bluuebunny/crossref_metadata_2025 huggingface dataset:
The conditioning of least‐squares problems in variational data assimilation
Authors: Tabeart Jemima M. , Dance Sarah L. , Haben Stephen A. , Lawless Amos S. , Nichols Nancy K. , Waller Joanne A.
Published: February 2018

In variational data assimilation a least‐squares objective function is minimised to obtain the most likely state of a dynamical system. This objective function combines observation and prior (or background) data weighted by their respective error statistics. In numerical weather prediction, data assimilation is used to estimate the current atmospheric state, which then serves as an initial condition for a forecast. New developments in the treatment of observation uncertainties have recently been shown to cause convergence problems for this least‐squares minimisation. This is important for operational numerical weather prediction centres due to the time constraints of producing regular forecasts. The condition number of the Hessian of the objective function can be used as a proxy to investigate the speed of convergence of the least‐squares minimisation. In this paper we develop novel theoretical bounds on the condition number of the Hessian. These new bounds depend on the minimum eigenvalue of the observation error covariance matrix and the ratio of background error variance to observation error variance. Numerical tests in a linear setting show that the location of observation measurements has an important effect on the condition number of the Hessian. We identify that the conditioning of the problem is related to the complex interactions between observation error covariance and background error covariance matrices. Increased understanding of the role of each constituent matrix in the conditioning of the Hessian will prove useful for informing the choice of correlated observation error covariance matrix and observation location, particularly for practical applications.
A unified framework for nonlinear path‐dependent sensitivity analysis in topology optimization
Authors: Alberdi Ryan , Zhang Guodong , Li Lei , Khandelwal Kapil
Published: February 2018

An adjoint sensitivity analysis framework to evaluate path‐dependent design sensitivities for problems involving inelastic materials and dynamic effects is presented and shown in the context of topology optimization. The overall aim is to present a framework that unifies the sensitivity analyses existing in the literature and provides clear guidelines on how to formulate sensitivity analysis for a wide range of path‐dependent system behaviors simulated using finite element analysis (FEA). In particular, the focus is on the identification of proper independent variables for constraint formulation, the overall structure of constraint derivatives arising from discrete FEA equations, and the consistent implementation of sensitivity analysis for diverse problem types. This framework is used to compute sensitivity values for a number of complex problems formulated within FEA for which sensitivity calculations are not available in the literature. The sensitivity values obtained are then rigorously verified using numerical differentiation based on the central‐difference method. Problem types include the use of enhanced assumed strain elements, plane‐stress constraints, nonlocal elastoplastic‐damage formulations, kinematic/isotropic hardening, rate‐dependent materials, finite deformations, and dynamics. Finally, topology optimization is carried out using some of the different problem types.
Bridge the college‐to‐career gap with more focused initiatives
Authors: Sutton Halley
Published: February 2018

SAN DIEGO — Career services should help to serve as the bridge between your students' academic present and their professional future, but do your career services actually help your students? According to a survey conducted by the California Community Colleges System, only 17 percent of CCCS students who used the career services available at their campus found them helpful. With the CCCS looking to create 1 million skilled workers for the state, the initiative to create the Strong Workforce Program, which targets outcomes in areas of student success, along with other measures of quality in curriculum, regional collaboration, and career pathways, was born.
Support students in getting credit for what they already know
Authors: Hope Joan
Published: February 2018

Marc P. Singer started his career teaching history at small colleges. But hearing the challenges and stories of adult learners led him to his current position as vice provost at the Center for the Assessment of Learning at Thomas Edison State University.
Weighing in on Bariatric Surgery: Effectiveness Among Medicaid Beneficiaries—Limited Evidence and Future Research Needs
Authors: Takemoto Erin , Andrea Sarah B. , Wolfe Bruce M. , Nagel Corey L. , Boone‐Heinonen Janne
Published: February 2018

Introduction

In the general population, bariatric surgery is well documented as the most effective obesity treatment for sustained weight loss and remission of comorbidities. Characterization of the patient populations most likely to benefit from surgical intervention is needed, but the heterogeneity of treatment effects across payer groups has not been reviewed.

Methods

A systematic review of published studies focusing on bariatric surgery outcomes among Medicaid beneficiaries was conducted. By using PubMed and Scopus, this study searched for studies that quantitatively compared clinical or social bariatric surgery outcomes for United States adult Medicaid recipients and commercially insured patients.

Results

Of the 568 titles reviewed, 21 met inclusion criteria. Weight loss and the remission of comorbidities at 1 or 2 years postoperatively were similar between groups despite differences in baseline health status. Short‐term health care utilization and mortality outcomes were worse in Medicaid recipients; for instance, Medicaid patients had an average length of stay that was 2 days longer and experienced three more deaths in the first postoperative year.

Conclusions

The critical research gaps in the evidence base needed to improve treatment guidelines for Medicaid patients undergoing bariatric surgery include an understanding of the causes of the baseline health differences and how these differences contribute to postoperative outcomes.
Genetics of Obesity in Consanguineous Populations: Toward Precision Medicine and the Discovery of Novel Obesity Genes
Authors: Saeed Sadia , Arslan Muhammad , Froguel Philippe
Published: February 2018

Objective

Consanguinity has been instrumental in the elucidation of many Mendelian genetic diseases. Here, the unique advantage of consanguineous populations was considered in the quest for genes causing obesity.

Methods

PubMed was searched for articles relevant to consanguinity and obesity published between 1995 and 2016. Some earlier articles of interest were also consulted.

