bluuebunny/crossref_metadata_2025 huggingface dataset:
A Pilot RCT of an Internet Intervention to Reduce the Risk of Alcohol‐Exposed Pregnancy
Authors: Ingersoll Karen , Frederick Christina , MacDonnell Kirsten , Ritterband Lee , Lord Holly , Jones Brogan , Truwit Lauren
Published: May 2018

Background

Preventing alcohol‐exposed pregnancies (AEPs) could reduce the incidence of fetal alcohol spectrum disorders. Previous face‐to‐face interventions significantly reduced risk for AEP, but a scalable intervention is needed to reach more women at risk.

Methods

This study compared a 6 Core automated, interactive, and tailored Internet intervention, the Contraception and Alcohol Risk Reduction Internet Intervention (CARRII), to a static patient education (PE) website for its effect on AEP risk. Participants were recruited online to a pilot randomized clinical trial (RCT) with baseline, 9 weeks posttreatment, and 6‐month (6‐M) follow‐up assessments. Seventy‐one women completed online questionnaires and telephone interviews and were randomized to CARRII (n = 36) or PE (n = 35). Primary outcomes were rates of risky drinking, unprotected sex episodes, and AEP risk, collected from online prospective diaries.

Results

CARRII participants showed significant reductions in rate of unprotected sex from pretreatment (88.9%) to posttreatment (70.6%) (p < 0.04) and to 6‐M follow‐up (51.5%) (p = 0.001); rate of risky drinking from pretreatment (75.0%) to posttreatment (50.0%) (p < 0.02), but insignificant change from pretreatment to 6‐M follow‐up (57.6%) (p < 0.09); and rate of AEP risk from pretreatment (66.7%) to posttreatment (32.4%) (p = 0.001) and to 6‐M follow‐up (30.3%) (p = 0.005). PE participants demonstrated no significant changes on all 3 variables across all time points. Intent‐to‐treat group‐by‐time tests were not significant, but power was limited by missing diaries. Over 72% of CARRII participants completed all 6 Cores. Exploratory analyses suggest that higher program utilization is related to change.

Conclusions

These data show that CARRII was acceptable, feasible, promising to reduce AEP risk, and merits further testing in a fully powered RCT.
Transethnic differences in GWAS signals: A simulation study
Authors: Zanetti Daniela , Weale Michael E.
Published: May 2018

Genome‐wide association studies (GWASs) have allowed researchers to identify thousands of single nucleotide polymorphisms (SNPs) and other variants associated with particular complex traits. Previous studies have reported differences in the strength and even the direction of GWAS signals across different populations. These differences could be due to a combination of (1) lack of power, (2) allele frequency differences, (3) linkage disequilibrium (LD) differences, and (4) true differences in causal variant effect sizes.

To determine whether properties (1)–(3) on their own might be sufficient to explain the patterns previously noted in strong GWAS signals, we simulated case–control data of European, Asian and African ancestry, applying realistic allele frequencies and LD from 1000 Genomes data but enforcing equal causal effect sizes across populations. Much of the observed differences in strong GWAS signals could indeed be accounted for by allele frequency and LD differences, enhanced by the Euro‐centric SNP bias and lower SNP coverage found in older GWAS panels. While we cannot rule out a role for true transethnic effect size differences, our results suggest that strong causal effects may be largely shared among human populations, motivating the use of transethnic data for fine‐mapping.
Enhanced Th1 and inflammatory mRNA responses upregulate NK cell cytotoxicity and NKG2D ligand expression in human pre‐eclamptic placenta and target it for NK cell attack
Authors: Vinnars Marie‐Therese , Björk Emma , Nagaev Ivan , Ottander Ulrika , Bremme Katarina , Holmlund Ulrika , Sverremark‐Ekström Eva , Mincheva‐Nilsson Lucia
Published: May 2018

Problem

Pre‐eclampsia (PE), a severe human pregnancy disorder, is associated with exaggerated systemic inflammation, enhanced cytokine production, and increased shedding of microvesicles leading to endothelial dysfunction, coagulopathy, and extensive placenta destruction. The cause of PE is still unclear. Evidence suggests that its origin lies in the placenta and that the maternal immune system is involved. A shift in cytokine production in PE pregnancy promotes NK cell activation, suggested to be important in PE pathogenesis. In line with this suggestion, we studied NK cell cytotoxicity in peripheral blood of PE patients and controls and the mRNA expression of cytokines and of the NKG2D receptor and its ligands MICA/B and ULBP1‐3 in PE‐ and normal placenta.

Method of study

The cytotoxic capacity of peripheral blood NK cells was analyzed using K562 target cells. The cytokine mRNA profiles and the mRNA expression of the NKG2D receptor and its ligands MICA/B and ULBP 1‐3 in PE placenta were assessed and compared to those in normal placenta using real‐time quantitative RT‐PCR.

Results

The cytotoxicity of peripheral blood NK cells was upregulated in PE cases. Further, we found an enhanced inflammatory cytokine mRNA response combined with a dysregulated regulatory response and a significant mRNA overexpression of NKG2D receptor and its ligands MICA/B and ULBP in PE placenta.

