bluuebunny/crossref_metadata_2025 huggingface dataset:
Significance of Immune-related Lipase Increase Induced by Antiprogrammed Death-1 or Death Ligand-1 Antibodies: A Brief Communication
Authors: Michot Jean-Marie , Ragou Parvady , Carbonnel Franck , Champiat Stéphane , Voisin Anne-Laure , Mateus Christine , Lambotte Olivier , Annereau Maxime
Published: December 2017

Antiprogrammed death-1 (anti-PD1) and antiprogrammed death ligand-1 (anti-PD-L1) antibodies are effective checkpoint inhibitors that stimulate the immune system against many types of cancers. The flip side of these immunotherapies is the generation of immune-related adverse events, which can theoretically affect all organs. Among these side effects, lipase increase is frequently observed; however the meaning of this biological abnormality remains poorly understood. We investigate in this case study all the lipase increases greater or equal to grade 2 that occurred in patients receiving anti-PD-1 or anti-PD-L1 treatments, to determine their biological and clinical significance. Twenty-one patients were retained with lipase increase related to the immune checkpoint inhibitor. Most of them (71%) were treated for a metastatic melanoma. The peak of lipase increase was observed at a median of 2.8 (range, 0.4–11.4) months after the initiation of the anti-PD1 or anti-PD-L1 treatment, which correlates with cycle 5 of treatment. Three of 21 patients (14%) had a clinical or radiologic immune-related pancreatitis that led to a permanent discontinuation of the treatment. In 15 of 21 (71%) patients, the lipase increase was not considered as clinically significant, and the treatment was continued without complications. The 3 remaining patients discontinued the treatment for progressive disease. These data indicate that lipase increase related to anti-PD1 or anti-PD-L1 is not associated with a significant clinical event in most cases. On the basis of these data, we propose that lipase increase in an asymptomatic patient and without radiographic abnormalities of the pancreas can be reasonably regarded as a not clinically significant event, allowing the continuation of the anti-PD-1 or anti-PD-L1 treatment.
Sources of Parent-Child Transmission of Drug Abuse
Authors: Kendler Kenneth S. , Ohlsson Henrik , Sundquist Kristina , Sundquist Jan
Published: December 2017

To clarify the origins of parent-child resemblance for drug abuse (DA), using national Swedish data, we fit path models to information on DA in parents and children from six informative family types: i) not-lived-with father, ii) not-lived-with mother, iii) stepfather, iv) stepmother, v) triparental, and vi) adoptive. From these families, we estimated parent-offspring resemblance reflecting the effects of genes + rearing, genes only, and rearing only. The estimates of parent-offspring correlations were statistically homogenous across family types. The weighted estimate of the father-offspring correlation for DA for genes + rearing, genes-only, and rearing-only relationships were, respectively, +0.26, +0.19, and +0.06. Parallel figures for mother-offspring relationships were +0.19, +0.13, and +0.09. In both genes + rearing and genes-only parent-offspring relationships, DA correlations were stronger for fathers than for mothers. Both genetic and environmental factors contribute substantially to parent-offspring resemblance for DA and seem to be additive.
Ubiquitin ligase LNX1 is a major regulator of glycine recapture by the presynaptic transporter GlyT2
Authors: Núñez E , Arribas-González E , López-Corcuera B , Aragón C , de Juan-Sanz J
Published: December 2017

The neuronal glycine transporter GlyT2 is an essential regulator of glycinergic neurotransmission that recaptures glycine in presynaptic terminals to facilitate quantal transmitter packaging in synaptic vesicles. Alterations in GlyT2 expression or activity result in lower cytosolic glycine levels, emptying glycinergic synaptic vesicles and impairing neurotransmission. Lack of glycinergic neurotransmission caused by GlyT2 loss-of-function mutations results in Hyperekplexia, a rare neurological disease characterized by generalized stiffness and motor alterations that may result in sudden infant death. Although the importance of GlyT2 in pathology is known, how this transporter is regulated at the molecular level is poorly understood, limiting current therapeutic strategies. Guided by an unbiased screening, we discovered that the E3 ubiquitin ligase Ligand of Numb protein X1 (LNX1) modulates the ubiquitination status of GlyT2. LNX1 ubiquitinates a cytoplasmic C-terminal lysine cluster in GlyT2 (K751, K773, K787 and K791) through its N-terminal RING-finger domain, and this process regulates the expression levels and transport activity of GlyT2 in neurons. These experiments reveal for the first time the identity of an E3 ubiquitin-ligase acting on GlyT2 and identify a novel regulatory mechanism by which neurons regulate GlyT2 expression and activity.
The Anorexia Nervosa Genetics Initiative: Overview and Methods
Authors: Thornton Laura M , Munn-Chernoff Melissa A , Baker Jessica H , Juréus Anders , Parker Richard , Henders Anjali K , Larsen Janne T , Petersen Liselotte , Watson Hunna J , Yilmaz Zeynep , Kirk Katherine M , Gordon Scott , Leppä Virpi M , Martin Felicity C , Whiteman David C , Olsen Catherine M , Werge Thomas M , Pedersen Nancy L , Kaye Walter , Bergen Andrew W , Halmi Katherine A , Strober Michael , Kaplan Allan S , Woodside D. Blake , Mitchell James , Johnson Craig L , Brandt Harry , Crawford Steven , Horwood L. John , Boden Joseph M , Pearson John F , Duncan Laramie E , Grove Jakob , Mattheisen Manuel , Jordan Jennifer , Kennedy Martin A , Birgegård Andreas , Lichtenstein Paul , Norring Claes , Wade Tracey D , Montgomery Grant W , Martin Nicholas G , Landén Mikael , Mortensen Preben Bo , Sullivan Patrick F , Bulik Cynthia M
Published: December 2017

Background:

Genetic factors contribute to anorexia nervosa (AN); and the first genome-wide significant locus has been identified. We describe methods and procedures for the Anorexia Nervosa Genetics Initiative (ANGI), an international collaboration designed to rapidly recruit 13000 individuals with AN as well as ancestrally matched controls. We present sample characteristics and the utility of an online eating disorder diagnostic questionnaire suitable for large-scale genetic and population research.

