bluuebunny/crossref_metadata_2025 huggingface dataset:
Mitotic chromosomes fold by condensin-dependent helical winding of chromatin loop arrays
Authors: Gibcus Johan H. , Samejima Kumiko , Goloborodko Anton , Samejima Itaru , Naumova Natalia , Kanemaki Masato , Xie Linfeng , Paulson James R. , Earnshaw William C. , Mirny Leonid A. , Dekker Job
Published: August 2017

During mitosis, chromosomes fold into compacted rod shaped structures. We combined imaging and Hi-C of synchronous DT40 cell cultures with polymer simulations to determine how interphase chromosomes are converted into compressed arrays of loops characteristic of mitotic chromosomes. We found that the interphase organization is disassembled within minutes of prophase entry and by late prophase chromosomes are already folded as arrays of consecutive loops. During prometaphase, this array reorganizes to form a helical arrangement of nested loops. Polymer simulations reveal that Hi-C data are inconsistent with solenoidal coiling of the entire chromatid, but instead suggest a centrally located helically twisted axis from which consecutive loops emanate as in a spiral staircase. Chromosomes subsequently shorten through progressive helical winding, with the numbers of loops per turn increasing so that the size of a helical turn grows from around 3 Mb (~40 loops) to ~12 Mb (~150 loops) in fully condensed metaphase chromosomes. Condensin is essential to disassemble the interphase chromatin conformation. Analysis of mutants revealed differing roles for condensin I and II during these processes. Either condensin can mediate formation of loop arrays. However, condensin II was required for helical winding during prometaphase, whereas condensin I modulated the size and arrangement of loops inside the helical turns. These observations identify a mitotic chromosome morphogenesis pathway in which folding of linear loop arrays produces long thin chromosomes during prophase that then shorten by progressive growth of loops and helical winding during prometaphase.

One Sentence Summary

Mitotic chromosome morphogenesis occurs through condensin-mediated disassembly of the interphase conformation and formation of extended prophase loop arrays that then shorten by loop growth and condensin-dependent helical winding.
A Linear Algebra Approach to Fast DNA Mixture Analysis Using GPUs
Authors: Samsi Siddharth , Helfer Brian , Kepner Jeremy , Reuther Albert , Ricke Darrell O.
Published: August 2017

Analysis of DNA samples is an important tool in forensics, and the speed of analysis can impact investigations. Comparison of DNA sequences is based on the analysis of short tandem repeats (STRs), which are short DNA sequences of 2-5 base pairs. Current forensics approaches use 20 STR loci for analysis. The use of single nucleotide polymorphisms (SNPs) has utility for analysis of complex DNA mixtures. The use of tens of thousands of SNPs loci for analysis poses significant computational challenges because the forensic analysis scales by the product of the loci count and number of DNA samples to be analyzed. In this paper, we discuss the implementation of a DNA sequence comparison algorithm by re-casting the algorithm in terms of linear algebra primitives. By developing an overloaded matrix multiplication approach to DNA comparisons, we can leverage advances in GPU hardware and algoithms for dense matrix multiplication (DGEMM) to speed up DNA sample comparisons. We show that it is possible to compare 2048 unknown DNA samples with 20 million known samples in under 6 seconds using a NVIDIA K80 GPU.
Deciphering Transcriptional Regulation of Human Core Promoters
Authors: Weingarten-Gabbay Shira , Nir Ronit , Lubliner Shai , Sharon Eilon , Kalma Yael , Weinberger Adina , Segal Eran
Published: August 2017

Despite its pivotal role in regulating transcription, our understanding of core promoter function, architecture, and cis-regulatory elements is lacking. Here, we devised a highthroughput assay to quantify the activity of ∼15,000 fully designed core promoters that we integrated and expressed from a fixed location within the human genome. We find that core promoters drive transcription unidirectionally, and that sequences originating from promoters exhibit stronger activity than sequences originating from enhancers. Testing multiple combinations and distances of core promoter elements, we observe a positive effect of TATA and Initiator, a negative effect of BREu and BREd, and a 10bp periodicity in the optimal distance between the TATA and the Initiator. By comprehensively screening TF binding-sites, we show that site orientation has little effect, that the effect of binding site number on expression is factor-specific, and that there is a striking agreement between the effect of binding site multiplicity in our assay and the tendency of the TF to appear in homotypic clusters throughout the genome. Overall, our results systematically assay the elements that drive expression in core- and proximal-promoter regions and shed light on organization principles of regulatory regions in the human genome.
Multi-Transition Systems: A theory for neural spatial navigation
Authors: Waniek Nicolai
Published: August 2017

Spatial navigation is considered fundamental for animals and is attributed primarily to place and grid cells in the rodent brain. Commonly believed to either perform path integration or localization, the true objective of grid cells, their hexagonal grid fields, and especially their discrete scales remain puzzling. Here it is proposed that grid cells efficiently encode transitions in sequences. A biologically plausible model for dendritic computation in grid cells is presented. A network of competitive cells shows positive gridness scores early in simulations and realigns the orientation of all cells over time. Then, a scale-space model of grid cells is introduced. It improves behaviorally questionable run-times of a single scale significantly by look-ahead in multiple scales, and it is shown that the optimal scale-increment between consecutive scales is√2. Finally, a formal theory for sequences and transitions is stated. It is demonstrated that hexagonal transition encoders are optimal to encode transitions in Euclidean space and emerge due to the sampling theorem. The paper concludes with a discussion about the suggested purpose, makes testable predictions, and highlights relevant connections to computational neuroscience as well as computer science and robotics.
Humans incorporate attention-dependent uncertainty into perceptual decisions and confidence
Authors: Denison Rachel N. , Adler William T. , Carrasco Marisa , Ma Wei Ji
Published: August 2017

