bluuebunny/crossref_metadata_2025 huggingface dataset:
Supratherapeutic Psychotropic Drug Levels in the Emergency Department and Their Association with Delirium Duration: A Preliminary Study
Authors: Han Jin H. , Chen Alex , Vasilevskis Eduard E. , Schnelle John F. , Ely E. Wesley , Chandrasekhar Rameela , Morrison Ryan D. , Ryan Timothy P. , Daniels J. Scott , Sutherland Jeff J. , Simmons Sandra F.
Published: September 2019

Objectives

Polypharmacy is associated with delirium, but the mechanisms for this connection are unclear. Our goal was to determine the frequency of supratherapeutic psychotropic drug levels (SPDLs) in older hospitalized patients and if it is associated with the duration of emergency department (ED) delirium.

Design

Secondary analysis of a prospective cohort study.

Setting

Tertiary care academic medical center.

Participants

ED patients 65 years or older who were admitted to the hospital.

Measurements

Delirium was assessed in the ED and during the first 7 days of hospitalization using the modified Brief Confusion Assessment Method. Drug concentrations were determined in serum samples collected at enrollment via a novel platform based on liquid chromatography–tandem mass spectrometry capable of identifying and quantitating 78 clinically approved medications including opioids, benzodiazepines, antidepressants, antipsychotics, and amphetamines. Patients with serum psychotropic drug concentrations above established reference ranges were considered supratherapeutic and have a SPDL. We performed proportional odds logistic regression to determine if SPDLs were associated with ED delirium duration adjusted for confounders. Medical record review was performed to determine if the doses of medications associated with SPDLs were adjusted at hospital discharge.

Results

A total of 158 patients were enrolled; of these, 66 were delirious in the ED. SPDLs were present in 11 (17%) of the delirious and 4 (4%) of the non‐delirious ED patients. SPDLs were significantly associated with longer ED delirium duration (adjusted proportional odds ratio = 6.0; 95% confidence interval = 2.1‐17.3) after adjusting for confounders. Of the 15 medications associated with SPDLs, 9 (60%) were prescribed at the same or higher doses at the time of hospital discharge.

Conclusion

SPDLs significantly increased the odds of prolonged ED delirium episodes. Approximately half of the medications associated with SPDLs were continued after hospital discharge at the same or higher doses. J Am Geriatr Soc 67:2387–2392, 2019
Neurobehavioural complications of sleep deprivation: Shedding light on the emerging role of neuroactive steroids
Authors: Frau Roberto , Traccis Francesco , Bortolato Marco
Published: September 2019

Sleep deprivation (SD) is associated with a broad spectrum of cognitive and behavioural complications, including emotional lability and enhanced stress reactivity, as well as deficits in executive functions, decision making and impulse control. These impairments, which have profound negative consequences on the health and productivity of many individuals, reflect alterations of the prefrontal cortex (PFC) and its connectivity with subcortical regions. However, the molecular underpinnings of these alterations remain elusive. Our group and others have begun examining how the neurobehavioural outcomes of SD may be influenced by neuroactive steroids, a family of molecules deeply implicated in sleep regulation and the stress response. These studies have revealed that, similar to other stressors, acute SD leads to increased synthesis of the neurosteroid allopregnanolone in the PFC. Whereas this up‐regulation is likely aimed at counterbalancing the detrimental impact of oxidative stress induced by SD, the increase in prefrontal allopregnanolone levels contributes to deficits in sensorimotor gating and impulse control, signalling a functional impairment of PFC. This scenario suggests that the synthesis of neuroactive steroids during acute SD may be enacted as a neuroprotective response in the PFC; however, such compensation may in turn set off neurobehavioural complications by interfering with the corticolimbic connections responsible for executive functions and emotional regulation.
Atypical koebner phenomenon on a tattoo
Authors: Tammaro Antonella , Chello Camilla , Magri Francesca , Gelormini Enza , Parisella Francesca Romana , Daniele Alessandra , Signati Federica , Persechino Severino , Raffa Salvatore
Published: September 2019

Tattooing is more and more popular in developed countries in recent years and many side effects are associated with this practice, including psoriatic lesions and Koebner phenomenon. We report the case of a lichenoid reaction to red pigment in a patient affected by psoriasis.
Dexmedetomidine versus sufentanil with high‐ or low‐concentration ropivacaine for labor epidural analgesia: A randomized trial
Authors: Cheng Qiuju , Bi Xiaobao , Zhang Weiqiang , Lu Yanling , Tian Hang
Published: September 2019

Aim

To study analgesic effects of dexmedetomidine or sufentanil, both combined with ropivacaine, in epidural analgesia during labor.

Methods

We recruited 160 primigravidae with full‐term pregnancy who received epidural anesthesia during labor and randomized them into four groups to receive epidural administration of ropivacaine combined with sufentanil (RS1 and RS2 groups) or with dexmedetomidine (RD1 and RD2 groups). Systolic blood pressure, diastolic blood pressure and heart rate before anesthesia (T1), 15 min after anesthesia induction (T2), on delivery (T3) and 2 h postpartum (T4), together with visual analogue scale scores, Bromage scores, Ramsay scores, adverse reactions during analgesia and urinary retention at 6 and 24 h postpartum were recorded; the pH, PCO2 and PO2 of umbilical cord arterial blood and Apgar scores at 1, 5 and 10 min after childbirth were assessed.

