bluuebunny/crossref_metadata_2025 huggingface dataset:
Fabrication of Biocompatible Composites of Poly(lactic acid)/Hydroxyapatite Envisioning Medical Applications
Authors: Backes Eduardo Henrique , Pires Laís De Nóbile , Beatrice Cesar Augusto Gonçalves , Costa Lidiane Cristina , Passador Fabio Roberto , Pessan Luiz Antonio
Published: January 2020

Over the last years, orthopedic procedures for bone repairs have been developed due to an increase in trauma and diseases. The development of bioactive composites using biodegradable polymers like poly(lactic acid) (PLA) and bioactive fillers as hydroxyapatite (HA) originate biomaterials, which combine bioactivity of HA and PLA biocompatibility. Therefore, using additive manufacturing is possible for the production of customized products made from these materials; however, a thorough study of these materials is required. In this context, melt‐compounding has been used to manufacture bioactive composites of PLA/HA, and rheological, molecular, and thermomechanical behavior were assessed. The biocomposite of PLA with 10 wt% HA presented a strong shear thinning behavior, which makes it more suitable for fused filament fabrication since lower printing pressure is required. Furthermore, this composite presented an enhancement of 12% in thermomechanical properties in comparison to PLA and a slight increase in cell proliferation. PLA and PLA/HA were fabricated and used to produce 3D calibrations cube as a proof of concept. They presented good printability and high accuracy, and therefore, further investigation needs to be performed to unleash its use in bone tissue engineering applications. POLYM. ENG. SCI., 60:636–644, 2020. © 2020 Society of Plastics Engineers
Mercy TAPE for Calculation‐Free Height Estimation in Pediatric Rehabilitation Patients
Authors: Modrcin Ann C. , Luce John , Abdel‐Rahman Susan M.
Published: January 2020

Background

In children, height is an essential element of a pediatric assessment, yet this measure is less likely to occur in nonambulatory children or those with unique disabilities. There is compelling support for surrogate measures; however, many of these are accompanied by limitations.

Objective

This study was conducted to evaluate whether the U.S. Food and Drug Administration (FDA)–cleared Mercy TAPE could be adopted for height estimation.

Design

Development and external validation of a height‐estimation method were conducted with retrospectively collected data in nonrehabilitation children. Testing of the model was performed prospectively in a pediatric rehabilitation population.

Setting

U.S. pediatric rehabilitation outpatient clinic.

Participants

Data from 19 407 children were used to develop the model. Data from an independent cohort of 1472 children were used for external validation, and the model was tested in 195 pediatric rehabilitation patients. Of the 195 patients, 57% required no wheelchair, 18% could ambulate independently for short distances, 17% could ambulate with an assistive device, and 8% were full‐time wheelchair users.

Interventions

Not applicable.

Main Outcome Measurements

Relative error (RE), percentage error (PE), and percent predicted within 10% and 20% of actual height.

Results

Height estimated with the modified Mercy TAPE was highly predictive of actual height in nonrehabilitation children in the United States (RE [mean ± SD]: 1.1 ± 5.7 cm; PE [mean ± SD]: 1.0 ± 4.7%). In rehabilitation patients, height was underestimated to a greater extent (RE [mean ± SD]: 3.0 ± 7.4 cm; PE [mean ± SD]: −2.1 ± 5.6%).

Conclusions

The Mercy TAPE offers a reasonable approximation of height in ambulatory children, although it slightly underestimates height in the pediatric rehabilitation population. Consequently, this and other surrogate measures may be less suited to examining growth against a reference ambulatory population and more suited to following individual children over time.
Machine Learning in Drug Discovery and Development Part 1: A Primer
Authors: Talevi Alan , Morales Juan Francisco , Hather Gregory , Podichetty Jagdeep T. , Kim Sarah , Bloomingdale Peter C. , Kim Samuel , Burton Jackson , Brown Joshua D. , Winterstein Almut G. , Schmidt Stephan , White Jensen Kael , Conrado Daniela J.
Published: January 2020

Artificial intelligence, in particular machine learning (ML), has emerged as a key promising pillar to overcome the high failure rate in drug development. Here, we present a primer on the ML algorithms most commonly used in drug discovery and development. We also list possible data sources, describe good practices for ML model development and validation, and share a reproducible example. A companion article will summarize applications of ML in drug discovery, drug development, and postapproval phase.
Bayesian Data Assimilation to Support Informed Decision Making in Individualized Chemotherapy
Authors: Maier Corinna , Hartung Niklas , de Wiljes Jana , Kloft Charlotte , Huisinga Wilhelm
Published: January 2020