Results

Although obesity is the most heritable disorder, even in outbred populations, only 2% to 5% of severe obesity cases have so far been proven to be caused by single gene mutations. In some highly consanguineous populations, a remarkably higher proportion of obesity cases because of known and novel monogenic variants has been identified (up to 30%).

Conclusions

Combining the power conferred by consanguinity with current large‐capacity sequencing techniques should bring new genetic factors and molecular mechanisms to the fore, unveiling a large part of the yet‐elusive neurohumoral circuitry involved in the regulation of energy homeostasis and appetite. Importantly, the undertaking of such initiatives is destined to unfold novel targets for the development of precision medicine relevant to different forms of obesity.
Weight Control Program and Gestational Weight Gain in Disadvantaged Women with Overweight or Obesity: A Randomized Clinical Trial
Authors: Cahill Alison G. , Haire‐Joshu Debra , Cade W. Todd , Stein Richard I. , Woolfolk Candice L. , Moley Kelle , Mathur Amit , Schechtman Kenneth , Klein Samuel
Published: February 2018

Objective

This study aimed to evaluate the efficacy of a home‐based lifestyle intervention delivered through Parents as Teachers (PAT) to reduce excessive gestational weight gain (GWG).

Methods

This was a single‐blinded randomized controlled trial conducted as part of the LIFE‐Moms consortium at a single university‐based tertiary care institution from October 2012 to March 2016. There were 267 socioeconomically disadvantaged (SED) African American women with overweight or obesity (BMI 25.0‐45.0 kg/m2 before pregnancy. Participants were randomized to therapy with standard PAT alone (n = 134) or PAT plus a lifestyle intervention program embedded within the standard PAT program (PAT+) (n = 133). Both interventions were delivered in 10 biweekly home visits during pregnancy. The primary outcome was the percentage of women whose GWG exceeded the Institute of Medicine guidelines, and secondary outcomes included both weekly and total GWG.

Results

Compared with the standard PAT group in the intent‐to‐treat analysis, the PAT + group gained less weekly (0.4 kg vs. 0.5 kg/wk; P = 0.04) and total (8.0 kg vs. 9.6 kg; P = 0.02) weight during gestation. Fewer participants in the PAT + group had excessive total GWG (36.1% vs. 45.9%), but the difference between groups was not statistically significant (P = 0.11).

Conclusions

PAT + reduced the weekly and total GWG in SED African American women with overweight or obesity at the start of pregnancy.
Greater Neonatal Fat‐Free Mass and Similar Fat Mass Following a Randomized Trial to Control Excess Gestational Weight Gain
Authors: Gallagher Dympna , Rosenn Barak , Toro‐Ramos Tatiana , Paley Charles , Gidwani Sonia , Horowitz Michelle , Crane Janet , Lin Susan , Thornton John C. , Pi‐Sunyer Xavier
Published: February 2018

Objective

The objective of this study was to determine the effectiveness of controlling maternal gestational weight gain (GWG) in the second and third trimesters on neonate body composition.

Methods

Two hundred ten healthy women with overweight (25 > BMI < 30) or obesity (BMI ≥ 30) were randomly assigned to a lifestyle intervention (LI) program focused on controlling GWG through nutrition and activity behaviors or to usual obstetrical care (UC). Infant fat and fat‐free mass (FFM) at birth were measured by using air displacement plethysmography (PEA POD) and by using quantitative magnetic resonance (QMR).

Results

At baseline, there were no between‐group differences in maternal characteristics (mean [SD]): age: 33.8 (4.3) years, weight: 81.9 (13.7) kg, BMI: 30.4 (4.5), and gestational age at randomization: 14.9 (0.8) weeks. GWG was less in the LI group by 1.79 kg (P = 0.003) or 0.0501 kg/wk (P = 0.002). Compared with UC infants, LI infants had greater weight (131 ± 59 g P = 0.03), FFM (98 ± 45 g; P = 0.03) measured by PEA POD, and lean mass (105 ± 38 g; P = 0.006) measured by QMR. Fat mass and percent fat were not significantly different.

Conclusions

Intervening in women with overweight and obesity through behaviors promoting healthy diet and physical activity to control GWG resulted in neonates with similar fat and greater FFM.
Beauty and the Body of the Beholder: Raters’ BMI Has Only Limited Association with Ratings of Attractiveness of the Opposite Sex
Authors: Wang Guanlin , Ekeleme‐Egedigwe Chima A. , El Hamdouchi Asmaa , Sauciuvenaite Justina , Bissland Ruth , Djafarian Kurosh , Ojiambo Robert , Ramuth Harris , Holasek Sandra , Lackner Sonja , Diouf Adama , Hambly Catherine , Vaanholt Lobke M. , Cao Minxuan , Hacker Megan , Kruger Herculina S. , Seru Tumelo , Faries Mark D. , Speakman John R.
Published: February 2018

Objective

Assortative mating for adiposity increases the genetic burden on offspring, but its causes remain unclear. One hypothesis is that people who have high adiposity find other people with obesity more physically attractive than lean people.

Methods

The attractiveness of sets of images of males and females who varied in adiposity were rated by opposite sex subjects (559 males and 340 females) across 12 countries.

