bluuebunny/crossref_metadata_2025 huggingface dataset:
Self-Perceptions of Aging: Factorial Structure and Invariance by Gender
Authors: Turner Shelbie G , Hooker Karen , Geldhof G John
Published: May 2020

Background and Objectives

Self-perceptions of aging (SPA)—the appraisals people place on their own aging processes—predict well-being in later life. Researchers are increasingly hypothesizing that the overarching construct of SPA is comprised of two factors—positive SPA and negative SPA—and that SPA are gendered. The purpose of this study was to empirically test the hypothesized two-factor structure of SPA and to analyze how the two-factor structure varies between men and women.

Research Design and Methods

Data come from the 2012 wave of the Health and Retirement Study (N = 7,029; Mage = 68.08), which includes an 8-item SPA scale. We used confirmatory factor analysis (CFA) to assess (i) the positive SPA and negative SPA two-factor solution for the 8-item scale and (ii) whether the two-factor solution had configural, strong, or weak invariance across men and women.

Results

CFAs indicated a two-factor latent structure of the 8-item scale, with SPA being comprised of both a positive SPA factor and a negative SPA factor. The latent structure was the same for both men and women.

Discussion and Implications

Results suggest that SPA is a broader construct made up of positive and negative latent factors. Researchers should consider separating the SPA by positive and negative factors to analyze how each factor uniquely shapes health. Moreover, the two-factor solution was equivalent across men and women, possibly because of the generalized nature of the 8-item scale. Researchers can use the 8-item scale similarly for men and women and should continue to elucidate possible gender differences in SPA.
The Tudor-domain protein TDRD7, mutated in congenital cataract, controls the heat shock protein HSPB1 (HSP27) and lens fiber cell morphology
Authors: Barnum Carrie E , Al Saai Salma , Patel Shaili D , Cheng Catherine , Anand Deepti , Xu Xiaolu , Dash Soma , Siddam Archana D , Glazewski Lisa , Paglione Emily , Polson Shawn W , Chuma Shinichiro , Mason Robert W , Wei Shuo , Batish Mona , Fowler Velia M , Lachke Salil A
Published: May 2020

Mutations of the RNA granule component TDRD7 (OMIM: 611258) cause pediatric cataract. We applied an integrated approach to uncover the molecular pathology of cataract in Tdrd7−/− mice. Early postnatal Tdrd7−/− animals precipitously develop cataract suggesting a global-level breakdown/misregulation of key cellular processes. High-throughput RNA sequencing integrated with iSyTE-bioinformatics analysis identified the molecular chaperone and cytoskeletal modulator, HSPB1, among high-priority downregulated candidates in Tdrd7−/− lens. A protein fluorescence two-dimensional difference in-gel electrophoresis (2D-DIGE)-coupled mass spectrometry screen also identified HSPB1 downregulation, offering independent support for its importance to Tdrd7−/− cataractogenesis. Lens fiber cells normally undergo nuclear degradation for transparency, posing a challenge: how is their cell morphology, also critical for transparency, controlled post-nuclear degradation? HSPB1 functions in cytoskeletal maintenance, and its reduction in Tdrd7−/− lens precedes cataract, suggesting cytoskeletal defects may contribute to Tdrd7−/− cataract. In agreement, scanning electron microscopy (SEM) revealed abnormal fiber cell morphology in Tdrd7−/− lenses. Further, abnormal phalloidin and wheat germ agglutinin (WGA) staining of Tdrd7−/− fiber cells, particularly those exhibiting nuclear degradation, reveals distinct regulatory mechanisms control F-actin cytoskeletal and/or membrane maintenance in post-organelle degradation maturation stage fiber cells. Indeed, RNA immunoprecipitation identified Hspb1 mRNA in wild-type lens lysate TDRD7-pulldowns, and single-molecule RNA imaging showed co-localization of TDRD7 protein with cytoplasmic Hspb1 mRNA in differentiating fiber cells, suggesting that TDRD7–ribonucleoprotein complexes may be involved in optimal buildup of key factors. Finally, Hspb1 knockdown in Xenopus causes eye/lens defects. Together, these data uncover TDRD7’s novel upstream role in elevation of stress-responsive chaperones for cytoskeletal maintenance in post-nuclear degradation lens fiber cells, perturbation of which causes early-onset cataracts.
Repeated implantation failure (RIF): an iatrogenic meaningless definition that generates unnecessary and costly use of add-on procedures
Authors: Ben Rafael Zion
Published: May 2020

This opinion paper addresses the literature regarding repeated implantation failure (RIF) in IVF embryo transfer programmes. We provide several lines of discussion as to why such diagnosis might be wrong, why it should not be a call for action or a reason to change the course of treatment, and how RIF biases the quality of the publications and leads to the use of unnecessary and costly adjuvant procedures beyond basic IVF. We argue that these costly add-on procedures are being offered to patients in this highly privatized sector to prevent them from quitting the programme and as a by-product to increase the clinic income. The patients, on the other hand, often equate lucrative hi-tech procedures with possible success and request them despite the lack of proof of the efficacy of most of the procedures.
CpG Methylation inTGFβ1andIL-6Genes as Surrogate Biomarkers for Diagnosis of IBD in Children
Authors: Samarani Suzanne , Dupont-Lucas Claire , Marcil Valerie , Mack David , Israel David , Deslandres Colette , Jantchou Prevost , Ahmad Ali , Amre Devendra
Published: May 2020

Background

Diagnostic markers for distinguishing between Crohn disease (CD) and ulcerative colitis (UC) remain elusive. We studied whether methylation marks across the promoters of the transforming growth factor beta 1 (TGFβ1) and interleukin-6 genes have diagnostic utility.