An essential component of therapeutic drug/biomarker monitoring (TDM) is to combine patient data with prior knowledge for model‐based predictions of therapy outcomes. Current Bayesian forecasting tools typically rely only on the most probable model parameters (maximum a posteriori (MAP) estimate). This MAP‐based approach, however, does neither necessarily predict the most probable outcome nor does it quantify the risks of treatment inefficacy or toxicity. Bayesian data assimilation (DA) methods overcome these limitations by providing a comprehensive uncertainty quantification. We compare DA methods with MAP‐based approaches and show how probabilistic statements about key markers related to chemotherapy‐induced neutropenia can be leveraged for more informative decision support in individualized chemotherapy. Sequential Bayesian DA proved to be most computationally efficient for handling interoccasion variability and integrating TDM data. For new digital monitoring devices enabling more frequent data collection, these features will be of critical importance to improve patient care decisions in various therapeutic areas.
Entry diversion: Deterrence by diverting submarket entry
Authors: Uzunca Bilgehan , Cassiman Bruno
Published: January 2020

Research Summary

Going back to Bain (1956), strategy scholars have long recognized the importance of deterring entry for sustaining incumbents' profits in an industry. We introduce a new mechanism, entry diversion, to better understand the empirical phenomenon of persistent firm entry in spite of investments in entry deterrence by incumbents in some industries. Entry diversion happens when preemptive strategic investments by incumbents decrease the expected future profits from a target submarket such that entrants choose to enter another submarket within the same industry. Empirical evidence from the global semiconductor manufacturing industry suggests that incumbents expand their capacities beyond demand growth, and that these investments effectively divert entry into other submarkets. Greenfield entrants are more responsive to entry diversion than incumbents.

Managerial Summary

Managers have long understood that deterring entry of new players into their industry could sustain their firms' profits. In this article, we introduce a new mechanism, entry diversion, where the incumbent diverts potential entrants from its submarket toward other submarkets in the same industry. Entry diversion happens when preemptive strategic investments by incumbents decrease the expected future profits of the entrant in a submarket of the industry such that the entrant chooses not to enter the incumbent's submarket. Contrary to entry deterrence, new players will still enter the industry but settle in different submarkets. Empirical evidence from the global semiconductor manufacturing industry suggests that incumbents expand their capacities beyond demand growth, and that these investments effectively divert entry into other submarkets.
Considerations in Developing Reporter Gene Bioassays for Biologics
Authors: Grailer Jamison , Moravec Richard A. , Cheng Zhijie Jey , Grassi Manuela , Ott Vanessa , Fan Frank , Cong Mei
Published: January 2020

The establishment of a robust and reproducible functional bioassay that reliably measures drug potency while ascertaining its mode of action is essential in biologic drug development. Here we describe a simple bioluminescent reporter gene bioassay for assessing biologics targeting immune checkpoints without the complexity and variability of more traditional assay systems. This chapter provides an overview of key considerations in reporter gene bioassay design and optimization, as well as development of thaw-and-use cells as an assay reagent for biologic QC lot release.
Decreases in the Psoas Muscle Index Correlate More Strongly with Survival than Other Prognostic Markers in Esophageal Cancer After Neoadjuvant Chemoradiotherapy Plus Esophagectomy
Authors: Kawakita Yuta , Motoyama Satoru , Sato Yusuke , Wakita Akiyuki , Nagaki Yushi , Imai Kazuhiro , Minamiya Yoshihiro
Published: January 2020

Background

Despite wide acknowledgement of the importance of sarcopenia and prognostic markers such as the neutrophil‐to‐lymphocyte ratio, the impact on cancer patient survival of the timing of sarcopenia's emergence and its severity is not well understood, nor is the association between sarcopenia and prognostic markers. The aim of this study, therefore, was to investigate the effect of the severity and timing of changes in the psoas muscle index (PMI) on survival of advanced esophageal squamous cell carcinoma (ESCC) patients receiving neoadjuvant chemoradiotherapy (NACRT) plus esophagectomy and the association between PMI and known prognostic markers.

Methods

Included in this study were 113 ESCC patients who underwent NACRT followed by esophagectomy. PMI and prognostic markers were measured at their initial visit, just before surgery (after NACRT), and 3 months postoperatively.

Results

All patients were classified into four groups according to the percent decrease in PMI after NACRT and after NACRT plus esophagectomy. Patients exhibiting a larger PMI decrease (≥20%) after NACRT plus esophagectomy had significantly poorer overall survival than those showing a smaller PMI decrease. Furthermore, multivariable analysis showed that a larger decrease in PMI after NACRT plus esophagectomy was a significant risk factor for overall (P < 0.0001) and recurrence‐free (P = 0.0097) survival. Neither pretherapeutic PMI nor a decrease in PMI after NACRT significantly affected survival. PMI also showed weak, but significant, correlations with several prognostic markers postoperatively.

