truss coupling beams was evaluated using nonlinear time history analysis and compared with the response of reinforced concrete coupled wall system with reinforced concrete coupling beams under seismic loadings. Results show that the proposed replaceable steel truss coupling beam leads to a good seismic response with reduced interstory drifts of the systems and rotational demand in the beams and wall piers due to a large energy dissipation capacity and overstrength.
The Animator as Inventor: Labour and the New Animated Machine Comedy of the 2010s
Authors: Tai Peng-yi
Published: November 2018

Around 2010, the inventor character started to populate animated blockbusters. Computer 3D animated films and their sequels such as Robots (Chris Wedge and Carlos Saldanha, 2005), Cloudy with a Chance of Meatballs (Phil Lord and Christopher Miller, 2009), Despicable Me (Pierre Coffin and Chris Renaud, 2010) and Big Hero 6 (Don Hall and Chris Williams, 2014) all feature inventors and their extravagant machines. In this article, the author explores the inventive artisan character as a self-reflexive trope of the animator. She expands Crafton’s thesis of the animator’s self-figuration and Tom Gunning’s work on machine comedy and operational aesthetics to further discussions on the animator and thereby the labour of animation. The article seeks to reveal the political agenda in the new animated machine comedy of the 2010s, which not only reflects the modes of production of contemporary animation studios, but also the larger concerns in the post-Fordist mode of production.
The Ambivalent Image Factory: The Genealogy and Visual History of Chinese Independent Animation
Authors: Wu Weihua
Published: November 2018

This article examines how the emergence, constitution and diversification of independent animation in mainland China was formed with minjian discourse and the rise of independent creativity over the past two decades. This was an era in which the animation mainstream was transformed from a primarily political discourse to a fully commercialized entity, while the aesthetic parodies and pastiches of an imaginary ‘Chineseness’ have undergone a renaissance within a power struggle between individuality and independency in animation practice.
Adverse physiologic effects of Western diet on right ventricular structure and function: role of lipid accumulation and metabolic therapy
Authors: Brittain Evan L. , Talati Megha , Fortune Niki , Agrawal Vineet , Meoli David F. , West James , Hemnes Anna R.
Published: November 2018

Little is known about the impact of metabolic syndrome (MS) on right ventricular (RV) structure and function. We hypothesized that mice fed a Western diet (WD) would develop RV lipid accumulation and impaired RV function, which would be ameliorated with metformin. Male C57/Bl6 mice were fed a WD or standard rodent diet (SD) for eight weeks. A subset of mice underwent pulmonary artery banding (PAB). Treated mice were given 2.5 g/kg metformin mixed in food. Invasive hemodynamics, histology, Western, and quantitative polymerase chain reaction (qPCR) were performed using standard techniques. Lipid content was detected by Oil Red O staining. Mice fed a WD developed insulin resistance, RV hypertrophy, and higher RV systolic pressure compared with SD controls. Myocardial lipid accumulation was greater in the WD group and disproportionately affected the RV. These structural changes were associated with impaired RV diastolic function in WD mice. PAB‐WD mice had greater RV hypertrophy, increased lipid deposition, and lower RV ejection fraction compared with PAB SD controls. Compared to untreated mice, metformin lowered HOMA‐IR and prevented weight gain in mice fed a WD. Metformin reduced RV systolic pressure, prevented RV hypertrophy, and reduced RV lipid accumulation in both unstressed stressed conditions. RV diastolic function improved in WD mice treated with metformin. WD in mice leads to an elevation in pulmonary pressure, RV diastolic dysfunction, and disproportionate RV steatosis, which are exacerbated by PAB. Metformin prevents the deleterious effects of WD on RV function and myocardial steatosis in this model of the metabolic syndrome.
Wearable strain gauge-based technology measures manual tactile forces during the activities of daily living
Authors: Riddle Michael , MacDermid-Watts Kevin , Holland Sara , MacDermid Joy C , Lalone Emily , Ferreira Louis
Published: November 2018

Introduction

Current methods of determining applied forces in the hand rely on grip dynamometers or force-measurement gloves which are limited in their ability to isolate individual finger forces and interfere with the sense of touch. The objective of this study was to develop an improved force measurement system that could be used during various activities of daily living.

Methods

Custom-made strain gauge sensors were secured to the fingernail of four fingers and two middle phalanges and calibrated to measure hand forces in eight healthy individuals during five activities of daily living.