Methods:

ANGI recruited from the United States (US), Australia/New Zealand (ANZ), Sweden (SE), and Denmark (DK). Recruitment was via national registers (SE, DK); treatment centers (US, ANZ, SE, DK); and social and traditional media (US, ANZ, SE). All cases had a lifetime AN diagnosis based on DSM-IV or ICD-10 criteria (excluding amenorrhea). Recruited controls had no lifetime history of disordered eating behaviors. To assess the positive and negative predictive validity of the online eating disorder questionnaire (ED100K-v1), 109 women also completed the Structured Clinical Interview for DSM-IV (SCID), Module H.

Results:

Blood samples and clinical information were collected from 13,364 individuals with lifetime AN and from controls. Online diagnostic phenotyping was effective and efficient; the validity of the questionnaire was acceptable.

Conclusions:

Our multipronged recruitment approach was highly effective for rapid recruitment and can be used as a model for efforts by other groups. High online presence of individuals with AN rendered the Internet/social media a remarkably effective recruitment tool in some countries. ANGI has substantially augmented Psychiatric Genomics Consortium AN sample collection. ANGI is a registered clinical trial: clinicaltrials.gov NCT01916538; https://clinicaltrials.gov/ct2/show/NCT01916538?cond=Anorexia+Nervosa&draw=1&rank=3.
Transcription organizes euchromatin similar to an active microemulsion
Authors: Hilbert Lennart , Sato Yuko , Kimura Hiroshi , Jülicher Frank , Honigmann Alf , Zaburdaev Vasily , Vastenhouw Nadine L.
Published: December 2017

Chromatin is organized into heterochromatin, which is transcriptionally inactive, and euchromatin, which can switch between transcriptionally active and inactive states. This switch in euchromatin activity is accompanied by changes in its spatial distribution. How euchromatin rearrangements are established is unknown. Here we use super-resolution and live-cell microscopy to show that transcriptionally inactive euchromatin moves away from transcriptionally active euchromatin. This movement is driven by the formation of RNA-enriched microenvironments that exclude inactive euchromatin. Using theory, we show that the segregation into RNA-enriched microenvironments and euchromatin domains can be considered an active microemulsion. The tethering of transcripts to chromatin via RNA polymerase II forms effective amphiphiles that intersperse the two segregated phases. Taken together with previous experiments, our data suggest that chromatin is organized in the following way: heterochromatin segregates from euchromatin by phase separation, while transcription organizes euchromatin similar to an active microemulsion.
A tissue-specific self-interacting chromatin domain forms independently of enhancer-promoter interactions
Authors: Brown Jill M , Roberts Nigel A , Graham Bryony , Waithe Dominic , Lagerholm Christoffer , Telenius Jelena M , De Ornellas Sara , Oudelaar A Marieke , Szczerbal Izabela , Babbs Christian , Kassouf Mira T , Hughes Jim R , Higgs Douglas R , Buckle Veronica J
Published: December 2017

A variety of self-interacting domains, defined at different levels of resolution, have been described in mammalian genomes. These include Chromatin Compartments (A and B)1, Topologically Associated Domains (TADs)2,3, contact domains4,5, sub-TADs6, insulated neighbourhoods7 and frequently interacting regions (FIREs)8. Whereas many studies have found the organisation of self-interacting domains to be conserved across cell types389, some do form in a lineage-specific manner6710. However, it is not clear to what degree such tissue-specific structures result from processes related to gene activity such as enhancer-promoter interactions or whether they form earlier during lineage commitment and are therefore likely to be prerequisite for promoting gene expression. To examine these models of genome organisation in detail, we used a combination of high-resolution chromosome conformation capture, a newly-developed form of quantitative fluorescence in-situ hybridisation and super-resolution imaging to study a 70 kb self-interacting domain containing the mouse α-globin locus. To understand how this self-interacting domain is established, we studied the region when the genes are inactive and during erythroid differentiation when the genes are progressively switched on. In contrast to many current models of long-range gene regulation, we show that an erythroid-specific, decompacted self-interacting domain, delimited by convergent CTCF/cohesin binding sites, forms prior to the onset of robust gene expression. Using previously established mouse models we show that formation of the self-interacting domain does not rely on interactions between the α-globin genes and their enhancers. As there are also no tissue-specific changes in CTCF binding, then formation of the domain may simply depend on the presence of activated lineage-specific cis-elements driving a transcription-independent mechanism for opening chromatin throughout the 70 kb region to create a permissive environment for gene expression. These findings are consistent with a model of loop-extrusion in which all segments of chromatin, within a region delimited by CTCF boundary elements, can contact each other. Our findings suggest that activation of tissue-specific element(s)within such a self-interacting region is sufficient to influence all chromatin within the domain.
Speed dependent descending control of innate freezing behavior inDrosophila melanogaster
Authors: Zacarias Ricardo , Namiki Shigehiro , Card Gwyneth , Vasconcelos Maria Luisa , Moita Marta A.
Published: December 2017

