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The output of many healthy physiological systems displays fractal fluctuations with self-similar temporal structures. Altered fractal patterns are associated with pathological conditions. There is evidence that patients with bipolar disorder have altered daily behaviors.
To test whether fractal patterns in motor activity are altered in patients with bipolar disorder, we analyzed 2-week actigraphy data collected from 106 patients with bipolar disorder type I in a euthymic state, 73 unaffected siblings of patients, and 76 controls. To examine the link between fractal patterns and symptoms, we analyzed 180-day actigraphy and mood symptom data that were simultaneously collected from 14 patients.
Compared to controls, patients showed excessive regularity in motor activity fluctuations at small time scales (<1.5 h) as quantified by a larger scaling exponent (α1 > 1), indicating a more rigid motor control system. α1 values of siblings were between those of patients and controls. Further examinations revealed that the group differences in α1 were only significant in females. Sex also affected the group differences in fractal patterns at larger time scales (>2 h) as quantified by scaling exponent α2. Specifically, female patients and siblings had a smaller α2 compared to female controls, indicating more random activity fluctuations; while male patients had a larger α2 compared to male controls. Interestingly, a higher weekly depression score was associated with a lower α1 in the subsequent week.
Our results show sex- and scale-dependent alterations in fractal activity regulation in patients with bipolar disorder. The mechanisms underlying the alterations are yet to be determined.
Neurocognitive impairments robustly predict functional outcome. However, heterogeneity in neurocognition is common within diagnostic groups, and data-driven analyses reveal homogeneous neurocognitive subgroups cutting across diagnostic boundaries.
To determine whether data-driven neurocognitive subgroups of young people with emerging mental disorders are associated with 3-year functional course.
Model-based cluster analysis was applied to neurocognitive test scores across nine domains from 629 young people accessing mental health clinics. Cluster groups were compared on demographic, clinical and substance-use measures. Mixed-effects models explored associations between cluster-group membership and socio-occupational functioning (using the Social and Occupational Functioning Assessment Scale) over 3 years, adjusted for gender, premorbid IQ, level of education, depressive, positive, negative and manic symptoms, and diagnosis of a primary psychotic disorder.
Cluster analysis of neurocognitive test scores derived three subgroups described as ‘normal range’ (n = 243, 38.6%), ‘intermediate impairment’ (n = 252, 40.1%), and ‘global impairment’ (n = 134, 21.3%). The major mental disorder categories (depressive, anxiety, bipolar, psychotic and other) were represented in each neurocognitive subgroup. The global impairment subgroup had lower functioning for 3 years of follow-up; however, neither the global impairment (B = 0.26, 95% CI −0.67 to 1.20; P = 0.581) or intermediate impairment (B = 0.46, 95% CI −0.26 to 1.19; P = 0.211) subgroups differed from the normal range subgroup in their rate of change in functioning over time.
Neurocognitive impairment may follow a continuum of severity across the major syndrome-based mental disorders, with data-driven neurocognitive subgroups predictive of functional course. Of note, the global impairment subgroup had longstanding functional impairment despite continuing engagement with clinical services.
Birth order has long been thought to have a lasting influence on people’s lives through its effects on social customs and by fostering individual differences in personality and social behavior. Historically, birth order has been linked with well-documented differences in professional opportunities and achievement, emigration patterns, likelihood of reproduction, mortality rates, inheritance practices, and the politics of royal succession (Altus, 1966; Boone, 1986; Bu, 2016; Duby, 1977; Galton, 1874; Herlihy, 1977; Hrdy & Judge, 1993; Sulloway, 1996). An analysis of birth order and the social customs in 39 non-Western societies found that firstborns generally receive more extensive birth ceremonies than do their younger siblings, are allotted special privileges, and, even in adulthood, exert authority over their brothers and sisters (Rosenblaat & Skoogberg, 1974). Additionally, firstborns in these 39 societies received a greater share of parental property than did laterborns.
In June 2017, an outbreak of Salmonella Kottbus infection was suspected in Germany. We investigated the outbreak with whole-genome sequencing (WGS) and a case–control study. Forty-six isolates from 69 cases were subtyped. Three WGS clusters were identified: cluster 1 (n = 36), cluster 2 (n = 5) and cluster 3 (n = 3). Compared to controls, cluster 1 cases more frequently consumed raw smoked ham (odds ratio (OR) 10, 95% confidence interval (CI) 1.2–88) bought at supermarket chain X (OR 36, 95% CI 4–356; 9/10 consumed ham Y). All four cluster 2 cases interviewed had consumed quail eggs. Timely WGS was invaluable in distinguishing concurrent outbreaks of a rare Salmonella serotype.