Results

These sensors were capable of measuring forces as small as 0.17 N and did not saturate at high force tasks around 15 N, which is within the envelope of forces experienced during daily life. Preliminary data demonstrate the ability of these tactile sensors to reliably distinguish which fingers/segments were used in various tasks.

Conclusions

Until now, there has been no method for real-time unobtrusive monitoring of force exposure during the tasks of daily life. The system used in this study provides a new type of low-cost wearable technology to monitor forces in the hands without interfering with the contact surface of the hand.
Prediction of setup times for an advanced upper limb functional electrical stimulation system
Authors: Smith Christine , Kenney Laurence , Howard David , Waring Karen , Sun Minxgu , Luckie Helen , Hardiker Nicholas , Cotterill Sarah
Published: November 2018

Introduction

Rehabilitation devices take time to don, and longer or unpredictable setup time impacts on usage. This paper reports on the development of a model to predict setup time for upper limb functional electrical stimulation.

Methods

Participants’ level of impairment (Fugl Meyer-Upper Extremity Scale), function (Action Research Arm Test) and mental status (Mini Mental Scale) were measured. Setup times for each stage of the setup process and total setup times were recorded. A predictive model of setup time was devised using upper limb impairment and task complexity.

Results

Six participants with stroke were recruited, mean age 60 (±17) years and mean time since stroke 9.8 (±9.6) years. Mean Fugl Meyer-Upper Extremity score was 31.1 (±6), Action Research Arm Test 10.4 (±7.9) and Mini Mental Scale 26.1 (±2.7). Linear regression analysis showed that upper limb impairment and task complexity most effectively predicted setup time (51% as compared with 39%) (F(2,21) = 12.782, adjusted R2 = 0.506; p < .05).

Conclusions

A model to predict setup time based on upper limb impairment and task complexity accounted for 51% of the variation in setup time. Further studies are required to test the model in real-world settings and to identify other contributing factors.
Impact of the Americans With Disabilities Act Amendments Act on Documentation for Students With Disabilities in Transition to College: Implications for Practitioners
Authors: Keenan Walter R. , Madaus Joseph W. , Lombardi Allison R. , Dukes Lyman L.
Published: November 2018

The Americans With Disabilities Act Amendments Act of 2008 expanded the legal definition of disability to establish broader coverage for individuals with disabilities, including college students, than the definition in the Americans With Disabilities Act of 1990. The new interpretation of the definition of disability shifted the main purpose of documentation from proving eligibility for services as a person with a disability to determining appropriate academic accommodations. This change in the law, and subsequent Department of Justice regulations, enhances the importance of documentation from a student’s secondary education experience that may provide relevant information concerning functional limitations and the need for academic accommodations. This article provides practical guidance to high school professional staff in preparing disability documentation for students’ transition to college.
Clinical outcomes and survival rate of cementless modular distal fixation femoral stem for revision hip arthroplasty: A minimum 6-year follow-up
Authors: Kang Joon Soon , Na Yeop , Ko Bong Seong , Jeon Yoon Sang
Published: November 2018

Purpose:

Revision hip arthroplasty is a very challenging procedure. Use of a modular distal fixation stem is one of the available options for revision arthroplasty in patients with proximal femoral bone deficiency. The purpose of this study was to evaluate mid- to long-term outcomes of cementless modular distal fixation femoral stem implantation in revision hip surgery.

Methods:

Clinical and radiological findings, complications, and stem survival rate were analyzed for 46 patients (48 hips) who underwent revision hip arthroplasty using a cementless modular distal fixation femoral stem. The mean patient age was 58.8 years (range 31–82 years) and the mean follow-up period was 95 months (72–122 months). The preoperative diagnoses were aseptic loosening (36 hips), infection (4 hips), ceramic fracture (4 hips), and femoral periprosthetic fracture (4 hips).

Results:

The mean Harris hip score improved from 56.6 preoperatively to 88.2 postoperatively at the last follow-up. All hips showed stable osteointegration and firm fixation. Complications involved four hips (8.3%); there was one case each of periprosthetic fracture, delayed union of osteotomy site, femoral perforation, and infection. One stem re-revision was performed for deep infection of the femoral side. The Kaplan–Meier survival rate was 97.6% at the final follow-up.