The most fundamental choice an animal has to make when it detects a predator, or other threats, is whether to freeze, reducing its chances of being noticed, or to flee to safety. Here we show thatDrosophila melanogasterexposed to looming stimuli in a confined arena either froze or fled. The probability of freezing versus fleeing was modulated by the fly’s walking speed at the time of threat, demonstrating that freeze/flee decisions were context dependent. We describe a pair of descending neurons crucially implicated in freezing. Genetic silencing of DNp09 descending neurons disrupted freezing yet did not prevent fleeing. Optogenetic activation of both DNp09 neurons induced running and freezing in a state-dependent manner. Our findings establish walking speed as a key factor in defensive response choices and reveal a pair of descending neurons as a critical component in the circuitry mediating selection and execution of freezing or fleeing behaviors.
Genome-wide post-transcriptional dysregulation by microRNAs in human asthma as revealed by Frac-seq
Authors: Martinez-Nunez Rocio T. , Rupani Hitasha , Platé Manuela , Niranjan Mahesan , Chambers Rachel C. , Howarth Peter H. , Sanchez-Elsner Tilman
Published: December 2017

MicroRNAs are small non-coding RNAs that inhibit gene expression post-transcriptionally, implicated in virtually all biological processes. Although the effect of individual microRNAs is generally studied, the genome-wide role of multiple microRNAs is less investigated. We assessed paired genome-wide expression of microRNAs with total (cytoplasmic) and translational (polyribosome-bound) mRNA levels employing Frac-seq in human primary bronchoepithelium from healthy controls and severe asthmatics. Severe asthma is a chronic inflammatory disease of the airways characterized by poor response to therapy. We found genes (=all isoforms of a gene) and mRNA isoforms differentially expressed in asthma, with novel inflammatory and structural mechanisms disclosed solely by polyribosome-bound mRNAs. Gene expression (=all isoforms of a gene) and mRNA expression analysis revealed different molecular candidates and biological pathways, with differentially expressed polyribosome-bound and total mRNAs also showing little overlap. We reveal a hub of six dysregulated microRNAs accounting for ∼90% of all microRNA targeting, displaying preference for polyribosome-bound mRNAs. Transfection of this hub in healthy cells mimicked asthma characteristics. Our work demonstrates extensive post-transcriptional gene dysregulation in asthma, where microRNAs play a central role, illustrating the feasibility and importance of assessing post-transcriptional gene expression when investigating human disease.
Pharmacological manipulation of olfactory bulb granule cell excitability modulates beta oscillations: Testing a model
Authors: Osinski Boleslaw L. , Kim Alex , Xiao Wenxi , Mehta Nisarg , Kay Leslie M.
Published: December 2017

The mammalian olfactory bulb (OB) generates gamma (40 – 100 Hz) and beta (15 – 30 Hz) oscillations of the local field potential (LFP). Gamma oscillations arise at the peak of inhalation supported by dendrodendritic interactions between glutamatergic mitral cells (MCs) and GABAergic granule cells (GCs). Beta oscillations occur in response to odorants in learning or odor sensitization paradigms, but their generation mechanism and function are still poorly understood. When centrifugal inputs to the OB are blocked, beta oscillations disappear, but gamma oscillations persist. Centrifugal input targets primarily GABAergic interneurons in the GC layer (GCL) and regulates GC excitability, which suggests a causal link between beta oscillations and GC excitability. Previous modeling work from our laboratory predicted that convergence of excitatory/inhibitory inputs onto MCs and centrifugal inputs onto GCs can increase GC excitability sufficiently to drive beta oscillations primarily through voltage dependent calcium channel (VDCC) mediated GABA release, independently of NMDA channels. We test this model by examining the influence of NMDA and muscarinic acetylcholine receptors on GC excitability and beta oscillations. Intrabulbar scopolamine (muscarinic antagonist) infusion decreased or completely suppressed odor-evoked beta in response to a strong stimulus, but increased beta power in response to a weak stimulus, as predicted by our model. Piriform cortex (PC) beta power was unchanged. Oxotremorine (muscarinic agonist) tended to suppress all oscillations, probably from over-inhibition. APV, an NMDA receptor antagonist, suppressed gamma oscillations selectively (in OB and PC), lending support to the model’s prediction that beta oscillations can be supported by VDCC mediated currents.

New and Noteworthy:

Olfactory bulb beta oscillations rely on granule cell excitability.

Reducing granule cell excitability with scopolamine reduces high volatilityinduced beta power but increases low volatility-induced beta power.