Methods

A case-control study was carried out. Cases were treatment-naïve, diagnosed before age 20, and recruited from 3 pediatric gastroenterology clinics across Canada. Control patients did not have inflammatory bowel disease and were recruited from orthopedic clinics within the same hospitals as the gastroenterology clinics. Patient DNA from peripheral blood was processed to identify methylation sites (CpG) across the promoter regions of the TGFβ1 and interleukin-6 genes. After initial nonparametric univariate analyses, multivariate logistic regression models were fit. Models with the best fit (Akaike information criteria) and strongest discriminatory capabilities (area under the curve [AUC]) were identified, and P values were adjusted for multiple comparisons using the false discovery rate method.

Results

A total of 67 CD, 31 UC, and 43 control patients were included. The age distribution of the 3 groups was similar. Most CD patients had ileocolonic disease (44.8%) and inflammatory disease (88.1%). Most UC patients had extensive (71%) and moderate disease (51.6%). Logistic regression analysis revealed the following: 14 TGFβ1 CpG sites discriminated between CD and control patients (AUC = 0.94), 9 TGFβ1 CpG sites discriminated between UC and control patients (AUC = 0.99), 3 TGFβ1 CpG sites discriminated between CD and UC (AUC = 0.81), and 6 TGFβ1 CpG sites distinguished colonic CD from UC (AUC = 0.91).

Conclusions

We found that CpG methylation in the promoter of the TGFβ1 gene has high discriminative power for identifying CD and UC and could serve as an important diagnostic marker.
Early childhood growth trajectory and later cognitive ability: evidence from a large prospective birth cohort of healthy term-born children
Authors: Ahmed Asma , Kramer Michael S , Bernard Jonathan Y , Perez Trejo Maria Esther , Martin Richard M , Oken Emily , Yang Seungmi
Published: May 2020

Background

Most studies of associations between child growth and cognitive ability were based on size at one or two ages and a single measure of cognition. We aimed to characterize different aspects of early growth and their associations with cognitive outcomes in childhood through adolescence.

Methods

In a sample of 12 368 Belarusian children born at term, we examined associations of length/height and weight trajectories over the first 6.5 years of life with cognitive ability at 6.5 and 16 years and its change over time. We estimated growth trajectories using two random-effects models—the SuperImposition by Translation and Rotation to model overall patterns of growth and the Jenss-Bayley to distinguish growth in infancy from post infancy. Cognitive ability was measured using the Wechsler Abbreviated Scales of Intelligence at 6.5 years and the computerized NeuroTrax test at 16 years.

Results

Higher length/height between birth and 6.5 years was associated with higher cognitive scores at 6.5 and 16 years {2.7 points [95% confidence interval (CI): 2.1, 3.2] and 2.5 points [95% CI: 1.9, 3.0], respectively, per standard deviation [SD] increase}. A 1-SD delay in the childhood height-growth spurt was negatively associated with cognitive scores [–2.4 (95% CI: –3.0, –1.8) at age 6.5; –2.2 (95% CI: –2.7, –1.6) at 16 years]. Birth size and post-infancy growth velocity were positively associated with cognitive scores at both ages. Height trajectories were not associated with the change in cognitive score. Similar results were observed for weight trajectories.

Conclusions

Among term infants, the overall size, timing of the childhood growth spurt, size at birth and post-infancy growth velocity were all associated with cognitive ability at early-school age and adolescence.
Blow-up of error estimates in time-fractional initial-boundary value problems
Authors: Chen Hu , Stynes Martin
Published: May 2020

Time-fractional initial-boundary value problems of the form $D_t^\alpha u-p \varDelta u +cu=f$ are considered, where $D_t^\alpha u$ is a Caputo fractional derivative of order $\alpha \in (0,1)$ and the spatial domain lies in $\mathbb{R}^d$ for some $d\in \{1,2,3\}$. As $\alpha \to 1^-$ we prove that the solution $u$ converges, uniformly on the space-time domain, to the solution of the classical parabolic initial-boundary value problem where $D_t^\alpha u$ is replaced by $\partial u/\partial t$. Nevertheless, most of the rigorous analyses of numerical methods for this time-fractional problem have error bounds that blow up as $\alpha \to 1^-$, as we demonstrate. We show that in some cases these analyses can be modified to obtain robust error bounds that do not blow up as $\alpha \to 1^-$.
Danger-associated metabolic modifications during bacterial infection of macrophages
Authors: Dramé Mariatou , Buchrieser Carmen , Escoll Pedro
Published: May 2020