Results

RS1 group had significantly lower systolic blood pressure, diastolic blood pressure and heart rate than RD1 group at T2 and T3 (all P < 0.05), but not at T1. At T2 and T3, the other three groups were lower than RS2 group in visual analogue scale and Ramsay scores (all P < 0.05). After childbirth, RD2 group had significantly higher PO2 result than other three groups (P < 0.05). At 6 h postpartum, RD2 group had significantly fewer cases of urinary retention than RD1 and RS1 groups (both P < 0.05).

Conclusion

A relatively low concentration of ropivacaine, combined with dexmedetomidine, is better in analgesia during labor.
Defining the hepatitis C cure cascade in an Urban health system using the electronic health record
Authors: Miller Lesley S. , Millman Alexander J. , Lom Jennifer , Osinubi Ademola , Ahmed Farah , Dupont Sarah , Rein David , Vellozzi Claudia , Harris Aaron M.
Published: September 2019

Hepatitis C virus (HCV) infection is a public health threat. The electronic health record (EHR) can be used to monitor patients along the HCV cure cascade and highlight opportunities for interventions to improve cascade outcomes. We developed an HCV patient registry using data from Grady Health System's (GHS) EHR and performed a cross‐sectional analysis of 72 745 GHS patients who received anti‐HCV testing from 2004 to 2016. We created a testing cascade: (1) anti‐HCV reactive, (2) HCV RNA tested and (3) HCV RNA detectable; and a cure cascade: (1) HCV RNA detectable, (2) engaged in care, (3) treatment prescribed, (4) sustained virologic response (SVR) tested and (5) SVR documented. A total of 9893 (14%) had reactive anti‐HCV tests of 72 745 patients tested, 5109 (52%) of these had HCV RNA tested, and 4224 (43%) were HCV RNA detectable. A total of 2738 (65%) of 4224 with detectable RNA were engaged in care, 909 (22%) were prescribed antiviral therapy, and 354 (8%) achieved SVR. Factors associated with HCV treatment included cirrhosis, tobacco use, depression, diabetes, obesity, alcohol use, male gender, black race and Medicare insurance. Uninsured patients were significantly less likely to be prescribed HCV treatment. In conclusion, using EHR data, we identified high anti‐HCV prevalence and noted gaps in HCV RNA testing, linkage to care and treatment. The EHR can be used to evaluate the effectiveness of targeted interventions to overcome these gaps.
Characteristic analysis of simple sequence repeats in the ridgetail white prawn Exopalaemon carinicauda genome and its application in parentage assignment
Authors: Zhang Qian , Zhang Chengsong , Yu Yang , Wang Quanchao , Li Fuhua
Published: September 2019

The ridgetail white prawn, Exopalaemon carinicauda is one of the most valuable marine resources in China, but few studies have been conducted to describe the characteristics of the simple sequence repeats (SSRs) for this species. The present study provides a genome‐wide view to SSRs in E. carinicauda. A total of 3,243,071 SSRs were detected in the whole genome sequences, while the mononucleotide SSR was the most abundant type. Adenine and Thymine (AT)‐rich SSRs were more abundant than guanine and cytosine (GC)‐rich SSRs. These SSR resources will be very useful for genetic studies such as parentage assignment, genetic diversity evaluation, and marker‐assisted selection. Sustainable development of E. carinicauda aquaculture requires improved breeding stocks and systematically family‐based selective breeding that relies on accurate pedigree information for estimating genetic merits. Therefore, eight highly polymorphic SSRs were selected for parentage assignment analysis. A total of 180 individuals from the offspring of four full‐sib and two half‐sib families were used to examine the efficacy of parentage analysis of those SSRs. The results showed that 98% of the offspring were unambiguously assigned to their female parent. The high efficacy of parentage assignment showed that the developed polymorphic SSR markers could be used for selective breeding in E. carinicauda.
Factors that May Influence Treatment Effects: Helping Practitioners Select Early Numeracy Interventions
Authors: Nelson Gena , McMaster Kristen L.
Published: September 2019

Despite encouraging findings that show that interventions can improve students’ math understanding, achievement gaps in math often persist or even widen for students who struggle. Practitioners play a significant role in closing these achievement gaps because they have the responsibility to select or design interventions. Practitioners may wish to consider factors that influence intervention effectiveness. This study evaluated numeracy interventions and explored how features of the studies and interventions may have influenced reported effects. Exploratory analyses revealed smaller effects when only distal measures were considered (g = 0.35; SE = 0.05), or when studies reported including more than 30 percent of participants as English learners (g = 0.44; SE = 0.12). Results also indicated variable effects across the same intervention programs. Implications for practitioners related to selecting interventions are discussed.
Deficiency of canonical Wnt/β‐catenin signalling in hepatic dendritic cells triggers autoimmune hepatitis
Authors: Tan Kangan , Xie Xuehai , Shi Wanwan , Miao Liang , Dong Xiaoqin , Yang Wanna , Shao Chen , Zhao Hong , Wang Yan , Wang Guiqiang , Hou Fengqin , Hong Yuan
Published: September 2019

Background & Aims

Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease manifested with the aberrant activation of hepatic dendritic cells (HDCs) and the subsequent breakdown of immune homeostasis. As an important player, HDC maintains immunological balance between tolerance to self‐antigens versus destruction against pathogens in liver. However, the intracellular signalling networks that program HDC remain unclear. We have now found the role of canonical Wnt/β‐catenin signalling in HDCs.