Piriform cortex beta oscillations maintain power when olfactory bulb beta power is low, and the system maintains beta band coherence.
The tortoise and the hare: interactions between reinforcement learning and working memory
Authors: Collins Anne G.E.
Published: December 2017

Learning to make rewarding choices in response to stimuli depends on a slow but steady process, reinforcement learning, and a fast and flexible, but capacity limited process, working memory. Using both systems in parallel, with their contributions weighted based on performance, should allow us to leverage the best of each system: rapid early learning, supplemented by long term robust acquisition. However, this assumes that using one process does not interfere with the other. We use computational modeling to investigate the interactions between the two processes in a behavioral experiment, and show that working memory interferes with reinforcement learning. Previous research showed that neural representations of reward prediction errors, a key marker of reinforcement learning, were blunted when working memory was used for learning. We thus predicted that arbitrating in favor of working memory to learn faster in simple problems would weaken the reinforcement learning process. We tested this by measuring performance in a delayed testing phase where the use of working memory was impossible, and thus subject choices depended on reinforcement learning. Counter-intuitively, but confirming our predictions, we observed that associations learned most easily were retained worse than associations learned slower: using working memory to learn quickly came at the cost of long-term retention. Computational modeling confirmed that this could only be accounted for by working memory interference in reinforcement learning computations. These results further our understanding of how multiple systems contribute in parallel to human learning, and may have important applications for education and computational psychiatry.
A methodology for unsupervised clustering using iterative pruning to capture fine-scale structure
Authors: Chaichoompu Kridsadakorn , Yazew Fentaw Abegaz , Tongsima Sissades , Shaw Philip James , Sakuntabhai Anavaj , Cavadas Bruno , Pereira Luísa , Van Steen Kristel
Published: December 2017

SNP-based information is used in several existing clustering methods to detect shared genetic ancestry or to identify population substructure. Here, we present a methodology for unsupervised clustering using iterative pruning to capture fine-scale structure called IPCAPS. Our method supports ordinal data which can be applied directly to SNP data to identify fine-scale population structure. We compare our method to existing tools for detecting fine-scale structure via simulations. The simulated data do not take into account haplotype information, therefore all markers are independent. Although haplotypes may be more informative than SNPs, especially in fine-scale detection analyses, the haplotype inference process often remains too computationally intensive. Therefore, our strategy has been to restrict attention to SNPs and to investigate the scale of the structure we are able to detect with them. We show that the experimental results in simulated data can be highly accurate and an improvement to existing tools. We are convinced that our method has a potential to detect fine-scale structure.
Statistics of chromatin organization during cell differentiation revealed by heterogeneous cross-linked polymers
Authors: Shukron O. , Piras V. , Noordermeer D , Holcman D.
Published: December 2017

Chromatin of mammalian nucleus folds into discrete contact enriched regions such as Topologically Associating domains (TADs). The folding hierarchy of the TADs and their internal organization is highly dynamic through cellular differentiation, where structural changes within and between TADs are correlated with gene activation and silencing. To account for multiple interacting TADs, we developed a parsimonious randomly cross-linked (RCL) polymer model that maps high frequency encounters present in HiC data within and between TADs into direct local monomer interactions, characterized by the number of cross-links at a given base-pair resolution. We reconstruct three TADs obtained from the mammalian X chromosome for three stages of differentiation. We compute the radius of gyration of TADs and the encounter probability between genomic segments. We found 1) a synchronous compaction and decompaction of TADs throughout differentiation and 2) secondary structures such as meta-TADs in 5C data resulting from weak inter-TAD interactions. Finally, the present method links steady-state to dynamic properties of the chromatin revealed by the distribution of anomalous exponents of single loci trajectories, reconstructed from HiC data.
SLAM-ITseq: Sequencing cell type-specific transcriptomes without cell sorting
Authors: Matsushima Wayo , Herzog Veronika A , Neumann Tobias , Gapp Katharina , Zuber Johannes , Ameres Stefan L , Miska Eric A
Published: December 2017

Cell type-specific transcriptome analysis is an essential tool in understanding biological processes but can be challenging due to the limits of microdissection or fluorescence-activated cell sorting (FACS). Here, we report a novel in vivo sequencing method, which captures the transcriptome of a specific type of cells in a tissue without prior cellular or molecular sorting. SLAM-ITseq provides an accurate snapshot of the transcriptional state in vivo.
Stability, affinity and chromatic variants of the glutamate sensor iGluSnFR
Authors: Marvin Jonathan S. , Scholl Benjamin , Wilson Daniel E. , Podgorski Kaspar , Kazemipour Abbas , Müeller Johannes Alexander , Schoch-McGovern Susanne , Urra Quiroz Francisco José , Rebola Nelson , Bao Huan , Little Justin P. , Tkachuk Ariana N. , Hantman Adam W. , Wang Samuel S.-H. , Chapman Edwin R. , Dietrich Dirk , DiGregorio David A. , Fitzpatrick David , Looger Loren L.
Published: December 2017

Single-wavelength fluorescent reporters allow visualization of specific neurotransmitters with high spatial and temporal resolution. We report variants of the glutamate sensor iGluSnFR that are functionally brighter; can detect sub-micromolar to millimolar concentrations of glutamate; and have blue, green or yellow emission profiles. These variants allow in vivo imaging where original-iGluSnFR was too dim, reveal glutamate transients at individual spine heads, and permit kilohertz imaging with inexpensive, powerful fiber lasers.
In search of the socially critical in health education
Authors: Wright Jan , O’Flynn Gabrielle , Welch Rosie
Published: December 2017

Purpose

Health education still tends to be dominated by an approach designed to achieve individual behaviour change through the provision of knowledge to avoid risk. In contrast, a critical inquiry approach educates children and young people to develop their capacity to engage critically with knowledge, through reasoning, problem solving and challenging taken for granted assumptions, including the socially critical approach which investigates the impact of social and economic inequalities on, for example, health status and cultural understandings. The purpose of this paper is to explore the conditions of possibility for a socially critical approach to health education in schools. It examines the ways in which preservice health and physical education (HPE) teachers talked about their experiences of health education during their school-based practicum.