Conclusion:

Revision hip arthroplasty using a cementless modular distal fixation femoral stem showed satisfactory initial firm fixation and mid- to long-term survival rate. Complications can be minimized by careful surgical planning and meticulous procedure.
Mediating Effect of Engagement on Workplace Spirituality–Job Involvement Relationship: A Study among Generation Y Professionals
Authors: Mahipalan Manju , Sheena S.
Published: November 2018

The complexity of today’s world reflects on the professional lives of people as well. This complexity and its subsequent impact on work–life balance have necessitated organisations to thoughtfully consider the spiritual dimension of individuals at work, which has been neglected for years. The purpose of this study is to examine the interrelationships among workplace spirituality (WS), employee engagement and job involvement among Generation Y employees. Accordingly, a model is proposed which delineates the interactions among these constructs. Specifically, the mediating effect of employee engagement on the relationship between WS and job involvement is explored. The study uses two different forms of employee engagement, namely, job and organisational engagement. A questionnaire-based survey is adopted to test the aforementioned model, and data was collected from 353 professional consultants working in different sectors. The results of regression analyses support all the stated relationships, as well as provide evidence for the mediational effect of engagement. The findings of the study suggest the existence of significant relationships between spirituality and job and organisational engagement. Both forms of engagement partially mediate the relationship between WS and job involvement. The study illustrates that spirituality could be a significant predictor of employee engagement and job involvement among employees in the service sector. Based on the findings, it is reasonable to assume that spirituality could be a vital element in managing the work attitudes of Generation Y workers.
Is the First-Past-the-Post Necessarily the First?
Authors: Chakrabarty Arijit
Published: November 2018

In this short note, the probability of the event that in a first-past-the-post voting system, the party winning the maximum number of seats loses in terms of popular votes, is studied under a few simplifying assumptions. It turns out that the said probability is roughly 20 per cent. That is, one-fifth of the times, the said event will happen, on the average.

JEL Classifications: D04, D72, D78
What Keeps Older Adults With Hearing Impairment From Adopting Hearing Aids?
Authors: Tahden Maike A. S. , Gieseler Anja , Meis Markus , Wagener Kirsten C. , Colonius Hans
Published: November 2018

The aim of this study was to compare elderly individuals who are hearing impaired but inexperienced in using hearing aids (hearing aid non-users; HA-NU) with their aided counterparts (hearing aid users; HA-U) across various auditory and non-auditory measures in order to identify differences that might be associated with the low hearing aid uptake rate. We have drawn data of 72 HA-NU and 139 HA-U with a mild-to-moderate hearing loss, and matched these two groups on the degree of hearing impairment, age, and sex. First, HA-NU and HA-U were compared across 65 auditory, cognitive, health-specific, and socioeconomic test measures as well as measures assessing technology commitment. Second, a logistic regression approach was performed to identify relevant predictors for using hearing aids. Finally, we conducted a sensitivity analysis for the matching approach. Group comparisons indicated that HA-NU perceive their hearing problem as less severe than their aided counterparts. Furthermore, HA-NU showed worse technology commitment and lower socioeconomic status than HA-U. The logistic regression revealed self-reported hearing performance, technology commitment, and the socioeconomic and health status as the most important predictors for using hearing aids.
Definitive radiotherapy for localized follicular lymphoma staged by 18F-FDG PET-CT: a collaborative study by ILROG
Authors: Brady Jessica L. , Binkley Michael S. , Hajj Carla , Chelius Monica , Chau Karen , Balogh Alex , Levis Mario , Filippi Andrea Riccardo , Jones Michael , Mac Manus Michael , Wirth Andrew , Oguchi Masahiko , Vistisen Anders Krog , Andraos Therese Youssef , Ng Andrea K. , Aleman Berthe M. P. , Choi Seo Hee , Kirova Youlia , Hardy Sara , Reinartz Gabriele , Eich Hans T. , Bratman Scott V. , Constine Louis S. , Suh Chang-Ok , Dabaja Bouthaina , El-Galaly Tarec C. , Hodgson David C. , Ricardi Umberto , Yahalom Joachim , Hoppe Richard T. , Mikhaeel N. George
Published: November 2018