Methods

Liver sections from AIH patients and healthy subjects were stained for the markers of Wnt/β‐catenin signalling. Concanavalin A (ConA) and HDC/Hepa1‐6 vaccine‐induced AIH mouse models were examined for liver injury, inflammation and immune cell functions by serum biochemistry, histology, quantitative reverse transcription polymerase chain reaction (qRT‐PCR), enzyme‐linked immunosorbent assay (ELISA) and flow cytometry analysis. Wnt/β‐catenin signalling expression was measured using immunoblot and qRT‐PCR.

Results

Canonical Wnt/β‐catenin signalling in HDC is deficient in AIH patients and a mouse model, which coincides with the immunogenic function of HDCs. Furthermore, Wnt ligand engagement reactivates Wnt/β‐catenin signalling and recovers the immunoregulatory phenotype of HDCs, in turn alleviating the severity of AIH. Likewise, pharmacologic activation of Wnt/β‐catenin signalling attenuates AIH progression.

Conclusions

We report here that the constitutively active canonical Wnt/β‐catenin signalling confers HDCs tolerogenicity under steady‐state conditions. Deficiency of this pathway gives rise to T cell‐mediated immune response and incidence of AIH. It may act as a new pathogenesis and treatment target for AIH.
Albumin‐bilirubin grade‐based nomogram of the BCLC system for personalized prognostic prediction in hepatocellular carcinoma
Authors: Ho Shu‐Yein , Hsu Chia‐Yang , Liu Po‐Hong , Hsia Cheng‐Yuan , Lei Hao‐Jan , Huang Yi‐Hsiang , Ko Chih‐Chieh , Su Chien‐Wei , Lee Rheun‐Chuan , Hou Ming‐Chih , Huo Teh‐Ia
Published: September 2019

Background & Aims

The prognostic accuracy of individual hepatocellular carcinoma (HCC) patient in each Barcelona Clinic Liver Cancer (BCLC) stage is unclear. We aimed to develop and validate an albumin‐bilirubin (ALBI) grade‐based nomogram of BCLC to estimate survival for individual HCC patient.

Methods

Between 2002 and 2016, 3690 patients with newly diagnosed HCC were prospectively enrolled and retrospectively analysed. Patients were randomly split into derivation and validation cohort by 1:1 ratio. Multivariate Cox proportional hazards model was used to generate the nomogram from tumour burden, ALBI grade and performance status (PS). The concordance index and calibration plot were determined to evaluate the performance of this nomogram.

Results

Beta coefficients from the Cox model were used to assign nomogram points to different degrees of tumour burden, ALBI grade and PS. The scores of the nomogram ranged from 0 to 24, and were used to predict 3‐ and 5‐year patient survival. The concordance index of this nomogram was 0.77 (95% confidence interval [CI]: 0.71‐0.81) in the derivation cohort and 0.76 (95% CI: 0.71‐0.81) in the validation cohort. The calibration plots to predict both 3‐ and 5‐year survival rate well matched with the 45‐degree ideal line for both cohorts, except for ALBI‐based BCLC stage 0 in the validation cohort.

Conclusions

The proposed ALBI‐based nomogram of BCLC system is a simple and feasible strategy in the precision medicine era. Our data indicate it is a straightforward and user‐friendly prognostic tool to estimate the survival of individual HCC patient except for very early stage patients.
Temperature‐ and size‐associated differences in the skeletal structures and osculum cross‐sectional area influence the pumping rate of contractile sponge Cinachyrella cf. cavernosa
Authors: Dahihande Azraj S. , Thakur Narsinh L.
Published: September 2019

Sponges alter the proportion of structural and morphological components such as spicule skeleton and number of oscula in response to environment, development and growth. Such mechanisms indicate morphological and physiological variations within populations. We measured the pumping rate of different sized specimens of contractile sponge Cinachyrella cf. cavernosa present in the intertidal rock pools, during morning and afternoon low tides along the central west coast of India. Additionally, we measured the exhalant opening (oscular cross‐sectional area—OSA), tissue density, spicule skeleton weight and the abundance of choanocyte chambers to assess the morphological variations. Water temperature and sponge size showed a significant positive effect on pumping rate. OSA and the number of oscula increased with sponge size, but the sponge volume‐specific pumping rate did not increase (0.029 ± 0.020 ml/s ml‐1). Histological sections showed the abundance of chaonocyte chambers increased marginally with the sponge size, but the contraction state affected the count. Both tissue density and spicule skeleton weight were positively correlated with sponge size, particularly the increase in the size and number of spicule bundles radiating from the centre indicated a denser core in larger specimens. The subcortical lacunae and the peripheral choanosome with high abundance of canals appear to be the major volume reduction zones during contraction events. Our results indicate that the size and number of spicule bundles increase with sponge volume and the variation in temperature, contraction state, and size and number of oscula influence the pumping rate of C. cf. cavernosa.
Fuegian Museums and Anthropological Discourses: A Comparison of the Representations of Indigenous Societies from Tierra del Fuego in the Two Southernmost Museums in the World (Museo del Fin del Mundo, Argentina, and Museo Antropológico Martín Gusinde, Chile)
Authors: Fiore Danae , Butto Ana
Published: September 2019