Perceptual decisions are better when they take uncertainty into account. Uncertainty arises not only from the properties of sensory input but also from cognitive sources, such as different levels of attention. However, it is unknown whether humans appropriately adjust for such cognitive sources of uncertainty during perceptual decision making. Here we show that human categorization and confidence decisions take into account uncertainty related to attention. We manipulated uncertainty in an orientation categorization task from trial to trial using only an attentional cue. The categorization task was designed to disambiguate decision rules that did or did not depend on attention. Using formal model comparison to evaluate decision behavior, we found that category and confidence decision boundaries shifted as a function of attention in an approximately Bayesian fashion. This means that the observer’s attentional state on each trial contributed probabilistically to the decision computation. This responsiveness of an observer’s decisions to attention-dependent uncertainty should improve perceptual decisions in natural vision, in which attention is unevenly distributed across a scene.
Development of fresh cheese made from coconut milk in combination with cow’s milk
Authors: Tipvarakarnkoon Tatsawan , Sornsa-ard Sangrawee , Imcha Wutcharee
Published: August 2017

Purpose

The purpose of this paper is to develop fresh cheese made from different types of coconut milk (fresh, UHT, and reconstituted coconut milk) mixed with pasteurized cow’s milk (50:50) by rennet coagulation. The main aim of this study was to achieve successful formation of cheese curd with fully coconut milk aroma and flavor.

Design/methodology/approach

Fresh cheese made from different types of coconut milk mixed with cow’s milk (50:50) were developed and compared to fresh cheese made from cow’s milk (100:0). Physicochemical analysis including pH, acidity, percentage of yield, protein and fat content, texture analysis and sensory evaluation has been performed. The nine-point hedonic preference test (n=35) and consumer testing (n=235) were conducted.

Findings

In comparison, fresh cheese made with the presence of coconut milk (50:50) had higher fat content, lower crude protein content, higher firmness, and adhesiveness than those made from cow’s milk alone (0:100). The cheese with the presence of coconut milk was liked better by consumers (7.35 out of 9). Rehydrated coconut milk was mostly preferred to use among all three types of coconut milk which showed firmer texture and admired flavor. The texture of the developed product was proved to be similar to commercial cottage cheese. Using the rehydrated coconut milk in the formulation gave successful results for making fresh coconut milk cheese, which has also not been used previously in any research.

Research limitations/implications

In this paper, the effect of process conditions on the quality of cheese curd formation was not yet investigated and discussed. The process parameters including heat treatment and renneting time should be further studied.

Originality/value

A novel fresh cheese made from coconut milk mixed with pasteurized cow’s milk was successfully developed. The cheese curd was formed with fully coconut milk aroma and flavor.
The product development of Thai fermented sausage with mixed Tomyum ingredients
Authors: Panjapiyakul Pornpen , Srinin Tongsuk , Kitsawad Kamolnate
Published: August 2017

Purpose

The purpose of this paper is to study for the product development of Sai Krok Isan or Thai fermented sausage with Tomyum ingredients (TFS-TY) such as kaffir lime leaves, lemon grass, galangal root and chili.

Design/methodology/approach

To study the proper formula of TFS-TY in order to obtain certain characteristics of both fermented sausage and Tomyum attributes by varying the ratio of cooked glutinous rice to cooked rice of total rice content and Tomyum ingredients content. The nine-point hedonic preference method was conducted to evaluate TFS-TY with 30 untrained panelists. Consumer survey from 200 respondents were asked about their behaviors on fermented sausage and opinions to the new products.

Findings

The preference score of the 3:1 (cooked glutinous rice: cooked rice) gained the highest score in all sensory attributes as same as 16 percent of Tomyum ingredients. According to the consumer survey, the TFS-TY was accepted by 90 percent of the total 200 respondents and gained an overall score equal to 7.30±1.11.

Research limitations/implications

The varied preference of Thai respondents has affected on the acceptance of the new products. For example, some preferred very strong tastes either in sourness or spiciness, and some may be disliked.

Originality/value

The balancing characteristics of both products were very important. The new product should be identified by certain attributes in Thai fermented sausage and Tomyum. Over or less in any products gained lower preference attributes scores.
Generation Y consumers’ buying behaviour in fashion apparel industry: a moderation analysis
Authors: Valaei Naser , Nikhashemi S.R.
Published: August 2017

Purpose

The advent of media and technology has led to growing inclination among Generation Y (Gen-Y) consumers towards diverse fashion influences and they tend to dress either to fit in with their peers or to articulate self-identity and conform to the society. This trend has become a fashion dilemma and the purpose of this paper is to leverage on this matter by investigating the factors influencing the Gen-Y consumers’ attitude and purchase intention towards fashion apparel.