To evaluate the National Health Safety Network (NHSN) hospital-onset Clostridioides difficile infection (HO-CDI) standardized infection ratio (SIR) risk adjustment for general acute-care hospitals with large numbers of intensive care unit (ICU), oncology unit, and hematopoietic cell transplant (HCT) patients.
Retrospective cohort study.
Eight tertiary-care referral general hospitals in California.
We used FY 2016 data and the published 2015 rebaseline NHSN HO-CDI SIR. We compared facility-wide inpatient HO-CDI events and SIRs, with and without ICU data, oncology and/or HCT unit data, and ICU bed adjustment.
For these hospitals, the median unmodified HO-CDI SIR was 1.24 (interquartile range [IQR], 1.15–1.34); 7 hospitals qualified for the highest ICU bed adjustment; 1 hospital received the second highest ICU bed adjustment; and all had oncology-HCT units with no additional adjustment per the NHSN. Removal of ICU data and the ICU bed adjustment decreased HO-CDI events (median, −25%; IQR, −20% to −29%) but increased the SIR at all hospitals (median, 104%; IQR, 90%–105%). Removal of oncology-HCT unit data decreased HO-CDI events (median, −15%; IQR, −14% to −21%) and decreased the SIR at all hospitals (median, −8%; IQR, −4% to −11%).
For tertiary-care referral hospitals with specialized ICUs and a large number of ICU beds, the ICU bed adjustor functions as a global adjustment in the SIR calculation, accounting for the increased complexity of patients in ICUs and non-ICUs at these facilities. However, the SIR decrease with removal of oncology and HCT unit data, even with the ICU bed adjustment, suggests that an additional adjustment should be considered for oncology and HCT units within general hospitals, perhaps similar to what is done for ICU beds in the current SIR.
Neonatal aortic thrombosis is a rare occurrence but can be life-threatening. Most aortic thrombosis in neonates is related to umbilical artery catheters. A case of a neonate with a spontaneous aortic thrombosis is described here along with a comprehensive review of the literature for cases of neonatal aortic thrombosis not related to any intravascular device or procedure. The aetiologies of these spontaneous thromboses and the relevance of hypercoagulable disorders are discussed. The cases were analysed for odds of death by treatment method adjusted for era. The reference treatment method was thrombolysis and anticoagulation. No other treatment modality had significantly lower odds than the reference. Surgery alone had higher odds for death than the reference, but this may be confounded by severity of case. The management recommendations for clinicians encountering neonates with spontaneous neonatal aortic thrombosis are discussed.
Post-traumatic stress disorder (PTSD) is a serious mental disorder that develops in some individuals following exposure to severe psychological stressors. In this chapter, we provide an overview of the conceptual issues, specific methods, and practical considerations in evidence-based assessment of PTSD. First, we outline the conceptual issues and practical components of a comprehensive assessment of PTSD. Second, we provide an overview of the most widely used self-rated and clinician-rated measures of trauma exposure and PTSD, comorbid disorders, and response bias. Third, we discuss cultural considerations in assessing PTSD. Fourth, we offer practical guidelines for conducting a clinically sensitive assessment of PTSD, highlighting some of the unique considerations in engaging trauma survivors in the assessment process and optimizing the information obtained. Last, we briefly summarize conceptual considerations and specific measures for other trauma- and stressor-related disorders.
Several studies have reported diminished learning from non-social outcomes in depressed individuals. However, it is not clear how depression impacts learning from social feedback. Notably, mood disorders are commonly associated with deficits in social functioning, which raises the possibility that potential impairments in social learning may negatively affect real-life social experiences in depressed subjects.
Ninety-two participants with high (HD; N = 40) and low (LD; N = 52) depression scores were recruited. Subjects performed a learning task, during which they received monetary outcomes or social feedback which they were told came from other people. Additionally, participants answered questions about their everyday social experiences. Computational models were fit to the data and model parameters were related to social experience measures.