Results

There was tremendous individual variability in attractiveness ratings. For female attractiveness, most males favored the leanest subjects, but others favored intermediate fatness, some were indifferent to body composition, and others rated the subjects with obesity as most attractive. For male images rated by females, the patterns were more complex. Most females favored subjects with low levels of adiposity (but not the lowest level), whereas others were indifferent to body fatness or rated the images depicting individuals with obesity as the most attractive. These patterns were unrelated to rater BMI. Among Caucasian males who rated the images of the thinnest females as being more attractive, the magnitude of the effect depended on rater BMI, indicating limited “mutual attraction.”

Conclusions

Individual variations in ratings of physical attractiveness were broadly unrelated to rater BMI and suggest that mutual attraction is an unlikely explanation for assortative mating for obesity.
Development of a Food Frequency Questionnaire for Assessing Dietary Intake in Children and Adolescents in South America
Authors: Saravia Luisa , González‐Zapata Laura I. , Rendo‐Urteaga Tara , Ramos Jamile , Collese Tatiana Sadalla , Bove Isabel , Delgado Carlos , Tello Florencia , Iglesia Iris , Gonçalves Sousa Ederson Dassler , De Moraes Augusto César Ferreira , Carvalho Heráclito Barbosa , Moreno Luis A.
Published: February 2018

Objective

This study aimed to describe the development of a food frequency questionnaire (FFQ) to assess dietary intake in South American children and adolescents.

Methods

A total of 345 children (aged 3‐10 years) and 357 adolescents (aged 11‐17 years) were included for analysis. The FFQ was designed to be self‐administered and to assess dietary intake over the past 3 months. It was developed in Spanish and translated into Portuguese. Multiple approaches were considered to compile the food list, and 11 food groups were included. A food photo booklet was produced as supporting material.

Results

The FFQ items maintained a common core list among centers (47 items) and country‐specific foods. The FFQ for Buenos Aires and Lima had a total of 63 items; there were 55 items for the FFQ in Medelin, 60 items for Montevideo, 58 items for Santiago, 67 items for Sao Paulo, and 68 items for Teresina. Alcohol was also incorporated in the adolescents' FFQ.

Conclusions

We developed a semiquantitative, culturally adapted FFQ to assess dietary intake in children and adolescents in South America. It has an optimal size allowing its completion in a high proportion of the population; therefore, it can be used in epidemiological studies with South American children and adolescents.
Reliability and Validity of a Questionnaire for Physical Activity Assessment in South American Children and Adolescents: The SAYCARE Study
Authors: Nascimento‐Ferreira Marcus Vinícius , De Moraes Augusto César Ferreira , Toazza‐Oliveira Paulo Vinícius , Forjaz Claudia L.M. , Aristizabal Juan Carlos , Santaliesra‐Pasías Alba M. , Lepera Candela , Nascimento‐Junior Walter Viana , Skapino Estela , Delgado Carlos Alberto , Moreno Luis Alberto , Carvalho Heráclito Barbosa
Published: February 2018

Objective

The objective of this article is to test the reliability and validity of the new and innovative physical activity (PA) questionnaire.

Methods

Subsamples from the South American Youth/Child Cardiovascular and Environment Study (SAYCARE) study were included to examine its reliability (children: n = 161; adolescents: n = 177) and validity (children: n = 82; adolescents: n = 60). The questionnaire consists of three dimensions of PA (leisure, active commuting, and school) performed during the last week. To assess its validity, the subjects wore accelerometers for at least 3 days and 8 h/d (at least one weekend day). The reliability was analyzed by correlation coefficients. In addition, Bland‐Altman analysis and a multilevel regression were applied to estimate the measurement bias, limits of agreement, and influence of contextual variables.

Results

In children, the questionnaire showed consistent reliability (ρ = 0.56) and moderate validity (ρ = 0.46), and the contextual variable variance explained 43.0% with −22.9 min/d bias. In adolescents, the reliability was higher (ρ = 0.76) and the validity was almost excellent (ρ = 0.88), with 66.7% of the variance explained by city level with 16.0 min/d PA bias.

Conclusions

The SAYCARE PA questionnaire shows acceptable (in children) to strong (in adolescents) reliability and strong validity in the measurement of PA in the pediatric population from low‐ to middle‐income countries.
CD Obesity‐Prone Rats, but not Obesity‐Resistant Rats, Robustly Ferment Resistant Starch Without Increased Weight or Fat Accretion
Authors: Obanda Diana , Page Ryan , Guice Justin , Raggio Anne M. , Husseneder Claudia , Marx Brian , Stout Rhett W. , Welsh David A. , Taylor Christopher M. , Luo Meng , Blanchard Eugene E. , Bendiks Zach , Coulon Diana , Keenan Michael J.
Published: February 2018

Objective

This study used CD obesity‐prone (OP) and obesity‐resistant (OR) rats to examine how weight gain and fat accretion relate to fermentation levels and microbiota composition after feeding resistant starch (RS).

Methods

After feeding OP rats and OR rats a high‐fat (HF) diet for 4 weeks, rats were stratified into three groups: they were fed either an HF diet (group 1: HF‐HF) or were switched to a low‐fat (LF) diet (group 2: HF‐LF) or an LF diet supplemented with 20% RS by weight for 4 weeks (group 3: HF‐LFRS). Energy intake, body weight, fermentation variables, and microbiota composition were determined.