Conclusion

The destruction of chorionic villi observed in PE placenta might be conveyed by an enhanced local cytotoxic response through the NKG2D receptor‐ligand pathway, which in turn might be promoted by an intense inflammatory response not counteracted by regulatory cytokine responses.
Why and for Whom May Coping Planning Have Adverse Effects? A Moderated Mediation Analysis
Authors: Inauen Jennifer , Stocker Andrea , Scholz Urte
Published: May 2018

Background

Coping planning, the formation of plans to overcome behavioral barriers is assumed to promote health behavior maintenance, but the literature on this is inconsistent. In this study, we aimed to investigate the mechanisms of a coping planning intervention that adversely affected maintained safe water consumption. We also explored perceived behavioral difficulty as a potential moderator of coping planning interventions.

Methods

In the second phase of a cluster‐randomised trial, households (N = 177 analyzed) were randomly allocated to a coping planning intervention or a comparison group (repetition of interventions from first intervention phase). Safe water consumption, the mechanisms of coping planning, and perceived difficulty were measured pre‐post. The data were analyzed using mediation and moderated mediation analysis.

Results

Changes in behavioral intention mediated the intervention effects on behavioral maintenance (b = −0.36, 95% CI [−0.91, −0.03]). Changes in perceived coping planning (b = 0.08, 95% CI [−0.12, 0.34]), and maintenance self‐efficacy (b = −0.13, 95% CI [−0.45, 0.01]) did not mediate the effects. Prior perceived difficulty moderated the coping planning intervention effects on maintenance via intention.

Conclusions

Coping planning may decrease motivation for health behavior maintenance for persons who experienced few barriers prior to the planning intervention.
Proton pump inhibitor and histamine‐2 receptor antagonist use and risk of liver cancer in two population‐based studies
Authors: Tran K. T. , McMenamin Ú. C. , Hicks B. , Murchie P. , Thrift A. P. , Coleman H. G. , Iversen L. , Johnston B. T. , Lee A. J. , Cardwell C. R.
Published: May 2018

Background

Proton pump inhibitors (PPIs) and histamine‐2 receptor antagonists (H2RAs) are commonly used.PPIs have been shown to promote liver cancer in rats; however, only one study has examined the association in humans.

Aims

To investigatePPIs and H2RAs and risk of primary liver cancer in two large independent study populations.

Methods

We conducted a nested case‐control study within the Primary Care Clinical Informatics Unit (PCCIU) database in which up to five controls were matched to cases with primary liver cancer, recorded by General Practitioners. Odds ratios (ORs) and 95% confidence intervals (95%CIs) for associations with prescribedPPIs and H2RAs were calculated using conditional logistic regression. We also conducted a prospective cohort study within theUKBiobank using self‐reported medication use and cancer‐registry recorded primary liver cancer. Hazard ratios (HRs) and 95%CIs were calculated using Cox regression.

Results

In thePCCIUcase‐control analysis, 434 liver cancer cases were matched to 2103 controls. In theUKBiobank cohort, 182 of 475 768 participants developed liver cancer. In both, ever use ofPPIs was associated with increased liver cancer risk (adjustedOR1.80, 95%CI1.34, 2.41 and adjustedHR1.99, 95%CI1.34, 2.94 respectively). There was little evidence of association with H2RAuse (adjustedOR1.21, 95%CI0.84, 1.76 and adjustedHR1.70, 95%CI0.82, 3.53 respectively).

Conclusions

We found some evidence thatPPIuse was associated with liver cancer. Whether this association is causal or reflects residual confounding or reverse causation requires additional research.
The social work services in screening process of compulsory treatment interventions in addicts in Iran: A content analysis study
Authors: Moghanibashi‐Mansourieh Amir , Fathi Mansour , Barati Sedeh Farid , Deilamizade Abbas , Puyan Daryush
Published: May 2018

Compulsory treatment has had a detrimental impact on drug abuse treatment policies and programs in Iran. Physicians are currently required to conduct initial treatment screening. Social workers are a part of the treatment team but have no authority to initiate a compulsory drug treatment plan. For this reason, the present article investigates social work service participation in the process of compulsory drug treatment. The study methodology is content analysis. Nine social workers participated in seven focus group discussions. Overall, 110 codes were extracted from the sessions and were categorized into five main themes: interview and initial assessment; referral; investigation of ineligibility criteria; report to judicial authority; and follow‐up and advocacy. The results of this research suggest amending executive bylaws based on a social work approach to the screening process for compulsory drug treatment.
Language barriers and epistemic injustice in healthcare settings
Authors: Peled Yael
Published: May 2018

Contemporary realities of global population movement increasingly bring to the fore the challenge of quality and equitable health provision across language barriers. While this linguistic challenge is not unique to immigration contexts and is likewise shared by health systems responding to the needs of aboriginal peoples and other historical linguistic minorities, the expanding multilingual landscape of receiving societies renders this challenge even more critical, owing to limited or even non‐existing familiarity of modern and often monolingual health systems with the particular needs of new linguistic minorities. The centrality of language to health beliefs, attitudes, practices, cultural scripts, and conceptual frameworks emphasizes its pivotal role in the healthcare process, and consequently in the adverse effects of treatment that is language‐insensitive and unaware. Such an attitude on the part of medical authorities risks considerable epistemic injustice in the form of a (mis)judgement of patients’ intelligence, credibility, and rationality based on the language that they speak and the manner in which they speak it, consequently impacting the quality and equity of care provided. This danger, I argue, may be effectively countered by fostering among the participants in the healthcare process a sense of epistemic humility through greater metalinguistic awareness. Outlining a range of operative steps that can be used to facilitate this. I argue that the reality of language barriers in the healthcare process, while not entirely eliminable, may nevertheless be successfully addressed, in order to mitigate the challenge of quality and equitable healthcare provision in multilingual societies.
Astrocytes, an active player in Aicardi–Goutières syndrome
Authors: Sase Sunetra , Takanohashi Asako , Vanderver Adeline , Almad Akshata
Published: May 2018