Conclusions

Decreased PMI after NACRT plus esophagectomy is a strong prognostic indicator in ESCC patients.
An inverse optimization approach to understand human acquisition of kinematic coordination in bimanual fine manipulation tasks
Authors: Yao Kunpeng , Billard Aude
Published: January 2020

Tasks that require the cooperation of both hands and arms are common in human everyday life. Coordination helps to synchronize in space and temporally motion of the upper limbs. In fine bimanual tasks, coordination enables also to achieve higher degrees of precision that could be obtained from a single hand. We studied the acquisition of bimanual fine manipulation skills in watchmaking tasks, which require assembly of pieces at millimeter scale. It demands years of training. We contrasted motion kinematics performed by novice apprentices to those of professionals. Fifteen subjects, ten novices and five experts, participated in the study. We recorded force applied on the watch face and kinematics of fingers and arms. Results indicate that expert subjects wisely place their fingers on the tools to achieve higher dexterity. Compared to novices, experts also tend to align task-demanded force application with the optimal force transmission direction of the dominant arm. To understand the cognitive processes underpinning the different coordination patterns across experts and novice subjects, we followed the optimal control theoretical framework and hypothesize that the difference in task performances is caused by changes in the central nervous system’s optimal criteria. We formulated kinematic metrics to evaluate the coordination patterns and exploit inverse optimization approach to infer the optimal criteria. We interpret the human acquisition of novel coordination patterns as an alteration in the composition structure of the central nervous system’s optimal criteria accompanied by the learning process.
Adolescent Sexual Behavior Patterns in a British Birth Cohort: A Latent Class Analysis
Authors: Xu Yin , Norton Sam , Rahman Qazi
Published: January 2020

This study examined adolescent sexual behaviors patterns, and the consistency between sexual behavior and sexual orientation, in a prospective birth cohort. We used data on 5150 young people from the Avon Longitudinal Study of Parents and Children. Sexual orientation was assessed using a 5-point scale of sexual attraction at 15.5 years. Fourteen sexual activities were assessed using the Adolescent Sexual Activities Index at 13.5 and 15.5 years. Latent class analysis suggested four subgroups of adolescent sexual behaviors at 13.5: a “high-intensity sexual behaviors exclusively with other-sex, no same-sex intimacy” group (3.87%); a “moderate-intensity sexual behaviors exclusively with other-sex, no same-sex intimacy” group (16.57%); a “low-intensity sexual behaviors exclusively with other-sex, no same-sex intimacy” group (34.21%); and a “no sexual behavior” group (45.35%). There were five subgroups at 15.5 where four of them (23.42%, 18.37%, 28.12%, and 24.52%, respectively) were interpreted the same as at 13.5 years and a new “high-intensity sexual behaviors, some same-sex intimacy” subgroup (5.57%). Latent transition analysis showed approximately half the adolescents moved toward greater engagement in higher intensity sexual activities with other-sex at 15.5. Boys and girls who were in groups without same-sex intimacy were predominantly attracted to the other-sex, whereas there were moderate consistencies between same-sex intimacy and same-sex attraction for boys and low consistency for girls. Findings suggest that it may be important to include low-intensity sexual behaviors when assigning adolescents to sexual orientation groupings (via sexual behaviors) in order to reduce selection biases and increase statistical power via the increase in sample size.
Phase I dose-escalation study of the safety, tolerability, and pharmacokinetics of aflibercept in combination with S-1 in Japanese patients with advanced solid malignancies
Authors: Doi Toshihiko , Boku Narikazu , Onozawa Yusuke , Takahashi Keishiro , Kawaguchi Osamu , Ohtsu Atsushi
Published: January 2020

Background Aflibercept, a recombinant fusion protein binding VEGF-A, VEGF-B and placental growth factor, inhibits tumor growth by blocking angiogenesis. The aim of this phase I dose-escalation study was to determine the recommended phase II dose (RP2D) of aflibercept in combination with S-1 in Japanese patients with solid tumors. Patients and methods Sequential cohorts of 3–6 patients with metastatic or unresectable solid tumors, who had failed at least one prior line of standard treatment or who were not suitable for such treatment, were to receive escalating doses of aflibercept every 2 weeks, starting at 2 mg/kg, combined with S-1 at 40 mg/m2 twice daily (80 mg/m2/day; 4 weeks on/2 weeks off). Dose-escalation was to be based on the incidence of dose-limiting toxicity (DLT). Blood samples were collected for pharmacokinetic analysis. Results At the first dose level (aflibercept 2 mg/kg plus S-1) 1 of 6 patients experienced a DLT (grade 4 proteinuria). The aflibercept dose was consequently escalated to 4 mg/kg; 1 of 3 patients treated at this dose level had a DLT (grade 2 pleural effusion), and another patient experienced grade 3 reversible posterior leukoencephalopathy syndrome after the DLT assessment period. Additional patients were therefore enrolled into the first dose level to explore safety and tolerability. The study was subsequently terminated prematurely. The maximum tolerated dose was not reached and the RP2D was not determined in Japanese patients. Conclusions The tolerability and safety of aflibercept 2 mg/kg in combination with S-1 was confirmed in Japanese patients with advanced solid tumors.
Positive Aspects of Emotional Competence in Preventing Internalizing Symptoms in Children with and without Developmental Language Disorder: A Longitudinal Approach
Authors: Samson Andrea C. , van den Bedem Neeltje P. , Dukes Daniel , Rieffe Carolien
Published: January 2020