Results

In OP rats, RS elicited robust fermentation (increased cecal contents, short‐chain fatty acids, and serum glucagon‐like peptide 1). Total bacteria, species of the Bacteroidales family S24‐7, and the archaean Methanobrevibacter smithii increased. The robust fermentation did not elicit higher weight or fat accretion when compared with that of control rats fed the same isocaloric diets (HF‐LF ± RS). In OR rats, body weight and fat accretion were also not different between HF‐LF ± RS diets, but RS elicited minimal changes in fermentation and microbiota composition.

Conclusions

Robust fermentation did not contribute to greater weight. Fermentation levels and changes in microbiota composition in response to dietary RS differed by obesity phenotype.
Evaluation of an exercise programme for post‐bariatric surgery patients: views of participants
Authors: Gill D. L. , Fasczewski K. S. , Reifsteck E. J. , Rothberger S. M. , Davis P. G.
Published: February 2018

Objective

Exercise programmes typically are evaluated with fitness assessments and psychological survey measures but seldom include participants' insights. The purpose of this study was to evaluate the benefits, facilitators and barriers of a 12‐week exercise programme for post‐bariatric surgery patients from the participants' perspective.

Method

Over a 2‐year period, 20 patients recently having undergone bariatric surgery completed a 12‐week programme that included participation in structured exercise and in focus groups designed to supplement standard evaluation data and provide insight into participants' views.

Results

Participants were highly adherent to the programme, and focus group results reflected a clear positive evaluations. Benefits included helpful information, developing commitment, physical fitness and social support; notably, weight was seldom mentioned. Participants cited structure, accountability and group support as facilitators of exercise. Participants cited few barriers, although very few had set plans for continuing exercise after programme completion.

Conclusion

Participants saw many benefits to the exercise programme, and those benefits reflected lifestyle changes rather than a focus on weight. Programme structure, accountability and the support of the group were facilitators to exercise. Participants cited few barriers. However, the lack of plans for continued exercise suggested the need for a transition phase to help participants continue an active lifestyle after the 12‐week structured programme.
Breaking the oncostatin M feed‐forward loop to suppress metastasis and therapy failure
Authors: Smigiel Jacob , Parvani Jenny G , Tamagno Ilaria , Polak Kelsey , Jackson Mark W
Published: February 2018

Deciphering the complex milieu that makes up the tumor microenvironment (TME) and the signaling engaged by TME cytokines continues to provide novel targets for therapeutic intervention. The IL‐6 family member oncostatin M (OSM) has recently emerged as a potent driver of tumorigenesis, metastasis, and therapy failure, molecular programs most frequently attributed to IL‐6 itself. In a recent issue of The Journal of Pathology, Kucia‐Tran et al describe how elevated oncostatin M receptor (OSMR) expression results in a feed‐forward loop involving the de novo production of both OSM and OSMR to facilitate aggressive properties in squamous cell carcinoma (SCC). Here, we discuss how new findings implicating OSM in conferring aggressive cancer cell properties can be leveraged to suppress metastatic outgrowth and therapy failure in SCC as well as other cancers. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
LC‐MS based metabolic and metabonomic studies of Panax ginseng
Authors: Wu Wei , Jiao Chuanxi , Li Hui , Ma Yue , Jiao Lili , Liu Shuying
Published: February 2018

Introduction

Panax ginseng has received much attention as a valuable health supplement with medicinal potential. Its chemical diversity and multiple pharmacological properties call for comprehensive methods to better understand the effects of ginseng and ginsenosides. Liquid chromatography‐mass spectrometry (LC‐MS) based metabonomic approaches just fit the purpose.

Objective

Aims to give a review of recent progress on LC‐MS based pharmacokinetic, metabolic, and phytochemical metabolomic studies of ginseng, and metabonomic studies of ginseng intervention effects.

Methods

The review has four sections: the first section discusses metabolic studies of ginsenosides based on LC‐MS, the second focuses on ginsenoside‐drug interactions and pharmacokinetic interaction between herb compounds based on LC‐MS, the third is phytochemical metabolomic studies of ginseng based on LC‐MS, and the fourth deals with metabonomic studies of ginseng intervention effects based on LC‐MS.

Results

LC‐MS based metabonomic research on ginseng include analysis of single ginsenoside and total ginsenosides. The theory of multi‐components and multi‐targeted mechanisms helps to explain ginseng effects.

Conclusion

LC‐MS based metabonomics is a promising way to comprehensively assess ginseng. It is valuable for quality control and mechanism studies of ginseng.
A case of prenatal isolated talipes and 22q11.2 deletion syndrome—an important chromosomal disorder missed by noninvasive prenatal screening
Authors: Cheung Ka Wang , Lai Carman Wing Sze , Mak Christopher Chun Yu , Hui Pui Wah , Chung Brian Hon Yin , Kan Anita Sik Yau
Published: February 2018

What's already known about this topic?

NIPS is commonly used to screen for chromosomal abnormality. The test can be extended to screen for microdeletions such as 22q11.2 deletion syndrome.

What does this study add?