Aicardi–Goutières syndrome (AGS) is an early‐onset, autoimmune and genetically heterogeneous disorder with severe neurologic injury. Molecular studies have established that autosomal recessive mutations in one of the following genes are causative: TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR1 and IFIH1/MDA5. The phenotypic presentation and pathophysiology of AGS is associated with over‐production of the cytokine Interferon–alpha (IFN‐α) and its downstream signaling, characterized as type I interferonopathy. Astrocytes are one of the major source of IFN in the central nervous system (CNS) and it is proposed that they could be key players in AGS pathology. Astrocytes are the most ubiquitous glial cell in the CNS and perform a number of crucial and complex functions ranging from formation of blood‐brain barrier, maintaining ionic homeostasis, metabolic support to synapse formation and elimination in healthy CNS. Involvement of astrocytic dysfunction in neurological diseases—Alexander's disease, Epilepsy, Alzheimer's and amyotrophic lateral sclerosis (ALS)—has been well‐established. It is now known that compromised astrocytic function can contribute to CNS abnormalities and severe neurodegeneration, nevertheless, its contribution in AGS is unclear. The current review discusses known molecular and cellular pathways for AGS mutations and how it stimulates IFN‐α signaling. We shed light on how astrocytes might be key players in the phenotypic presentations of AGS and emphasize the cell‐autonomous and non‐cell‐autonomous role of astrocytes. Understanding the contribution of astrocytes will help reveal mechanisms underlying interferonopathy and develop targeted astrocyte specific therapeutic treatments in AGS.
Alexander disease: an astrocytopathy that produces a leukodystrophy
Authors: Sosunov Alexander , Olabarria Markel , Goldman James E.
Published: May 2018

Alexander Disease (AxD) is a degenerative disorder caused by mutations in the GFAP gene, which encodes the major intermediate filament of astrocytes. As other cells in the CNS do not express GFAP, AxD is a primary astrocyte disease. Astrocytes acquire a large number of pathological features, including changes in morphology, the loss or diminution of a number of critical astrocyte functions and the activation of cell stress and inflammatory pathways. AxD is also characterized by white matter degeneration, a pathology that has led it to be included in the “leukodystrophies.” Furthermore, variable degrees of neuronal loss take place. Thus, the astrocyte pathology triggers alterations in other cell types. Here, we will review the neuropathology of AxD and discuss how a disease of astrocytes can lead to severe pathologies in non‐astrocytic cells. Our knowledge of the pathophysiology of AxD will also lead to a better understanding of how astrocytes interact with other CNS cells and how astrocytes in the gliosis that accompanies many neurological disorders can damage the function and survival of other cells.
Genetic defects disrupting glial ion and water homeostasis in the brain
Authors: Min Rogier , van der Knaap Marjo S.
Published: May 2018

Electrical activity of neurons in the brain, caused by the movement of ions between intracellular and extracellular compartments, is the basis of all our thoughts and actions. Maintaining the correct ionic concentration gradients is therefore crucial for brain functioning. Ion fluxes are accompanied by the displacement of osmotically obliged water. Since even minor brain swelling leads to severe brain damage and even death, brain ion and water movement has to be tightly regulated. Glial cells, in particular astrocytes, play a key role in ion and water homeostasis. They are endowed with specific channels, pumps and carriers to regulate ion and water flow. Glial cells form a large panglial syncytium to aid the uptake and dispersal of ions and water, and make extensive contacts with brain fluid barriers for disposal of excess ions and water. Genetic defects in glial proteins involved in ion and water homeostasis disrupt brain functioning, thereby leading to neurological diseases. Since white matter edema is often a hallmark disease feature, many of these diseases are characterized as leukodystrophies. In this review we summarize our current understanding of inherited glial diseases characterized by disturbed brain ion and water homeostasis by integrating findings from MRI, genetics, neuropathology and animal models for disease. We discuss how mutations in different glial proteins lead to disease, and highlight the similarities and differences between these diseases. To come to effective therapies for this group of diseases, a better mechanistic understanding of how glial cells shape ion and water movement in the brain is crucial.
Vanishing white matter: a leukodystrophy due to astrocytic dysfunction
Authors: Bugiani Marianna , Vuong Caroline , Breur Marjolein , van der Knaap Marjo S.
Published: May 2018