Design/methodology/approach

In total, 13 preservice HPE teachers who were about to graduate with a Bachelor of Health and Physical Education from a university in New South Wales, Australia were interviewed for the study. Five group interviews and one individual interview were conducted. The interviews were coded for themes and interpreted drawing on a biopedagogical theoretical framework as a way of understanding the salience of particular forms of knowledge in health education, how these are promoted and with what effects for how living healthily is understood.

Findings

The HPETE students talked with some certainty about the purpose of health education as a means to improve the health of young people – a certainty afforded by a medico-scientific view of health imbued with individualised, risk discourses. This purpose was seen as being achieved through using pedagogies, particularly those involving technology, that produced learning activities that were “engaging” and “relevant” for young people. Largely absent from their talk was evidence that they valued or practiced a socially critical approach to health education.

Practical implications

This paper has practical implications for designing health education teacher programmes that are responsive to expectations that contemporary school health education curricula employ a critical inquiry approach.

Originality/value

This paper addresses an empirical gap in the literature on the conditions of possibility for a socially critical approach to health education. It is proposed that rather than challenging HPE preservice teachers’ desires to improve the lives of young people, teacher educators need to work more explicitly within an educative approach that considers social contexts, health inequalities and the limitations of a behaviour change model.
Market structure in the Vietnamese banking system: a non-structural approach
Authors: Nguyen Thao Ngoc , Stewart Chris , Matousek Roman
Published: December 2017

Purpose

This paper aims to examine the market structure of Vietnam’s banking sector during 1999-2009, which is after the introduction of the two-tier banking system, using the non-structural (Panzar–Rosse) model.

Design/methodology/approach

The authors consider a more comprehensive range of specifications, in terms of a greater number of environmental covariates and different dependent variables, than in the previous applications of this model. Further, this is the first study that uses lagged input prices (to avoid endogeneity), excludes assets (to avoid specification bias) and includes a lagged dependent variable (to avoid dynamic panel bias) in such a study of the Vietnamese banking system.

Findings

The authors find that the Vietnamese banking system operates in monopoly.

Originality/value

The main contribution of this paper is to determine the market structure in the recent period after the Vietnamese banking system was transformed into a less centralised, two-tier system. This study is the first to uniquely identify the market structure of this developing economy’s banking system (using data only for Vietnam and not observations from other countries) in a post-transition period.
Graphical Illustration of Interaction Effects in Binary Choice Models: A Note
Authors: Franken Jason R.V. , Pennings Joost M.E. , Garcia Philip
Published: December 2017

Graphing procedures for evaluating power or interaction terms in binary logit and probit models are illustrated in an application to hog producers’ decisions based on transaction cost economics’ hypothesised positive effect of the interaction of uncertainty and asset specificity on contract use. Results support the hypothesis, particularly for producers that are otherwise on the cusp (near the 50/50 probability) of choosing either contract or spot transactions based on their responses for other variables. Such insights may not be drawn without use of the demonstrated graphing procedures.
Housing Price Dynamics, Mortgage Credit and Reverse Mortgage Demand: Theory and Empirical Evidence
Authors: Chen Kuo‐Shing , Yang J. Jimmy
Published: December 2017

This article presents some theoretical and empirical approaches for identifying interactions among fundamental economic variables that determine housing prices. Using home equity conversion mortgage (HECM) loan‐level data, this study quantifies the major risks of reverse mortgages and shows that higher housing prices induce higher demand for reverse mortgages among elderly homeowners. Senior citizens rationally hold pessimistic expectations about future housing price appreciation and lock in their home‐equity gains by obtaining reverse mortgages, which in turn led to the substantial HECM growth prior to the financial crisis of 2008. A novel simulation also forecasts HECM loans under various economic scenarios. From a mortgage credit perspective, these findings generate several policy implications for the implementation of “HECM 3.0.”
The Role of the Dynamic Sensory Perception in the Reformulation of Shakes: Use of TDS for Studying the Effect of Milk, Fiber, and Flavor Addition
Authors: Tomadoni Barbara , Fiszman Susana , Moreira María R. , Tarrega Amparo
Published: December 2017

Various factors need to be taken into account when reformulating a food or beverage. The food components, not only macronutrients but also minor ingredients such as flavoring agents, could affect the perception of the sensory sensations, importantly their dynamic aspects, as rising and duration, which are not normally considered. The novelty of this approach is the study of the effects of the addition of several ingredients (fiber, extra milk powder, and strawberry flavoring) on the dynamic perception of a food item (strawberry shakes) using the temporal dominance of sensations (TDS) technique. The occurrence and duration of the key sensory sensations (acid, natural strawberry flavor, thick, sweet, candy strawberry flavor, and milk flavor) extracted from the TDS curves were analyzed and linked to the composition factors and liking and expectations of satiety scores. For example, the addition of flavoring increased the liking scores (increments ranging from 0.3 to 1.1) that was linked to the attenuation of acid sensation; and the addition of extra milk powder increased the expectation of satiety scores (increments ranging from 0.5 to 0.7) that was linked to the perception of early thick sensation in the mouth. In general, the more complex sensory profiles the higher liking and expectations of satiety.