Design/methodology/approach

A sample of 250 respondents is used to assess the measurement and structural models, by applying a partial least squares-structural equation modelling (PLS-SEM) approach.

Findings

The results indicate that brand and self-identity are the factors that most shape Gen-Y consumers’ attitudes towards fashion apparel. Furthermore, brand, style, price, and social identity are the most influential factors of Gen-Y consumers’ purchase intention for fashion apparels. The findings also show that style, price, country of origin, and social identity are not relevant to Gen-Y consumers’ attitudes towards fashion apparel, and that country of origin and self-identity do not have any relationship with the Gen-Y consumers’ purchase intention.

Originality/value

This study is among the few attempts to investigate the Gen-Y consumers’ buying behaviour of fashion apparel based on the theory of planned behaviour, optimal distinctiveness theory, and social identity theory. PLS-multi-group analysis reveals that age, gender, and income are moderating variables of several proposed structural relationships.
Corporate social responsibility: comparing different models
Authors: Lyra Franciane Reinert , Barbosa De Souza Maria José , Verdinelli Miguel Angel , Lana Jeferson
Published: August 2017

Purpose

The purpose of this paper is to present theoretical investigation into two corporate social responsibility (CSR) models proposed by Schwartz and Carroll (2003, 2008).

Design/methodology/approach

A descriptive study was conducted using a quantitative approach with 200 visitors. Data analysis involved, first, a factor analysis and, subsequently, a canonical analysis.

Findings

The results reveal that there is indeed the characteristic of convergence on the CSR dimensions, as well as confirm the correlation between the two models.

Research limitations/implications

This is a single case study wherein data cannot be generalized and there is a lack, so far, of a specific measure scale for the VBA (value, balance and accountability) model.

Practical implications

The results can contribute to studies on the development of CSR scales directed toward consumers, particularly tourist companies in emerging countries, as well as a guidance for managers in planning socially responsible actions and achieving legitimacy of their consumers.

Originality/value

Studies on CSR from customers’ standpoint are still scarce in developing countries, and the existing ones do not use reliable measure scales, based on theoretical models and adapted to the features of this audience. The present paper helps this discussion by considering the perspective of an emerging market for the first time.
What drives employees to participate in corporate volunteering programs?
Authors: Sekar Srinivasan , Dyaram Lata
Published: August 2017

Purpose

The purpose of this paper is to examine how some of the key aspects of employee motivation and their perception of volunteering programs impact their participation in corporate volunteering. Specifically, this study argues that employee’s self-oriented motives to significantly influence employee participation than other-oriented motives. Similarly, this study also hypothesized that the corporate volunteering program characteristics to significantly relate to employee participation in corporate volunteering.

Design/methodology/approach

The data were collected from 461 employee volunteers representing various industries across four different locations in India. A self-reported method was used to collect the data by administering the questionnaires.

Findings

The structural equation modeling results indicate that other-oriented motives (altruistic) and characteristics of corporate volunteering programs to significantly predict employee participation in corporate volunteering and self-oriented motives did not show significance in predicting employee participation.

Research limitations/implications

Results suggest that employee participation in volunteering is a function of not merely employee motivation but also how the volunteering programs are conceptualized and implemented.

Originality/value

This research study moves beyond mere role of employee motives analysis and considered the role of characteristics of corporate volunteering programs to impact employee volunteering behavior. Further, it highlights there is a differential impact of self- and other-oriented motives in predicting employee participation.
Women in the boardroom and their impact on climate change related disclosure
Authors: Hossain Mohammed , Farooque Omar Al , Momin Mahmood Ahmed , Almotairy Obaid
Published: August 2017

Purpose

This paper aims to investigate the relationship between gender diversity and the Carbon Disclosure Project (CDP) score/index. Specifically, the study describes extant research on theoretical perspectives, and the impact of women on corporate boards (WOBs) on carbon emission issues in the global perspective.

Design/methodology/approach

This study uses the carbon disclosure scores of the CDP from 2011 to 2013 (inclusive). A total observation for the three-year periods is 1,175 companies. However, based on data availability for the model, the sample size totals 331 companies in 33 countries with firms in 12 geographical locations. The authors used a model which is estimated using the fixed-effects estimator.

Findings

The outcomes of the study reveal that there is a positive relationship between gender diversity (WOB) and carbon disclosure information. In addition to establishing a relationship between CDP score and other control variables, this study also found a relationship with Board size, asset size, energy consumption and Tobin’s Q, which is common in the existing literature.

Research limitations/implications

The limitations of the study mostly revolve around samples and the time period. To further test the generalizability and cross-sectional validity of the outcomes, it is suggested that the proposed framework be tested in more socially responsible firms.

Practical implications

There are increasing pressures for WOBs from diverse stakeholders, such as the European Commission, national governments, politicians, employer lobby groups, shareholders, Fortune and Financial Times Stock Exchange (FTSE) rankings and best places for women to work lists. The study offers insights to policy makers implementing gender quota legislation.