In order to better understand protective factors for internalizing problems, this longitudinal study examined positive emotions, emotion awareness and (non-)emotional communication skills in relation to somatic complaints and social anxiety in children with (N = 104) and without (N = 183) Developmental Language Disorder (DLD) using self-reported measures twice with a 9-month interval. Additionally, parents reported on their child’s communication problems and emotion communication at Time 1. Most importantly, since we found that increasing levels of emotion awareness related to decreases in social anxiety and somatic complaints in children with and without DLD, we conclude that children with DLD are likely to benefit from interventions aimed at improving their emotion awareness in addition to language interventions.
Victimization and Its Consequences for Well-Being: A Between- and Within-Person Analysis
Authors: Janssen Heleen J. , Oberwittler Dietrich , Koeber Goeran
Published: January 2020

Objectives

We examined the effects of victimization on several aspects of well-being in a longitudinal study of a general population sample. Previous research has often been inconclusive, as it was largely based on cross-sectional data and prone to problems of unobserved heterogeneity and selection bias. We examined both between-person differences and within-person changes in well-being in relation to property and violent victimization. We investigated psychological and behavioral dimensions of well-being, controlling for and comparing with the effects of other negative life events.

Methods

We used data from a two-wave panel survey of 2928 respondents aged 25–89 nested in 140 neighborhoods in two large German cities. We applied random-effects modeling to separate between-person from within-person effects.

Results

The within-person detrimental effects of victimization were considerably smaller than between-person effects, which reflected preexisting, time-stable factors that distinguish individuals who have experienced victimization from individuals who have not. Detrimental effects concerned fear of crime, generalized trust, and neighborhood satisfaction, but did not extend to emotional well-being or life satisfaction, in contrast to other negative life events. We found empirical support both for adaptation (‘recovery’) effects as well as for anticipation effects. Violent victimization had stronger effects than property victimization, and victimization near the home had stronger effects than victimization elsewhere.

Conclusion

The findings indicate that violent victimization has palpable detrimental effects on security perceptions, trust and neighborhood satisfaction—but not on emotional well-being and life satisfaction—and that individuals largely recover from the victimization within 18 months.
Four Dimensions of Criticism Against Gender-Fair Language
Authors: Vergoossen Hellen Petronella , Renström Emma Aurora , Lindqvist Anna , Gustafsson Sendén Marie
Published: January 2020

The gender-neutral third-person pronoun singular hen was recently introduced in Swedish as a complement to she (hon) and he (han). The initiative to add hen initially received strong criticism. In the present study, we analyzed 208 arguments from 168 participants with critical attitudes toward hen. We used Blaubergs’ (1980) and Parks and Roberton’s (1998) taxonomies of critical arguments against past gender-fair language reforms in English in the 1970s and 1990s as a basis for coding the arguments. A majority of arguments (80.7%) could be coded into existing categories, indicating that criticisms of gender-fair language initiatives are similar across different times and cultural contexts. Two categories of arguments did not fit existing categories (19.3%): gender-neutral pronouns are distracting in communication and gender information is important in communication. Furthermore, we established four overarching dimensions that capture assumptions and beliefs underlying gender-fair language criticism: (a) Defending the Linguistic Status Quo (39.4%), (b) Sexism and Cisgenderism (27.4%), (c) Diminishing the Issue and Its Proponents (26.9%), and (d) Distractor In Communication (6.3%). These dimensions of criticisms should be considered and addressed in different ways when implementing gender-fair language.
Exploring seagrass fish assemblages in relation to the habitat patch mosaic in the brackish Baltic Sea
Authors: Staveley Thomas A.B. , Hernvall Patrick , Stjärnkvist Nellie , van der Meijs Felix , Wikström Sofia A. , Gullström Martin
Published: January 2020

Assessing the influence of habitat patch dynamics on faunal communities is a growing area of interest within marine ecological studies. This study sets out to determine fish assemblage composition in Zostera marina (L.) meadows and ascertain how habitat structural complexity and seascape structure (i.e. composition and configuration of habitat patches) influenced these assemblages in the northern Baltic Sea. Using ten seascapes (600 m in diameter), the fish assemblage was surveyed both in summer and autumn using beach seine. We found that the fish assemblage was clearly dominated by sticklebacks, followed by pipefish and with a general absence of larger piscivorous species. Biomass of fish did not differ between seasons, and low-level carnivores dominated the trophic structure. Overall, at the larger seascape-scale in summer, the proportion of bare soft sediment showed a negative relationship with fish biomass, while diversity of patches was found to exhibit a positive association with fish biomass. At the smaller habitat scale, both seagrass shoot height and density had a negative influence on fish biomass in both seasons. This study outlines new knowledge regarding how the mosaic of habitat patches shape seagrass fish assemblages in the northern Baltic Sea.
An integrated workflow to perform reservoir and completion parametric study on a shale gas reservoir
Authors: Mahmoud Mohamed , Aleid Ahmed , Ali Abdulwahab , Kamal Muhammad Shahzad
Published: January 2020