In this review, we propose that certain modifications in cellular metabolism might function as danger signals triggering inflammasome-mediated immune responses. We propose to call them danger-associated metabolic modifications (DAMMs). As intracellular bacteria can actively modulate macrophage metabolism for their benefit, infected host cells might sense bacteria-induced metabolic alterations and activate immune reactions. Here we report the known metabolic interactions that occur during infection of macrophages by intracellular bacteria and discuss the possible emergence of DAMMs upon bacteria-induced alterations of cellular metabolism.
How did a Quality Premium financial incentive influence antibiotic prescribing in primary care? Views of Clinical Commissioning Group and general practice professionals
Authors: Borek Aleksandra J , Anthierens Sibyl , Allison Rosalie , McNulty Cliodna A M , Lecky Donna M , Costelloe Ceire , Holmes Alison , Butler Christopher C , Walker A Sarah , Tonkin-Crine Sarah
Published: May 2020

Background

The Quality Premium (QP) was introduced for Clinical Commissioning Groups (CCGs) in England to optimize antibiotic prescribing, but it remains unclear how it was implemented.

Objectives

To understand responses to the QP and how it was perceived to influence antibiotic prescribing.

Methods

Semi-structured telephone interviews were conducted with 22 CCG and 19 general practice professionals. Interviews were analysed thematically.

Results

The findings were organized into four categories. (i) Communication: this was perceived as unstructured and infrequent, and CCG professionals were unsure whether they received QP funding. (ii) Implementation: this was influenced by available local resources and competing priorities, with multifaceted and tailored strategies seen as most helpful for engaging general practices. Many antimicrobial stewardship (AMS) strategies were implemented independently from the QP, motivated by quality improvement. (iii) Mechanisms: the QP raised the priority of AMS nationally and locally, and provided prescribing targets to aim for and benchmark against, but money was not seen as reinvested into AMS. (iv) Impact and sustainability: the QP was perceived as successful, but targets were considered challenging for a minority of CCGs and practices due to contextual factors (e.g. deprivation, understaffing). CCG professionals were concerned with potential discontinuation of the QP and prescribing rates levelling off.

Conclusions

CCG and practice professionals expressed positive views of the QP and associated prescribing targets and feedback. The QP helped influence change mainly by raising the priority of AMS and defining change targets rather than providing additional funding. To maximize impact, behavioural mechanisms of financial incentives should be considered pre-implementation.
CpxR regulates the colistin susceptibility of Salmonella Typhimurium by a multitarget mechanism
Authors: Zhai Ya-Jun , Sun Hua-Run , Luo Xing-Wei , Liu Jian-Hua , Pan Yu-Shan , Wu Hua , Yuan Li , Liang Jun , He Dan-Dan , Hu Gong-Zheng
Published: May 2020

Background

The two-component signalling systems PmrAB and PhoPQ of Salmonella have been extensively studied with regard to colistin resistance. We previously showed that overexpressed CpxR could significantly increase the colistin susceptibility (16-fold compared with the WT strain) of Salmonella enterica serovar Typhimurium (Salmonella Typhimurium) through PmrAB and PhoPQ.

Objectives

To identify the potential target genes of CpxR in PmrAB- and PhoPQ-related signalling pathways.

Methods

His6-CpxR was prokaryotically expressed and purified by Ni-NTA resin affinity chromatography. β-Galactosidase activity assays were conducted to investigate whether CpxR could regulate the promoters of colistin resistance-related genes (CRRGs). Electrophoretic mobility shift assays (EMSAs) were used to further detect His6-CpxR complexes with promoters of CRRGs.

Results

We demonstrated for the first time (to the best of our knowledge) that CpxR and the AcrAB–TolC efflux pump have reciprocal effects on CRRG transcription. Additionally, CpxR could regulate the colistin susceptibility of Salmonella Typhimurium by binding directly to the promoters of phoPQ, pmrC, pmrH and pmrD at the CpxR box-like sequences or indirectly through other regulators including pmrAB and mgrB.

Conclusions

CpxR could regulate the colistin susceptibility of Salmonella Typhimurium by a multitarget mechanism.
Performance of Two Fentanyl Immunoassays against a Liquid Chromatography–Tandem Mass Spectrometry Method
Authors: Feng Sheng , Rutledge Theodore J , Manzoni Maureen , Le Thuan , Gardiner JoAnn , Milone Michael , Shaw Leslie , Wang Ping
Published: May 2020

Rapid and automated fentanyl screening assays are in need due to the prevalence of fentanyl abuse. In the present study, we evaluated the clinical performance of two FDA-cleared automated fentanyl immunoassays, the Immunalysis SEFRIA fentanyl assay and the ARK fentanyl assay. Liquid chromatography–tandem mass spectrometry (LC–MS-MS) was used as a gold standard. Two groups of urine specimens were tested, including 225 specimens from patients presenting to the emergency department (ED) for whom urine drugs of abuse screens were ordered and 57 specimens from patients in chronic pain management programs. The SEFRIA assay generated higher assay imprecision than ARK assay (intraday CV%, 7.15 vs. 4.7%; interday CV%, 6.6 vs. 5.3%). Clinical sensitivity and specificity for detection of fentanyl exposure were 100 and 96% for the ARK assay and 95 and 80% for the SEFRIA assay. An ‘auto-repeating’ issue was observed for some validation specimens flagged with high absorbance values (OD > 3.0), generating false repeat results. The frequency of auto-repeating was lower in the ARK assay than SEFRIA (0.7 vs. 15.5%). Auto-repeating occurred for only previously frozen specimens in the ARK assay, but 9% of fresh specimens were also flagged and repeated in the SEFRIA assay. Positive predictive value (PPV) of the ARK assay was 73% in the ED population and 67% in the non-ED populations. The concentrations of fentanyl and norfentanyl were higher in specimens from ED patients than patients from pain management programs. High prevalence of morphine, methamphetamine, benzoylecgonine and 6-MAM was observed in specimens positive for fentanyl in both populations.
Racial/Ethnic Disparities in Lost Earnings From Cancer Deaths in the United States
Authors: Zhao Jingxuan , Miller Kimberly D , Islami Farhad , Zheng Zhiyuan , Han Xuesong , Ma Jiemin , Jemal Ahmedin , Yabroff K Robin
Published: May 2020