Originality/value

The study has important implications for putting into practice good corporate governance and, in particular, gender diversity. The outcomes of the analyses advocate that companies that included women directors and had a smaller board size may expect to achieve a higher level of carbon emission performance and to voluntarily disclose the level of carbon information assessment requested by the CDP.
The small RNA ReaL: a novel regulatory element embedded in the Pseudomonas aeruginosa quorum sensing networks
Authors: Carloni Sara , Macchi Raffaella , Sattin Sara , Ferrara Silvia , Bertoni Giovanni
Published: August 2017

The small RNA ReaL of the opportunistic pathogen Pseudomonas aeruginosa has been characterized. Our results indicate that ReaL contributes to P. aeruginosa virulence. In the Galleria mellonella infection model, reaL gene deletion resulted in decreased virulence, while ReaL overexpression resulted in a hyper‐virulent phenotype. We also demonstrate that ReaL is embedded in the P. aeruginosa quorum sensing (QS) with the role of linking las to pqs systems. We show that ReaL is negatively regulated by the las regulator LasR and impacts positively the synthesis of the pqs quinolone signal PQS by a positive post‐transcriptional effect on the pqsC gene. Perturbations of ReaL levels affect pyocyanin synthesis, biofilm formation and swarming motility, processes that are known to be influenced by PQS synthesis. In addition to being regulated by LasR, ReaL is also responding to infection relevant cues that P. aeruginosa can experience in mammalian hosts such as temperature and oxygen availability. Furthermore, ReaL shows a growth phase‐dependent pattern of expression, being up‐regulated in stationary phase, due to the activity of the alternative σ factor RpoS. Together, these regulations of ReaL expression are expected to contribute to the fine co‐modulation of PQS synthesis and, ultimately, virulence.
Locational disadvantage and the spatial distribution of government expenditure on urban infrastructure and services in metropolitan Sydney (1988–2015)
Authors: Wiesel Ilan , Liu Fanqi , Buckle Caitlin
Published: August 2017

Provision of public services by state governments rather than municipalities is considered an important urban governance factor preventing deeper levels of socio‐spatial inequality in Australian cities. The paper examines the spatial patterns of investment by the New South Wales state government in a wide range of services and infrastructure in metropolitan Sydney over 28 budget years from 1988/89 to 2015/16. We examined the relationship between volume and type of investment in infrastructure and services, and considered a local area's socioeconomic characteristics, distance from the central business district, and designation as a strategic site in metropolitan plans. Despite an overall redistributive approach favouring relatively disadvantaged areas, the most disadvantaged suburbs in metropolitan Sydney had significantly lower levels of investment. When funding was directed to the most disadvantaged suburbs, it was often in the form of new social housing development, reinforcing both the concentration of poverty and disadvantage in resource access. The findings suggest that this is a case of under‐investment by the state government in areas already populated by disadvantaged communities rather than a market‐driven process whereby disadvantaged households move into poorly resourced neighbourhoods.
Validation of 走肖爲王: Can insects write letters on leaves?
Authors: Seo Woong , Lee Bora , Choi In‐Su , Min Kyung‐Jin
Published: August 2017

The Annals of the Joseon Dynasty report that large‐scale reformations undertaken by Jungjong, 11th king of the Joseon dynasty, were stopped after Kwang‐Jo Cho was slandered and subsequently executed. Reportedly, a party opposing the reformations wrote a phrase “走肖爲王” on a leaf in the palace by using sugary water; subsequently, insects ingested the sugary parts of leaf and the phrase was left behind. The phrase “走肖爲王” means “Cho will become king” and Jungjong accepted the phrase as a warning sign from heaven that Cho was attempting a coup d'état. Although there are several historical records that report such insect writing, it has not been determined whether creating a phrase on a leaf by using insects is possible. In a field study conducted on Gwanak Mountain, Korea, we tested whether writing letters on leaves by insects is possible. The results showed no sign of selective insect ingestion creating the form of a letter on a leaf after sugary water was applied. There is a high possibility that 走肖爲王 incident was fictional; particularly when considering the complexity of the phrase and the life history and behavior of insects.
Does paying service providers by results improve recovery outcomes for drug misusers in treatment in England?
Authors: Jones Andrew , Pierce Matthias , Sutton Matt , Mason Thomas , Millar Tim
Published: August 2017

Aim

To compare drug recovery outcomes in commissioning areas included in a ‘payment by results’ scheme with all other areas.

Design

Observational and data linkage study of the National Drug Treatment Monitoring System, Office for National Statistics mortality database and Police National Computer criminal records, for 2 years before and after introduction of the scheme. Pre–post controlled comparison compared outcomes in participating versus non‐participating areas following adjustment for drug use, functioning and drug treatment status.

Setting

Drug services in England providing publicly funded, structured treatment.

Participants

Adults in treatment (between 2010 and 2014): 154 175 (10 716 in participating areas, 143 459 non‐participating) treatment journeys in the 2 years before and 148 941 (10 012 participating, 138 929 non‐participating) after the introduction of the scheme.

Intervention

Scheme participation, with payment to treatment providers based on patient outcomes versus all other areas.

Measurements

Rate of treatment initiation; waiting time (> or < 3 weeks); treatment completion; and re‐presentation; substance use; injecting; housing status; fatal overdose; and acquisitive crime.

Findings

In participating areas, there were relative decreases in rates of: treatment initiation [difference‐in‐differences odds ratio (DID OR) = 0.17, 95% confidence interval (CI) = 0.14, 0.21]; treatment completion (DID OR = 0.60, 95% CI = 0.53, 0.67); and treatment completion without re‐presentation (DID OR = 0.63, 95% CI = 0.52, 0.77) compared with non‐participating areas. Within treatment, relative abstinence (DID OR = 1.50, 95% CI = 1.30, 1.72) and non‐injecting (DID OR = 1.32, 95% CI = 1.10, 1.59) rates were improved in participating areas. No significant changes in mortality, recorded crime or housing status were associated with the scheme.