The main objectives of this paper are to assess the long-term and short-term production based on both reservoir parameters and completion parameters of shale gas reservoirs. The effects of the reservoir parameters (permeability and the initial reservoir pressure) and completion parameters (fracture geometry, stimulated reservoir volume, etc.) on the short-term and long-term production of shale gas reservoirs were investigated. The currently used approach relies mainly on the decline curve analysis or analogs from a similar shale play to forecast the gas production from shale gas reservoirs. Both these approaches are not satisfactory because they are calibrated on short production history and do not assess the impact of uncertainty in reservoir and well data. For the first time, this study integrates initial production analysis, probabilistic evaluation, and sensitivity analysis to develop a robust workflow that will help in designing a sustainable production from shale gas plays. The reservoir and completion parameters were collected from different available resources, and the probability distributions of gathered uncertain data were defined. Then analytical models were used to forecast the production. Two well evaluation results are presented in this paper. Based on the results, completion parameters affected the short-term and long-term production, while the reservoir parameters controlled the long-term production. Long-term well performance was mainly controlled by the fracture half-length and fracture height, whereas other completion and reservoir parameters have an insignificant effect. Stimulation treatment design defines the initial well performance, while well placement decision defines well long-term performance. The findings of this study would help in better understanding the production performance of shale gas reservoirs, maximizing production by selecting effective completion parameters and considering the governing reservoir parameters. Moreover, it would help in accomplishing more effective stimulation treatments and define the potentiality of the basin.
Friction and wear behavior of carbon fiber reinforced lithium aluminosilicate composites sliding against GCr15 steel
Authors: Ma Haibao , Wu Xin , Xia Long , Huang Longnan , Xiong Li , Yang Hua , Zhong Bo , Zhang Tao , Yang Zhiwei , Gao Feng , Wen Guangwu
Published: January 2020

Carbon fibers reinforced lithium aluminosilicate matrix composites (Cf/LAS) were prepared by slurry infiltration combined with a hot press procedure. The friction, wear behavior, and wear mechanisms of Cf/LAS composites under dry sliding conditions were investigated. The results show that the coefficient of friction (COF) initially increased with the increase in carbon fiber content, and reached the maximum value of 0.20 for the 33%Cf/LAS composite. The COF increased sharply with increasing sample temperature from RT to 300 °C. The COF remained stable in the temperature range of 300–500 °C. The two wear mechanisms of LAS glassceramics are fatigue wear and abrasive wear. The Cf/LAS composites demonstrate slight spalling and shallow scratches. These results show that carbon fibers improve the mechanical properties and wear resistance of Cf/LAS composites.
The GDPR and International Organizations
Authors: Kuner Christopher
Published: January 2020

The entry into application of the EU General Data Protection Regulation (GDPR) on May 25, 2018 has raised questions about its impact on data processing by intergovernmental organizations that operate under public international law (referred to here as international organizations or IOs). EU data protection law can have impact beyond EU borders, and the global reach of EU law is a well-recognized phenomenon. The GDPR contains numerous references to IOs but does not state whether it applies to them, and this uncertainty has led to tensions between IOs and the European Commission. The issues surrounding IOs’ processing of personal data show how the GDPR can give rise to unexpected questions under public international law, and illustrate the need for greater engagement between EU law and international law.
Official advice improves mortgage-holders’ perceptions of switching: experimental evidence
Authors: TIMMONS SHANE , BARJAKOVÁ MARTINA , MCELVANEY TERENCE J. , LUNN PETER D.
Published: January 2020

Encouraging consumers to switch to lower-rate mortgages is important both for the individual consumer's finances and for functioning competitive markets, but switching rates are low. Given the complexity of mortgages, one potential regulatory intervention that may increase switching rates is to provide independent advice on how to select good mortgage products and how to navigate the switching process. Working with a government consumer protection agency, we conducted an experiment with mortgage-holders to test whether such advice alters perceptions of switching. The experiment tested how the attributes of the offer, perceptions about the switching process, individual feelings of competence and comprehension of the product affect willingness to switch to better offers, both before and after reading the official advice. The advice made consumers more sensitive to interest rate decreases, especially over longer terms. It also increased consumers’ confidence in their ability to select good offers. Overall, the findings imply that advice from policy-makers can change perceptions and increase switching rates. Moreover, the experiment demonstrates how lab studies can contribute to behaviourally informed policy development.
The 2018 Italian general election: a ‘new Italy’ or a ‘dead end’?
Authors: Pinto Luca
Published: January 2020

To what extent can the 2018 Italian general election be considered as critical? This article examines how the contributors of six volumes published in the aftermath of the election answer this question by focusing on three major dimensions of change in comparison with the 2013 election: changes in the patterns of party competition; changing patterns of voting behaviour in terms of socio-economic characteristics of the electorate; changes in the salience of issue cleavages and in the way new issues affected the electoral outcomes. The picture originating from the volumes under review is not so sharp as that emerging from the literature that flourished after the 2013 election, whereas several contributions stressed the revolutionary traits of that electoral contest. Despite the important changes observed in comparison to 2013, defining the 2018 general election as critical is adequate only to a certain extent.
Prenatal alcohol exposure is associated with early motor, but not language development in a South African cohort
Authors: Hendricks Gaironeesa , Malcolm-Smith Susan , Stein Dan J. , Zar Heather J. , Wedderburn Catherine J. , Nhapi Raymond T. , Chivese Tawanda , Adnams Colleen M. , Donald Kirsten A.
Published: January 2020

Objective:

To investigate the association of prenatal alcohol exposure (PAE) and early neurodevelopment in the first 2 years of life, adjusting for maternal socio-demographic and psychosocial factors, in the Drakenstein Child Health Study (DCHS), a South African birth cohort study.