HD subjects reported a reduced quality and quantity of social experiences compared to LD controls, including an increase in the amount of time spent in negative social situations. Moreover, HD participants showed lower learning rates than LD subjects in the social condition of the task. Interestingly, across all participants, reduced social learning rates predicted higher amounts of time spent in negative social situations, even when depression scores were controlled for.
These findings indicate that deficits in social learning may affect the quality of everyday social experiences. Specifically, the impaired ability to use social feedback to appropriately update future actions, which was observed in HD subjects, may lead to suboptimal interpersonal behavior in real life. This, in turn, may evoke negative feedback from others, thus bringing about more unpleasant social encounters.
To apply a dietary modelling approach to investigate the impact of substituting beef intakes with three types of alternative fatty acid (FA) composition of beef on population dietary fat intakes.
Cross-sectional, national food consumption survey – the National Adult Nutrition Survey (NANS). The fat content of the beef-containing food codes (n 52) and recipes (n 99) were updated with FA composition data from beef from animals receiving one of three ruminant dietary interventions: grass-fed (GRASS), grass finished on grass silage and concentrates (GSC) or concentrate-fed (CONC). Mean daily fat intakes, adherence to dietary guidelines and the impact of altering beef FA composition on dietary fat sources were characterised.
Beef consumers (n 1044) aged 18–90 years.
Grass-based feeding practices improved dietary intakes of a number of individual FA, wherein myristic acid (C14 : 0) and palmitic acid (C16 : 0) were decreased, with an increase in conjugated linoleic acid (C18 : 2c9,t11) and trans-vaccenic acid (C18 : 1t11; P < 0·05). Improved adherence with dietary recommendations for total fat (98·5 %), SFA (57·4 %) and PUFA (98·8 %) was observed in the grass-fed beef scenario (P < 0·001). Trans-fat intakes were increased significantly in the grass-fed beef scenario (P < 0·001).
To the best of our knowledge, the present study is the first to characterise the impact of grass-fed beef consumption at population level. The study suggests that habitual consumption of grass-fed beef may have potential as a public health strategy to improve dietary fat quality.
Distinguishing between hypertrophic cardiomyopathy and other causes ofleft ventricular hypertrophy can be difficult in children. We hypothesised that cardiac MRI T1 mapping could improve diagnosis of paediatric hypertrophic cardiomyopathy and that measures of myocardial function would correlate with T1 times and extracellular volume fraction.
Thirty patients with hypertrophic cardiomyopathy completed MRI with tissue tagging, T1-mapping, and late gadolinium enhancement. Left ventricular circumferential strain was calculated from tagged images. T1, partition coefficient, and synthetic extracellular volume were measured at base, mid, apex, and thickest area of myocardial hypertrophy. MRI measures compared to cohort of 19 healthy children and young adults. Mann–Whitney U, Spearman’s rho, and multivariable logistic regression were used for statistical analysis.
Hypertrophic cardiomyopathy patients had increased left ventricular ejection fraction and indexed mass. Hypertrophic cardiomyopathy patients had decreased global strain and increased native T1 (−14.3% interquartile range [−16.0, −12.1] versus −17.3% [−19.0, −15.7], p < 0.001 and 1015 ms [991, 1026] versus 990 ms [972, 1001], p = 0.019). Partition coefficient and synthetic extracellular volume were not increased in hypertrophic cardiomyopathy. Global native T1 correlated inversely with ejection fraction (ρ = −0.63, p = 0.002) and directly with global strain (ρ = 0.51, p = 0.019). A logistic regression model using ejection fraction and native T1 distinguished between hypertrophic cardiomyopathy and control with an area under the receiver operating characteristic curve of 0.91.
In this cohort of paediatric hypertrophic cardiomyopathy, strain was decreased and native T1 was increased compared with controls. Native T1 correlated with both ejection fraction and strain, and a model using native T1 and ejection fraction differentiated patients with and without hypertrophic cardiomyopathy.
The science of studying diamond inclusions for understanding Earth history has developed significantly over the past decades, with new instrumentation and techniques applied to diamond sample archives revealing the stories contained within diamond inclusions. This chapter reviews what diamonds can tell us about the deep carbon cycle over the course of Earth’s history. It reviews how the geochemistry of diamonds and their inclusions inform us about the deep carbon cycle, the origin of the diamonds in Earth’s mantle, and the evolution of diamonds through time.