Conclusion

Drug addiction recovery services in England that are commissioned on a payment‐by‐results basis tend to have lower rates of treatment initiation and completion but higher rates of in‐treatment abstinence and non‐injecting than other services.
Silicon Micropore‐Based Parallel Plate Membrane Oxygenator
Authors: Dharia Ajay , Abada Emily , Feinberg Benjamin , Yeager Torin , Moses Willieford , Park Jaehyun , Blaha Charles , Wright Nathan , Padilla Benjamin , Roy Shuvo
Published: August 2017

Extracorporeal membrane oxygenation (ECMO) is a life support system that circulates the blood through an oxygenating system to temporarily (days to months) support heart or lung function during cardiopulmonary failure until organ recovery or replacement. Currently, the need for high levels of systemic anticoagulation and the risk for bleeding are main drawbacks of ECMO that can be addressed with a redesigned ECMO system. Our lab has developed an approach using microelectromechanical systems (MEMS) fabrication techniques to create novel gas exchange membranes consisting of a rigid silicon micropore membrane (SμM) support structure bonded to a thin film of gas‐permeable polydimethylsiloxane (PDMS). This study details the fabrication process to create silicon membranes with highly uniform micropores that have a high level of pattern fidelity. The oxygen transport across these membranes was tested in a simple water‐based bench‐top set‐up as well in a porcine in vivo model. It was determined that the mass transfer coefficient for the system using SµM‐PDMS membranes was 3.03 ± 0.42 mL O2 min−1 m−2 cm Hg−1 with pure water and 1.71 ± 1.03 mL O2 min−1 m−2 cm Hg−1 with blood. An analytic model to predict gas transport was developed using data from the bench‐top experiments and validated with in vivo testing. This was a proof of concept study showing adequate oxygen transport across a parallel plate SµM‐PDMS membrane when used as a membrane oxygenator. This work establishes the tools and the equipoise to develop future generations of silicon micropore membrane oxygenators.
Retrospective cohort study shows that the risks for retinopathy of prematurity included birth age and weight, medical conditions and treatment
Authors: Ali Aliaa A. , Gomaa Nancy A.S. , Awadein Ahmed R. , Al‐Hayouti Huda H. , Hegazy Ahmed I.
Published: August 2017

Aim

This study described the characteristics and risk factors of neonates who developed retinopathy of prematurity (ROP) and severe treatable ROP in two Egyptian neonatal intensive care units (NICUs).

Methods

This retrospective cohort study comprised 108 preterm neonates who were screened for ROP after being admitted to the two NICUs run by Cairo University Hospital from June 2014 to May 2015. Patients were examined using digital fundus photography and indirect ophthalmoscopy was performed if ROP was detected.

Results

Retinopathy of prematurity occurred in 75 patients. Late‐onset sepsis, ventilation and hypercapnia were independently associated with ROP. Patients who developed severe treatable ROP had a younger gestational age (GA) than patients who did not develop ROP or developed mild or moderate ROP (29 weeks, range 27–33 weeks versus 32 weeks, range 28–36 weeks, p = 0.002) and a lower birthweight (1200 g, range 980–1590 g versus 1460 g, range 770–2475 g, p = 0.029). The risk factors associated with severe treatable ROP included the duration of admission, the duration of incubator oxygen, late‐onset sepsis, intraventricular haemorrhage, total parenteral nutrition and the duration of caffeine citrate therapy.

Conclusion

This study showed that the risks for ROP were wide‐ranging and included GA and weight, medical conditions and treatment.
Utilization of porcine in vitro‐produced parthenogenetic embryos for co‐transfer with vitrified and warmed embryos
Authors: Nakamura Yoshiyuki , Kikuchi Kazuhiro
Published: August 2017

The present study was conducted to evaluate the possibility of using in vitro‐produced parthenogenetic (PA) embryos for co‐transfer with morulae that had been collected in vivo and cryopreserved. The proportion of PA blastocysts (20.5%) was higher than that of their in vitro fertilization (IVF) counterparts (16.6%). Although there were no differences in morphology or diameter between the two groups, the number of cells in early PA blastocysts after in vitro culture for 6 days was lower than for IVF blastocysts (25.7 and 30.4 cells, respectively), and the number in recovered PA blastocysts was also smaller than that in recovered IVF blastocysts (37.4 and 50.2 cells, respectively). When 10 morulae warmed after vitrification were co‐transferred with 10 PA blastocysts (total 20 embryos) to the uterus of five recipients, the rates of pregnancy and farrowing did not differ, but the average period until spontaneous abortion tended to be longer relative to the control (when 20 morulae were transferred). These data suggest that in vitro‐produced PA embryos offer the possibility of assisted pregnancy for cryopreserved embryos; further experiments will be needed to confirm the beneficial effect of this approach on piglet production.
In vivo and in vitro palatability testing of a new paediatric formulation of valaciclovir
Authors: Bastiaans Diane E. T. , Immohr Laura I. , Zeinstra Gertrude G. , Strik‐Albers Riet , Pein‐Hackelbusch Miriam , van der Flier Michiel , de Haan Anton F. J. , Boelens Jaap Jan , Lankester Arjan C. , Burger David M. , Warris Adilia
Published: August 2017

Aims

The palatability of a new paediatric formulation of valaciclovir was assessed in children and their parents: non‐inferiority of the new paediatric formulation (test formulation) compared to the reference formulation was investigated.