Background

Little is known about disparities in economic burden due to premature cancer deaths by race or ethnicity in the United States. This study aimed to compare person-years of life lost (PYLLs) and lost earnings due to premature cancer deaths by race/ethnicity.

Methods

PYLLs were calculated using recent national cancer death and life expectancy data. PYLLs were combined with annual median earnings to generate lost earnings. We compared PYLLs and lost earnings among individuals who died at age 16-84 years due to cancer by racial/ethnic groups (non-Hispanic [NH] White, NH Black, NH Asian or Pacific Islander, and Hispanic).

Results

In 2015, PYLLs due to all premature cancer deaths were 6 512 810 for NH Whites, 1 196 709 for NH Blacks, 279 721 for NH Asian or Pacific Islanders, and 665 968 for Hispanics, translating to age-standardized lost earning rates (per 100 000 person-years) of $34.9 million, $43.5 million, $22.2 million, and $24.5 million, respectively. NH Blacks had higher age-standardized PYLL and lost earning rates than NH Whites for 13 of 19 selected cancer sites. If age-specific PYLL and lost earning rates for NH Blacks were the same as those of NH Whites, 241 334 PYLLs and $3.2 billion lost earnings (22.6% of the total lost earnings among NH Blacks) would have been avoided. Disparities were also observed for average PYLLs and lost earnings per cancer death for all cancers combined and 18 of 19 cancer sites.

Conclusions

Improving equal access to effective cancer prevention, screening, and treatment will be important in reducing the disproportional economic burden associated with racial/ethnic disparities.
Sucrose regulates wall ingrowth deposition in phloem parenchyma transfer cells in Arabidopsis via affecting phloem loading activity
Authors: Wei Xiaoyang , Nguyen Suong T T , Collings David A , McCurdy David W
Published: May 2020

In Arabidopsis thaliana, phloem parenchyma transfer cells (PPTCs) occur in leaf minor veins and play a pivotal role in phloem loading. Wall ingrowth formation in PPTCs is induced by the phloem loading activity of these cells, which is regulated by sucrose (Suc). The effects of endogenous versus exogenous Suc on wall ingrowth deposition, however, differ. Elevating endogenous Suc levels by increased light enhanced wall ingrowth formation, whereas lowering endogenous Suc levels by dark treatment or genetically in ch-1 resulted in lower levels of deposition. In contrast, exogenously applied Suc, or Suc derived from other organs, repressed wall ingrowth deposition. Analysis of pAtSUC2::GFP plants, used as a marker for phloem loading status, suggested that wall ingrowth formation is correlated with phloem loading activity. Gene expression analysis revealed that exogenous Suc down-regulated expression of AtSWEET11 and 12, whereas endogenous Suc up-regulated AtSWEET11 expression. Analysis of a TREHALOSE 6-PHOSPHATE (T6P) SYNTHASE overexpression line and the hexokinase (HXK)-null mutant, gin2-1, suggested that Suc signalling of wall ingrowth formation is independent of T6P and HXK. Collectively, these results are consistent with the conclusion that Suc regulates wall ingrowth formation via affecting Suc exporting activity in PPTCs.
EMTALA and Deferred Care
Authors: Brenner Jay M.
Published: May 2020

As physicians, we have the inherent duty to care for all patients, and as emergency physicians, we have the ability to stabilize and treat myriad problems that present to us in our emergency departments. A patient’s ability to pay should not matter. This ethical obligation was enshrined into law when US President Ronald Reagan signed the Emergency Medical Treatment and Active Labor Act (EMTALA). This law, however, has undergone several clarifications over the three decades since it went into effect, and the application of it in the clinical arena can sometimes be nuanced. The need to address emergency medical treatment and active labor may occur. One must always perform a medical screening exam (MSE) and arrange for appropriate transfer when indicated.
Self-Inflicted Gunshot Wound/Self-Reported No Code Status: The Doctor’s Dilemma
Authors: Schears Raquel M. , Schears Markayle R.
Published: May 2020

Suicidal ideation and attempted suicide are important presenting complaints in the emergency department (ED). The juxtaposition of a self-inflicted gunshot wound and self-reported no code status may serve to amplify the moral distress of attending emergency providers. Imagine caring for a terminal yet capable patient, who independently attempts suicide unsuccessfully and is brought to the ED with an advance directive (AD) requesting no treatment. The exceptional consideration in this suicidal context is whether the treatment can be effective. In a case with a very low likelihood that any intervention could produce a good outcome, clinical judgment becomes the basis for withholding or withdrawing treatment, not the AD.
The Reluctant Consultant
Authors: Zaidi Sara R. , Simon Jeremy R.
Published: May 2020

