bluuebunny/crossref_metadata_2025 huggingface dataset:
Mad identity I: Controversial and failed identities
Authors: Rashed Mohammed Abouelleil
Published: February 2019

This chapter, “Mad identity I: Controversial and failed identities,” examines the viability of Mad identity as a route to recognition. It develops a distinction between “controversial” and “failed” identities; the former are cases where subjects are wrong about who they think they are but where this can potentially call for revision of the collective category with which they identify, and the latter are cases where subjects are wrong about who they think they are but where this cannot call for such revision. Only identity claims that are judged to be “controversial” can be considered within the scope of recognition. Using four examples of “delusional” identities, the chapter develops an epistemological framework for distinguishing failed from controversial identities, a framework where the notion of “truth value” plays a key role.
Madness and the limits of recognition
Authors: Rashed Mohammed Abouelleil
Published: February 2019

This chapter, “Madness and the limits of recognition,” explores ways of bringing madness within the scope of recognition. This can be achieved by resolving the impairments to identity formation that remove madness from this scope. Resolution is to be understood in dialectical terms as a process governed by two requirements: (1) Preserve something of the phenomenology of madness; (2) resolve the impairments to identity formation. The chapter explores a range of narratives that appear relevant to this task, in each case assessing whether it can satisfy these two requirements: subjective narratives, professional narratives, and Mad narratives. The latter include the following: spiritual transformation, healing voices, and dangerous gifts. The chapter demonstrates how Mad narratives can play a role in resolving disunity of self and discontinuity of self, and hence at bringing madness within the scope of recognition.
Electronic healthcare records and prognosis research
Authors: Jordan Kelvin P , Moons Karel GM
Published: February 2019

Electronic healthcare record (EHR) data, collected during the daily business of patient consultations and treatments, offer huge opportunities to expand the range and scale of prognosis research, in particular because of the real-time and continuous recording of potential prognostic factors and health-related events, and the amount of data and individuals involved. However, with these opportunities come challenges related to the size and complexity of EHR data. This chapter provides an overview of these issues.
Leading up to The Myth of Mental Illness
Authors: Pols Jan
Published: February 2019

The Myth of Mental Illness was the book that launched Szasz’s reputation as a critical psychiatrist. Although he was aware of its controversial nature, the storm it generated in the United States and beyond took him by surprise. Examining the early years of Szasz’s career and contermplating certain contextual factors, in particular the sociopolitical background that shines through his work in many ways, as well as the social circumstances around psychiatry at the time, show to what extent his publications before 1961 predicted his later rebellion against the psychiatric establishment. In these early discussions of such topics as pain, psychosomatic illness, and scientific reductionism, one sees germs of his bent toward libertarian sociological, philosophical, and ideological theories of psychoanalyis, the physician-patient relationship, sociopolitical psychology, and culture in general.
Myths, projections, and overextensions: The conceptual landscape of Thomas Szasz
Authors: Church Jennifer
Published: February 2019

This chapter distinguishes among myths, projections, and overextensions as they occur within the practice of psychiatry—adding to the conceptual complexity of Szasz’s own analyses and reflecting on how his focal concept of autonomy may itself fall prey to myth, projection, or overextension. Szasz offers detailed explications of his use of the term “myth,” yet many questions remain regarding his application of that term and its relevance to psychiatry. How is a metaphor “literalized,” and when is this problematic? What terms, in addition to the term “mental illness,” serve to support the myths of psychiatry? How do myths relate to the projections and overextensions that can also be found in the language and practice of psychiatry? With these distinctions in mind, it is appropriate to ask whether Szasz’s own reliance on the notion of autonomous agency might itself qualify as a myth, a projection, or an overextension.
Thomas Szasz and the insanity defense
Authors: Pickering Neil
Published: February 2019

Szasz stoutly opposed the use of the insanity defense. This chapter considers the persuasiveness of Szasz’s arguments against it, which fall into three broad categories: (1) arguments that the insanity defense is immoral; (2) arguments that it relies on a nonexistent entity, namely mental illness; and (3) arguments that the sciences of psychiatry offer no grounds for supporting it. Each category of argument is explored in its various forms. The most persuasive type of argument is found to be the third. Unlike the other two, it does not require us to buy into strong and broad beliefs which are indeed characteristically Szaszian (such as that mental illness is a myth), but which lack widespread acceptance. In contrast, Szasz’s argument that the sciences associated with psychiatry (such as psychology) do not offer grounds for the existence of the insanity defense appeals to a commonly held and highly plausible multifactorial account of the causes of human behavior. In short, analysed carefully, Szasz’s writing provides more persuasive grounds for taking exception to the insanity defense than his own best-known views offer.
Non-Immune Hydrops
Authors: Clark Robin D. , Curry Cynthia J.
Published: February 2019