Methods

In vivo palatability testing was performed in a randomized, two‐period, multicentre, cross‐over study. Children and their parents scored the liking of the new paediatric valaciclovir formulation and the reference formulation on a 100 mm visual analogue scale (VAS). To support formulation development and palatability testing, electronic tongue measurements were applied.

Results

The electronic tongue measurement indicated taste‐masking capabilities for three different formulations in the developmental phase. A glycerol‐based formulation was further tested and compared to the reference formulation prepared out of crushed and suspended tablets. The mean difference (95% CI) in VAS scores between both formulations, as indicated by the children (n = 20), was 2.4 (−8.5, 13) mm, in favour of the new paediatric valaciclovir formulation. The mean (95% CI) difference in VAS scores indicated by the parents (n = 20) was −0.9 (−12, 9.8) mm.

Conclusion

The palatability of the new paediatric valaciclovir formulation was considered non‐inferior to the reference formulation prepared out of crushed tablets. We were able to optimize the study design and number of children to be included in the palatability testing by using electronic tongue measurements.
Suboptimal cotrimoxazole prophylactic concentrations in HIV‐infected children according to the WHO guidelines
Authors: Pressiat Claire , Mea‐Assande Veronique , Yonaba Caroline , Treluyer Jean‐Marc , Dahourou Désiré‐Lucien , Amorissani‐Folquet Madeleine , Blanche Stéphane , Eboua François , Ye Diarra , Lui Gabrielle , Malateste Karen , Zheng Yi , Leroy Valeriane , Hirt Déborah ,   for the MONOD Study Group
Published: August 2017

Aims

A clinical study was conduct in HIV‐infected children to evaluate the prophylactic doses of cotrimoxazole [sulfamethoxazole (SMX) and trimethoprim (TMP)] advised by the WHO.

Methods

Children received lopinavir‐based antiretroviral therapy with cotrimoxazole prophylaxis (200 mg of SMX/40 mg of TMP once daily). A nonlinear mixed effects modelling approach was used to analyse plasma concentrations. Factors that could impact the pharmacokinetic profile were investigated. The model was subsequently used to simulate individual exposure and evaluate different administration schemes.

Results

The cohort comprised 136 children [average age: 1.9 years (range: [0.7–4]), average weight: 9.5 kg (range: [6–16.3])]. A dose per kg was justified by the significant influence of implementing an allometrically scaled body size covariate on SMX and TMP pharmacokinetics. SMX and TPM clearance were estimated at 0.49 l h−1/9.5 kg and 3.06 l h−1/9.5 kg, respectively. The simulated exposures obtained after administration of oral dosing recommended by the WHO for children from 10 to 15 kg were significantly lower than in adults for SMX and TMP. This could induce a reduction of effectiveness of cotrimoxazole. Simulations show that regimens of 30 mg kg−1 of SMX and 6 mg kg−1 of TMP in the 5–10 kg group and 25 mg kg−1 of SMX and 5 mg kg−1 of TMP in the 10–15 kg group are more suitable doses.

Conclusions

In this context of high prevalence of opportunistic infections, a lower exposure to cotrimoxazole in children than adults was noted. To achieve comparable exposure to adults, a dosing scheme per kg was proposed.
The role of the appropriate adult in supporting vulnerable adults in custody: Comparing the perspectives of service users and service providers
Authors: Jessiman Tricia , Cameron Ailsa
Published: August 2017

Accessible Summary

When a vulnerable adult is in police custody, they should have someone with them to help them understand what is happening. This person is called an appropriate adult (AA).

Previous research has shown that the role of the AA is not always well understood. This study compares the views of both professionals and vulnerable adults.

Adults with learning disabilities and mental health problems said looking after them and helping them communicate were the most important things an AA should do.

Like other studies have shown, not all adults who should be provided with an AA in custody have had one. This may be because no agency has a statutory duty to provide one.

This study recommends that AA services should try and engage more effectively with vulnerable adults.

Background

Police custody sergeants have a duty to secure an AA to safeguard the rights and welfare of vulnerable people detained or questioned by the police. This study focuses on the role of the AA in supporting vulnerable adults and seeks to examine what stakeholders would expect from an effective AA service.

Methods

This was a qualitative study of four AA services in England. Interviews were undertaken with 25 professionals, and two focus groups were held with service‐user groups (13 participants).

Results

There is disparity between the expectations of professionals, and service users, on what comprises an effective service. Professionals tend to prioritise the availability and response time of AAs, while service users prioritise their personal attributes and demeanour.