This chapter discusses the obligations under the Emergency Medical Treatment and Active Labor Act (EMTALA) of both emergency physicians and on-call consultants to patients who present to the emergency department with a medical complaint. Whereas emergency physicians, by the nature of their work, cannot avoid being present to treat patients when they arrive, consultants may be reluctant to fulfill their obligation and come to the emergency department to treat an unstable patient who cannot be discharged without their services. Techniques for avoiding and resolving such impasses are discussed, as well as what to do in the case of true intransigence.
Contributions of Epidemiology to Our Understanding of Bipolar Disorder
Authors: Merikangas Kathleen Ries , Stapp Emma K.
Published: May 2020

This chapter reviews the evidence on the prevalence, correlates, and burden of bipolar disorder from community-based surveys of general population samples. The pooled lifetime (12-month) prevalence for bipolar I disorder is about 1%, and for bipolar II disorder it is about 1.6%, with slightly lower rates for 12-month prevalence of about 0.7% and 0.5%, respectively. However, prevalence of the bipolar spectrum is substantially greater, approximating 5 to 6%. Rates of bipolar disorder are equivalent in males and females and do not differ substantially by ethnic status or social class. The onset of bipolar disorder occurs before age 18 years in about half of those who will eventually develop bipolar disorder, and by age 30 years in nearly all adults with this condition. Comorbidity is pervasive among both adolescents and adults with bipolar disorder in the general population, suggesting disturbances in multiple systems of emotion, cognition, and behavior. Population research has also highlighted the tremendous impact of bipolar disorder across levels of the individual, family, and society. Now that descriptive epidemiology has reached its maturity, ongoing research is providing information on risk factors, causal pathways, and consequences of bipolar disorder.
Comorbidity of Bipolar and Substance Use Disorders
Authors: Becker Josh E. , Brown E. Sherwood
Published: May 2020

Bipolar disorder and substance use disorder co-occur at very high rates. The high rate is likely due to a complex interaction of biological, social, and psychological factors, and some research suggests that use of substances may be to mitigate symptoms associated with bipolar disorder. Some studies have shown that men with bipolar disorder may be at a higher risk for a substance use disorder than women. The co-occurrence of these disorders leads to poorer treatment outcomes because of higher rates of suicidality, poor treatment adherence, lower quality of life, and more frequent relapse. This population deserves special treatment consideration.
Comorbidity of Bipolar and Other Psychiatric Disorders
Authors: Vaughn Samuel E. , Strawn Jeffrey R.
Published: May 2020

Psychiatric comorbidity is common in children, adolescents, and adults with bipolar disorder. For clinicians, this comorbidity has significant implications for assessment and treatment. Comorbid conditions may be associated with distinct trajectories of improvement following both psychotherapeutic and psychopharmacological treatment. In this chapter, personality disorders, post-traumatic stress disorder, obsessive-compulsive disorder, anxiety disorders, attention-deficit/hyperactivity disorder, and eating disorders are reviewed with regard to their prevalence as well as their implications for assessment and treatment in both children and adults with bipolar disorder. Consideration of comorbidity is critical in enhancing treatment outcomes for patients and in terms of personalizing treatment approaches, whether pharmacological or psychotherapeutic.
Genetics of Bipolar Disorder
Authors: Kirsch Dylan , Lippard Elizabeth T. C.
Published: May 2020

An individual’s genetic makeup has the power to inform medical practice and shape disease prevention, diagnosis, and treatment to improve lifelong outcomes. Genetics has integrated into some aspects of general medicine; however, there has been less success in incorporating genetics into psychiatry. This chapter discusses the genetics of bipolar disorder. As revealed from family, twin, and adoption studies, bipolar disorder is highly heritable, with estimates suggesting the disorder coincides with the highest heritability compared with other psychiatric disorders. While association studies have identified genes of interest that may contribute to risk for the disorder, these studies have been difficult to replicate, and genes identified have shown small effect sizes on their own. More recent approaches to studying polygenic risk and epigenetics modifications of the genome are starting to be applied to bipolar disorder. Early findings utilizing these approaches are discussed. Additionally, this chapter discusses emerging work suggesting genetic associations that may cross diagnostic boundaries in psychiatry and genetic endophenotypes that may one day be incorporated into clinical practice for improving prediction, diagnosis, and treatment of bipolar disorder. While more work is needed to understand the genetics of bipolar disorder and ways to integrate genetics into clinical practice, there is hope on the horizon, and familial information can already guide clinical practice.
Psychopharmacological Treatments for Bipolar Disorder
Authors: Strakowski Stephen M. , Almeida Jorge R. C. , DelBello Melissa P.
Published: May 2020