Radiotherapy (RT) can be curative in patients with localized follicular lymphoma (FL), with historical series showing a 10-year disease-free survival of 40 to 50%. As 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography with computerized tomography (PET-CT) upstages 10 to 60% of patients compared to CT, we sought to evaluate outcomes in patients staged by PET-CT, to determine if more accurate staging leads to better patient selection and results. We conducted a multicenter retrospective study under the direction of the International Lymphoma Radiation Oncology Group (ILROG). Inclusion criteria were: RT alone for untreated stage I to II FL (grade 1-3A) with dose equivalent ≥24 Gy, staged by PET-CT, age ≥18 years, and follow-up ≥3 months. End points were freedom from progression (FFP), local control, and overall survival (OS). A total of 512 patients treated between 2000 and 2017 at 16 centers were eligible for analysis; median age was 58 years (range, 20-90); 410 patients (80.1%) had stage I disease; median RT dose was 30 Gy (24-52); and median follow-up was 52 months (3.2-174.6). Five-year FFP and OS were 68.9% and 96%. For stage I, FFP was 74.1% vs 49.1% for stage II (P < .0001). Eight patients relapsed in-field (1.6%). Four had marginal recurrences (0.8%) resulting in local control rate of 97.6%. On multivariable analysis, stage II (hazard ratio [HR], 2.11; 95% confidence interval [CI], 1.44-3.10) and BCL2 expression (HR, 1.62; 95% CI, 1.07-2.47) were significantly associated with less favorable FFP. Outcome after RT in PET-CT staged patients appears to be better than in earlier series, particularly in stage I disease, suggesting that the curative potential of RT for truly localized FL has been underestimated.
IDH2 inhibition enhances proteasome inhibitor responsiveness in hematological malignancies
Authors: Bergaggio Elisa , Riganti Chiara , Garaffo Giulia , Vitale Nicoletta , Mereu Elisabetta , Bandini Cecilia , Pellegrino Elisa , Pullano Verdiana , Omedè Paola , Todoerti Katia , Cascione Luciano , Audrito Valentina , Riccio Anna , Rossi Antonio , Bertoni Francesco , Deaglio Silvia , Neri Antonino , Palumbo Antonio , Piva Roberto
Published: November 2018

Proteasome inhibitors (PI) are extensively used for the therapy of multiple myeloma (MM) and mantle cell lymphoma. However, patients continuously relapse or are intrinsically resistant to this class of drugs. Here, to identify targets that synergize with PI, we carried out a functional screening in MM cell lines using a short hairpin RNA library against cancer driver genes. Isocitrate dehydrogenase 2 (IDH2) was identified as a top candidate, showing a synthetic lethal activity with the PI carfilzomib (CFZ). Combinations of US Food and Drug Administration–approved PI with a pharmacological IDH2 inhibitor (AGI-6780) triggered synergistic cytotoxicity in MM, mantle cell lymphoma, and Burkitt lymphoma cell lines. CFZ/AGI-6780 treatment increased death of primary CD138+ cells from MM patients and exhibited a favorable cytotoxicity profile toward peripheral blood mononuclear cells and bone marrow–derived stromal cells. Mechanistically, the CFZ/AGI-6780 combination significantly decreased tricarboxylic acid cycle activity and adenosine triphosphate levels as a consequence of enhanced IDH2 enzymatic inhibition. Specifically, CFZ treatment reduced the expression of nicotinamide phosphoribosyltransferase (NAMPT), thus limiting IDH2 activation through the NAD+-dependent deacetylase SIRT3. Consistently, combination of CFZ with either NAMPT or SIRT3 inhibitors impaired IDH2 activity and increased MM cell death. Finally, inducible IDH2 knockdown enhanced the therapeutic efficacy of CFZ in a subcutaneous xenograft model of MM, resulting in inhibition of tumor progression and extended survival. Taken together, these findings indicate that NAMPT/SIRT3/IDH2 pathway inhibition enhances the therapeutic efficacy of PI, thus providing compelling evidence for treatments with lower and less toxic doses and broadening the application of PI to other malignancies.
Obsessive–compulsive disorder and child safeguarding
Authors: Gupta Sumeet , Kiran Shashi
Published: November 2018

Obsessive–compulsive disorder (OCD) is a common psychiatric condition and many patients have childcare responsibilities. A small proportion have aggressive and sexual thoughts about their children. There is little risk that they will act on these thoughts, but primary healthcare and social care professionals are often unaware of this and instigate unnecessary and potentially harmful child safeguarding processes. Psychiatrists have an essential role in educating and liaising with other professionals to prevent these inappropriate interventions.