Methods:

The DCHS comprises a population-based birth cohort of 1143 children, of which a subsample completed the Bayley Scales of Infant Development-III (BSID-III) at 6 (n= 260) and 24 months of age (n= 734). A subset of alcohol-exposed and -unexposed children was included in this analysis at age 6 (n= 52 exposed;n= 104 unexposed) and 24 months (n= 92 exposed;n= 184 unexposed). Multiple hierarchical regression was used to explore the associations of PAE with motor and language development.

Results:

PAE was significantly associated with decreased gross motor [odds ratio (OR) = 0.16, 95% confidence interval (CI) = 0.06–0.44,p= 0.001] or fine motor (OR = 0.16, 95% CI = 0.06–0.46,p= 0.001) functioning after adjusting for maternal socio-demographic and psychosocial factors at 6 months of age only. No significant effects were found in either receptive or expressive communication and cognitive outcomes at either time points.

Conclusion:

PAE has potentially important consequences for motor development in the first 2 years of life, a period during which the most rapid growth and maturation occur. These findings highlight the importance of identifying high-risk families in order to provide preventive interventions, particularly in antenatal clinics and early intervention services.
Reconstructing Saharan dust transport to the Eastern Mediterranean Sea during the last 180 ka using endmember modelling of grain size data
Authors: Beuscher Sarah , Ehrmann Werner , Krüger Stefan , Schmiedl Gerhard
Published: January 2020

Endmember modelling on the terrigenous silt fraction of nine marine sediment cores spanning up to 180,000 years reveals the influx of North African dust into the Eastern Mediterranean Sea. The dust grain size modes decrease with transport distance, from >50 µm off the African coast to ca. 30 µm in the Aegean Sea. The dust signal is strongly influenced by hydrological changes in northern Africa. Changes from arid to humid periods are documented in the grain size data of all cores. The climatic signal gets weaker with growing distance from the source and close to large fluvial sediment sources such as the Nile. Frequency and wavelet analyses show a strong orbital precession signal that is known to trigger the migration of the monsoonal rain belt in northern Africa. The influence of climate changes on suborbital time scales on dust influx is less distinct, but Dansgaard-Oeschger interstadials and Heinrich-like events are documented in some cores. In the sediment core closest to the source, three endmembers represent one or more dust sources in northern Africa. With growing distance from the source, the three modes cannot be separated anymore and appear as one multimodal dust endmember.
Making Space for Past Futures: Rural Landscape Temporalities in Roman Britain
Authors: Gardner Andrew , Wallace Lacey
Published: January 2020

In this paper, we seek to explore the ways in which landscapes become venues not only for manipulations of the past in a present, but also for shaping possible futures. Considerations of temporality and being in the landscape have been more strongly focused on the past and social memory than the future, anticipation and projectivity, but these are vital considerations if we are to preserve the possibility that past people imagined alternative futures. A fruitful archaeological context for an exploration of past futures can be found in the choices people made during the late Iron Age and Roman period in Britain, which has an increasingly rich and high-resolution material record for complex changes and continuities during a period of cultural interactions and imperial power dynamics. More specifically, recent research into the architectural and material practices evident on rural settlement sites and across landscapes forces us to challenge preconceptions about the reactive/reactionary culture of rural societies. Case-studies from Kent and the West Country will be deployed to develop the argument that in the materializing of time, the future has a very significant part to play.
Weight loss supplement causing acute heart block in a child
Authors: O’Brien Daniel R. , Szymczuk Vivian , Albaro Cecilia A.
Published: January 2020

A 16-year-old male was admitted to the paediatric ICU with acute onset of vomiting, somnolence, and chest pain, and electrocardiogram showing 2nd degree heart block after ingesting an Aleurites moluccana (Candlenut) seed as a herbal weight loss supplement. Electrocardiogram showed progressively worsening heart block with down-sloping of the ST segments, resembling digoxin toxicity. After 2 days of ICU observation, his symptoms began to improve and eventually resolved. The side effects of herbal supplements are often unknown but by analysing cases such as these, physicians can develop a better understanding of these substances to help guide management.
Double-edged sword of federalism: variation in essential health benefits for mental health and substance use disorder coverage in states
Authors: Willison Charley E. , Singer Phillip M. , Grazier Kyle L.
Published: January 2020