The discovery of lithium in 1946 led to a revolution in the management of bipolar disorder as well as other psychiatric conditions. Since that time and especially in the past 20 years, treatment options for bipolar disorder have progressively advanced such that a modern practitioner has a number of evidence-based options to manage the illness. However, the evidence is strongest in adults for acute mania and weakens in other mood states and in youth. Nonetheless, based on the available evidence, this chapter provides recommendations for first-, second-, and third-line pharmacological treatments for bipolar illness to guide clinicians. Additionally, specific considerations for the various medications are reviewed. Suggestions are provided for both adults and youth.
A teamwork approach to neurological rehabilitation
Authors: Wade Derick
Published: May 2020

People with neurological disability present healthcare systems with a large range of complex problems covering many different domains and often lasting a long-time. Consequently, they need a large range of different professional staff, often from different organizations. These people will be considering different, small parts of the overall set of difficulties. In order to ensure both that all problems are considered and that all those involved work in an efficient and effective way one should have a system of cooperation and collaboration. The key features are that the group should work within an agreed model of illness, the biopsychosocial model of illness, using a patient-centred goal-setting process. For this to work effectively people need to work with a consistent set of colleagues, and within a single managerial and budgetary organization based in a single geographical place. This chapter discusses evidence concerning teamwork in rehabilitation, highlighting the importance of social and cultural considerations.
Predicting activities after stroke
Authors: Kwakkel Gert , Kollen Boudewijn
Published: May 2020

Knowledge about the functional prognosis of stroke patients admitted to a stroke unit has increased substantially over the past years. Prospective cohort studies suggest that the return of some finger extension and voluntary activity in the shoulder abductors within days post-stroke onset predicts a favourable recovery of the upper extremity function at 6 months. The Barthel index and the ability to sit unsupported are the main predictors for recovery of gait and activities of daily living (ADL) independency. Almost all developed prediction models identify patients with a favourable prognosis but are less suitable to predict accurately individuals who will not regain dexterity, mobility, and ADL independence following stroke. In individuals with an unfavourable prognosis, this entails measuring clinical determinants frequently and longitudinally during the post-stroke course. Moreover, future research should focus on cross-validating prediction models, which should also incorporate presently excluded stroke subtypes, such as brain stem strokes, intraparenchymal, and subarachnoid haemorrhages.
Designing a clinical trial for neurorehabilitation
Authors: Dobkin Bruce , Martinez Clarisa
Published: May 2020

The design, implementation, and analysis of clinical trials for the types of complex therapies needed to lessen impairments and disabilities that result from neurological diseases are reviewed. A multistep progression from feasibility testing in small groups of selected participants to the demonstration of efficacy in large-scale, multicentre randomized clinical trials is presented. Designs other than the ‘gold standard’ parallel-group trial can be used to optimize the contents of a new therapeutic strategy. Emphasis is placed on defining clinical characteristics and establishing a stable functional baseline for study participants. How the choices of outcome measure and comparison intervention affect the statistical and clinical significance of trial results are highlighted. Discussion of methodological concerns about randomization and blinded outcome assessment is followed by a review of common statistical confounders in neurorehabilitation trials. The use of consensus standards about trial reporting provides a valuable checklist for basic decisions in trial design.
Neuropsychological rehabilitation of higher cortical functions after brain damage
Authors: Ptak Radek , Schnider Armin
Published: May 2020

Neuropsychological interventions for impairments of higher cognitive functions can be divided into four different approaches: restoration of function, compensation, physiological stimulations, and metacognitive strategies. Training that aims to restore an impaired function or to increase processing speed or capacity is repetitive and often stereotyped. Such training may lead to task-specific learning with little generalization, as may be observed in particular in the domain of attention rehabilitation. However, it remains a matter of debate whether such practice effects really reflect the restoration of function or improved processing due to preserved procedural learning skills. For some cognitive domains (such as memory), restoration of function is mostly impossible; consequently, training mainly relies on compensatory strategies. For example, enhancement of learning may be achieved by improving memory encoding with mental imagery, while everyday memory is supported with systematic training of external aids, such as, memory notebooks. A third approach is applied in neglect rehabilitation and uses physiological stimulations to bias attention and sensory representations (e.g. optokinetic stimulation) or decrease interhemispheric inhibition (transcranial magnetic stimulation). Finally, the fourth approach is to structure behaviour and to enhance metacognitive abilities; this strategy is applied in the rehabilitation of complex problem-solving skills and impaired emotional regulation. Although it is difficult to control experimental biases in intervention studies targeting cognitive and behavioural disturbances, an increasing number of controlled clinical trials provide evidence for the efficacy of each of the four therapeutic approaches.
Application of orthoses and neurostimulation in neurorehabilitation
Authors: Carpaneto Jacopo , Micera Silvestro
Published: May 2020

Electrical stimulation can allow the recruitment of muscles to achieve functional movements. This approach is therefore very interesting to restore motor functions in subjects who have lost them because of neurological problems. In this chapter the main approaches to restoration of grasping and of locomotor functions using electrical stimulation and also the combined use of electrical stimulation and mechanical orthoses are presented. The potentials and limits related to the use of these different non-invasive or invasive techniques are highlighted and examined. Finally, a brief description of future trends and current limitations is also provided.
Virtual reality for neurorehabilitation
Authors: Bannwart Mathias , Riener Robert
Published: May 2020