VWM is one of the most prevalent leukodystrophies with unique clinical, pathological and molecular features. It mostly affects children, but may develop at all ages, from birth to senescence. It is dominated by cerebellar ataxia and susceptible to stresses that act as factors provoking disease onset or episodes of rapid neurological deterioration possibly leading to death. VWM is caused by mutations in any of the genes encoding the five subunits of the eukaryotic translation initiation factor 2B (eIF2B). Although eIF2B is ubiquitously expressed, VWM primarily manifests as a leukodystrophy with increasing white matter rarefaction and cystic degeneration, meager astrogliosis with no glial scarring and dysmorphic immature astrocytes and increased numbers of oligodendrocyte progenitor cells that are restrained from maturing into myelin‐forming cells. Recent findings point to a central role for astrocytes in driving the brain pathology, with secondary effects on both oligodendroglia and axons. In this, VWM belongs to the growing group of astrocytopathies, in which loss of essential astrocytic functions and gain of detrimental functions drive degeneration of the white matter. Additional disease mechanisms include activation of the unfolded protein response with constitutive predisposition to cellular stress, failure of astrocyte‐microglia crosstalk and possibly secondary effects on the oxidative phosphorylation. VWM involves a translation initiation factor. The group of leukodystrophies due to defects in mRNA translation is also growing, suggesting that this may be a common disease mechanism. The combination of all these features makes VWM an intriguing natural model to understand the biology and pathology of the white matter.
N‐back Working Memory Task: Meta‐analysis of Normative fMRI Studies With Children
Authors: Yaple Zachary , Arsalidou Marie
Published: May 2018

The n‐back task is likely the most popular measure of working memory for functional magnetic resonance imaging (fMRI) studies. Despite accumulating neuroimaging studies with the n‐back task and children, its neural representation is still unclear. fMRI studies that used the n‐back were compiled, and data from children up to 15 years (n = 260) were analyzed using activation likelihood estimation. Results show concordance in frontoparietal regions recognized for their role in working memory as well as regions not typically highlighted as part of the working memory network, such as the insula. Findings are discussed in terms of developmental methodology and potential contribution to developmental theories of cognition.
Examining Ecological Constraints on the Intergenerational Transmission of Attachment Via Individual Participant Data Meta‐analysis
Authors: Verhage Marije L. , Fearon R.M. Pasco , Schuengel Carlo , van IJzendoorn Marinus H. , Bakermans‐Kranenburg Marian J. , Madigan Sheri , Roisman Glenn I. , Oosterman Mirjam , Behrens Kazuko Y. , Wong Maria S. , Mangelsdorf Sarah , Priddis Lynn E. , Brisch Karl‐Heinz ,   The Collaboration on Attachment Transmission Synthesis
Published: May 2018

Parents’ attachment representations and child–parent attachment have been shown to be associated, but these associations vary across populations (Verhage et al., 2016). The current study examined whether ecological factors may explain variability in the strength of intergenerational transmission of attachment, using individual participant data (IPD) meta‐analysis. Analyses on 4,396 parent–child dyads (58 studies, child age 11–96 months) revealed a combined effect size of r = .29. IPD meta‐analyses revealed that effect sizes for the transmission of autonomous‐secure representations to secure attachments were weaker under risk conditions and weaker in adolescent parent–child dyads, whereas transmission was stronger for older children. Findings support the ecological constraints hypothesis on attachment transmission. Implications for attachment theory and the use of IPD meta‐analysis are discussed.
Assessment and management of bone health in women with oestrogen receptor‐positive breast cancer receiving endocrine therapy: Position statement of the Endocrine Society of Australia, the Australian and New Zealand Bone & Mineral Society, the Australasian Menopause Society and the Clinical Oncology Society of Australia
Authors: Grossmann Mathis , Ramchand Sabashini K. , Milat Frances , Vincent Amanda , Lim Elgene , Kotowicz Mark A. , Hicks Jill , Teede Helena
Published: May 2018

To formulate clinical consensus recommendations on bone health assessment and management of women with oestrogen receptor‐positive early breast cancer receiving endocrine therapy, representatives appointed by relevant Australian Medical Societies used a systematic approach for adaptation of guidelines (ADAPTE) to derive an evidence‐informed position statement addressing 5 key questions. Women receiving adjuvant aromatase inhibitors and the subset of premenopausal woman treated with tamoxifen have accelerated bone loss and increased fracture risk. Both bisphosphonates and denosumab prevent bone loss; additionally, denosumab has proven antifracture benefit. Women considering endocrine therapy need fracture risk assessment, including clinical risk factors, biochemistry and bone mineral density (BMD) measurement, with monitoring based on risk factors. Weight‐bearing exercise, vitamin D and calcium sufficiency are recommended routinely. Antiresorptive treatment should be considered in women with prevalent or incident clinical or morphometric fractures, a T‐score (or Z‐scores in women <50 years) of <−2.0 at any site, or if annual bone loss is ≥5%, considering baseline BMD and other fracture risk factors. Duration of antiresorptive treatment can be individualized based on absolute fracture risk. Relative to their skeletal benefits, risks of adverse events with antiresorptive treatments are low. Skeletal health should be considered in the decision‐making process regarding choice and duration of endocrine therapy. Before and during endocrine therapy, skeletal health should be assessed regularly, optimized by nonpharmacological intervention and where indicated antiresorptive treatment, in an individualized, multidisciplinary approach. Clinical trials are needed to better delineate long‐term fracture risks of adjuvant endocrine therapy and to determine the efficacy of interventions designed to minimize these risks.
Body mass index and obesity in children with cerebral palsy
Authors: Stevenson Richard D
Published: May 2018