DECLARATION OF INTEREST

None.
Phase II Trial of Trastuzumab and Docetaxel in Patients With Human Epidermal Growth Factor Receptor 2–Positive Salivary Duct Carcinoma
Authors: Takahashi Hideaki , Tada Yuichiro , Saotome Takashi , Akazawa Kohei , Ojiri Hiroya , Fushimi Chihiro , Masubuchi Tatsuo , Matsuki Takashi , Tani Kaori , Osamura Robert Y. , Hirai Hideaki , Yamada Shuhei , Kawakita Daisuke , Miura Kouki , Kamata Shin-etsu , Nagao Toshitaka
Published: November 2018

Purpose

Clinical evidence demonstrating the effectiveness of systemic therapy for advanced salivary duct carcinoma (SDC) is lacking because of the disease’s rarity. We assessed the efficacy and toxicity of trastuzumab plus docetaxel in patients with locally advanced and/or recurrent or metastatic human epidermal growth factor receptor 2–positive SDC.

Patients and Methods

This was a single-center, single-arm, open-label, phase II study in Japan. The patients received trastuzumab at a loading dose of 8 mg/kg, followed by 6 mg/kg every 3 weeks. Docetaxel 70 mg/m2 was administrated every 3 weeks. The primary end point was the overall response rate; the secondary end points included the clinical benefit rate, progression-free survival, overall survival, and toxicity. This study is registered with the University Hospital Medical Information Network Clinical Trials Registry (Identification No. UMIN000009437).

Results

Fifty-seven eligible patients with SDC were enrolled. The overall response rate was 70.2% (95% CI, 56.6% to 81.6%), and the clinical benefit rate was 84.2% (95% CI, 72.1% to 92.5%). Median progression-free and overall survival times were 8.9 months (95% CI, 7.8 to 9.9 months) and 39.7 months (95% CI, not reached), respectively. The most frequent adverse event was anemia (52 patients [91%]), followed by a decreased WBC count (51 patients [89%]) and neutropenia (50 patients [88%]). The most frequently observed grade 4 adverse event was a decreased neutrophil count (34 patients [60%]). Grade 3 febrile neutropenia was reported in eight patients (14%). No grade 2 or greater adverse events of heart failure or left ventricular ejection fraction decline to less than 50% occurred.

Conclusion

Our data show encouraging efficacy of trastuzumab plus docetaxel therapy in patients with human epidermal growth factor receptor 2–positive SDC, with a manageable toxicity profile.
Influence of Outdoor Temperature and Relative Humidity on Incidence and Etiology of Hyponatremia
Authors: Sailer Clara O , Winzeler Bettina , Nigro Nicole , Bernasconi Luca , Mueller Beat , Christ-Crain Mirjam
Published: November 2018

Context

Hyponatremia is the most common electrolyte disturbance in hospitalized patients. Known risk factors are heart or renal failure, excessive drinking, or the use of diuretics. The incidence of hyponatremia may also be influenced by climate.

Objective

Analyzing the influence of outdoor temperature and relative humidity on the incidence and etiology of hyponatremia.

Design

Cohort A: cross-sectional study from January 2011 to December 2016. Cohort B: prospective observational study from June 2011 to August 2013.

Setting

Emergency departments of two tertiary centers.

Patients

Cohort A: patients with plasma sodium ≤145 mmol/L (n = 222,217). Cohort B: consecutive patients (n = 294) with profound hyponatremia (plasma sodium ≤125 mmol/L).

Main Outcome Measure

The effects of outdoor temperature and relative humidity on the incidence of mild (sodium 126 to 134 mmol/L) and profound hyponatremia (sodium ≤125 mmol/L) were investigated via logistic regression models. The effects of outdoor temperature and relative humidity on hyponatremia etiology were evaluated.

Results

In cohort A, 9.9% had mild and 1.08% had profound hyponatremia. Outdoor temperature was significantly associated with the incidence of profound but not mild hyponatremia (P < 0.01, P = 0.3). Relative humidity was not associated with the incidence of hyponatremia. In cohort B, diuretic-induced hyponatremia occurred more frequently with higher outdoor temperatures, whereas other etiologies showed no clear variation with outdoor temperature or relative humidity.