This chapter reviews the incidence, risk factors, genetics, recurrence risk, and epidemiology of isolated and syndromic non-immune hydrops fetalis (NIH). The discussion on the differential diagnosis of various types of NIH summarizes common causes, including chromosome anomalies (Down syndrome, Turner syndrome and others), congenital infections ( CMV, Parvovirus and Syphilis) , and multiple congenital anomaly syndromes (Noonan spectrum disorders, Neu Laxova syndrome, Hennekam syndrome and others), skeletal dysplasias and a number of lysosomal storage diseases. A through evaluation both before and after birth including maternal history, infectious work-up, microarray, autopsy and selected molecular testing including exome sequencing can achieve a diagnosis in an increasing number of cases. The mortality and morbidity of NIH remains high and relatively few are amenable to specific interventions. A clinical case presentation features an infant with congenital parvovirus B19 infection.
Cleft Lip
Authors: Clark Robin D. , Curry Cynthia J.
Published: February 2019

This chapter reviews background information about the incidence, risk factors, family history, genetics, recurrence risk, and epidemiology of isolated and syndromic cleft lip with or without cleft palate. Microforms of cleft lip are described. The distinctive anatomy of bilateral cleft lip is contrasted with premaxillary agenesis, a wider defect caused by absence of the frontonasal process. The discussion on the differential diagnosis of cleft lip summarizes its common causes, including teratogenic agents (alcohol, maternal diabetes, phenytoin), chromosome anomalies (aneuploidy, recurrent deletion syndromes), and Mendelian clefting disorders that include associated malformations in other organ systems. The chapter gives recommendations for evaluation and management. A clinical case presentation features an infant with an oral cleft who has a positive family history of cleft lip and palate with paramedian lip pits due to Van der Woude syndrome.
Detecting galaxy–filament alignments in the Sloan Digital Sky Survey III
Authors: Chen Yen-Chi , Ho Shirley , Blazek Jonathan , He Siyu , Mandelbaum Rachel , Melchior Peter , Singh Sukhdeep
Published: February 2019

Previous studies have shown the filamentary structures in the cosmic web influence the alignments of nearby galaxies. We study this effect in the LOWZ sample of the Sloan Digital Sky Survey using the ‘Cosmic Web Reconstruction' filament catalogue. We find that LOWZ galaxies exhibit a small but statistically significant alignment in the direction parallel to the orientation of nearby filaments. This effect is detectable even in the absence of nearby galaxy clusters, which suggests it is an effect from the matter distribution in the filament. A non-parametric regression model suggests that the alignment effect with filaments extends over separations of 30–40 Mpc. We find that galaxies that are bright and early-forming align more strongly with the directions of nearby filaments than those that are faint and late-forming; however, trends with stellar mass are less statistically significant, within the narrow range of stellar mass of this sample.
On the iron ionization balance of cool stars
Authors: Tsantaki M , Santos N C , Sousa S G , Delgado-Mena E , Adibekyan V , Andreasen D T
Published: February 2019

High-resolution spectroscopic studies of solar-type stars have revealed higher iron abundances derived from singly ionized species compared to neutral, violating the ionization equilibrium under the assumption of local thermodynamic equilibrium. In this work, we investigate the overabundances of Fe ii lines reported in our previous work for a sample of 451 solar-type HARPS stars in the solar neighborhood. The spectroscopic surface gravities of this sample, which emerge from the ionization balance, appear underestimated for the K-type stars. In order to understand this behaviour, we search our Fe ii line list for unresolved blends and outliers. First, we use the Vienna Atomic Line Database to identify possible unresolved blends around our lines and calculate which ones are strong enough to cause overestimations in the equivalent width measurements. Second, for our sample we use reference parameters (effective temperature and metallicity) and the Gaia DR2 parallaxes to derive surface gravities (trigonometric gravities) and calculate the Fe i and Fe ii abundances from different line lists. We exclude the Fe ii lines which produce overabundances above 0.10 dex. The derived surface gravities from the clean line list are now in agreement with the trigonometric. Moreover, the difference between Fe i and Fe ii abundance does not show now a correlation with the effective temperature. Finally, we show that the ionization balance of Ti can provide better estimates of surface gravities than iron. With this analysis, we provide a solution to the ionization balance problem observed in the atmospheres of cool dwarfs.
Concurrent Alcohol Use and Waterpipe Tobacco Smoking: Smoking Topography, Toxicant Exposure, and Abuse Liability
Authors: Leavens Eleanor L S , Morgan Taylor L , Brett Emma I , Patzkowsky Kelsey , Son Jessica , Molina Neil , Eissenberg Thomas , Shihadeh Alan , Leffingwell Thad R , Wagener Theodore L
Published: February 2019

Introduction

Relative to non-waterpipe (WP) smokers, WP smokers are more than twice as likely to use alcohol and frequently consume alcohol before or during smoking sessions. Co-use of alcohol and WP may result in greater toxicant exposure compared to WP smoking alone. To date, no study systematically has investigated the impact of acute alcohol intoxication on WP smoking topography, exposure to tobacco-related toxicants, or abuse liability.

Methods

Dyads of current WP smokers and drinkers (N = 42; age = 21–32 years) completed two in-laboratory ad libitum smoking sessions (≤2 hours) following 12-hour nicotine abstinence in a double-blind, randomized crossover design in which they consumed a placebo versus active drink (sustained breath alcohol concentration = .08). Exhaled carbon monoxide (eCO) and plasma nicotine concentration were assessed. Questionnaires assessed smoking experience and smoking urge. Smoking topography was measured continuously throughout each smoking session.