Practical Application

This work is a case study on how temporal sensory methods can contribute important information on the actual perception of food during consumption. Depending on the ingredients added these sensory properties appear at different times and with different dominance during evaluation affecting liking or fullness expectations. In consequence, the temporal sensory properties should be taken into account when designing or reformulating food.
Effects of Pro‐Oxidants and Antioxidants on the Total Antioxidant Capacity and Lipid Oxidation Products of Milk During Refrigerated Storage
Authors: Gutierrez Angelica M. , Boylston Terri D. , Clark Stephanie
Published: December 2017

Oxidized flavor is a major problem that affects the dairy industry because of its adverse effect on milk acceptability. The objectives of this research were to examine the roles of pro‐oxidants and antioxidants on the oxidative stability of whole milk. In the 1st experiment, the effect of light (2300 Lux) and/or cupric sulfate (0, 0.5, and 1.0 mg/kg) as pro‐oxidants in milk were investigated during an 11‐d refrigerated storage period. The effects of added retinyl palmitate (1.16 mg/L; 2113 IU Vitamin A/L) and tocopheryl acetate (100 mg/kg milk fat; 5.02 IU Vitamin E/L) as antioxidants in the presence of light (2300 Lux) and light with cupric sulfate (0.05 mg/kg) during a 7‐d study were investigated in the 2nd experiment. The presence of pro‐oxidants significantly (P < 0.05) decreased the total antioxidant capacity (TAC) and increased the lipid oxidation products in milk during storage. Light had a greater effect in the decrease of TAC, although cupric sulfate in the presence of light significantly increased the formation of lipid oxidation products. The addition of antioxidants resulted in a significant (P < 0.05) increase in TAC on day 0. However, with exposure to light and light with cupric sulfate, the antioxidants did not result in a higher TAC in comparison to the treatments without added antioxidant. Analysis of lipid oxidation products by instrumental and sensory methods showed that the presence of light and cupric sulfate significantly (P < 0.05) increased the oxidized flavor from the control, but no significant (P > 0.05) difference in oxidized flavor intensity was detected between milk with and without added antioxidants.

Practical Application

Production and processing variables can affect the content of pro‐oxidants and antioxidants in milk, which has an impact on flavor. An understanding of the role of these components in contributing to or minimizing off‐flavor formation in milk, will help dairy producers to provide quality products to consumers.
Serum pepsinogen 1 and anti‐Helicobacter pylori IgG antibodies as predictors of gastric cancer risk in Finnish males
Authors: Song M. , Camargo M. C. , Weinstein S. J. , Murphy G. , Freedman N. D. , Koshiol J. , Stolzenberg‐Solomon R. Z. , Abnet C. C. , Männistö S. , Albanes D. , Rabkin C. S.
Published: December 2017

Background

Serum pepsinogen 1 (SPG1) and anti‐Helicobacter pylori serology have been used for gastric risk stratification in Asia.

Aim

To assess utility of these markers in a Western population.

Methods

SPG1 measurements were available for 21 895 Finnish male smokers in the Alpha‐Tocopherol, Beta‐Carotene Cancer Prevention Study. We used Cox proportional hazards models adjusted for potential confounders to estimate gastric cancer hazard ratios (HR) and 95% confidence intervals (95% CI) for low SPG1 (<25 μg/L). In a subset (n = 3555) with anti‐H. pylori serology, these markers jointly defined the following: Group A (H. pylori[−], SPG1[normal]; reference group), Group B (H. pylori[+], SPG1[normal]), Group C (H. pylori[+], SPG1[low]) and Group D (H. pylori[−], SPG1[low]). Odds ratios (ORs) and 95% CI were calculated using multivariate logistic regression.

Results

There were 329 gastric cancers diagnosed an average of 13.9 years after baseline. Pre‐diagnostic low SPG1 was significantly associated with increased gastric cancer risk (HR 2.68, 95% CI 1.99‐3.61). Among subjects with both SPG1 and H. pylori serology, groups B, C and D had increased gastric cancer ORs (95% CI) of 1.79 (1.21‐2.64), 3.85 (2.36‐6.28) and 6.35 (2.20‐18.34), respectively. CagA seropositives had significantly higher ORs than CagA seronegatives within group B (Pheterogeneity = 0.01). For groups B and C, repeat SPG1 level at 3 years did not further stratify gastric cancer risk.

Conclusions

Low SPG1 was associated with increased gastric cancer risk in our large Finnish cohort. A single measurement of SPG1 along with H. pylori whole cell and CagA serology provides potentially useful prediction of gastric cancer risk.
Effect of fructo‐oligosaccharides on nutrient digestibility and digesta retention time in adult guinea pigs
Authors: Kawasaki Kiyonori , Min Xiao , Sakaguchi Ei
Published: December 2017