Conclusions

Higher outdoor temperature, but not relative humidity, seems to be associated with the incidence of profound hyponatremia. Our data suggest that diuretics should be used with caution during hot weather.
Still Perfecting Radioiodine in Thyroid Cancer, After All These Years
Authors: Wirth Lori J
Published: November 2018

Dunn et al. report on vemurafenib redifferentiation in BRAFV660E DTC. Tumor biopsies showed pharmacologic reprogramming. Decades after RAI was brought into the clinic, we are still perfecting its use.
Characterization of spatial and temporal development of Type I and Type II hair cells in the mouse utricle using new cell-type-specific markers
Authors: McInturff Stephen , Burns Joseph C. , Kelley Matthew W.
Published: November 2018

The utricle of the inner ear, a vestibular sensory structure that mediates perception of linear acceleration, is comprised of two morphologically and physiologically distinct types of mechanosensory hair cells, referred to as Type Is and Type IIs. While these cell types are easily discriminated in an adult utricle, understanding their development has been hampered by a lack of molecular markers that can be used to identify each cell type prior to maturity. Therefore, we collected single hair cells at three different ages and used single cell RNAseq to characterize the transcriptomes of those cells. Analysis of differential gene expression identified Spp1 as a specific marker for Type I hair cells and Mapt and Anxa4 as specific markers for Type II hair cells. Antibody labeling confirmed the specificity of these markers which were then used to examine the temporal and spatial development of utricular hair cells. While Type I hair cells develop in a gradient that extends across the utricle from posterior-medial to anterior-lateral, Type II hair cells initially develop in the central striolar region and then extend uniformly towards the periphery. Finally, by combining these markers with genetic fate mapping, we demonstrate that over 98% of all Type I hair cells develop prior to birth while over 98% of Type II hair cells develop post-natally. These results are consistent with previous findings suggesting that Type I hair cells develop first and refute the hypothesis that Type II hair cells represent a transitional form between immature and Type I hair cells.
Gliding for a free lunch: biomechanics of foraging flight in common swifts (Apus apus)
Authors: Hedrick Tyson L. , Pichot Cécile , de Margerie Emmanuel
Published: November 2018

Although the biomechanics of animal flight have been well studied in laboratory apparatus such as wind tunnels for many years, the applicability of these data to natural flight behaviour has been examined in few instances and mostly in the context of long-distance migration. Here, we used rotational stereo-videography to record the free-flight trajectories of foraging common swifts. We found that, despite their exquisite manoeuvring capabilities, the swifts only rarely performed high-acceleration turns. More surprisingly, we also found that despite feeding on tiny insects probably moving with ambient flow, the birds adjust their air speed to optimize cost of transport over distance. Finally, swifts spent only 25% of their time flapping; the majority of their time (71%) was spent in extended wing gliding, during which the average power expended for changes in speed or elevation was 0.84 W kg−1 and not significantly different from 0. Thus, gliding swifts extracted sufficient environmental energy to pay the cost of flight during foraging.
Transcripts and tumors: regulatory and metabolic programming during biotrophic phytopathogenesis
Authors: Schmitz Lara , McCotter Sean , Kretschmer Matthias , Kronstad James W. , Heimel Kai
Published: November 2018

Biotrophic fungal pathogens of plants must sense and adapt to the host environment to complete their life cycles. Recent transcriptome studies of the infection of maize by the biotrophic pathogen Ustilago maydis are providing molecular insights into an ordered program of changes in gene expression and the deployment of effectors as well as key features of nutrient acquisition. In particular, the transcriptome data provide a deeper appreciation of the complexity of the transcription factor network that controls the biotrophic program of invasion, proliferation, and sporulation. Additionally, transcriptome analysis during tumor formation, a key late stage in the life cycle, revealed features of the remodeling of host and pathogen metabolism that may support the formation of tremendous numbers of spores. Transcriptome studies are also appearing for other smut species during interactions with their hosts, thereby providing opportunities for comparative approaches to understand biotrophic adaptation.
Exploring the context of diacidic motif DE as a signal for unconventional protein secretion in eukaryotic proteins
Authors: Padmanabhan Sreedevi , Biswal Malay Ranjan , Manjithaya Ravi , Prakash Meher K.
Published: November 2018