Virtual reality (VR) is a powerful tool to motivate its participants to active participation, while providing augmented feedback to instruct the subject and improve task performance. This chapter presents the technical prerequisites of different recording, display, and rendering technologies. VR does not replace the real environment, but is a tool for setting up automatic training schedules. VR can be a good solution to train dangerous or difficult tasks. VR is being applied in physiotherapy, occupational therapy to recover limb functionality after disease or accident, and to enhance cognitive learning. VR technologies can also be applied to provide feedback as assistance during activities of daily living—this is then typically called augmented reality (AR). Despite the many technological achievements and positive results in many therapeutic and assistive applications, the field of VR rehabilitation is still in an early phase. VR technologies will continue to grow, gain further mainstream acceptance and, eventually, have a significant positive effect on therapeutic outcome.
Background diabetic retinopathy
Authors: Stockwin Rachel , Shepherd Emma
Published: May 2020

Background diabetic retinopathy (DR) can involve several different microvascular pathologies, which will be explained with example images. These include microaneurysms, haemorrhages, exudates, cotton wool spots, and venous loops. The reader will learn how these features relate to the grading and referral criteria. This chapter aims to provide information on how these pathologies develop and why it is important that they are recognized in the earlier stages of background DR. The chapter will demonstrate how ischaemia can affect the capillary network and also how related conditions, such as hypertension and blood glucose, can contribute to vascular changes. In addition, this chapter will explain how to differentiate normal variants from DR changes.
Patients of concern
Authors: Wright Alexander D. , Dodson Paul M.
Published: May 2020

Some patients are of extra concern in diabetic retinopathy (DR) screening programmes. Failure to attend is a common problem and there are many reasons for this. Additional screening episodes may be required for medical reasons. The most commonly encountered situation is pregnancy, where special provision for screening services should be integrated into pre-conception and antenatal care. Rapid changes in glycaemic control may result in temporary deterioration in pre-existing retinopathy and, where possible, should be anticipated. This scenarios is likely to be seen more commonly with the availability of the insulin pump and bariatric surgery being considered more often. An aggravating effect of hypertension on DR needs to be recognized.
Imaging in diabetic retinopathy
Authors: Jacob Sarita , Sivaraj Ramesh R.
Published: May 2020

Imaging in diabetic retinopathy (DR) has developed over the years and the advantages are multifold. Various imaging modalities are currently available, which is of great diagnostic and prognostic value in the management of DR. Optical coherence tomography (OCT) has revolutionized the management of diabetic maculopathy. OCT has now become indispensable for initiating and assessing diabetic macular oedema (DMO) while on treatment with intravitreal injections. Recent introduction of optical coherence tomography angiography (OCTA) has significantly reduced the need for fundus fluorescein angiography (FFA) for macular ischaemia and proliferative retinopathy. Ultra-wide field (UWF) imaging modalities for colour fundus and UWF FFA are very useful to document and assess overall retinal state highlighting the periphery. Bscan ultrasonography of the fundus is an useful tool to assess retinal status in proliferative DR with vitreous haemorrhage.
New treatment strategies for diabetic eye disease
Authors: Joseph Sobha , Sivaraj Ramesh R.
Published: May 2020

Argon laser treatment was the mainstay of treatment for diabetic retinopathy (DR) and maculopathy up to the last decade. However, with the better understanding of pathophysiology of DR, newer medications have become available. Anti-vascular endothelial growth factors (anti-VEGF) and steroid implants for vision-threatening diabetic macular oedema have been widely adopted in clinical practice with several longer-acting drug molecules in the pipeline. In the United Kingdom, ranibizumab and aflibercept are licensed anti-VEGF drugs. Dexamethasone and fluocinolone acetonide implants are the steroids that are available. The emphasis on systemic control of diabetes and blood pressure remains very relevant even in the era of these newer drugs.
Difficulties of Determining Death
Authors: Childress James F.
Published: May 2020

This chapter considers what we should do with the “dead donor rule” in transplantation in light of controversies about different ways of determining death. The system of voluntary deceased organ donation depends on public trust, based in part on adherence to the “Dead Donor Rule” (DDR). However, this rule presupposes that the line between life and death can be reliably drawn for purposes of removing vital organs for transplantation. Different but serious conceptual, scientific, and ethical questions surround deceased donation after neurological determination of death and after circulatory determination of death in either controlled or uncontrolled forms. This chapter examines the ethical implications of different approaches to the DDR and asks which public policy should be adopted: (1) abandon the DDR and move to living vital organ donation; (2) retain the DDR but view the determination of death as a legal fiction; (3) retain the DDR but expand individual/familial choices of conceptions of and criteria for determining death; or (4) retain and strengthen the DDR and ethically improve its operation. This chapter argues for the fourth option and for improving the process of individual and familial informed consent to deceased organ donation.
Triage in a Public Health Crisis
Authors: Childress James F.
Published: May 2020