This commentary is on the original article by Duran et al. on pages 680–686 of this issue.
Why did the industrial diet triumph? The massification of dairy consumption in Spain, 1965–90
Authors: Collantes Fernando
Published: May 2018

The rise of a mass, agri‐industrial diet after the Second World War was crucial for the culmination of the nutritional transition that western countries had been involved in since the second half of the nineteenth century—but why did the industrial diet triumph? This article takes the massification of dairy consumption in Spain 1965–90 as a study case. Using a newly constructed database and qualitative material within an evolutionary socio‐economic framework, the article reaches two conclusions. First, the massification of dairy consumption was linked to most households’ transition to a softer budget constraint, which was driven mainly by increasing household incomes (and only secondarily by consumer price reductions caused by food industrialization). Second, the reason why the softening of the budget constraint played such a major role was that it was joined by a substantial increase in consumer trust in dairy products, which in turn resulted from industrial standardization. The article is in line with recent work that underlines the dietary change brought about by food industrialization, but questions whether the latter's major contribution was of a quantitative, price‐related nature and suggests that more attention should be paid to the qualitative, preferences‐related dimension.
Help‐seeking beliefs for mental disorders among medical and nursing students
Authors: Picco Louisa , Seow Esmond , Chua Boon Yiang , Mahendran Rathi , Verma Swapna , Xie Huiting , Wang Jia , Chong Siow Ann , Subramaniam Mythily
Published: May 2018

Aim

The current study aimed to investigate beliefs about help‐seeking, treatment options and expected outcomes for people with alcohol abuse, dementia, depression, obsessive‐compulsive disorder and schizophrenia, using a vignette‐based approach, among a sample of nursing and medical students.

Methods

This was a cross‐sectional online study among medical and nursing students (n = 1002) who were randomly assigned 1 of 5 vignettes. Questions were asked about whom could best help the person in the vignette, the likely helpfulness of a broad range of interventions, and the likely outcome for the person in the vignette with and without appropriate help.

Results

A total of 45.1% of students recommended seeing a psychiatrist, which was the most common source of help reported for all 5 vignettes. Help‐seeking preferences were significantly associated with age, academic year and vignette type. Respondents rated seeing a psychiatrist as the most helpful intervention (92.4%) and dealing with the problem on their own as the most harmful (68.1%). Then, 81.5% of students indicated that the condition of the person in the vignette would worsen if appropriate help was not sought.

Conclusion

Medical and nursing students most commonly recommended seeking help from a psychiatrist for mental health‐related problems, where help‐seeking preferences were associated with various age, academic year and vignette type. As these students will be the future medical and nursing workforce, they need to be equipped with the skills and ability to recognize signs and symptoms of mental illness, to aid timely and appropriate treatment for people with mental illness.
Structural causality in Spinoza's Ethics
Authors: Hulatt Owen
Published: May 2018

In this paper, I argue that Spinoza's claim at E1P15 that “Whatever is, is in God, and nothing can be or be conceived without God” remains exegetically troubling. Briefly noting some unresolved difficulties with the two dominant interpretations of Spinoza's account of the relationship between finite modes and God (these being the inherence and causal dependence readings), I move to claim that there is a third, neglected reading available which deserves consideration. I argue that, perhaps surprisingly, Althusser's notion of “structural causality,” putatively derived from Spinoza himself, can be used to construct this reading. Althusser's original notion of “structural causality” is explained and clarified further, its advantages outlined over competing readings of Spinoza, and exegetical evidence for its applicability to Spinoza is then produced.
Teaching & Learning Tips 8: Preparing to teach in ambulatory settings
Authors: Aluko Ashley , Rana Jasmine , Burgin Susan
Published: May 2018

Challenge: Clinical teaching in dermatology largely occurs in the outpatient setting. Herein, we review common barriers to teaching in the ambulatory setting and discuss strategies preceptors can take to “teach on the run” during clinic sessions.
Direct oral anticoagulants: When to consider laboratory testing?
Authors: ten Cate H. , Olie R. H. , ten Cate‐Hoek A. J. , Henskens Y. M. C.
Published: May 2018

Introduction

Direct oral anticoagulants (DOACs) are increasingly prescribed for prevention of thromboembolic stroke, as well as for prevention and treatment of venous thromboembolism. Dose adjustment based on laboratory testing is not required; however, there are several potential situations that deserve insight into a DOAC plasma activity level.

Methods

Based on a series of real‐life case descriptions, we discuss indications for dedicated DOAC testing, as well as the interpretation and consequences.

Results

Testing of DOACs in selected patients may help to better interpret acute situations such as bleeding or thrombosis while on anticoagulation, but also suspected drug failure, drug accumulation, or lack of adherence.