The Affordable Care Act requires all insurance plans sold on health insurance marketplaces and individual and small-group plans to cover 10 Essential Health Benefits (EHB), including behavioral health services. Instead of applying a uniform EHB plan design, the Department of Health and Human Services let states define their own EHB plan. This approach was seen as the best balance between flexibility and comprehensiveness, and assumed there would be little state-to-state variation. Limited federal oversight runs the risk of variation in EHB coverage definitions and requirements, as well as potential divergence from standardized medical guidelines. We analyzed 112 EHB documents from all states for behavioral health coverage in effect from 2012 to 2017. We find wide variation among states in their EHB plan required-coverage, and divergence between medical-practice guidelines and EHB plans. These results emphasize consideration of federated regulation over health insurance coverage standards. Federal flexibility in states benefit design nods to state-specific policymaking-processes and population needs. However, flexibility becomes problematic if it leads to inadequate coverage that reduces access to critical health care services. The EHBs demonstrate an incomplete effort to establish appropriate minimum standards of coverage for behavioral health services.
Intra-operative computed tomography in endovascular aneurysm	repair
Authors: Hansrani Vivak , Halim Usman A. , Goel Ravi R. , Antoniou George A.
Published: January 2020

Summary. The study objective was to evaluate the ability of computed tomography (CT) to identify technical complications intra-operatively during endovascular aneurysm repair (EVAR). Frequency of complications seen by CT and their sequelae was compared with conventional completion angiography. Methods: We performed a systematic review that conformed to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. We considered studies reporting on the effectiveness of intra-operative CT during EVAR. Results: Our literature search yielded six studies that met our criteria for inclusion. In general, these showed intra-operative CT to be superior to completion angiogram at detecting intra-operative complications during EVAR. Despite concerns regarding irradiation, the use of intra-operative CT was found to expose patients to an overall lower radiation dose, since post-operative CT angiograms were no longer required. Moreover, no adverse effect on renal function has been demonstrated as a result of the increased intra-operative contrast usage when CT is used. Conclusions: The current body of evidence suggests that intra-operative CT is superior to completion angiography at detecting clinically important EVAR complications and incurs a lower total radiation dose with no added risk of contrast-induced renal impairment. Further research directly comparing the two modalities in the same cohort is required to determine sensitivity for individual complications.
A Global Perspective on Microplastics
Authors: Hale Robert C. , Seeley Meredith E. , La Guardia Mark J. , Mai Lei , Zeng Eddy Y.
Published: January 2020

Society has become increasingly reliant on plastics since commercial production began in about 1950. Their versatility, stability, light weight, and low production costs have fueled global demand. Most plastics are initially used and discarded on land. Nonetheless, the amount of microplastics in some oceanic compartments is predicted to double by 2030. To solve this global problem, we must understand plastic composition, physical forms, uses, transport, and fragmentation into microplastics (and nanoplastics). Plastic debris/microplastics arise from land disposal, wastewater treatment, tire wear, paint failure, textile washing, and at‐sea losses. Riverine and atmospheric transport, storm water, and disasters facilitate releases. In surface waters plastics/microplastics weather, biofoul, aggregate, and sink, are ingested by organisms and redistributed by currents. Ocean sediments are likely the ultimate destination. Plastics release additives, concentrate environmental contaminants, and serve as substrates for biofilms, including exotic and pathogenic species. Microplastic abundance increases as fragment size decreases, as does the proportion of organisms capable of ingesting them. Particles <20 μm may penetrate cell membranes, exacerbating risks. Exposure can compromise feeding, metabolic processes, reproduction, and behavior. But more investigation is required to draw definitive conclusions. Human ingestion of contaminated seafood and water is a concern. Microplastics indoors present yet uncharacterized risks, magnified by the time we spend inside (>90%) and the abundance of polymeric products therein. Scientific challenges include improving microplastic sampling and characterization approaches, understanding long‐term behavior, additive bioavailability, and organismal and ecosystem health risks. Solutions include improving globally based pollution prevention, developing degradable polymers and additives, and reducing consumption/expanding plastic reuse.
Processes Driving Global Interior Ocean pH Distribution
Authors: Lauvset S. K. , Carter B. R. , Pèrez F. F. , Jiang L.‐Q. , Feely R. A. , Velo A. , Olsen A.
Published: January 2020

Ocean acidification evolves on the background of a natural ocean pH gradient that is the result of the interplay between ocean mixing, biological production and remineralization, calcium carbonate cycling, and temperature and pressure changes across the water column. While previous studies have analyzed these processes and their impacts on ocean carbonate chemistry, none have attempted to quantify their impacts on interior ocean pH globally. Here we evaluate how anthropogenic changes and natural processes collectively act on ocean pH, and how these processes set the vulnerability of regions to future changes in ocean acidification. We use the mapped data product from the Global Ocean Data Analysis Project version 2, a novel method to estimate preformed total alkalinity based on a combination of a total matrix intercomparison and locally interpolated regressions, and a comprehensive uncertainty analysis. We find that the largest contribution to the interior ocean pH gradient comes from organic matter remineralization, with CaCO3 cycling being the second most important process. The estimates of the impact of anthropogenic CO2 changes on pH reaffirm the large and well‐understood anthropogenic impact on pH in the surface ocean, and put it in the context of the natural pH gradient in the interior ocean. We also show that in the depth layer 500–1,500 m natural processes enhance ocean acidification by on average 28 ± 15%, but with large regional gradients.
Applications of genome editing technology in the targeted therapy of human diseases: mechanisms, advances and prospects
Authors: Li Hongyi , Yang Yang , Hong Weiqi , Huang Mengyuan , Wu Min , Zhao Xia
Published: January 2020