In this essay, we analyze the museum scripts and exhibitions at the two southernmost museums in the world: Museo del Fin del Mundo (MFM, Ushuaia, Argentina) and Museo Antropológico Martín Gusinde (MAMG, Puerto Williams, Chile). The research focuses on the representations of Fuegian Indigenous peoples who inhabited (and still inhabit) Tierra del Fuego. To this end, comparative analyses are based on (a) the Indigenous societies represented; (b) the types of materials exhibited (archaeological, ethnographic, contemporary); (c) the uses of oral/written/photographic information; and (d) the types of museum displays used in each display case. The analyses aim to identify and discuss the different underlying anthropological discourses about the Indigenous Fuegian societies, their associations with past and present, prehistoric and historical events in Chile and Argentina, their visibility as “subjects” and/or “agents” within the contemporary local Fuegian communities, and their involvement in the formation of the museum's exhibitions.
The plant WEE1 kinase is involved in checkpoint control activation in nematode‐induced galls
Authors: Cabral Danila , Banora Mohamed Youssef , Antonino José Dijair , Rodiuc Natalia , Vieira Paulo , Coelho Roberta R. , Chevalier Christian , Eekhout Thomas , Engler Gilbert , De Veylder Lieven , Grossi‐de‐Sa Maria Fatima , de Almeida Engler Janice
Published: September 2019

Galls induced by plant‐parasitic nematodes involve a hyperactivation of the plant mitotic and endocycle machinery for their profit. Dedifferentiation of host root cells includes drastic cellular and molecular readjustments. In such a background, potential DNA damage in the genome of gall cells is evident.

We investigated whether DNA damage checkpoint activation followed by DNA repair occurred, or was eventually circumvented, in nematode‐induced galls.

Galls display transcriptional activation of the DNA damage checkpoint kinase WEE1, correlated with its protein localization in the nuclei. The promoter of the stress marker gene SMR7 was evaluated under the WEE1‐knockout background. Drugs inducing DNA damage and a marker for DNA repair, PARP1, were used to understand the mechanisms for coping with DNA damage in galls.

Our functional study revealed that gall cells lacking WEE1 conceivably entered mitosis prematurely, disturbing the cell cycle despite the loss of genome integrity. The disrupted nuclei phenotype in giant cells hinted at the accumulation of mitotic defects. In addition, WEE1‐knockout in Arabidopsis and downregulation in tomato repressed infection and reproduction of root‐knot nematodes. Together with data on DNA‐damaging drugs, we suggest a conserved function for WEE1 in controlling G1/S cell cycle arrest in response to a replication defect in galls.
The opposing effects of genetic drift and Haldane's sieve on floral‐morph frequencies in tristylous metapopulations
Authors: Roux Camille , Pannell John R.
Published: September 2019

Tristyly is a genetic floral polymorphism in which three floral morphs are maintained at equal frequencies by negative frequency‐dependent selection on alleles at two interacting loci. Because dominant alleles at these loci are maintained at a lower frequency than their recessive counterparts, they are more likely to be lost by founder events and genetic drift.

Here we examine the hypothesis that dominant alleles under negative frequency‐dependent selection should also be more likely to re‐invade populations than recessive alleles, due to Haldane's Sieve, because recessive alleles not expressed in a heterozygote state cannot benefit from positive selection when rare.

We used computer simulations of tristylous metapopulations to verify that Haldane's Sieve acting on migrants into occupied demes can indeed reverse the bias in allele frequencies expected for small single tristylous populations, particularly in situations of rapid population growth following colonisation. This effect is manifest both locally and at the metapopulation level.

Our study illustrates the potential effect of Haldane's Sieve in the novel context of an iconic plant sexual‐system polymorphism under the influence of metapopulation dynamics.
Evolution of clonal growth forms in angiosperms
Authors: Herben Tomáš , Klimešová Jitka
Published: September 2019

Clonal growth of plants is attained by a number of morphologically different organs (e.g. stolons, rhizomes, and roots), which are not functionally equivalent. Consequently, these clonal growth organ (CGO) types can determine functional traits that are associated with clonality, although little is known about their evolutionary flexibility or the constraining role they play on clonal traits.

We investigated the rates of evolutionary change by which individual CGOs are acquired and lost using a set of 2652 species of Central European flora. Furthermore, we asked how these individual CGOs constrain functionally relevant clonal traits, such as lateral spread, number of offspring, and persistence of connections.

We show that plants can easily switch in evolution among individual types of CGO and between clonal and nonclonal habits. However, not all these transitions are equally probable. Namely, stem‐based clonal growth and root‐based clonal growth constitute evolutionarily separate forms of clonal growth.