Conclusion

The 24/7 availability of target‐specific tests with adequate calibration is recommended to support the clinician in the interpretation and where needed adjustment of the management of patients on DOACs. The relevance of laboratory‐guided DOAC management, particularly in the elderly, merits further study.
Primary red cell hydration disorders: Pathogenesis and diagnosis
Authors: Caulier A. , Rapetti‐Mauss R. , Guizouarn H. , Picard V. , Garçon L. , Badens C.
Published: May 2018

Hydration status is critical for erythrocyte survival and is mainly determined by intracellular cation content. Active pumps, passive transporters, and ion channels are the key components of volume homeostasis, whereas water passively fits ionic movements. Whenever cation content increases, erythrocyte swells, whereas it shrinks when cation content decreases. Thus, inappropriate cation leak causes erythrocyte hydration disorders, hemolytic anemia, and characteristic red cell shape abnormalities named stomatocytosis. All types of stomatocytosis either overhydrated or dehydrated are linked to inherited or de novo mutations in genes encoding ion transporters or channels. Although intracellular ion content can be assessed by experimental methods, laboratory diagnosis is guided by a combination of red blood cell parameters and deformability measurement when possible, and confirmed by sequencing of the putative genes. A better knowledge of the mechanisms underlying erythrocyte hydration imbalance will further lead to therapeutic improvements.
Prenatal and preimplantation diagnosis of hemoglobinopathies
Authors: Vrettou C. , Kakourou G. , Mamas T. , Traeger‐Synodinos J.
Published: May 2018

The hemoglobinopathies, as a group, are one of the most common serious monogenic diseases in the world. An accepted and widely adopted approach to reduce the number of new cases involves carrier‐screening programs, with the option of prenatal diagnosis (PND) or preimplantation diagnosis (preimplantation genetic testing for monogenic disease, PGT‐M) for carrier couples. The aim of PND is to provide an accurate result as early in pregnancy as possible, which necessitates prior identification of the parental disease‐causing mutations, as well as safe and timely biopsy of fetal material. PGT‐M aims to characterize the genetic status of in vitro fertilized embryos during assisted reproductive technology (ART), in a few cells biopsied from oocytes/zygotes or embryos, in order to initiate an unaffected pregnancy. Another application of PGT‐M is preimplantation genetic diagnosis for human leukocyte antigen (PGD‐HLA), which, in addition to identifying unaffected embryos, also characterizes the embryos that are HLA compatible with an existing affected child requiring a hemopoietic stem cell transplantation (HSCT). This review outlines the current practices related to these procedures, with emphasis on the aspects related to laboratory techniques. Finally, future prospects related to developments in noninvasive prenatal diagnosis are discussed.
Pathogenesis and diagnosis of disseminated intravascular coagulation
Authors: Levi M.
Published: May 2018

Several clinical conditions, in particular those associated with a systemic inflammatory response, can cause some degree of activation of coagulation but when the procoagulant stimulus is sufficiently severe and overcomes the natural anticoagulant mechanisms of coagulation, disseminated intravascular coagulation (DIC) may occur. The clinical manifestations of DIC encompass multiorgan dysfunction caused by fibrin‐platelet clots in the microcirculation, and bleeding caused by consumption of platelets and coagulation factors. Molecular mechanisms that play a role in inflammation‐induced effects on coagulation have been recognized in much detail. Exposure of blood to tissue factor is the most common trigger, whereas the intravascular coagulation is propagated due to loss of function of physiological anticoagulants and impaired fibrinolysis. In patients with DIC, various abnormalities in routine coagulation parameters may be observed, including thrombocytopenia, prolonged global coagulation assays, or high levels of fibrin split products. In addition, more sophisticated tests for activation of individual factors or pathways of coagulation may point to specific involvement of these components in the pathogenesis of the disorder. A combination of readily available tests is usually sufficient in establishing the diagnosis of DIC, and for this purpose, several scoring algorithms have been developed. Some specific clinical situations may elicit coagulation responses that can be distinguished from DIC or may occur in combination with DIC, including dilutional coagulopathy, liver failure‐related coagulation derangement, and thrombotic microangiopathies.
Acute myeloid leukaemia: How to combine multiple tools
Authors: Merino A. , Boldú L. , Ermens A.
Published: May 2018

The pathogenesis of acute myeloid leukaemias (AML) frequently requires at least 3 mutations in different cellular pathways. In many cases, mutations in proliferation/survival mechanisms and differentiation pathways are involved. Genetic aberrations explain the pathogenesis of AML, provide prognostic criteria and guide drug design for future therapy. Since the last update of the World Health Organization (WHO) classification of tumours of the hematopoietic and lymphoid tissues in 2008, there have been many discovers regarding the genomic landscape of AML and molecular assays for the detection of minimal residual disease. The identification of unique biomarkers associated with AML, derived from gene expression analysis and next‐generation sequencing, may improve significantly the diagnostic criteria. In the new WHO classification published in 2017, several new AML entities are added. Moreover, the prognostic and diagnostic relevance of recently identified molecular features is reviewed and integrated into existing sets of criteria. This article reviews the most common tests and procedures for AML diagnosis, including morphology, immunophenotyping, cytogenetics and molecular genetic testing. The major changes in the new WHO classification for AML are also remarked.
Optimizing morphology through blood cell image analysis
Authors: Merino A. , Puigví L. , Boldú L. , Alférez S. , Rodellar J.
Published: May 2018

Introduction

Morphological review of the peripheral blood smear is still a crucial diagnostic aid as it provides relevant information related to the diagnosis and is important for selection of additional techniques. Nevertheless, the distinctive cytological characteristics of the blood cells are subjective and influenced by the reviewer's interpretation and, because of that, translating subjective morphological examination into objective parameters is a challenge.