Based on engineered or bacterial nucleases, the development of genome editing technologies has opened up the possibility of directly targeting and modifying genomic sequences in almost all eukaryotic cells. Genome editing has extended our ability to elucidate the contribution of genetics to disease by promoting the creation of more accurate cellular and animal models of pathological processes and has begun to show extraordinary potential in a variety of fields, ranging from basic research to applied biotechnology and biomedical research. Recent progress in developing programmable nucleases, such as zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeat (CRISPR)–Cas-associated nucleases, has greatly expedited the progress of gene editing from concept to clinical practice. Here, we review recent advances of the three major genome editing technologies (ZFNs, TALENs, and CRISPR/Cas9) and discuss the applications of their derivative reagents as gene editing tools in various human diseases and potential future therapies, focusing on eukaryotic cells and animal models. Finally, we provide an overview of the clinical trials applying genome editing platforms for disease treatment and some of the challenges in the implementation of this technology.
Identification of folate receptor α (FRα) binding oligopeptides and their evaluation for targeted virotherapy applications
Authors: Hulin-Curtis Sarah L. , Davies James A. , Nestić Davor , Bates Emily A. , Baker Alexander T. , Cunliffe Tabitha G. , Majhen Dragomira , Chester John D. , Parker Alan L.
Published: January 2020

Oncolytic virotherapies (OV) based on human adenoviral (HAdV) vectors hold significant promise for the treatment of advanced ovarian cancers where local, intraperitoneal delivery to tumour metastases is feasible, bypassing many complexities associated with intravascular delivery. The efficacy of HAdV-C5-based OV is hampered by a lack of tumour selectivity, where the primary receptor, hCAR, is commonly downregulated during malignant transformation. Conversely, folate receptor alpha (FRα) is highly expressed on ovarian cancer cells, providing a compelling target for tumour selective delivery of virotherapies. Here, we identify high-affinity FRα-binding oligopeptides for genetic incorporation into HAdV-C5 vectors. Biopanning identified a 12-mer linear peptide, DWSSWVYRDPQT, and two 7-mer cysteine-constrained peptides, CIGNSNTLC and CTVRTSAEC that bound FRα in the context of the phage particle. Synthesised lead peptide, CTVRTSAEC, bound specifically to FRα and could be competitively inhibited with folic acid. To assess the capacity of the elucidated FRα-binding oligopeptides to target OV to FRα, we genetically incorporated the peptides into the HAdV-C5 fiber-knob HI loop including in vectors genetically ablated for hCAR interactions. Unfortunately, the recombinant vectors failed to efficiently target transduction via FRα due to defective intracellular trafficking following entry via FRα, indicating that whilst the peptides identified may have potential for applications for targeted drug delivery, they require additional refinement for targeted virotherapy applications.
Coupling of terminal differentiation deficit with neurodegenerative pathology in Vps35-deficient pyramidal neurons
Authors: Tang Fu-Lei , Zhao Lu , Zhao Yang , Sun Dong , Zhu Xiao-Juan , Mei Lin , Xiong Wen-Cheng
Published: January 2020

Vps35 (vacuolar protein sorting 35) is a key component of retromer that regulates transmembrane protein trafficking. Dysfunctional Vps35 is a risk factor for neurodegenerative diseases, including Parkinson’s and Alzheimer’s diseases. Vps35 is highly expressed in developing pyramidal neurons, and its physiological role in developing neurons remains to be explored. Here, we provide evidence that Vps35 in embryonic neurons is necessary for axonal and dendritic terminal differentiation. Loss of Vps35 in embryonic neurons results in not only terminal differentiation deficits, but also neurodegenerative pathology, such as cortical brain atrophy and reactive glial responses. The atrophy of neocortex appears to be in association with increases in neuronal death, autophagosome proteins (LC3-II and P62), and neurodegeneration associated proteins (TDP43 and ubiquitin-conjugated proteins). Further studies reveal an increase of retromer cargo protein, sortilin1 (Sort1), in lysosomes of Vps35-KO neurons, and lysosomal dysfunction. Suppression of Sort1 diminishes Vps35-KO-induced dendritic defects. Expression of lysosomal Sort1 recapitulates Vps35-KO-induced phenotypes. Together, these results demonstrate embryonic neuronal Vps35’s function in terminal axonal and dendritic differentiation, reveal an association of terminal differentiation deficit with neurodegenerative pathology, and uncover an important lysosomal contribution to both events.
Correction: Inhibition of IRE1α RNase activity reduces NLRP3 inflammasome assembly and processing of pro-IL1β
Authors: Talty Aaron , Deegan Shane , Ljujic Mila , Mnich Katarzyna , Naicker Serika D. , Quandt Dagmar , Zeng Qingping , Patterson John B. , Gorman Adrienne M. , Griffin Matthew D. , Samali Afshin , Logue Susan E.
Published: January 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.