We present a case of 22q11.2 deletion syndrome missed by NIPS in a fetus with isolated bilateral talipes. Clinicians should be aware of the controversy surrounding the use of NIPS for 22q11.2 deletion syndrome and that a negative test does not exclude the diagnosis.
Oat of this world: Defining peptide markers for detection of oats in processed food
Authors: Dawson Charlotte , Mendoza‐Porras Omar , Byrne Keren , Hooper Thomas , Howitt Crispin , Colgrave Michelle
Published: February 2018

People affected by Coeliac disease rely on the purity and accurate labeling of food products in order to follow a strict gluten‐free diet, the only treatment for Coeliac disease. The safety of oats in the gluten‐free diet remains controversial because they contain the gluten‐like avenins. In the present study, global proteomic analyses were performed via LC‐MS/MS on gluten‐enriched fractions extracted from 22 diverse oat cultivars. A panel of oat peptides was assessed using multiple‐reaction monitoring mass spectrometry to define peptide markers that were unique to oats but were present in all 22 oat cultivars. The method was successfully applied to: (1) the detection of oat contamination in spelt, rice, rye, and buckwheat flours; and (2) the analysis of 7 highly processed commercial food products. The oat peptide markers were detected at high levels in a breakfast cereal and a muesli where oats were a named ingredient, but the presence of oats was also noted in 3 of the 5 breakfast cereals where oats were not named as an ingredient. LC‐MS/MS represents a rapid, sensitive, robust and reproducible method for detecting oat contamination in both processed and unprocessed foods.
Post‐polymerization modification of bio‐based polymers: maximizing the high functionality of polymers derived from biomass
Authors: Farmer Thomas J , Comerford James W , Pellis Alessandro , Robert Tobias
Published: February 2018

The renaissance of the bio‐based chemical industry over the last 20 years has seen an ever growing interest in the synthesis of new bio‐based polymers. The building blocks of these new polymers, so called platform molecules, contain significantly more chemical functionality than their petrochemical counterparts (such as ethene, propene and para‐xylene). As a result bio‐based polymers often contain greater residual chemical functionality in their chains, with groups such as alkenes and hydroxyls commonly observed. These functional groups can act as sites for post‐polymerization modification (PPM), thus further extending the range of applications for bio‐based polymers by tailoring the polymers' final properties. This mini‐review highlights some of the most recent and compelling examples of how to make use of bio‐based polymers with residual functional groups for PPM. It also looks at how the emerging interdisciplinary field of enzymatic polymer synthesis allows for increased functionality in polymers by avoiding side‐reactions as a result of milder reaction conditions, and additionally offers an alternative means of polymer surface modification. © 2018 Society of Chemical Industry
Proteogenomic Analysis to Identify Missing Proteins from Haploid Cell Lines
Authors: Lee Seung‐Eun , Song JongKeon , Bösl Korbinian , Müller André C. , Vitko Dijana , Bennett Keiryn L. , Superti‐Furga Giulio , Pandey Akhilesh , Kandasamy Richard K. , Kim Min‐Sik
Published: February 2018

Chromosome‐centric Human Proteome Project aims at identifying and characterizing protein products encoded from all human protein‐coding genes. As of early 2017, 19 837 protein‐coding genes have been annotated in the neXtProt database including 2691 missing proteins that have never been identified by mass spectrometry. Missing proteins may be low abundant in many cell types or expressed only in a few cell types in human body such as sperms in testis. In this study, we performed expression proteomics of two near‐haploid cell types such as HAP1 and KBM‐7 to hunt for missing proteins. Proteomes from the two haploid cell lines were analyzed on an LTQ Orbitrap Velos, producing a total of 200 raw mass spectrometry files. After applying 1% false discovery rates at both levels of peptide‐spectrum matches and proteins, more than 10 000 proteins were identified from HAP1 and KBM‐7, resulting in the identification of nine missing proteins. Next, unmatched spectra were searched against protein databases translated in three frames from noncoding RNAs derived from RNA‐Seq data, resulting in six novel protein‐coding regions after careful manual inspection. This study demonstrates that expression proteomics coupled to proteogenomic analysis can be employed to identify many annotated and unannotated missing proteins.
Improving the fluorescent probe acridonylalanine through a combination of theory and experiment
Authors: Sungwienwong Itthipol , Ferrie John J. , Jun Joomyung V. , Liu Chunxiao , Barrett Taylor M. , Hostetler Zachary M. , Ieda Naoya , Hendricks Amara , Muthusamy Anand K. , Kohli Rahul M. , Chenoweth David M. , Petersson George A. , Petersson E. James
Published: February 2018

Acridonylalanine (Acd) is a useful fluorophore for studying proteins by fluorescence spectroscopy, but it can potentially be improved by being made longer wavelength or brighter. Here, we report the synthesis of Acd core derivatives and their photophysical characterization. We also performed ab initio calculations of the absorption and emission spectra of Acd derivatives, which agree well with experimental measurements. The amino acid aminoacridonylalanine (Aad) was synthesized in forms appropriate for genetic incorporation and peptide synthesis. We show that Aad is a superior Förster resonance energy transfer acceptor to Acd in a peptide cleavage assay and that Aad can be activated by an aminoacyl tRNA synthetase for genetic incorporation. Together, these results show that we can use computation to design enhanced Acd derivatives, which can be used in peptides and proteins.
Calculations of the relative energies of the low‐lying electronic states of 2,7‐naphthoquinodimethane and 2,7‐naphthoquinone. Substitution of oxygen for CH2 is predicted to increase the singlet‐triplet energy difference (ΔEST)
Authors: Hrovat David A. , Wang Xue‐Bin , Borden Weston Thatcher
Published: February 2018