Results

The alcohol session was associated with increased inhaled volume, flow rate, and WP session duration compared to placebo. Compared to placebo, participants reported a more positive overall smoking experience following the alcohol session and greater smoking urges pre- and post-smoking session. Although both sessions resulted in significant increases in eCO and plasma nicotine, no significant differences emerged in eCO or nicotine exposure between the active and placebo sessions.

Conclusions

Co-use of alcohol and WP may contribute to the maintenance of WP smoking through enhanced smoking experiences, increased urge to smoke, and significant exposure to addictive nicotine. Regulations may be necessary to limit the sale of alcohol in WP smoking lounges and reduce exposure to secondhand smoke.

Implications

The findings suggest co-use of alcohol and WP tobacco likely maintain WP use and dependence by enhancing the smoking experience and increasing urges to smoke. These findings have implications for regulations aimed at limiting co-use of alcohol and WP tobacco in WP lounges and limiting exposure to secondhand smoke.

Clinical trials registration

NCT03096860
Justice and Home Affairs in the European Union
Authors: Trauner Florian , Servent Ariadna Ripoll
Published: February 2019

Justice and home affairs (JHA) has grown into a relevant and complex field of research. It encompasses European Union (EU) policies of high political salience including asylum, migration, border control, counterterrorism, and police cooperation, as well as criminal and civil law. The processes of European integration and “communitarization” have drawn the attention of the academic community. In the 1990s, the EU’s cooperation on JHA expanded when it embarked on the objective of creating an Area of Freedom, Security, and Justice (AFSJ). It implied that the member states lifted competences that touch upon core features of the state—notably, the capacity to control the territory and to exert the use of legitimate force—to the EU level. From the outset, this was too intrusive for some member states such as the United Kingdom, which gained far-reaching “opt-out” rights. As a matter of fact, JHA encompasses a range of highly sensitive policies and has become increasingly politicized since the 2000s. Questions of security, civil liberties, and belonging are now at the forefront of the political and media agenda. There is an intense struggle over how to define identities in an increasingly diverse European society and how to distinguish “oneself” from an external “other.” Having a clear stance on these questions can determine whether governments win or lose elections. The EU’s cooperation and role in JHA are therefore interlinked with the debate over the meaning of nationhood in the interconnected world of the early 21st century. To what extent can and should European states be free to decide on issues such as immigration? JHA has also become a defining factor in the EU’s relations with the rest of the world. It is a challenge for the EU to define—and implement—immigration regimes for third-country nationals as well as to cooperate with (at times authoritarian) third countries on counterterrorism and other JHA issues. This contribution offers a summary of the main literature in the JHA field. It is important to note that there are specialized debates and discussions in some subfields of JHA (for instance, migration studies). We only touch upon these policy debates and focus on studies looking at EU JHA more generally. Our approach is to offer a description of classic literature with newer JHA research. We start by looking at books discussing the development of JHA in the EU. We then outline the main debates in JHA research (e.g., security versus liberty), followed by an analysis of the main dynamics of EU decision-making. We also reflect upon different debates in the literature on the external dimension of EU JHA policies. The contribution ends with a discussion on data sources and networking opportunities.
Cecco d’Ascoli (Francesco Stabili)
Authors: Hannam James
Published: February 2019

Cecco d’Ascoli (c. 1269–1327) was the diminutive used by the writer and poet Francesco Stabili, from the commune of Ascoli Piceno in central Italy. He was a lecturer on astrology at the University of Bologna, best known for being burnt at the stake as a relapsed heretic. He was first convicted of heresy in Bologna in 1324 by the inquisitor Lambert of Cingoli (fl. 1316–1324), who stripped him of his lectureship and forbade him to practice astrology. Cecco moved to Florence where he became the court astrologer of Duke Charles of Calabria (1298–1328), then ruler of the city. However, he was quickly caught up in the politics of the ducal court. His rivalry with Duke Charles’s chancellor, the Bishop of Aversa, led to the Inquisition’s file on him being reopened. In 1327, following an investigation by the Florentine inquisitor, Accursius, Cecco was found to have relapsed into heresy and was burnt outside the Church of Santa Croce. It is likely that Cecco earned a master of the arts degree at Bologna before being appointed to teach astrology in about 1315. Astrology was then considered an essential adjunct to the practice of medicine and physicians were expected to be competent in casting horoscopes. Material from his lectures is preserved in his Latin commentaries, including one on the Sphere of John Sacrobosco (d. c. 1250). The Commentary on the Sphere was specifically condemned to be burned in 1327 at the same time as Cecco. Cecco also composed a long poem in Italian on the nature of the universe, with a focus on astrology and magic, called l’Acerba. This was also condemned by the Inquisition at the time of his execution. The poem of 4,867 lines is in five books, the last of which was left unfinished at the time of his death. L’Acerba covers the constitution of the heavens (Book 1), virtues and vices (Book 2), the magical properties of minerals and a bestiary (Book 3), questions of natural philosophy (Book 4), and an incomplete theology (Book 5). It is widely interpreted as a criticism of the natural philosophy of Dante Alighieri. It enjoyed some popularity in the early modern period, most likely because of the notoriety of its author. During the 19th century, Cecco’s fate at the hands of the Inquisition led to a revival of his reputation as a potential “martyr of science.” Since then, it has become clear that Cecco’s interests were not “scientific” in the modern sense and most scholarly attention has consequently been focused on l’Acerba.
Product Placement
Authors: Balasubramanian Siva K. , Pillai Deepa , Patwardhan Hemant , Zhao Tianyu
Published: February 2019