Apolipoprotein E (APOE) E4 is the main genetic risk factor for Alzheimer’s disease (AD). Due to the consistent association, there is interest as to whether E4 influences the risk of other neurodegenerative diseases. Further, there is a constant search for other genetic biomarkers contributing to these phenotypes, such as microtubule-associated protein tau (MAPT) haplotypes. Here, participants from the Ontario Neurodegenerative Disease Research Initiative were genotyped to investigate whether the APOE E4 allele or MAPT H1 haplotype are associated with five neurodegenerative diseases: (1) AD and mild cognitive impairment (MCI), (2) amyotrophic lateral sclerosis, (3) frontotemporal dementia (FTD), (4) Parkinson’s disease, and (5) vascular cognitive impairment.
Genotypes were defined for their respective APOE allele and MAPT haplotype calls for each participant, and logistic regression analyses were performed to identify the associations with the presentations of neurodegenerative diseases.
Our work confirmed the association of the E4 allele with a dose-dependent increased presentation of AD, and an association between the E4 allele alone and MCI; however, the other four diseases were not associated with E4. Further, the APOE E2 allele was associated with decreased presentation of both AD and MCI. No associations were identified between MAPT haplotype and the neurodegenerative disease cohorts; but following subtyping of the FTD cohort, the H1 haplotype was significantly associated with progressive supranuclear palsy.
This is the first study to concurrently analyze the association of APOE isoforms and MAPT haplotypes with five neurodegenerative diseases using consistent enrollment criteria and broad phenotypic analysis.
The understanding of the genetic basis of grain dormancy in wheat has rapidly improved in the last few years, and a number of genes have been identified related to that trait. We recently identified the wheat genes TaPM19-A1 and -A2 and we have now taken the first step towards understanding the role of this class of genes in seeds. By investigating the Arabidopsis homologous PM19-Like 1 (PM19L1) we have found that it has a seed-specific expression pattern and, while its expression is higher in dormant than in non-dormant seeds, knock-out mutations produced seeds with increased dormancy. Not only primary dormancy, but also secondary dormancy in response to high temperature was increased by the loss-of-function. We have also examined the function of PM19L1 by localizing the PM19 protein primarily to the cotyledon cells in seeds, possibly in membranes. By investigating the co-expression network of this gene we have found that it is connected to a small group of abscisic acid (ABA)-induced seed maturation and storage-related genes. The function of PM19L1 represents a good opportunity to explore the interactions of key factors that can influence seed dormancy such as ABA, temperature and membrane properties.
Cognitive deficits in depressed adults may reflect impaired decision-making. To investigate this possibility, we analyzed data from unmedicated adults with Major Depressive Disorder (MDD) and healthy controls as they performed a probabilistic reward task. The Hierarchical Drift Diffusion Model (HDDM) was used to quantify decision-making mechanisms recruited by the task, to determine if any such mechanism was disrupted by depression.
Data came from two samples (Study 1: 258 MDD, 36 controls; Study 2: 23 MDD, 25 controls). On each trial, participants indicated which of two similar stimuli was presented; correct identifications were rewarded. Quantile-probability plots and the HDDM quantified the impact of MDD on response times (RT), speed of evidence accumulation (drift rate), and the width of decision thresholds, among other parameters.
RTs were more positively skewed in depressed v. healthy adults, and the HDDM revealed that drift rates were reduced—and decision thresholds were wider—in the MDD groups. This pattern suggests that depressed adults accumulated the evidence needed to make decisions more slowly than controls did.
Depressed adults responded slower than controls in both studies, and poorer performance led the MDD group to receive fewer rewards than controls in Study 1. These results did not reflect a sensorimotor deficit but were instead due to sluggish evidence accumulation. Thus, slowed decision-making—not slowed perception or response execution—caused the performance deficit in MDD. If these results generalize to other tasks, they may help explain the broad cognitive deficits seen in depression.
The current crisis in trade policy affords an important opportunity to reexamine the quality of consent (and its absence) in trade law and policy today. Consent is an essential, constitutive element in trade— without it, we engage in some form of predation, coercion or exploitation, whether or not we call it “trade.” Consent is not only an element in trade between states, however— it is equally important in understanding the internal political and social bargains political communities make when they undertake trade liberalization policies, or what I call the “social contract of trade.” In exchange for pursuing free trade as a policy, a society has an obligation to compensate those within the polity who are vulnerable to trade's downside risks. One way this social obligation is met is through a collection of specialized labor support policies called trade adjustment assistance (TAA), which in the United States is explicitly linked to securing congressional support for free trade negotiations.