Clonal traits are strongly constrained by individual CGO types. Specifically, fast lateral spread is attained by stolons or hypogeogenous rhizomes, and persistent connections are attained by all rhizome types. However, the ease with which clonal organs appear and disappear in evolution implies that plants can overcome these constraints by adjusting their morphologies.
Spatial regulation of GPR64/ADGRG2 signaling by β‐arrestins and GPCR kinases
Authors: Azimzadeh Pedram , Talamantez‐Lyburn Sarah C. , Chang Katarina T. , Inoue Asuka , Balenga Nariman
Published: September 2019

Mechanisms of activation, signaling, and trafficking of adhesion G protein–coupled receptors (aGPCRs) have remained largely unknown. Several aGPCRs, including GPR56/ADGRG1 and GPR64/ADGRG2, show increased activity in the absence of their N‐terminal fragment (NTF). This constitutive signaling is plausibly caused by the binding of extracellular N‐terminal 15–25 amino acid–long tethered agonist to extracellular domains of the cognate aGPCRs. To test the role of NTF and tethered agonist in GPR64 signaling and endocytosis, we generated mutants that lack either NTF alone (ΔNTF) or NTF and tethered agonist (P622). We discover that unlike full‐length GPR64, ΔNTF and P622 mutants interact with β‐arrestin1 and β‐arrestins2 and are constitutively internalized in steady states. However, only ΔNTF shows exaggerated basal activation of the Gαs–cAMP–CRE signaling cascade. Neither ΔNTF nor P622 shows constitutive activation of the Gα13–SRE pathway, but both mutants respond to exogenously added agonistic peptide via CRE and SRE. GPCR kinases and dynamin mediate the constitutive internalization of ΔNTF and P622 to early endosomes, where ΔNTF constantly induces CRE. These data suggest that NTF not only shields the tethered agonist to prevent G protein signaling but also confers a conformation that inhibits the interaction with β‐arrestins and the consequent endocytosis and sustained signaling from endosomes.
Speech rhythm as naturally occurring and culturally transmitted behavioral patterns
Authors: Ordin Mikhail
Published: September 2019

Rhythm is fundamental to every motor activity. Neural and physiological mechanisms that underlie rhythmic cognition, in general, and rhythmic pattern generation, in particular, are evolutionarily ancient. As speech production is a kind of motor activity, investigating speech rhythm can provide insight into how general motor patterns have been adapted for more specific use in articulation and speech production. Studies on speech rhythm may further provide insight into the development of speech capacity in humans. As speech capacity is putatively a prerequisite for developing a language faculty, studies on speech rhythm may cast some light on the mystery of language evolution in the human genus. Hereby, we propose an approach to exploring speech rhythm as a window on speech emergence in ontogenesis and phylogenesis, as well as on diachronic linguistic changes.
The Clinical Relevance of Pain Severity Changes: Is There Any Difference Between Asian and Caucasian Patients With Osteoarthritis Pain?
Authors: Yue Li , Wang Jianing , Enomoto Hiroyuki , Fujikoshi Shinji , Alev Levent , Cheng Yan Yolanda , Skljarevski Vladimir
Published: September 2019

The objective of the present analysis was to determine whether changes in Brief Pain Inventory (BPI) average pain scores by patient global impression of improvement (PGI‐I) category and the cut‐off for clinically important difference (CID) were different between Asian and Caucasian patients with chronic pain due to osteoarthritis. This analysis used data from 3 (Caucasian) and 2 (Asian) randomized, placebo‐controlled, 10‐ to 14‐week duloxetine studies for the treatment of patients ≥40 years of age with osteoarthritis pain. The receiver operating characteristic (ROC) analysis was used to characterize the association between changes in BPI average pain scores and PGI‐I levels at study endpoint. The CID was characterized by PGI‐I, and the cut‐off point for CID in BPI average pain scores was determined by the intersection of a 45‐degree tangent line with each ROC curve. Data from 668 Asian and 868 Caucasian patients were available for analysis. Baseline BPI average pain ratings including worst and least pain were comparable between Asians and Caucasians. Ratings for percentage change from baseline to endpoint for BPI average pain scores in Asian patients and Caucasian patients were similar across the 7 PGI‐I categories, regardless of age, gender, study, and treatment. The ROC analysis results of cut‐off points in BPI average pain scores demonstrated the raw change cut‐off was −3.0, and percentage change cut‐off was −40% for both Asian and Caucasian patients. Overall, the present analysis concludes changes in BPI average pain scores by PGI‐I category and the cut‐off for CID were similar for Asian and Caucasian patients with chronic pain due to osteoarthritis.
Endothelin‐1 and α‐melanocortin have redundant effects on global genome repair in UV‐irradiated human melanocytes despite distinct signaling pathways
Authors: Swope Viki B. , Starner Renny J. , Rauck Corinne , Abdel‐Malek Zalfa A.
Published: September 2019

Human melanocyte homeostasis is sustained by paracrine factors that reduce the genotoxic effects of ultraviolet radiation (UV), the major etiological factor for melanoma. The keratinocyte‐derived endothelin‐1 (End‐1) and α‐melanocyte‐stimulating hormone (α‐MSH) regulate human melanocyte function, proliferation and survival, and enhance repair of UV‐induced DNA photoproducts by binding to the Gq‐ and Gi‐protein‐coupled endothelin B receptor (EDNRB), and the Gs‐protein‐coupled melanocortin 1 receptor (MC1R), respectively. We hereby report that End‐1 and α‐MSH regulate common effectors of the DNA damage response to UV, despite distinct signaling pathways. Both factors activate the two DNA damage sensors ataxia telangiectasia and Rad3‐related and ataxia telangiectasia mutated, enhance DNA damage recognition by reducing soluble nuclear and chromatin‐bound DNA damage binding protein 2, and increase total and chromatin‐bound xeroderma pigmentosum (XP) C. Additionally, α‐MSH and End‐1 increase total levels and chromatin localization of the damage verification protein XPA, and the levels of γH2AX, which facilitates recruitment of DNA repair proteins to DNA lesions. Activation of EDNRB compensates for MC1R loss of function, thereby reducing the risk of malignant transformation of these vulnerable melanocytes. Therefore, MC1R and EDNRB signaling pathways represent redundant mechanisms that inhibit the genotoxic effects of UV and melanomagenesis.
NOX4 activation is involved in ROS‐dependent Jurkat T‐cell death induced by Entamoeba histolytica
Authors: Lee Young Ah , Kim Kyeong Ah , Min Arim , Shin Myeong Heon
Published: September 2019