(12/12)CASSCF and CASPT2 calculations have been performed on the triplet and two lowest‐lying singlet states of the 2,7‐naphthoquinodimethane (NQDM) and 2,7‐naphthoquinone (NQ) diradicals. Both diradicals are predicted to have triplet ground states but to differ in the ordering of the two lowest singlet states, with E(1A1) < E(1B2) in NQDM, but E(1A1) > E(1B2) in NQ. The reason for the difference in ordering of the singlet states in these two diradicals is discussed. The state reordering is shown to be responsible for the prediction that the substitution of the oxygens in NQ for the CH2 groups in NQDM increases, rather than decreases, the singlet‐triplet energy separation (ΔEST).
Posttraumatic growth in head and neck cancer survivors: Is it possible and what are the correlates?
Authors: Sharp Linda , Redfearn Devon , Timmons Aileen , Balfe Myles , Patterson Joanne
Published: February 2018

Objectives

Posttraumatic growth (PTG) is a possible positive consequence of a traumatic event, such as cancer. Head and neck cancer (HNC) may be particularly traumatic, given its adverse effects on functional, psychological, and social wellbeing. We investigated the extent of PTG, factors associated with PTG, and associations between PTG and health‐related quality‐of‐life (HRQoL) in HNC survivors.

Methods

HNC survivors (ICD10 C00‐C14, C32), identified from the population‐based National Cancer Registry Ireland, completed a postal survey. PTG was assessed using the Posttraumatic Growth Inventory (PTG‐I) and HRQoL with FACT‐G and FACT‐H&N. Associations between socio‐economic characteristics, social support, and clinical variables and PTG were examined using multivariable linear regression. Total HRQoL scores were compared in those with none‐low PTG vs moderate‐high PTG.

Results

A total of 583 survivors participated (response rate = 59%). The mean PTG score was 55.74 (95%CI 53.15‐58.33); 60% had moderate‐high PTG. Survivors scored highest in the PTG‐I domain appreciation of life. In multivariable analysis, being female, being younger, having more social support, and having cancer‐related financial stress were significantly associated with more PTG. HRQoL was significantly higher in those with moderate‐high than no‐little PTG (P < .01).

Conclusions

A notable proportion of HNC survivors report PTG but growth is, on average, lower than reported for other cancers. Nonetheless, higher PTG appears related to better HRQoL. Further research would be valuable to understand the pathways by which HNC may lead to PTG and inform development of strategies to support and encourage PTG in this survivor population.
Formation of lateral chemical gradients in plasma polymer films shielded by an inclined mask
Authors: Vandenbossche Marianne , Petit Laurène , Mathon‐Lagresle Julie , Spano Fabrizio , Rupper Patrick , Bernard Laetitia , Hegemann Dirk
Published: February 2018

Low pressure plasma deposition conditions are investigated yielding oxygen‐containing lateral gradient coatings (aC:H:O) by means of an inclined static mask partly shielding the substrate. Such lateral gradient coatings are formed by the diffusion of film‐forming species with different reactivities underneath the mask. Surface characterization revealed varying film growth conditions below the mask different from direct plasma exposure with increasing distance from the mask/plasma edge: i) exponentially decreasing film growth; ii) decreasing roughness following the thickness trend; iii) decreasing hydrophilicity; iv) variation in cross‐linking; and v) different chemical composition. Oxygen‐rich film‐forming species appeared to react closer to the mask/plasma edge, while oxygen‐poor film‐forming species can diffuse deeper, leading to a pronounced gradient in chemical composition and in cross‐linking in the masked area.
The relationship between inflammation and remodeling in childhood asthma: A systematic review
Authors: Castro‐Rodriguez Jose A. , Saglani Sejal , Rodriguez‐Martinez Carlos E. , Oyarzun Maria A. , Fleming Louis , Bush Andrew
Published: February 2018

Objectives

We aimed to perform a systematic review of all studies with direct measurements of both airway inflammation and remodeling in the subgroup of children with repeated wheezing and/or persistent asthma severe enough to warrant bronchoscopy, to address whether airway inflammation precedes remodeling or is a parallel process, and also to assess the impact of remodeling on lung function.

Methods

Four databases were searched up to June 2017. Two independent reviewers screened the literature and extracted relevant data.

Results

We found 526 references, and 39 studies (2390 children under 18 years old) were included. Airway inflammation (eosinophilic/neutrophilic) and remodeling were not present in wheezers at a mean age of 12 months, but in older pre‐school children (mean 2.5 years), remodeling (mainly increased reticular basement membrane [RBM] thickness and increased area of airway smooth muscle) and also airway eosinophilia was reported. This was worse in school‐age children. RBM thickness was similar in atopic and non‐atopic preschool wheezers. Airway remodeling was correlated with lung function in seven studies, with FeNO in three, and with HRCT‐scan in one. Eosinophilic inflammation was not seen in patients without remodeling. There were no invasive longitudinal or intervention studies.

Conclusion

The relationship between inflammation and remodeling in children cannot be determined. Failure to demonstrate eosinophilic inflammation in the absence of remodeling is contrary to the hypothesis that inflammation causes these changes. We need reliable, non‐invasive markers of remodeling in particular if this is to be addressed.
Does docetaxel prolong survival of patients with non‐metastatic castration‐resistant prostate cancer?
Authors: Ito Kagenori , Kimura Takahiro , Onuma Hajime , Tabata Ryuji , Shimomura Tatsuya , Miki Kenta , Tomita Masayuki , Egawa Shin
Published: February 2018

Background

Guidelines define docetaxel as a first‐line therapeutic option for metastatic castration‐resistant prostate cancer (mCRPC). However, the role of docetaxel in non‐metastatic castration‐resistant prostate cancer (nmCRPC) has not been fully investigated. The aim of this retrospective study was to evaluate the potential role of docetaxel in nmCRPC. Clinical outcomes including overall survival were compared between CRPC patients who had docetaxel introduced while in nonmetastatic versus metastatic diseases.