Conclusions

Professionals involved in commissioning and management of AA services should monitor whether the rights of vulnerable adults in custody are protected and better engage vulnerable adults beyond service delivery.
Mitotic inheritance of the Golgi complex and its role in cell division
Authors: Ayala Inmaculada , Colanzi Antonino
Published: August 2017

The Golgi apparatus plays essential roles in the processing and sorting of proteins and lipids, but it can also act as a signalling hub and a microtubule‐nucleation centre. The Golgi complex (GC) of mammalian cells is composed of stacks connected by tubular bridges to form a continuous membranous system. In spite of this structural complexity, the GC is highly dynamic, and this feature becomes particularly evident during mitosis, when the GC undergoes a multi‐step disassembly process that allows its correct partitioning and inheritance by daughter cells. Strikingly, different steps of Golgi disassembly control mitotic entry and progression, indicating that cells actively monitor Golgi integrity during cell division. Here, we summarise the basic mechanisms and the molecular players that are involved in Golgi disassembly, focussing in particular on recent studies that have revealed the fundamental signalling pathways that connect Golgi inheritance to mitotic entry and progression.
Linking Avicennia germinans (Acanthaceae) architecture to gall richness and abundance in Brazilian Amazon mangroves
Authors: Silva Luzinete L. , Santos Rita C. O. , Fernandes Marcus E. B.
Published: August 2017

The diversity and abundance of gall‐inducing organisms are directly proportional to the structural complexity of the host plant. This hypothesis is controversial for forest environments, such as mangroves. Avicennia germinans (L.), a principal mangrove tree species found in the Neotropical region, is considered to be a superhost for gall‐inducing insects. Using a generalized linear mixed model (GLMM) based on the analysis of 1000 apical branches from 50 A. germinans trees, we examined the diversity and abundance of gall morphotypes (GM), together with the structural attributes of replanted 5‐ to 9‐year‐old mangroves, in the Amazon coast of Brazil. A total of 7602 galls were registered, averaging 1.3 ± 0.4 galls per leaf. Sixteen of the 22 morphotypes identified were found at all study sites. Two gall morphotypes (GM7 and GM4) were the most abundant, representing approximately 40 percent of the total. The structural complexity of the plant (mainly based on the number of leaves) directly affected the abundance and diversity of these organisms. While A. germinans is a superhost, this type of parasitism did not affect plant development or survival. The ample distribution of A. germinans, the formation of monospecific forests, and the high palatability of this plant make it an essential resource for the survival of the gall‐inducing guild in the mangroves of the Neotropics.
The transition to adulthood from care as a struggle for recognition
Authors: Paulsen Veronika , Thomas Nigel
Published: August 2017

This article explores young people's experiences in the transition to adulthood from child welfare services and how Honneth's theory of recognition can be useful as an analytical tool to help us understand these experiences. The underpinning empirical research consisted of interviews and focus groups with 43 adolescents who had been in contact with Norwegian child welfare services. Three themes emerged as particularly important: having good relationships to caring adults, being listened to and able to influence their own lives, and receiving support and encouragement. The research shows how young people's difficulties in leaving care can be understood as experiences of misrecognition and points to some ways in which these can be overcome.
Immunohistochemistry reveals an increased proportion of MYC‐positive cells in subcutaneous panniculitis‐like T‐cell lymphoma compared with lupus panniculitis
Authors: Fernandez‐Pol Sebastian , De Stefano Danielle , Kim Jinah
Published: August 2017

Background

Subcutaneous panniculitis‐like T‐cell lymphoma (SPTCL) is a malignant primary cutaneous T‐cell lymphoma that shares significant clinical, histopathologic and immunophenotypic overlap with lupus erythematosus panniculitis (LEP).

Methods

We performed immunohistochemistry for the MYC oncoprotein on 23 cases of SPTCL (1 CD8 negative) and 12 cases of LEP to evaluate if there are quantitative or qualitative differences in protein expression of this marker in these entities.

Results

In SPTCL cases, the percentage of all cells that were c‐Myc positive ranged from 0.8% to 16%, with a mean of 5.0% and a median of 4.4%. In contrast, in the LEP cases, the percentage of c‐Myc‐positive cells in the cases ranged from 0.34% to 3.7%, averaged 1.4% and the median was 0.8%. The difference between the means of these 2 diagnostic categories was statistically significant. Fluorescence in situ hybridization performed on 4 cases of SPTCL with a relatively high level of MYC immunohistochemical staining, however, failed to demonstrate evidence of MYC rearrangement or amplification.

Conclusions

Our work demonstrates that MYC expression levels differ between these 2 histologic mimics and suggests that this important oncoprotein may play a role in the pathogenesis of SPTCL.
Efficacy and safety of alirocumab in people with prediabetes vs those with normoglycaemia at baseline: a pooled analysis of 10 phase III ODYSSEY clinical trials
Authors: Leiter L. A. , Müller‐Wieland D. , Baccara‐Dinet M. T. , Letierce A. , Samuel R. , Cariou B.
Published: August 2017

Aim

To assess the lipid‐lowering efficacy and safety of alirocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, in people with hypercholesterolaemia and prediabetes at baseline vs people with normoglycaemia at baseline in a pooled analysis of 10 ODYSSEY phase III trials.