This chapter examines triage in a public health crisis resulting from a bioterrorist attack. Systems of triage, whether informal or formal, generally have an implicit or explicit utilitarian rationale—they are usually designed to produce the greatest good for the greatest number under conditions of scarcity. It is important to distinguish medical utility from social utility and, within the latter, between broad and narrow social utilitarian judgments. Judgments of broad social utility recognize the differential social value of people’s lives, whereas judgments of narrow social utility recognize the differential value of specific social functions and roles and assign priority to the individuals discharging certain functions and performing certain roles. Judgments of broad social utility infringe the egalitarian principle of equal regard in a way that judgments of medical utility do not. It is not justifiable to use broad social utility as a basis for rationing in general or in an emergency, but it is possible to justify triage based on medical utility and also on narrow social utility. Public trust will be essential in any public health crisis—hence, the public needs to have confidence that the procedures and standards of triage are fair and are fairly implemented.
Halting the Vicarious Liability Juggernaut: Barclays Bank PLC v Various Claimants
Authors: Purshouse Craig
Published: May 2020

In Barclays Bank plc v Various Claimants [2020] UKSC 13, the Supreme Court rejected the claimants’ argument that Barclays should be vicariously liable for the sexual assaults of a doctor hired on as a contractor to perform medical examinations on employees and job candidates at the bank. It upheld the traditional rule that a defendant is not vicariously liable for the torts of independent contractors. This commentary examines the law on liability for independent contractors and considers whether the Supreme Court decision is consistent with modern employment trends. The implications of the decision for medical law are then discussed.
Non-ideal magnetohydrodynamics versus turbulence – I. Which is the dominant process in protostellar disc formation?
Authors: Wurster James , Lewis Benjamin T
Published: May 2020

Non-ideal magnetohydrodynamics (MHD) is the dominant process. We investigate the effect of magnetic fields (ideal and non-ideal) and turbulence (sub- and transsonic) on the formation of circumstellar discs that form nearly simultaneously with the formation of the protostar. This is done by modelling the gravitational collapse of a 1 M⊙ gas cloud that is threaded with a magnetic field and imposed with both rotational and turbulent velocities. We investigate magnetic fields that are parallel/antiparallel and perpendicular to the rotation axis, two rotation rates, and four Mach numbers. Disc formation occurs preferentially in the models that include non-ideal MHD where the magnetic field is antiparallel or perpendicular to the rotation axis. This is independent of the initial rotation rate and level of turbulence, suggesting that subsonic turbulence plays a minimal role in influencing the formation of discs. Aside from first core outflows that are influenced by the initial level of turbulence, non-ideal MHD processes are more important than turbulent processes during the formation of discs around low-mass stars.
Apparent evidence for Hawking points in the CMB Sky★
Authors: An Daniel , Meissner Krzysztof A , Nurowski Paweł , Penrose Roger
Published: May 2020

This paper presents strong observational evidence of numerous previously unobserved anomalous circular spots, of significantly raised temperature, in the cosmic microwave background sky. The spots have angular radii between 0.03 and 0.04 rad (i.e. angular diameters between about 3° and 4°). There is a clear cut-off at that size, indicating that each anomalous spot would have originated from a highly energetic point-like source, located at the end of inflation – or else point-like at the conformally expanded Big Bang, if it is considered that there was no inflationary phase. The significant presence of these anomalous spots, was initially noticed in the Planck 70 GHz satellite data by comparison with 1000 standard simulations, and then confirmed by extending the comparison to 10 000 simulations. Such anomalous points were then found at precisely the same locations in the WMAP (Wilkinson Microwave Anisotropy Probe) data, their significance was confirmed by comparison with 1000 WMAP simulations. Planck and WMAP have very different noise properties and it seems exceedingly unlikely that the observed presence of anomalous points in the same directions on both maps may come entirely from the noise. Subsequently, further confirmation was found in the Planck data by comparison with 1000 FFP8.1 MC simulations (with l ≤ 1500). The existence of such anomalous regions, resulting from point-like sources at the conformally stretched-out big bang, is a predicted consequence of conformal cyclic cosmology, these sources being the Hawking points of the theory, resulting from the Hawking radiation from supermassive black holes in a cosmic aeon prior to our own.
High-velocity interstellar absorption associated with the supernova remnant W28
Authors: Ritchey Adam M
Published: May 2020

We present an analysis of moderately high-resolution optical spectra obtained for the sightline to CD−23 13777, an O9 supergiant that probes high-velocity interstellar gas associated with the supernova remnant W28. Absorption components at both high positive and high negative velocity are seen in the interstellar Na i D and Ca ii H and K lines towards CD−23 13777. The high-velocity components exhibit low Na i/Ca ii ratios, suggesting efficient grain destruction by shock sputtering. High column densities of CH+, and high CH+/CH ratios, for the components seen at lower velocity may be indicative of enhanced turbulence in the clouds interacting with W28. The highest positive and negative velocities of the components seen in Na i and Ca ii absorption towards CD−23 13777 imply that the velocity of the blast wave associated with W28 is at least 150 km s−1, a value that is significantly higher than most previous estimates. The line of sight to CD−23 13777 passes very close to a well-known site of interaction between the supernova remnant and a molecular cloud to the north-east. The north-east molecular cloud exhibits broad molecular line emission, OH maser emission from numerous locations, and bright extended GeV and TeV γ-ray emission. The sightline to CD−23 13777 is thus a unique and valuable probe of the interaction between W28 and dense molecular gas in its environs. Future observations at ultraviolet and visible wavelengths will help to better constrain the abundances, kinematics, and physical conditions in the shocked and quiescent gas along this line of sight.