Aims

Entamoeba histolytica can induce host cell death through induction of various intracellular signalling pathways. The responses triggered by E. histolytica are closely associated with tissue pathogenesis and immune evasion. Although E. histolytica can induce reactive oxygen species (ROS) in host cells, which NADPH oxidase (NOX) isoform contributes to amoeba‐triggered Jurkat T‐cell death is unclear. In this study, we investigated the signalling role of NOX4‐derived ROS in E. histolytica‐induced Jurkat T‐cell death process.

Methods and results

In resting‐state Jurkat T cells, NOX4 is strongly expressed. When Jurkat T cells were incubated with live E. histolytica trophozoites, intracellular ROS was significantly increased compared to cells incubated with medium alone. E. histolytica‐induced ROS production was inhibited by pretreating Jurkat T cells with a NOX inhibitor. In addition, pretreating Jurkat T cells with a NOX inhibitor (Diphenyleneiodonium chloride) effectively blocked E. histolytica‐induced phosphatidylserine (PS) exposure and DNA fragmentation of host cells. Moreover, siRNA‐mediated knockdown of NOX4 protein expression in Jurkat T cells prevented E. histolytica‐induced ROS generation and DNA fragmentation.

Conclusion

These results suggest that NOX4 has a critical role in ROS‐dependent cell death process in Jurkat T cells induced by E. histolytica.
Monitoring severe acute maternal morbidity across Europe: A feasibility study
Authors: Chantry Anne A. , Berrut Sylvan , Donati Serena , Gissler Mika , Goldacre Raphael , Knight Marian , Maraschini Alice , Monteath Kirsten , Morris Anna , Teixeira Cristina , Wood Rachael , Zeitlin Jennifer , Deneux‐Tharaux Catherine
Published: September 2019

Background

Monitoring severe acute maternal morbidity (SAMM) appears essential for optimising care and informing health care policies, especially given changes in obstetric practices and mother profiles. International comparisons can identify areas where improvement is needed, but the comparability of indicators must be evaluated.

Objective

To assess the feasibility of monitoring SAMM using common definitions from hospital discharge databases across Europe.

Methods

We used hospital discharge data in eight countries (2 826 868 deliveries) to identify women with SAMM among all hospitalisations of women of reproductive age admitted for antenatal or delivery care. Five SAMM indicators were investigated: eclampsia, septicaemia, hysterectomy, hysterectomy associated with a diagnosis of obstetric haemorrhage, and red blood cell (RBC) transfusion associated with a diagnosis of obstetric haemorrhage. Between‐country variation was described, by the ratio of the highest to lowest rates, while external validation was assessed by comparing with population‐based studies on maternal morbidity.

Results

Ratios for hysterectomy and red blood cell (RBC) transfusion in the context of obstetric haemorrhage were 1:2.1 and 1:3.5, respectively. High values of hysterectomy and low values of transfusion were both consistent with high maternal mortality from haemorrhage (France, Italy, Portugal). Ratios across countries were relatively low for eclampsia (1:3.4) but very high for septicaemia (1:22.5). Compared to population‐based morbidity estimates, eclampsia was over‐reported in hospital databases whereas the two indicators of severe haemorrhage had good external validity.

Conclusions

In association with diagnosis codes indicating obstetric haemorrhage, hysterectomy and RBC transfusion appear to be good candidates for surveillance of maternal morbidity in Europe.
Gestational age, kindergarten‐level literacy, and effect modification by maternal socio‐economic and demographic factors
Authors: Mallinson David C. , Grodsky Eric , Ehrenthal Deborah B.
Published: September 2019

Background

Shorter gestational age at birth is associated with worse academic performance in childhood. Socio‐economic and demographic factors that affect a child's development may modify the relationship between gestational age and later academic performance.

Objective

The purpose of this study was to investigate socio‐economic and demographic effect modification of gestational age's association with kindergarten‐level literacy skills in a longitudinal Wisconsin birth cohort.

Methods

We sampled 153 145 singleton births (2007‐2010) that linked to Phonological Awareness Literacy Screening—Kindergarten (PALS‐K) scores (2012‐2016 school years). PALS‐K outcomes included meeting the screening benchmark (≥28 points, range 0‐102 points) and the standardised score. Multivariable linear regressions of PALS‐K outcomes on gestational age (completed weeks) included individual interactions for five maternal attributes measured at delivery: Medicaid coverage, education, age, race/ethnicity, and marital status.

Results

Each additional completed gestational week was associated with a 0.5 percentage point increase in the probability of meeting the PALS‐K literacy benchmark. The benefit of an additional week of gestational age was 0.5 percentage points (95% confidence interval 0.3, 0.7 percentage points) greater for Medicaid‐covered births (0.8 percentage points) relative to non‐Medicaid births (0.3 percentage points). Relative to only completing high school, having college education weakened this association by 0.3‐0.6 percentage points, depending on years in college. Similar but modest relations emerged with standardised scores.