Methods

People classified as having prediabetes had baseline HbA1c ≥39 mmol/mol (5.7%) and <48 mmol/mol (6.5%), or two baseline fasting plasma glucose values ≥5.6 mmol/l (100 mg/dl) but no more than one fasting plasma glucose value ≥7.0 mmol/l (126 mg/dl), or had specific terms reported in their medical history; people diagnosed with diabetes at baseline were excluded, and the remainder were classified as having normoglycaemia. Participants received alirocumab or control (placebo/ezetimibe) for 24–104 weeks, with maximally tolerated statin in most cases. The primary efficacy endpoint was LDL cholesterol reductions from baseline to week 24 in the intention‐to‐treat population using the mixed‐effect model with a repeated measures approach.

Results

Reductions in LDL cholesterol from baseline to week 24 with alirocumab were 44.0–61.8% (prediabetes group) and 45.8–59.5% (normoglycaemia group). In both subgroups, LDL cholesterol reductions were generally similar in those with and without baseline triglycerides ≥1.7 mmol/l (150 mg/dl). Alirocumab was not associated with changes in HbA1c or fasting plasma glucose over time in either subgroup (up to 24 months' follow‐up). Adverse event rates were generally similar in those with and without prediabetes.

Conclusions

Over a mean follow‐up of 24–104 weeks, alirocumab treatment resulted in significant LDL cholesterol reductions from baseline that were similar in participants with prediabetes and those with normoglycaemia at baseline, with no effect on glycaemia and a safety profile similar to that of the control.
Mesenchymal stromal cells contribute to quiescence of therapy‐resistant leukemic cells in acute myeloid leukemia
Authors: Wang Wenwen , Bochtler Tilmann , Wuchter Patrick , Manta Linda , He Haiju , Eckstein Volker , Ho Anthony D. , Lutz Christoph
Published: August 2017

Objective

Persistence of leukemic cells after induction therapy has been shown to correlate with poor survival in acute myeloid leukemia (AML). In this study, we tested if human mesenchymal stromal cells (hMSCs) have protective effects on leukemic cells undergoing chemotherapy.

Methods

Persistent disease was used as marker to identify cases with therapy‐resistant leukemic cells in 95 patients with AML. Immunophenotyping, cell cycle, and apoptosis assays were assessed by flow cytometry. AML coculture studies were performed with hMSC of healthy donors.

Results

Samples from patients with persistent disease had increased fractions of CD34+CD38− and quiescent leukemic cells. Comparison of sample series collected at time points of diagnosis and blast persistence showed a relative therapy resistance of quiescent leukemic cells. Consistent with these observations, relapsed disease always displayed higher proportions of quiescent cells compared to samples of first diagnosis suggesting that quiescence is an important therapy escape mechanism of resistant cells. Co‐culture studies demonstrated that hMSC protect leukemic cells from the effect of AraC treatment by enriching for quiescent cells, mimicking the effects observed in patients. This effect was even detectable when no direct stromal contact was established.

Conclusions

Our data suggest that hMSC contribute to quiescence and therapy resistance of persistent AML cells.
Intracranial elastance is increased in idiopathic intracranial hypertension
Authors: Chisholm J. T. , Sudhakar P. , Alhajeri A. N. , Smith J. H.
Published: August 2017

Background and purpose

To date, no pathophysiological model has sufficiently accounted for all the findings encountered in patients with idiopathic intracranial hypertension (IIH). Intracranial elastance is an index of volume‐buffering capacity known to play a role in certain disorders of cerebrospinal fluid (CSF) dynamics, which has not been previously investigated in relation to IIH patients.

Methods

This was a single‐center retrospective cohort study from 1 July 2011 to 1 July 2016. Values for opening pressure (PO), closing pressure (PC) and volume (V) of CSF removed were collected, as well as demographic and clinical covariates. Intracranial elastance (E) and pressure−volume index (PVI) were calculated according to established equations: E = (PO−PC)/V and PVI = V/log10(PO/PC), respectively. Those with an alternative central nervous system pathology, including meningitis, encephalitis and normal pressure hydrocephalus were excluded. Eligible patients were subdivided into two groups based on final diagnosis: a control group and an IIH group.

Results

In our cohort (n = 49), a significant association of both E (P < 0.0001) and PVI (P = 0.005) with a diagnosis of IIH was observed. Median E was 0.45 [interquartile range (IQR) 0.29–0.63] in the control group and 1 (IQR 0.59–1.29) in the IIH group, and median PVI was 98.07 (IQR 59.92–135.86) in the control group and 64.1 (IQR 42.4–91.7) in the IIH group. Neither E nor PVI were significantly associated with age, gender or body mass index. PVI was independent of opening pressure.

Conclusions

As calculated by clinically accessible indices, our study provides evidence that intracranial elastance is increased in IIH, reflecting a novel insight into disease pathogenesis.
Adapting the CMIM algorithm for multilabel feature selection. A comparison with existing methods
Authors: Bermejo Pablo , Gámez José A. , Puerta José M.
Published: August 2017

The multilabel paradigm has recently attracted the attention of the machine learning community, multilabel problems being those which do not have only one class but several binomial classes instead. Although intensive research has been carried on lately into the multilabel classification paradigm, this is not the case of feature subset selection methods. In this work, we propose an adaptation of the well‐known CMIM feature selection algorithm, which is capable of approximating the conditional multivariate mutual information of each candidate attribute with respect to the whole set of labels. This capacity to search any degree of interaction among labels is the reason why our proposal performs better than other state‐of‐the‐art algorithms when the dataset on which it is run contains correlated labels.