A previous study suggested that addition of fructo‐oligosaccharides (FOS) to the diet improved nitrogen (N) utilization and decreased acid detergent fiber (ADF) digestibility in guinea pigs. The present study was conducted to clarify the relationship between ADF digestibility and gastrointestinal mean retention time (MRT) in guinea pigs under FOS supplementation. Adult male guinea pigs were fed a commercial diet (50 g/day) with either 5% glucose (glucose group) or 5% FOS (FOS group) for 12 days in individual metabolism cages. Unlike the glucose group, N utilization improved, but ADF digestibility significantly (P < 0.05) decreased in the FOS group. MRT of solid digesta also significantly (P < 0.05) decreased in the FOS group compared with that in the glucose group. We concluded that reduction of MRT of solid digesta containing FOS decreased ADF digestibility in guinea pigs.
Ovarian cancer risk, ALDH2 polymorphism and alcohol drinking: Asian data from the Ovarian Cancer Association Consortium
Authors: Ugai Tomotaka , Kelemen Linda E. , Mizuno Mika , Ong Jue‐Sheng , Webb Penelope M. , Chenevix‐Trench Georgia ,   on behalf of the Australian Ovarian Cancer Study Group, Wicklund Kristine G. , Doherty Jennifer Anne , Rossing Mary Anne , Thompson Pamela J. , Wilkens Lynne R. , Carney Michael E. , Goodman Marc T. , Schildkraut Joellen M. , Berchuck Andrew , Cramer Daniel W. , Terry Kathryn L. , Cai Hui , Shu Xiao‐Ou , Gao Yu‐Tang , Xiang Yong‐Bing , Van Den Berg David , Pike Malcom C , Wu Anna H. , Pearce Celeste Leigh , Matsuo Keitaro ,   on behalf of the Ovarian Cancer Association Consortium
Published: December 2017

The aldehyde dehydrogenase 2 (ALDH2) polymorphism rs671 (Glu504Lys) causes ALDH2 inactivation and adverse acetaldehyde exposure among Asians, but little is known of the association between alcohol consumption and rs671 and ovarian cancer (OvCa) in Asians. We conducted a pooled analysis of Asian ancestry participants in the Ovarian Cancer Association Consortium. We included seven case‐control studies and one cohort study comprising 460 invasive OvCa cases, 37 borderline mucinous OvCa and 1274 controls of Asian descent with information on recent alcohol consumption. Pooled odds ratios (OR) with 95% confidence intervals (CI) for OvCa risk associated with alcohol consumption, rs671 and their interaction were estimated using logistic regression models adjusted for potential confounders. No significant association was observed for daily alcohol intake with invasive OvCa (OR comparing any consumption to none = 0.83; 95% CI = 0.58‐1.18) or with individual histotypes. A significant decreased risk was seen for carriers of one or both Lys alleles of rs671 for invasive mucinous OvCa (OR = 0.44; 95% CI = 0.20‐0.97) and for invasive and borderline mucinous tumors combined (OR = 0.48; 95% CI = 0.26‐0.89). No significant interaction was observed between alcohol consumption and rs671 genotypes. In conclusion, self‐reported alcohol consumption at the quantities estimated was not associated with OvCa risk among Asians. Because the rs671 Lys allele causes ALDH2 inactivation leading to increased acetaldehyde exposure, the observed inverse genetic association with mucinous ovarian cancer is inferred to mean that alcohol intake may be a risk factor for this histotype. This association will require replication in a larger sample.
Clinical and radiographic peri‐implant parameters and proinflammatory cytokine levels among cigarette smokers, smokeless tobacco users, and nontobacco users
Authors: Akram Zohaib , Vohra Fahim , Bukhari Ishfaq A. , Sheikh Saeed A. , Javed Fawad
Published: December 2017

Background

It is postulated that clinical and radiographic peri‐implant parameters are worse and levels of interleukin (IL)‐1β and matrix metalloproteinase (MMP)‐9 in the peri‐implant sulcular fluid (PISF) are higher in cigarette‐smokers (CS) and smokeless‐tobacco users (STU) compared with nontobacco user (NTU).

Purpose

The present study aimed to compare clinical and radiographic peri‐implant inflammatory parameters and levels of IL‐1β and MMP‐9 levels among CS, STU, and NTU.

Materials and Methods

Forty‐five CS (Group‐1), 42 STU (Group‐2), and 44 NTU (Group‐3) were included. Demographic data was collected using a structured baseline questionnaire. Peri‐implant plaque index (PI), bleeding on probing (BOP), and probing depth (PD) were recorded and crestal bone loss (CBL) were assessed using standardized digital radiographs. PISF volume and levels of IL‐1β and MMP‐9 in PISF were quantified using enzyme‐linked immunosorbent assay. Clinical peri‐implant parameters and PISF IL‐1β and MMP‐9 concentrations were analyzed with Kruskal‐Wallis test. Bonferroni post hoc adjustment test was used for multiple comparisons. P‐value was set at .05.

Results

Peri‐implant PI and PD were significantly worse in group‐1 and group‐2 patients as compared to group‐3 individuals (P < .05). Peri‐implant CBL was also significantly higher in group‐1 and group‐2 compared with group‐3 (P < .05). Peri‐implant BOP was significantly higher in group‐2 and group‐3 as compared to group‐1 individuals (P < .05). The PISF volume (P < .05) collected and levels of IL‐1β and MMP‐9 were statistically significantly elevated among individuals in group‐1 and group‐2 compared with group‐3 (P < .01). There was no significant difference in PI, PD, CBL, and PISF levels of IL‐1β and MMP‐9 among participants in groups 1 and 2.

Conclusion

Clinical and radiographic peri‐implant parameters were compromised among CS and STU as compared to NTU. Increased expression of local proinflammatory cytokines may explain greater susceptibility of CS and STU to peri‐implant breakdown.
The Tyneside Pegboard Test: development, validation, and observations in unilateral cerebral palsy
Authors: Basu Anna P , Kirkpatrick Emma V , Wright Blythe , Pearse Janice E , Best Kate E , Eyre Janet A
Published: December 2017

Aim

The aims of this study were twofold: first, to develop and validate a timed test of unimanual and bimanual dexterity suitable for those with disability affecting hand function; second, to explore relationships between unimanual and bimanual completion times.