Conclusions

Socio‐economic advantage as indicated by non‐Medicaid coverage or higher levels of completed maternal education may diminish the cost of preterm birth on a child's kindergarten‐level literacy skills.
Capacity Building toward Resilience: How Communities Recover, Learn, and Change in the Aftermath of Extreme Events
Authors: Albright Elizabeth A. , Crow Deserai A.
Published: September 2019

When faced with natural disasters, communities respond in diverse ways, with processes that reflect the extent of damage experienced by the community, their resource availability, and stakeholder needs. Local‐level processes drive decisions about mitigating future flood risks, such as if, how, and where to rebuild, as well as changes in zoning practices and public outreach programs. Because of their potentially recurring nature, floods offer an opportunity for communities to learn from and adapt to these experiences with the goal of increasing resiliency through deliberation, modification of former policies, and adoption of new policies. By following the response to the September 2013 floods in seven Colorado communities, this study investigates if, how, and why communities successfully learn from extreme events and change their local government policies to increase resilience and decrease vulnerability to future floods. We find that greater openness of post‐flood decision process is associated with more in‐depth deliberation, learning, and more substantive and frequent policy change.
Maternal influences on effortful control in adolescence: Developmental pathways to externalizing behaviors
Authors: Ruof Ariana K. , Elam Kit K. , Chassin Laurie
Published: September 2019

Adolescents' effortful control is subject to numerous maternal influences. Specifically, a mother's own effortful control is associated with her child's effortful control. However, maternal substance use, psychopathology, and stress within the parenting role may also lead to poor effortful control for their child. Poor effortful control during adolescence can subsequently contribute to a variety of negative outcomes, including externalizing behaviors. A sample of 460 adolescents (47% female, 59.3% Non‐Hispanic Caucasian) was selected from a longitudinal, multigenerational study. The goal was to examine maternal effortful control, substance use, psychopathology, and stress in their offspring's childhood (Mage = 6.27) and their influence on their children's effortful control in early adolescence (Mage = 12.21) and the subsequent effect of effortful control on adolescents’ externalizing behavior (Mage = 13.53). Maternal effortful control (measured via conscientiousness) and psychopathology were associated with adolescent effortful control, which was associated with externalizing behavior a year later. Additionally, there was a significant indirect association between maternal effortful control and adolescent externalizing behaviors via adolescent effortful control. Thus, adolescent effortful control is associated with maternal effortful control but also subject to specific maternal risk factors in childhood. These results inform potential maternal strategies for promoting positive developmental outcomes in adolescents.
Theories of Change in Rural Policy Evaluation
Authors: Maye Damian , Enticott Gareth , Naylor Rhiannon
Published: September 2019

Rural policy evaluation helps to understand the extent to which policies have met pre‐defined objectives, achieve value for money and learn from implementation failures. However, there is increasing debate over the quality of policy evaluation and the extent to which its methods can fully contribute to an understanding of rural policy. Responding to these calls, this article employs a theory driven approach to policy evaluation to assess the social impacts of attempts to reduce animal disease on farms in England. Popular in other policy arenas, theory driven evaluation relies on developing a theory of change to examine the interactions between policy contexts and mechanisms and policy outcomes and determine what works for whom. Drawing on longitudinal qualitative and quantitative research, the article identifies two mechanisms of change to evaluate the Badger Vaccine Deployment Project (BVDP) in England to reduce incidence of bovine Tuberculosis (bTB) in cattle. The article shows how these mechanisms – ‘seeing is believing’ and ‘practice similarity’ – are triggered by different contextual factors leading to the failure to deliver expected policy outcomes. We also consider the advantages and limitations to theory based evaluation, and the contribution it can make to the evaluation of other rural development programmes.
Characterization of the novel HLA‐DQB1*06:01:22 allele by next‐generation sequencing
Authors: Quan Zhan‐Rou , Zou Hong‐Yan , Zhong Yan‐Ping , Deng Zhi‐Hui , Hong Wen‐Xu
Published: September 2019

HLA‐DQB1*06:01:22 differs from HLA‐DQB1*06:01:01:01 by one nucleotide substitution in codon 189 in exon 4.
Major shoreline retreat and sediment starvation following Snowball Earth
Authors: Nordsvan Adam R. , Barham Milo , Cox Grant , Kirscher Uwe , Mitchell Ross N.
Published: September 2019

While cap dolostones are integral to the Snowball Earth hypothesis, the current depositional model does not account for multiple geological observations. Here we propose a model that rationalises palaeomagnetic, sequence‐stratigraphic and sedimentological data and supports rapid deglaciation with protracted cap dolostone precipitation. The Snowball Earth hypothesis posits that a runaway ice‐albedo can explain the climate paradox of Neoproterozoic glacial deposits occurring at low palaeolatitudes. This scenario invokes volcanic degassing to increase atmospheric greenhouse gases to a critical threshold that overcomes the albedo effect and brings the planet back from the ice‐covered state. Once this occurs, Earth should shift rapidly from a snowball to an extreme greenhouse. However, cap dolostone units overlying glacial sediments, typically interpreted as transgressive deposits, exhibit multiple magnetic reversals indicating they accumulated in >105 years. By reviewing modern post‐glacial systems, sequence stratigraphic concepts and principles of sedimentology, we suggest that cap dolostones are not restricted to the transgression but rather represent sediment starvation following a major landward shoreline migration associated with the demise of Snowball Earth. Thus, the duration in which cap dolostone accumulated is not directly coupled to the timescale of the Snowball Earth deglaciation.
Effect of storage of platelet concentrates in PAS‐B, PAS‐C, or plasma on transfusion reactions
Authors: van Hout Fabienne M.A. , Middelburg Rutger A. , van der Meer Pieter F. , Pors Aad , Wiersum‐Osselton Johanna C. , Schipperus Martin R. , Kerkhoffs Jean‐Louis , van der Bom Johanna G.
Published: September 2019