Methods

The use of digital microscopy systems has been extended in the clinical laboratories. As automatic analyzers have some limitations for abnormal or neoplastic cell detection, it is interesting to identify quantitative features through digital image analysis for morphological characteristics of different cells.

Result

Three main classes of features are used as follows: geometric, color, and texture. Geometric parameters (nucleus/cytoplasmic ratio, cellular area, nucleus perimeter, cytoplasmic profile,RBCproximity, and others) are familiar to pathologists, as they are related to the visual cell patterns. Different color spaces can be used to investigate the rich amount of information that color may offer to describe abnormal lymphoid or blast cells. Texture is related to spatial patterns of color or intensities, which can be visually detected and quantitatively represented using statistical tools.

Conclusion

This study reviews current and new quantitative features, which can contribute to optimize morphology through blood cell digital image processing techniques.
High prevalence of diabetes before and after lung transplantation: target for improving outcome?
Authors: Fazekas‐Lavu Monika , Reyes Michael , Malouf Monique , Plit Marshall , Havryk Adrian , Campbell Lesley V. , Center Jacqueline R. , Glanville Allan R. , Greenfield Jerry R.
Published: May 2018

Background

Diabetes increases morbidity and mortality of lung transplantation. However, the reported prevalence of diabetes varies post‐transplantation partly due to lack of detection protocols.

Aim

To determine the prevalence of diabetes in patients (i) waitlisted for lung transplant and (ii) early post‐transplantation.

Methods

We analysed patients on the St Vincent's Heart Lung database from 1 April 2014 to 30 September 2015 on the waitlist (Study 1) and those transplanted (Study 2). Standard of care required all non‐diabetic patients to have an oral glucose tolerance test (modified for patients with cystic fibrosis (CF) to screen for CF‐related hyperglycaemia (CFRH) (plasma glucose ≥8.2 mmol/L at 60 or 90 min).

Results

Study 1 included 114 patients (32 with CF and 82 without CF). Of 30 CF patients with glycaemic data, 27 (90%) had abnormal glucose metabolism: 18 had diabetes and nine had CFRH. In 50 patients without CF, 20 (40%) had abnormal glucose metabolism: eight had diabetes and 12 had impaired fasting glucose and/or impaired glucose tolerance. Study 2 included 78 transplanted patients (25 with CF and 53 without CF). Fourteen CF patients had pre‐existing diabetes and seven had pre‐existing CFRH. All but one patient were diagnosed with diabetes post‐transplantation. Hence, diabetes prevalence in CF patients post‐transplantation was 96%. Among 53 transplanted patients without CF, seven (13%) had abnormal glucose metabolism but 30 (57%) were diagnosed with post‐transplant diabetes.

Conclusion

There is a high prevalence of diabetes in lung transplant patients. Earlier endocrine participation in lung transplant services is likely to lower diabetes‐related morbidity and mortality further.
What are the effects of cash transfers for refugees in the context of protracted displacement? Findings from Jordan
Authors: Hagen‐Zanker Jessica , Ulrichs Martina , Holmes Rebecca
Published: May 2018

The current refugee crisis requires new thinking and durable policies which move beyond simply meeting the short‐term immediate needs of refugees. In the context of this protracted crisis, the humanitarian response has included a focus on cash transfer programming as a way to support Syrian refugees in Jordan to meet their basic needs. While evidence on cash transfers in stable contexts has been well‐documented over the last two decades, little is known about the potential effects of cash transfers on populations in protracted displacement. This article examines the economic and social effects of a UNHCR cash transfer programme for Syrian refugees in urban areas in Jordan. We find that almost all beneficiaries used the transfer to pay rent, and that this reduces stress and anxiety among beneficiaries. These effects are important, but depend on the continuation of cash transfer support. For longer‐term impacts, assistance for refugees needs to move beyond short‐term support and align better with national interventions and a broader enabling policy environment, including refugees' right to work.
The targeting effectiveness of Egypt’s Food Subsidy Programme: Reaching the poor?
Authors: Talaat Walaa
Published: May 2018

In Egypt, the Food Subsidy Programme (FSP) contributes greatly to social stability, yet there is academic and political pressure to reform the system to prioritize the effective targeting of the poor. This has been particularly so since the 2011 Egyptian revolution, and in the light of claims by the government and international organizations that the programme is relatively expensive and ineffective in targeting the poor. Accordingly, the ability to measure the programme’s targeting performance is crucial, not least to assess the targeting outcome of this anti‐poverty intervention. Most previous studies of the Egyptian FSP address the challenges of exclusion and inclusion errors exclusively from an econometric approach. However, in this study a mixed approach method is developed to better explain the programme and to explore how its governance structure might play an important role in determining its effectiveness. This method generates both a statistically reliable measure of the magnitude of the targeting performance as well as a greater depth of understanding of the programme’s effectiveness in achieving targeting outcomes. Additionally, understanding the actual targeting mechanism should help policy‐makers improve its effectiveness, and ultimately support a comprehensive reform to build an effective social protection system.
Genetically determined pattern of left ventricular function in normal and hypertensive hearts
Authors: Kovács Attila , Molnár Andrea Ágnes , Kolossváry Márton , Szilveszter Bálint , Panajotu Alexisz , Lakatos Bálint Károly , Littvay Levente , Tárnoki Ádám Domonkos , Tárnoki Dávid László , Voros Szilard , Jermendy György , Sengupta Partho P. , Merkely Béla , Maurovich‐Horvat Pál
Published: May 2018