Product placements represent the paid inclusion of branded products through audiovisual means within mass media programming. Placements reflect a “hybrid” characteristic that integrates key elements of advertising and publicity messages. Specifically, advertising messages are paid for and identify the brand sponsor; publicity messages are not paid for and do not identify the brand sponsor; hybrid messages are paid for and do not identify the brand sponsor. Given this hybrid characteristic, placements are attractive to brand sponsors: the “paid for” characteristic allows the brand sponsor to exercise control over the message (content, format, how it is presented, etc.); the lack of identification of the brand sponsor enhances the credibility of the perceived message source, thereby encouraging the audience to process the message as editorial content. In other words, the message is processed less defensively than, say, how the audience processes advertising messages. Product placements have registered impressive growth as evident from increased marketing expenditures devoted to placements, the expanding scope of placements (their popularity in TV programs, movies, songs, etc.), and the remarkable degree to which audiences embrace, accept, or tolerate placements worldwide. Historically, the United States has led the world market for product placements. PQ Media reports predict that the value of US product placements will reach an astounding $11.44 billion in 2019 from $7.39 billion in 2011. Several factors have contributed to this development, ranging from the fragmentation of media, decreased effectiveness of ads, and the general lack of regulation of product placements. For example, industry observers note the diminishing effectiveness of the thirty-second television ad. TV viewers often rely on devices such as digital video recorders (DVRs) to avoid or zip through commercials. Product placements have a strategic advantage over traditional ads in that they lie embedded within the editorial content that audiences actively seek. Additionally, exposure to product placements often occur in a setting (e.g., a movie theater) with a captive audience. When taken together, they provide ideal circumstances to influence audiences unobtrusively for commercial benefit using a message format that projects a non-commercial character. As a result, audiences are less likely to be aware of persuasive character of product placements and thereby process them differently than, say, how they respond to ads. It is noteworthy that ads engender instant audience awareness of their persuasive character, but this outcome is less likely for placements. Research indicates that the credibility of the message source decreases when audiences become aware of the sponsored nature of placement messages, compared to situations where they lack such awareness. However, empirical evidence also shows that this negative outcome or damage does not spillover to the sponsoring brand.
Strategic Alliances
Authors: Das T.K.
Published: February 2019

Strategic alliances have proliferated apace in recent decades, reflecting their distinct potential for aiding business and other organizations to compete better in an increasingly complex world. Briefly, strategic alliances are voluntary agreements between two or more organizations to cooperatively pursue their mutual strategic objectives. In business, where these alliances continue to flourish, the partner firms remain independent entities even as they may be actual or potential competitors. The goal is to improve their respective competitive performance and to create value by bringing together the distinctive resources and capabilities of separate firms. At the same time, it must be appreciated that the management of alliances connotes certain special complexities that are not present in managing single organizations, and carries with it certain distinctive risks. The formation, operation, and outcome stages of alliance development, as well as the interpartner dynamics concerning cooperation, resources, trust, risk, control, and so on, are unique in many ways. Strategic alliances also tend to take a variety of forms, so it is necessary to be clear about the nature of these entities. They cover the gamut from buyer-supplier arrangements, joint R&D, manufacturing, and marketing, to joint ventures that could be cross-border, public-private, multipartner, etc., with each type having different issues of governance and interpartner management.
Increased risk of coronary heart disease among patients with idiopathic inflammatory myositis: a nationwide population study in Taiwan
Authors: Weng Meng-Yu , Lai Edward Chia-Cheng , Kao Yang Yea-Huei
Published: February 2019

Objective

To evaluate the risk of incident coronary heart disease (CHD) among patients with DM and PM in a general population context.

Methods

We conducted a retrospective cohort study using the Taiwan National Health Insurance Research Database containing records covering the years from 2000 to 2010. DM and PM were confined for the purposes of this study to those aged ⩾18 years who were eligible for the Taiwan catastrophic illness certificate. The diagnoses, CHD outcomes and cardiovascular risk factors were identified from electronic claims data. We conducted two cohort analyses: CHD and DM, and CHD and PM, excluding for each analysis individuals with CHD already identified at baseline. Data for the comparison group was obtained from the Longitudinal Health Insurance database, comprising 1 million persons randomly sampled from the total beneficiaries during 2000. We estimated hazard ratios comparing myositis with comparison cohorts, adjusting for potential cardiovascular risk factors.