BACKGROUND

Reports on the clinical consequences of longer storage time of platelet concentrates are contradictory. The objective of this study was to assess whether longer storage times are associated with a higher risk of transfusion reactions.

STUDY DESIGN AND METHODS

We gathered storage times of pooled platelet concentrates related to transfusion reactions reported to the national hemovigilance office from 2004 to 2015. These were combined with storage times of platelet concentrates in the reference population to compare incidences of transfusion‐associated circulatory overload, transfusion‐related acute lung injury, allergic reactions, febrile nonhemolytic reactions, and “other” reactions between storage time categories.

RESULTS

A total of 567,053 platelet concentrates and 1870 transfusion reactions were analyzed. Among platelet additive solution (PAS)‐B platelet recipients, the odds ratio of a storage time of 4 to 5 days compared to 1 to 3 days was 1.60 (95% confidence interval [CI], 1.17‐2.18) for allergic, and 1.47 (1.09‐1.98) for febrile reactions. For PAS‐C platelet recipients, the odds ratio for allergic reactions was 3.78 (95% CI, 1.31‐10.9) for 4 to 5 days, and 4.57 (95% CI, 1.57‐13.4) for 6‐ to 7‐day‐old platelets when compared to 1‐ to 3‐day‐old units. In all other studied reaction types, no statistically significant association was observed in platelets in plasma, PAS‐B, and PAS‐C.

CONCLUSIONS

In plasma platelets, longer storage time was not associated with a higher incidence of transfusion reactions. In PAS platelets, longer storage time was associated with higher transfusion reaction incidences, in particular for allergic reactions with both PAS fluids and febrile reactions with PAS‐B. This indicates that the effect of storage time is different for different reaction types and depends on the storage fluid.
Expanded feasibility of ferritin testing: stability of ferritin stored as whole blood and validation of plastic tubes
Authors: Spencer Bryan R. , Brodsky Jaye P. , Holley Gary C. , Foster Gregory A. , Winton Colleen , Stramer Susan L.
Published: September 2019

BACKGROUND

Ferritin testing is a recommended strategy to mitigate iron depletion in blood donors. A barrier for some testing platforms is a requirement to complete sample management and testing within a temporal window incompatible with the logistics of many blood collectors. The ability to delay separation of plasma/serum from red cells and subsequent testing would enhance the feasibility of ferritin testing on a broader scale.

STUDY DESIGN AND METHODS

Thirty blood donors provided a research donation of 12, 4‐mL sample tubes of whole blood. Six pairs of serum and K2‐EDTA‐plasma tubes were centrifuged and samples tested in triplicate on day of collection and on each of the next 5 days following storage at 4°C. Comparison of ferritin values for serum versus K2‐EDTA‐plasma at baseline was performed to validate plastic EDTA‐containing tubes. Variation of ferritin values during storage was assessed for direction and strength of any detectable changes.

RESULTS

Ferritin values were comparable between EDTA‐plasma and serum, with baseline values from EDTA‐plasma samples 7% lower on average than serum (p < 0.0001 by paired t‐test). Variability over five storage days was within approved parameters in the manufacturer's instructions. Within‐run precision averaged 2% to 3% for each test day and within‐subject precision across all samples averaged less than 5% for both serum and EDTA‐plasma. Repeated measures showed no difference in changes during storage by tube type or day of testing.

CONCLUSION

These results support flexible testing procedures, expanding the opportunity for blood centers to adopt this measure for assessing donor iron status.
A Simulation-Based Approach to Data Center Thermal Efficiency Optimization
Authors: Fouladi Kamran , Schaadt Joseph
Published: September 2019

The energy consumption for cooling electronic equipment in data centers using central systems is significant and will continue to rise. The motivation of the present research study is based on the need to determine optimization strategies to improve and optimize the thermal efficiency of data centers using a simulation-based approach. Here, simulation is used to model and optimize a proposed research data center for use as an environment to test equipment and investigate best practices and strategies such as containment and hybrid cooling. The optimization technique used in this study finds the optimal operating conditions and containment strategies of the data center while meeting specific thermal conformance criteria. More specifically, optimum supply airflow rate and temperature setpoint of cooling units are sought under different containment configurations, including both hot aisle and cold aisle containment strategies in both full and partial setups. The results of the computational fluid dynamics (CFD) simulations indicated a lower probability of hot spots with full hot aisle containment strategy in a data center operating at lower supply airflow rate and higher supply temperature setpoint. The optimization approach helped to determine a more efficient cooling system without the risk of under-provisioning. The study considered steady-state conditions with static heat load and fixed equipment layout. However, the generalized optimization process developed in the present study should add to the repertoire of tools presently used for the optimization of new air-cooled data centers.