We sought to assess the inheritance of left ventricular (LV) function using speckle‐tracking echocardiography and the impact of hypertension on modifying the genetically determined pattern of contraction in a population of twins. We recruited 92 Caucasian twin pairs, including 74 hypertensive (HTN) siblings. Beyond standard echocardiographic protocol, a speckle‐tracking analysis was performed, including global longitudinal strain (GLS). Systolic function, as assessed by ejection fraction, showed moderate heritability (61%); however, GLS showed higher and dominant heritability (75%). Heterogeneity models revealed that there were no differences between the HTN and non‐HTN subjects regarding the heritability of GLS. However, the heritability estimates of diastolic function parameters, including early diastolic strain rate, were low. LV systolic biomechanics is highly heritable. GLS shows dominant heritability, despite the presence of early‐stage hypertensive heart disease. Early diastolic parameters are rather determined by environmental factors. These findings suggest the presence of a genetic framework that conserves systolic function despite the expression of diastolic dysfunction and may underlie the phenotypic progression towards heart failure with preserved ejection fraction.
Phylogenetic comparative analysis supports aposematic colouration–body size association in millipede assassins (Hemiptera: Reduviidae: Ectrichodiinae)
Authors: Forthman Michael , Weirauch Christiane
Published: May 2018

The diversity of colour patterns and its importance in interactions with the environment make colouration in animals an intriguing research focus. Aposematic colouration is positively correlated with body size in certain groups of animals, suggesting that warning colours are more effective or that crypsis is harder to achieve in larger animals. Surprisingly, this relationship has not been recovered in studies investigating insects, which may have been confounded by a focus on aposematic taxa that are also gregarious. Millipede assassin bugs (Hemiptera: Reduviidae: Ectrichodiinae) comprise species with cryptic and aposematic colour patterns across a range of body sizes, are typically solitary as adults and are thus an excellent model for investigating a possible association between colouration and body size. Here, we use a comprehensive phylogeny for Ectrichodiinae, ancestral state reconstruction of colouration, and phylogenetic comparative methods to test for a colouration–body size association. The ancestor of Ectrichodiinae is reconstructed as cryptically coloured, with multiple subsequent transitions between aposematic and cryptic colouration. Aposematic colouration is positively associated with male body length and supports the hypothesis that selection on Ectrichodiinae body size may influence evolutionary transitions between aposematic and cryptic colouration or alternatively that selection for aposematic colouration influences body size evolution.
Back to the future: Viewing a 1992 flood risk study through a 2017 lens
Authors: Kok M. , van de Riet O. , Walker W.E.
Published: May 2018

Here we examine whether a study conducted 25 years ago (1992) would have had different conclusions if concepts and analytical methods developed since then had been used. The 1992 problem was to identify a strategy for reducing flood risk in the Netherlands by, for example, strengthening the river dikes against the risk of flooding. Since then, conditions related to flooding have been recognised as increasingly uncertain. In response, a new paradigm for strategic planning has emerged: the “adaptive planning approach,” which aims to identify and assess strategies allowing for change, learning, and adaptation over time. We found that using the adaptive planning approach in 1992 would not have changed the main conclusions. But, it would have made explicit the need for the identification of vulnerabilities of the chosen strategy, a monitoring system to keep track of the uncertainties, and the possible actions to deal with the vulnerabilities that can be taken as the world evolves.
Probiotics to Prevent Respiratory Infections in Nursing Homes: A Pilot Randomized Controlled Trial
Authors: Wang Biao , Hylwka Tammy , Smieja Marek , Surrette Michael , Bowdish Dawn M.E. , Loeb Mark
Published: May 2018

Objectives

To assess the feasibility of conducting a large clinical trial to evaluate the effectiveness of probiotics to reduce influenza and other respiratory virus infections in residents of long‐term and chronic care facilities (LTCFs).

Design

Randomized, double‐blind, placebo‐controlled pilot trial.

Setting

Fourteen nursing homes in Hamilton and surrounding region, Ontario, Canada.

Participants

Nursing home residents aged 65 and older (N=209). Those who were taking immunosuppressives (steroids or other immunosuppressives) or had a hematological malignancy, structural heart disease, or gastroesophageal or intestinal injury and others at high risk of an endovascular infection were excluded.

Intervention

Participants were randomized to receive study probiotics—2 capsules of Lactobacillus rhamnosus GG (estimated 10 billion colony forming units of L. rhamnosus GG per capsule) or placebo (calcium carbonate) daily for 6 months.

Measurements

Laboratory‐confirmed respiratory viral infections.

Results

One hundred ninety‐six individuals were included in the analysis: 100 in the probiotics group and 96 in the placebo group. Laboratory‐confirmed respiratory viral infections were observed in 14 (15.0%) residents in the probiotic group and 21 (22.9%) in the placebo group (hazard ratio=0.65, 95% confidence interval=0.32–1.31).

Conclusion

A larger trial is warranted to determine whether probiotics reduce influenza and other respiratory virus infections in residents of LTCFs.