Results

A total of 1145 patients with idiopathic myositis were identified, along with 732 723 control patients aged ⩾18 years. The incidence rates of CHD were 15.1 in DM and 30.1 in PM per 1000 person-years, vs 8.4 and 10.5 per 1000 person-years in the comparison cohort. The adjusted hazard ratios for CHD in patients with idiopathic myositis were 2.21 (95% CI 1.64, 2.99) for DM and 3.73 (95% CI 2.83, 4.90) for PM.

Conclusion

Results of this general population-based cohort study suggest that DM and PM are associated with an increased risk of CHD.
Spica MRI predictors for epiphyseal osteonecrosis after closed reduction treatment of dysplasia of the hip
Authors: Haruno Lee S. , Kan J. Herman , Rivlin Michael J. , Rosenfeld Scott B. , Schallert Erica K. , Zhu Huirong , Shenava Vinitha R.
Published: February 2019

Spica MRI with intravenous gadolinium contrast after closed reduction for developmental dysplasia of the hip (DDH) helps to determine successful reduction and attempts to identify patients at risk for epiphyseal osteonecrosis. The objective of our study was to evaluate spica MRI predictors for epiphyseal osteonecrosis after closed reduction. This was a retrospective study of all patients undergoing closed reduction for DDH followed by gadolinium-enhanced spica MRI between July 2011 and November 2014. Patient demographics and clinical follow-up through 2017, including the development of epiphyseal osteonecrosis and need for reintervention after the initial reduction, were recorded. MRI data included hip abduction angles and quantifying the percentage of femoral head enhancement. Twenty-five hips in 21 patients (16 girls, five boys, mean age: 0.99 years, range: 0.4–3.1 years) were included in our study. The mean follow-up period was 3 ± 1.5 years (range: 0.65–6.1 years). Eight (32%) of 25 hips went on to develop osteonecrosis. Epiphyseal osteonecrosis was more likely with less than 80% enhancement (sensitivity 87.5%, specificity 88.25%, positive predictive value 78%, negative predictive value 94%). The mean contrast enhancement for patients developing osteonecrosis compared with those who did not was 37.5 and 86.5%, respectively; P = 0.001. Immediate postspica MRI with gadolinium is a useful prognostic tool for determining future risk for epiphyseal osteonecrosis in children treated for DDH. Our data complement existing literature and suggest that even in cases with partial epiphyseal enhancement, osteonecrosis may still develop. When the epiphyseal enhancement is less than 80%, it is recommended that spica cast revision is considered.
Plate Fixation of Expansive Open-Door Laminoplasty Decreases the Incidence of Postoperative C5 Palsy
Authors: Kobayashi Yoshiomi , Matsumaru Satoshi , Kuramoto Tetsuya , Nagoshi Narihito , Iwanami Akio , Tsuji Osahiko , Okada Eijiro , Fujita Nobuyuki , Yagi Mitsuru , Tsuji Takashi , Ogawa Jun , Nakamura Masaya , Masumoto Morio , Ishii Ken , Watanabe Kota
Published: February 2019

Study Design:

Retrospective study.

Objective:

To compare outcomes for plate fixation versus suture suspension in expansive open-door laminoplasty (ELAP) for cervical spondylotic myelopathy (CSM).

Summary of Background Data:

C5 palsy and laminar closure have been reported to occur after ELAP when suture suspension is used to anchor the opened lamina.

Materials and Methods:

We assessed 174 patients with CSM who were treated by ELAP using either suture suspension (114 patients, mean age 63.3 y, 83 men and 31 women, mean follow-up 12.0 mo) or laminoplasty plate (60 patients, mean age 65.6 y, 45 men and 15 women, mean follow-up 12.6 mo) to maintain the position of the opened laminae. We compared clinical outcomes, radiographic findings, and complications between the 2 groups.

Results:

Mean Japanese Orthopaedic Association scores had improved significantly for both groups at the final follow-up (P<0.001), with similar recovery rates: scores improved from 10.8±2.8 to 13.4±2.8 points in the suture-suspension (SS) group and from 11.3±2.7 to 13.6±2.2 points in the laminoplasty plate (LP) group. The incidence of C5 palsy was significantly higher in the SS group (7.9%) than in the LP group (1.7%; P<0.05). Computed tomography (CT) showed larger mean angles of the opened laminae in the SS group compared with the LP group (P<0.01). Magnetic resonance imaging (MRI) showed that the mean anterior spinal-cord space at the C5 level was larger in the SS group than in the LP group (P<0.01).