Method

We developed the Tyneside Pegboard Test (TPT), an electronically timed test with three peg sizes, incorporating an asymmetrical bimanual task. Nine hundred and seventy‐four participants (455 males, 519 females; age range 4–80y) provided normative data. Test–retest reliability and construct validity were assessed (50 adults: 14 males, 36 females; 15–73y) on two occasions 2 weeks apart. Bimanual and unimanual completion times were measured in 87 children (51 males, 36 females) with unilateral cerebral palsy (CP) and 498 individuals in a comparison group (238 males, 260 females; 5–15y).

Results

The comparison group showed an asymmetrical U‐shaped relationship between completion times and age. Intraclass correlation coefficients ranged from 0.74 to 0.91, indicating moderate test–retest reliability. There was a negative relationship between average TPT bimanual times and Purdue pegboard bimanual scores (Spearman's rho −0.611, degrees of freedom 44, p<0.001). Children with unilateral CP had greater prolongation of bimanual than unimanual completion times compared with the comparison group (mean difference 20.31s, 95% confidence interval 18.13–22.49, p<0.001).

Interpretation

The TPT is accessible for those with impaired hand function. Children with unilateral CP demonstrated disproportionate bimanual deficits, even allowing for unimanual dexterity: this has implications for therapy.

What this paper adds

We developed an adapted, electronically timed 9‐hole pegboard test.

Our modifications facilitate use by those with disability affecting hand function.

The test incorporates an asymmetrical bimanual task.

Children with unilateral cerebral palsy showed disproportionate bimanual dexterity deficits even allowing for unimanual dexterity.
The Performance of Gender Diverse Teams: What Is the Relation between Diversity Attitudes and Degree of Diversity?
Authors: Lauring Jakob , Villesèche Florence
Published: December 2017

While gender diversity is slowly becoming an expected characteristic of teams, both academics and practitioners still need to better understand the relation between contextual characteristics and team composition for the performance of gender diverse teams. In this article, we investigate the relationship between diversity attitudes and the performance of gender diverse teams, and further, we show how numerical team gender composition is a key link in this relationship. Based on survey responses from 1,085 academic team leaders, we show that openness to diversity is strongly associated with team performance. We also find a moderating effect of the degree of gender diversity, so that the effect of openness to diversity, as positive team level diversity attitudes, is stronger when team gender composition converges towards numerical balance. These findings bridge critical mass theory and diversity and performance scholarship by establishing the joint effect of compositional and contextual characteristics on the performance of gender diverse teams.
Adapting the Ideas of Translational Science for Translational Family Science
Authors: Grzywacz Joseph G. , Allen Jeffrey W.
Published: December 2017

Family science has been doing translational science since before it came into vogue. Nevertheless, the field has been subjected to the same forces in the broader academy that have created a widening chasm between discovery and practice. Thus, the primary objective of this article is to translate the principles, concepts, and models of translational science to solidify an identity for family science and help the field move forward in broader academic, care delivery, and policy arenas. Alternative models of translational science, primarily from biomedicine but also from other disciplines, are reviewed and critically analyzed, and core concepts and principles are isolated, elaborated, and applied to family science. Family science's long‐standing commitment to the doctrine of evidence‐based practice, and its ongoing endorsement of the principles of scientific duality and multidisciplinary utility, places it in a preeminent position for using the zeitgeist of translational science to move forward. Nonetheless, the field has important epistemological, practical, professional, and curricular steps to complete to better position itself as a distinct and valued body of scientists. Ultimately, we argue that embracing the principles, concepts, and models of translational science should be leveraged by family science to help brand itself as a unique and essential social science field for enhancing the human condition.
Venous leg ulcer management in clinical practice in the UK: costs and outcomes
Authors: Guest Julian F , Fuller Graham W , Vowden Peter
Published: December 2017

The aim of this study was to estimate the patterns of care and annual levels of health care resource use attributable to managing venous leg ulcers (VLUs) in clinical practice by the UK's National Health Service (NHS) and the associated costs of patient management. This was a retrospective cohort analysis of the records of 505 patients in The Health Improvement Network (THIN) Database. Patients' characteristics, wound‐related health outcomes and health care resource use were quantified, and the total NHS cost of patient management was estimated at 2015/2016 prices. Overall, 53% of all VLUs healed within 12 months, and the mean time to healing was 3·0 months. 13% of patients were never prescribed any recognised compression system, and 78% of their wounds healed. Of the 87% who were prescribed a recognised compression system, 52% of wounds healed. Patients were predominantly managed in the community by nurses with minimal clinical involvement of specialist clinicians. Up to 30% of all the VLUs may have been clinically infected at the time of presentation, and only 22% of patients had an ankle brachial pressure index documented in their records. The mean NHS cost of wound care over 12 months was an estimated £7600 per VLU. However, the cost of managing an unhealed VLU was 4·5 times more than that of managing a healed VLU (£3000 per healed VLU and £13 500 per unhealed VLU). This study provides important insights into a number of aspects of VLU management in clinical practice that have been difficult to ascertain from other studies and provides the best estimate available of NHS resource use and costs with which to inform policy and budgetary decisions.