In trade terms, the 2016 US presidential election was a wake-up call for many. A significant element within the US polity feels betrayed by our current trade policies and believes that free trade is being imposed on them for others’ benefits, but at a cost for them. This reflects in part the widely acknowledged failure of TAA as it is currently designed and implemented. To restore trade's social contract, TAA needs to be significantly transformed to guarantee effective retraining, relocation support and adequate wage insurance benefits. Funding for a revamped TAA could come from incorporating a financial transaction tax (FTT) into all trade agreements, which would support domestic adjustment assistance programs. This reform will be an effective way to honor the social contract of trade and make it self-sustaining.
Trade and the “Country within the Country”
The social contract of trade
The social contract of trade involves the decisions we make as a society to pursue a free trade policy and, as part of those decisions, the commitments we make to vulnerable groups within our own society who are at risk when we engage in free trade. The choice to enact a free trade regime forms part of what John Rawls calls the “basic structure of a society”: a set of institutions, policies and practices that fundamentally shape the allocation of social resources and the life prospects of a community's members.
IN A LETTER TO Hannah Arendt dated January 9, 1961, Lowell refers to “Pigeons,” his enclosed imitation of Rainer Maria Rilke's “Taube, die draußen blieb” (Pigeon that stayed outside, 1950) as “really my own credo” and wonders if it “isn't quietly my finest poem,” which may reflect his dropping of the confessional “I” of Life Studies (1959). He wanted to put it out of chronological order and have it end his forthcoming Imitations (1961), which began with Homer and would otherwise have finished with Boris Pasternak, who had died in 1960. Lowell separated “Pigeons” from his four other Rilke imitations and dedicated it to Arendt, whom he thanks in the acknowledgments for her help with the German poems. His letter to her had begun “here's the Rilke,” as if she had been expecting it. Best known as a political philosopher, she was also a poet and keen reader of Rilke, with a particular fondness for “Taube, die draußen blieb.” I suspect that Arendt had put Lowell on to it.
This essay first addresses Lowell's poetics in Imitations with regard to how he made Rilke's “Taube, die draußen blieb” a poem of his own featuring two of his major tropes, hands and touch, exile and return, which underlie the “credo” embodied in “Pigeons.” He was probably attracted to Rilke's poem because the same tropes are central to it, and he responded to its rhythmical phrasing by adapting it within his own versification. I read “Pigeons” against the foil of his manic-depressive illness and his stubborn faith in the power of his art to transmute and transcend that illness. My interpretation of the poem along these lines will take account of two important studies as a key to Lowell's poetics, Kay Redfield Jamison's Robert Lowell: Setting the River on Fire—A Study of Genius, Mania, and Character (2017) and Nikki Skillman's The Lyric in the Age of the Brain (2016).
In the introduction, Lowell informs readers of Imitations that it is “partly self-sufficient and separate from its sources, and should be first read as a sequence, one voice running through many personalities, contrasts and repetitions.”
Rapid increases in herbicide resistance have highlighted the ability of weeds to undergo genetic change within a short period of time. That change, in turn, has resulted in an increasing emphasis in weed science on the evolutionary ecology and potential adaptation of weeds to herbicide selection. Here we argue that a similar emphasis would also be invaluable for understanding another challenge that will profoundly alter weed biology: the rapid rise in atmospheric carbon dioxide (CO2) and the associated changes in climate. Our review of the literature suggests that elevated CO2 and climate change will impose strong selection pressures on weeds and that weeds will often have the capacity to respond with rapid adaptive evolution. Based on current data, climate change and rising CO2 levels are likely to alter the evolution of agronomic and invasive weeds, with consequences for distribution, community composition, and herbicide efficacy. In addition, we identify four key areas that represent clear knowledge gaps in weed evolution: (1) differential herbicide resistance in response to a rapidly changing CO2/climate confluence; (2) shifts in the efficacy of biological constraints (e.g., pathogens) and resultant selection shifts in affected weed species; (3) climate-induced phenological shifts in weed distribution, demography, and fitness relative to crop systems; and (4) understanding and characterization of epigenetics and the differential expression of phenotypic plasticity versus evolutionary adaptation. These consequences, in turn, should be of fundamental interest to the weed science community.