Unconventional protein secretion (UPS) is an important phenomenon with fundamental implications to cargo export. How eukaryotic proteins transported by UPS are recognized without a conventional signal peptide has been an open question. It was recently observed that a diacidic amino acid motif (ASP-GLU or DE) is necessary for the secretion of superoxide dismutase 1 (SOD1) from yeast under nutrient starvation. Taking cue from this discovery, we explore the hypothesis of whether the diacidic motif DE, which can occur fairly ubiquitously, along with its context, can be a generic signal for unconventional secretion of proteins. Four different contexts were evaluated: a physical context encompassing the structural order and charge signature in the neighbourhood of DE, two signalling contexts reflecting the presence of either a phosphorylatable amino acid (‘X’ in XDE, DXE, DEX) or an LC3 interacting region (LIR) which can trigger autophagy and a co-evolutionary constraint relative to other amino acids in the protein interpreted by examining sequences across different species. Among the 100 proteins we curated from different physiological or pathological conditions, we observe a pattern in the unconventional secretion of heat shock proteins in the cancer secretome, where DE in an ordered structural region has higher odds of being a UPS signal.
Peirce’s garden of forking metaphors
Authors: Feodorov Aleksandar
Published: November 2018

The philosophic system of the founder of pragmatism Charles Sanders Peirce is rarely grasped from the point of view of its metaphoric usage. However, some of his most original yet often misunderstood and contested ideas such as those of ‘matter as effete mind’ and ‘the play of musement’ are metaphoric representations. In the present paper I am offering a new way to discuss the role of metaphors in Peirce’s philosophy by taking a twofold approach to the problem. On the one hand, metaphor itself becomes an object of inquiry. I touch upon the appearances of metaphoric thinking at the level of his classes of signs and metaphor’s relation to abductive inference. I trace those appearances in the process of their becoming from the spontaneity of Firstness towards the actuality of Secondness via the generalizing effects of Thirdness. Then I propose a flexible graphic model of metaphor that is parallel to Peirce’s inherent evolutionism. This model is seen as a “gentle” methodological tool for deriving meaning. To illustrate its applicability I include a playful nod to the literary works of Jorge Luis Borges to show how hard logical thought and aesthetic beauty complement each other.
A post-structuralist revised Weil–Lévi-Strauss transformation formula for conceptual value-fields
Authors: Harrod James B.
Published: November 2018

The structuralist André-Weil–Claude-Lévi-Strauss transformation formula (CF), initially applied to kinship systems, mythology, ritual, artistic design and architecture, was rightfully criticized for its rationalism and tendency to reduce complex transformations to analogical structures. I present a revised non-mathematical revision of the CF, a general transformation formula (rCF) applicable to networks of complementary semantic binaries in conceptual value-fields of culture, including comparative religion and mythology, ritual, art, literature and philosophy. The rCF is a rule-guided formula for combinatorial conceptualizing in non-representational, presentational mythopoetics and other cultural symbolizations. I consider poststructuralist category-theoretic and algebraic mathematical interpretations of the CF as themselves only mathematical analogies, which serve to stimulate further revision of the logic model of the rCF. The rCF can be used in hypothesis-making to advance understanding of the evolution and prehistory of human symbolic behaviour in cultural space, philosophical ontologies and categories, definitions and concepts in art, religion, psychotherapy, and other cultural-value forms.
Animal language before Sebeok
Authors: Eco Umberto
Published: November 2018

Publication of the text of Umberto Eco’s talk given at a symposium held in honour of Thomas A. Sebeok (1920–2001) in San Marino in 2002.
Methodology of regional studies
Authors: Лубский Анатолий , Lubsky Anatoly
Published: November 2018

The textbook reveals the scientific and methodological foundations of regional research, discusses its specifics, structure, models, types and logic. Special attention is paid to the geospatial approach as a methodological basis for regional studies, the heuristic possibilities of geographical, geohistorical, geopolitical, geo-economic, geoideological, geo-religious and geocultural paradigms in the study of regional society are revealed. The most actual methodological problems of regional studies and prospects of their solution within the framework of multidimensional methodological constructs are revealed.
The content of the publication meets the requirements of the Federal state educational standards of higher education of the last generation.
The manual is intended for undergraduates of higher educational institutions, students in areas of training: 41.04.01 "Foreign regional studies", 41.04.02 "regional Studies of Russia", 39.04.01 "Sociology".