Conclusions:

Plate fixation in ELAP produced comparable clinical outcomes and significantly lowered the incidence of C5 palsy compared with suture suspension. CT and MRI findings indicated that laminoplasty plate fixation prevented excessive opening of the lamina and decreased dorsal spinal-cord shift, which might explain the lower incidence of C5 palsy.
Blood Conservation
Authors: Hudgins Kerstin , Carter Esther
Published: February 2019

The conservation of blood products and the use of alternatives to blood transfusion are the best practice. Patients treated with blood conservation techniques will have a reduced risk of blood-borne diseases and a reduced risk of human error that can occur during blood processing. The bedside nurse plays a vital role in educating the patient and the caregiver regarding risks, benefits, and alternatives. A combination of techniques explored focuses on minimizing blood loss, building the patient's own blood supply, or both. Medications, herbs, and supplements can increase bleeding and place the patient at risk for a transfusion. Evidence from a variety of sources indicates that postoperative patients who receive a blood transfusion will have a harder time with wound healing and overall recovery. Allogeneic blood transfusions can induce clinically significant immunosuppression, as well as other effects in recipients, to include a re-occurrence of cancer. For the Jehovah's Witnesses patient, receiving blood transfusions against their conscience is equal to rape. Therefore, appropriate management entails an understanding of ethical and legal issues involved. Providing meticulous medical care, such as essential interventions and techniques to reduce blood loss, can minimize the risk of subsequent need for blood transfusions and decrease the financial burden to the health care system and its consumers.
Long-term impacts of prenatal and infant exposure to fine particulate matter on wheezing and asthma
Authors: Shao Jingyi , Wheeler Amanda J. , Zosky Graeme R. , Johnston Fay H.
Published: February 2019

Background:

This systematic review aimed to summarize epidemiologic evidence regarding long-term effects of prenatal and infant particulate matter with an aerodynamic diameter less than 2.5 µm (PM2.5) exposure on wheezing and asthma.

Methods:

Epidemiologic data investigating the associations between ambient PM2.5 exposures during prenatal or the first 2 years of life and wheezing or asthma throughout life were extracted from five databases. All included studies were assessed according to the Critical Appraisal Skills Programme checklists. We performed meta-analyses if ≥2 studies estimated the effects of continuous PM2.5.

Results:

Nine of 18 eligible studies were suitable for meta-analyses. For prenatal PM2.5 exposure and asthma by 10 years of age (n = 4), the overall risk estimate per 10-unit increase (95% confidence interval) was 1.12 (1.00, 1.26). Although meta-analysis of prenatal exposure and wheezing by 4 years of age (n = 5) was not possible due to inconsistent exposure and outcome assessments, four studies found strong positive associations with wheeze by 2 years of age. The overall risk of developing asthma (n = 5) and wheezing (n = 3) by 8 years of age for infant PM2.5 exposure was 1.14 (0.96, 1.35) and 1.49 (0.99, 2.26), respectively. One large high-quality study reporting risk differences not suitable for meta-analysis demonstrated significant associations between prenatal or infant PM2.5 exposure and childhood asthma. High heterogeneity was present among studies of prenatal exposures and asthma, whereas studies of other associations showed low heterogeneity. There was insufficient evidence about susceptible subgroups.

Conclusions:

The limited and inconsistent evidence is suggestive of an association between early life PM2.5 exposure and wheezing/asthma. Large standardized studies are needed to explore the associations and identify vulnerable populations.
Development and Validation of a Fast Ultra-High Performance Liquid Chromatography–Fluorescent Method for the Quantification of Hydroxychloroquine and Its Metabolites in Patients With Lupus
Authors: Noé Gaëlle , Amoura Zahir , Combarel David , Lori Lesli , Tissot Nadine , Seycha Aguila , Funck-Brentano Christian , Zahr Noël
Published: February 2019

Background:

Hydroxychloroquine (HCQ) is approved for the treatment of systemic lupus erythematosus (SLE). Therapeutic drug monitoring of HCQ is necessary to detect nonadherence and to improve treatment efficacy in patients with SLE. Liquid chromatographic–tandem mass spectroscopy and high performance liquid chromatography (HPLC)–fluorescent methods are currently used to measure whole blood concentrations of HCQ and its 2 main metabolites desethylhydroxychloroquine and desethylchloroquine in patients with SLE. This study reports the development and validation of an ultra-HPLC (U-HPLC) method with fluorescence detection for the simultaneous quantification of HCQ and its metabolites in whole blood.

Methods:

After adding chloroquine (internal standard) to the samples, a single-step protein precipitation and a subsequent filtration were used for blood sample preparation. Analytes were separated under isocratic elution on a U-HPLC RP18 column with a total run time of 7 minutes. The mobile phase consisted of piperazine buffer (46.4 mM, pH = 9.8) and acetonitrile (68:32, vol/vol), which was delivered at a flow rate of 0.4 mL/min. Fluorescence excitation and emission wavelengths were 335 and 390 nm, respectively. Assay performance parameters were evaluated per FDA bioanalytical guidelines.

Results:

The calibration curve was linear from 125 to 4000 ng/mL for HCQ. The lower limit of quantification was 10 ng/mL for all analytes. For HCQ, desethylchloroquine, and desethylhydroxychloroquine, accuracies and imprecisions ranged from −7.90% to 7.85% and 1.14% to 8.78%, respectively.