Methods

A total of 98 CRPC patients had docetaxel therapy. Of these 46 patients received docetaxel for nmCRPC, and 52 had distant metastases. Clinical outcomes from the time of diagnosis of CRPC were compared retrospectively between groups.

Results

The median observation period after the diagnosis of CRPC in these patients was 42 months (range, 3‐166). Overall survival (OS) was significantly longer in the nmCRPC group than in the mCRPC group (not reached vs 52.2 months, respectively, P = 0.006). Multivariate analysis showed that longer time to CRPC, docetaxel use in nmCRPC, and use of abiraterone acetate and/or enzalutamide were significant predictors for improved OS (P = 0.04, 0.019 and 0.002, respectively). The incidence and profile of adverse events did not differ significantly between groups.

Conclusions

Earlier induction of docetaxel in nmCRPC patients may prolong OS. Further prospective studies in more patients will be required to confirm our findings.
The effect of digital rectal exam on the 4Kscore for aggressive prostate cancer
Authors: Maccini Michael A. , Westfall Nicholas J. , Van Bokhoven Adrie , Lucia Marshall Scott , Poage Wendy , Maroni Paul D. , Wilson Shandra S. , Glodé Leonard Michael , Arangua Paul , Newmark Jay , Steiner Mitchell , Werahera Priya N. , Crawford Elward David
Published: February 2018

Background

The 4Kscore is a new commercially available blood‐based diagnostic test which predicts risk for aggressive, clinically significant prostate cancer on prostate biopsy. The 4Kscore is currently restricted to patients who have not had a digital rectal exam (DRE) in the previous 96 h, owing to prior mixed data suggesting that prostate specific antigen (PSA) isoforms may increase by a statistically significant—if not necessarily clinically significant—amount shortly after DRE. Our primary objective was to determine if 4Kscore test results are affected by a preceding DRE.

Methods

Participants at a Prostate Cancer Awareness Week screening event sponsored by the Prostate Conditions Education Council filled out clinical history questionnaires and had blood samples for 4Kscore testing drawn prior to DRE, then 15‐45 min following DRE. Patients with prior cancer diagnosis, 5‐alpha reductase inhibitor medication use, or lower urinary tract procedures in the prior 6 months were excluded, resulting in a population of 162 participants for analysis. Values were then compared to determine if there was a significant difference in 4Kscore following DRE.

Results

A statistically significant increase was seen in levels of 3 kallikreins measured (total PSA, free PSA, and intact PSA; median <0.03 ng/mL for all). This resulted in a small but statistically significant decrease in post‐DRE 4Kscore (median absolute score decrease 0.43%). Using a 4Kscore cutoff of 7.5% resulted in reclassification of 10 patients (6.2%), nine of whom were “downgraded” from above the cutoff to below.

Conclusions

If the blood draw for the 4 K score is performed after a screening DRE, there is a statistically significant difference in the 4 K score results, but in the vast majority of cases it would not affect clinical decision making.
The androgen receptor malignancy shift in prostate cancer
Authors: Copeland Ben T. , Pal Sumanta K. , Bolton Eric C. , Jones Jeremy O.
Published: February 2018

Background

Androgens and the androgen receptor (AR) are necessary for the development, function, and homeostatic growth regulation of the prostate gland. However, once prostate cells are transformed, the AR is necessary for the proliferation and survival of the malignant cells. This change in AR function appears to occur in nearly every prostate cancer. We have termed this the AR malignancy shift.

Methods

In this review, we summarize the current knowledge of the AR malignancy shift, including the DNA‐binding patterns that define the shift, the transcriptome changes associated with the shift, the putative drivers of the shift, and its clinical implications.

Results

In benign prostate epithelial cells, the AR primarily binds consensus AR binding sites. In carcinoma cells, the AR cistrome is dramatically altered, as the AR associates with FOXA1 and HOXB13 motifs, among others. This shift leads to the transcription of genes associated with a malignant phenotype. In model systems, some mutations commonly found in localized prostate cancer can alter the AR cistrome, consistent with the AR malignancy shift. Current evidence suggests that the AR malignancy shift is necessary but not sufficient for transformation of prostate epithelial cells.

Conclusions

Reinterpretation of prostate cancer genomic classification systems in light of the AR malignancy shift may improve our ability to predict clinical outcomes and treat patients appropriately. Identifying and targeting the molecular factors that contribute to the AR malignancy shift is not trivial but by doing so, we may be able to develop new strategies for the treatment or prevention of prostate cancer.
Race affects SVR12 in a large and ethnically diverse hepatitis C‐infected patient population following treatment with direct‐acting antivirals: Analysis of a single‐center Department of Veterans Affairs cohort
Authors: Benhammou Jihane N. , Dong Tien S. , May Folasade P. , Kawamoto Jenna , Dixit Ram , Jackson Samuel , Dixit Vivek , Bhattacharya Debika , Han Steven B. , Pisegna Joseph R.
Published: February 2018