Conclusions:

A sensitive, accurate, and fast U-HPLC–fluorescent method was validated and successfully applied to quantify whole blood concentrations to perform therapeutic drug monitoring of HCQ in pediatric and adult lupus patients.
PHOTOCOAGULATION VERSUS RANIBIZUMAB FOR PROLIFERATIVE DIABETIC RETINOPATHY
Authors: Bressler Susan B. , Beaulieu Wesley T. , Glassman Adam R. , Gross Jeffrey G. , Melia Michele , Chen Eric , Pavlica Michael R. , Jampol Lee M. ,   for the Diabetic Retinopathy Clinical Research Network
Published: February 2019

Purpose:

Among eyes with proliferative diabetic retinopathy, identify whether baseline characteristics impact the benefit of ranibizumab over panretinal photocoagulation (PRP) in DRCR.net Protocol S.

Methods:

Participants had proliferative diabetic retinopathy, visual acuity of 20/320 or better, and no previous PRP. Eyes were randomized to PRP or intravitreous 0.5-mg ranibizumab.

Results:

Ranibizumab was superior to PRP for change in visual acuity and development of vision-impairing central-involved diabetic macular edema over 2 years (P < 0.001). Among 25 characteristics, there were none in which participants assigned to PRP had superior outcomes relative to ranibizumab-assigned participants. The relative benefit of ranibizumab over PRP for change in visual acuity seemed greater in participants with higher mean arterial pressure (P = 0.03), without previous focal/grid laser (P = 0.03), with neovascularization of the disk and elsewhere on clinical examination (P = 0.04), and with more advanced proliferative diabetic retinopathy on photographs (P = 0.02). For development of vision-impairing central-involved diabetic macular edema, the relative benefit of ranibizumab over PRP seemed greater among nonwhite participants (P = 0.01) and those with higher mean arterial pressure (P = 0.01).

Conclusion:

There were no characteristics identified in which outcomes were superior with PRP compared with ranibizumab. These exploratory analyses provide additional support that ranibizumab may be a reasonable alternative to PRP for proliferative diabetic retinopathy over a 2-year period.
Interpretation of Mismatch Repair Protein Immunohistochemistry in Endometrial Carcinoma Should Consider Both Lynch Syndrome Screening and Immunotherapy Susceptibility: An Illustrative Case Report
Authors: Chapel David B. , Lengyel Ernst , Ritterhouse Lauren L. , Lastra Ricardo R.
Published: February 2019

We present an instructive case of FIGO grade 1 endometrioid endometrial carcinoma with a biphasic morphology, corresponding to subclonal loss of mismatch repair proteins (MMRP) MLH1 and PMS2 by immunohistochemistry and subclonal microsatellite instability. A pulmonary metastasis represented only the tumor component with retention of MMRPs. This case illustrates the need for pathologists to recognize and report heterogenous expression of MMRPs in endometrial carcinoma, to consider tumor heterogeneity when selecting foci for molecular studies, and to re-evaluate MMRP expression in tumor metastases, when clinically indicated. These considerations are particularly important as the relevance of MMRP expression in endometrial cancer expands beyond Lynch syndrome screening, into a new role as a predictive marker for immunotherapy.
Correlation of MRI Findings With Patterns of Visual Field Loss in Patients With Pituitary Tumors
Authors: Kane Emily J. , Ashton David E. , Mews Peter J. , Reid Kate , Neely Andrew , Lueck Christian J.
Published: February 2019

Background:

Compression of the optic chiasm by pituitary tumors typically results in bitemporal hemianopia, implying that nasal retinal fibers are preferentially damaged. The reason for this is not clear. One theory suggests that nasal fibers are selectively vulnerable simply because they cross each other. This study investigated the “crossing theory” by correlating visual field (VF) loss with chiasmal elevation and with the degree of eccentric compression on MRI scans.

Methods:

Our hospital database was searched to identify patients with a) chiasmal compression by a pituitary tumor; b) documented preoperative evidence of VF loss; and c) preoperative MRI scan performed within 1 month of VF testing. Temporality and bitemporality indices were derived from pattern deviation VF plots. Elevations of the central and peripheral parts of the chiasm were obtained from MRI scans, from which the eccentricity of compression was calculated. Temporality indices and hemifield loss were compared with central chiasmal elevation, and nasal hemifield loss in each eye was plotted against eccentricity.

Results:

Eleven patients were suitable for analysis. The degree of bitemporal VF involvement was significantly correlated with elevation of the central chiasm (P = 0.004). However, there was minimal involvement of nasal VFs, and no demonstrable increase in nasal field loss with increasing eccentricity of compression.

Conclusions:

This study provides support for the crossing theory. These findings will inform further finite element models of chiasmal compression. A larger, prospective study is planned.
Live long and prosper: durable benefits of early-life care in banded mongooses
Authors: Vitikainen Emma I. K. , Thompson Faye J. , Marshall Harry H. , Cant Michael A.
Published: February 2019

Kin selection theory defines the conditions for which altruism or ‘helping’ can be favoured by natural selection. Tests of this theory in cooperatively breeding animals have focused on the short-term benefits to the recipients of help, such as improved growth or survival to adulthood. However, research on early-life effects suggests that there may be more durable, lifelong fitness impacts to the recipients of help, which in theory should strengthen selection for helping. Here, we show in cooperatively breeding banded mongooses (
Mungos mungo
) that care received in the first 3 months of life has lifelong fitness benefits for both male and female recipients. In this species, adult helpers called ‘escorts’ form exclusive one-to-one caring relationships with specific pups (not their own offspring), allowing us to isolate the effects of being escorted on later reproduction and survival. Pups that were more closely escorted were heavier at sexual maturity, which was associated with higher lifetime reproductive success for both sexes. Moreover, for female offspring, lifetime reproductive success increased with the level of escorting received
per se
, over and above any effect on body mass. Our results suggest that early-life social care has durable benefits to offspring of both sexes in this species. Given the well-established developmental effects of early-life care in laboratory animals and humans, we suggest that similar effects are likely to be widespread in social animals more generally. We discuss some of the implications of durable fitness benefits for the evolution of intergenerational helping in cooperative animal societies, including humans.

This article is part of the theme issue ‘Developing differences: early-life effects and evolutionary medicine’.
Variable DNA methylation in neonates mediates the association between prenatal smoking and birth weight
Authors: Hannon Eilis , Schendel Diana , Ladd-Acosta Christine , Grove Jakob , Hansen Christine Søholm , Hougaard David Michael , Bresnahan Michaeline , Mors Ole , Hollegaard Mads Vilhelm , Bækvad-Hansen Marie , Hornig Mady , Mortensen Preben Bo , Børglum Anders D. , Werge Thomas , Pedersen Marianne Giørtz , Nordentoft Merete ,   iPSYCH-Broad ASD Group, Buxbaum Joseph D. , Daniele Fallin M. , Bybjerg-Grauholm Jonas , Reichenberg Abraham , Mill Jonathan
Published: February 2019

There is great interest in the role epigenetic variation induced by non-genetic exposures may play in the context of health and disease. In particular, DNA methylation has previously been shown to be highly dynamic during the earliest stages of development and is influenced by
in utero
exposures such as maternal smoking and medication. In this study we sought to identify the specific DNA methylation differences in blood associated with prenatal and birth factors, including birth weight, gestational age and maternal smoking. We quantified neonatal methylomic variation in 1263 infants using DNA isolated from a unique collection of archived blood spots taken shortly after birth (mean = 6.08 days; s.d. = 3.24 days). An epigenome-wide association study (EWAS) of gestational age and birth weight identified 4299 and 18 differentially methylated positions (DMPs) respectively, at an experiment-wide significance threshold of
p
< 1 × 10
−7
. Our EWAS of maternal smoking during pregnancy identified 110 DMPs in neonatal blood, replicating previously reported genomic loci, including
AHRR
. Finally, we tested the hypothesis that DNA methylation mediates the relationship between maternal smoking and lower birth weight, finding evidence that methylomic variation at three DMPs may link exposure to outcome. These findings complement an expanding literature on the epigenomic consequences of prenatal exposures and obstetric factors, confirming a link between the maternal environment and gene regulation in neonates.

This article is part of the theme issue ‘Developing differences: early-life effects and evolutionary medicine’.
Developmental plasticity as adaptation: adjusting to the external environment under the imprint of maternal capital
Authors: Wells Jonathan C. K.
Published: February 2019

Plasticity is assumed to enable beneficial adjustment to the environment. In this context, developmental plasticity is generally approached within a two-stage framework, whereby adjustments to ecological cues in stage 1 are exposed to selection in stage 2. This conceptual approach may have limitations, because in species providing parental investment, particularly placental mammals such as humans, initial adjustments are not to the environment directly, but rather to the niche generated by parental phenotype (in mammals, primarily that of the mother). Only as maternal investment is withdrawn is the developing organism exposed directly to prevailing ecological conditions. A three-stage model may therefore be preferable, where developmental trajectory first adjusts to maternal investment, then to the external environment. Each offspring experiences a trade-off, benefitting from maternal investment during the most vulnerable stages of development, at the cost of exposure to investment strategies that maximize maternal fitness. Maternal life-history trade-offs impact the magnitude and schedule of her investment in her offspring, generating lifelong effects on traits related to health outcomes. Understanding the imprint of maternal capital on offspring is particularly important in species demonstrating social hierarchy. Interventions targeting maternal capital might offer new opportunities to improve health outcomes of both mother and offspring.

This article is part of the theme issue ‘Developing differences: early-life effects and evolutionary medicine’.
Developing differences: early-life effects and evolutionary medicine
Authors: Kuijper Bram , Hanson Mark A. , Vitikainen Emma I. K. , Marshall Harry H. , Ozanne Susan E. , Cant Michael A.
Published: February 2019

Variation in early-life conditions can trigger developmental switches that lead to predictable individual differences in adult behaviour and physiology. Despite evidence for such early-life effects being widespread both in humans and throughout the animal kingdom, the evolutionary causes and consequences of this developmental plasticity remain unclear. The current issue aims to bring together studies of early-life effects from the fields of both evolutionary ecology and biomedicine to synthesise and advance current knowledge of how information is used during development, the mechanisms involved, and how early-life effects evolved. We hope this will stimulate further research into early-life effects, improving our understanding of why individuals differ and how this might influence their susceptibility to disease.

This article is part of the theme issue ‘Developing differences: early-life effects and evolutionary medicine’.