Hepatitis C virus (HCV) infection is a major cause of chronic liver disease. HCV cure has been linked to improved patient outcomes. In the era of direct‐acting antivirals (DAAs), HCV cure has become the goal, as defined by sustained virological response 12 weeks (SVR12) after completion of therapy. Historically, African‐Americans have had lower SVR12 rates compared to White people in the interferon era, which had been attributed to the high prevalence of non‐CC interleukin 28B (IL28B) type. Less is known about the association between race/ethnicity and SVR12 in DAA‐treated era. The aim of the study is to evaluate the predictors of SVR12 in a diverse, single‐center Veterans Affairs population. We conducted a retrospective study of patients undergoing HCV therapy with DAAs from 2014 to 2016 at the VA Greater Los Angeles Healthcare System. We performed a multivariable logistic regression analysis to determine predictors of SVR12, adjusting for age, HCV genotype, DAA regimen and duration, human immunodeficiency virus (HIV) status, fibrosis, nonalcoholic fatty liver disease (NAFLD) fibrosis score, homelessness, mental health, and adherence. Our cohort included 1068 patients, out of which 401 (37.5%) were White people and 400 (37.5%) were African‐American. Genotype 1 was the most common genotype (83.9%, N = 896). In the adjusted models, race/ethnicity and the presence of fibrosis were statistically significant predictors of non‐SVR. African‐Americans had 57% lower odds for reaching SVR12 (adj.OR = 0.43, 95% CI = 1.5‐4.1) compared to White people. Advanced fibrosis (adj.OR = 0.40, 95% CI = 0.26‐0.68) was also a significant predictor of non‐SVR. In a single‐center VA population on DAAs, African‐Americans were less likely than White people to reach SVR12 when adjusting for covariates.
Management of genital herpes: a guide for GPs
Authors: Draeger Eleanor
Published: February 2018

Although there is no curative treatment for genital herpes, antiviral therapy can reduce the duration of symptoms and the frequency and severity of recurrences. This article discusses the diagnosis of genital herpes, the treatment options available and the GP's role in management.
Accounting for cardiovascular risk when prescribing NSAIDs
Authors: Laight David
Published: February 2018

It is now recognised that oral NSAIDs can increase the risk of cardiovascular events, including myocardial infarction and stroke. This article discusses the potential mechanisms involved and how the risk can be minimised.
Cladribine for highly active relapsing multiple sclerosis
Authors: Chaplin Steve
Published: February 2018

Cladribine (Mavenclad) is a new oral treatment for adults with highly active relapsing multiple sclerosis. This article summarises its dosing and monitoring requirements, efficacy in the CLARITY trial and place in therapy.
Ageing by feet? Regional migration, neighbourhood choice and local demographic change in German cities
Authors: Neumann Uwe
Published: February 2018

In countries with an ageing population, regional migration affects the local consequences of demographic change. This paper investigates whether ageing implicates a more distinct residential segregation by age and results in an accelerated “ageing by feet” in urban districts not favoured by younger people. The large urban regions of North Rhine‐Westphalia in Germany serve as a case study that comprises both growing and stagnating cities. Thriving cities in the Rhineland (Bonn, Cologne and Düsseldorf) contrast with the Ruhr, where the population stagnates and ageing proceeds even more rapidly than in Germany as a whole. Intraurban variation in demographic change over the period 1998–2008 is examined using municipal statistics. The underlying segregation process is studied on the basis of a discrete choice model of neighbourhood sorting, using microdata from a representative survey carried out in the Ruhr in 2010. The analysis shows that in the course of an urban revival during the 1990s and 2000s, it was typical of individuals aged under 30 to prefer residence close to city centres. However, in the Ruhr, young adults were not underrepresented in households moving to ageing neighbourhoods that are located within a certain distance to centres either. It appears, therefore, that regional ageing will not necessarily lead to a self‐reinforcing agglomeration of young adults in the most popular central city quarters. Given a continued desire for urban centrality, however, it will become difficult for households with children to find suitable and affordable accommodation in the more central parts of large cities.
The Effect of Strain and Grain Size on Phonon and Electron Confinements in TiO2 Thin Films
Authors: Nassar Zaher Mahmoud , Yükselici Mehmet Hikmet
Published: February 2018

Titanium dioxide (TiO2) powder in anatase phase is thermally evaporated by physical vapor deposition (PVD) on glass substrates. Different‐thickness TiO2 thin films are deposited on glass slides. The samples are then optically and structurally investigated using optical absorption (ABS) and Raman scattering (RS). Optical absorption spectroscopy shows that Urbach energy (EU) related to the width of the long‐wavelength tail decreased from 212 to 176 meV as the film thickness increased from 143 to 221 nm, respectively. The grain size, which depends on thickness of the film, a00nd the grain size distribution are evaluated by fitting the absorption coefficient α experimental data to a model of α as a function of energy E. Absorption edge energy (ER) is also calculated, it decreases by 165 meV as the film thickness increases from 143 to 221 nm. The energies of band gap transitions are also determined from the observed data of absorption. There are two types of transitions, i.e., direct and indirect transitions, in the TiO2 compound. The phonon confinement model is used to interpret the size effect in Raman scattering. Relative to the Raman active Eg mode of bulk TiO2 crystal, a size‐dependent blue shift is noticed in the Raman bands for the first and second Eg modes (: ≈144 cm−1 and : 197 cm−1, respectively). In this study, the results of Raman scattering and optical absorption are combined together in order to investigate the grain size effect, structural disorder, and thickness‐dependent strain. In ABS spectroscopy, it is noticed that (at certain wavelength) the intensity of the transmitted light for the thinner sample is higher than that for the thicker one, which is compatible with the relation I = I0e−αt, where α is the absorption coefficient and t is the thickness.