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OBJECTIVES/GOALS: Time restricted feeding (TRF) in diet induced obesity (DIO) has several health benefits, including improved metabolic rhythms and inflammation. Our lab has shown that TRF in DIO significantly reduces renal and aortic damage. The main goal of our research is to understand how TRF impacts aortic function, organ damage, and T cell activation in DIO. METHODS/STUDY POPULATION: We will use a 20-week DIO model, where mice will be on 20 weeks of normal fat diet (ND) or high fat diet (HFD). During weeks 18-20, mice will go through TRF intervention
where food is restricted to the 12-hour active period or continue ad libitum feeding. At the end of the 2-week TRF intervention or continued ad libitum feeding, aortic stiffness will be measured via pulse wave velocity measurements. We will also collect kidney, aorta, and small intestine at the end of the 20-week protocol for flow cytometric analysis of tissue T cell activation as well as histological assessments. This will allow us to determine the relationship with organ damage, organ function, and the T cell response. We will also analyze tissue and circulating levels of inflammatory T cell-derived cytokines such as interleukin-17A (IL-17A) via ELISA. RESULTS/ANTICIPATED RESULTS: DIO mice showed significantly increased aortic stiffness (measured by pulse wave velocity) compared to mice on ND. Interestingly, TRF intervention in DIO mice reduced aortic stiffness compared to DIO ad libitum. Histological assessments also showed that TRF abolished aortic and kidney fibrosis suggesting a role for the timing of feeding in regulating aortic function and organ damage from chronic HFD. We have several ongoing experiments to determine the T cell response with TRF in DIO mice. We predict that TRF in DIO mice will significantly decrease inflammatory T cells and reduce cytokine abundance in target organs. DISCUSSION/SIGNIFICANCE: Our lab has shown that TRF reduces aortic thickness and aortic and kidney fibrosis, but the driving mechanisms are unknown. We propose that TRF reduces T cell activation in DIO mice leading to reduced organ damage. Our work will provide insight on how TRF in DIO regulates the T cell response and may improve inflammation in the kidney and aorta.
This paper proposes a novel origami-inspired adult diaper design that improves discretion by reducing sag and increasing wicking across the entire diaper pad. While other diapers rely on supporting elastics to reduce the sag of the diaper as a whole, this paper proposes an absorbent core that uses liquid activated shaping to take a specified shape. Origami-based folds are also incorporated into the diaper design to increase wicking performance. The paper introduces a disposable compliant mechanism waistband used to deploy the diaper, making it easier to put onto one’s body.
Identifying the most effective ways to support career development of early stage investigators in clinical and translational science should yield benefits for the biomedical research community. Institutions with Clinical and Translational Science Awards (CTSA) offer KL2 programs to facilitate career development; however, the sustained impact has not been widely assessed.
Methods:
A survey comprised of quantitative and qualitative questions was sent to 2144 individuals that had previously received support through CTSA KL2 mechanisms. The 547 responses were analyzed with identifying information redacted.
Results:
Respondents held MD (47%), PhD (36%), and MD/PhD (13%) degrees. After KL2 support was completed, physicians’ time was divided 50% to research and 30% to patient care, whereas PhD respondents devoted 70% time to research. Funded research effort averaged 60% for the cohort. Respondents were satisfied with their career progression. More than 95% thought their current job was meaningful. Two-thirds felt confident or very confident in their ability to sustain a career in clinical and translational research. Factors cited as contributing to career success included protected time, mentoring, and collaborations.
Conclusion:
This first large systematic survey of KL2 alumni provides valuable insight into the group’s perceptions of the program and outcome information. Former scholars are largely satisfied with their career choice and direction, national recognition of their expertise, and impact of their work. Importantly, they identified training activities that contributed to success. Our results and future analysis of the survey data should inform the framework for developing platforms to launch sustaining careers of translational scientists.
We examined whether preadmission history of depression is associated with less delirium/coma-free (DCF) days, worse 1-year depression severity and cognitive impairment.
Design and measurements:
A health proxy reported history of depression. Separate models examined the effect of preadmission history of depression on: (a) intensive care unit (ICU) course, measured as DCF days; (b) depression symptom severity at 3 and 12 months, measured by the Beck Depression Inventory-II (BDI-II); and (c) cognitive performance at 3 and 12 months, measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) global score.
Setting and participants:
Patients admitted to the medical/surgical ICU services were eligible.
Results:
Of 821 subjects eligible at enrollment, 261 (33%) had preadmission history of depression. After adjusting for covariates, preadmission history of depression was not associated with less DCF days (OR 0.78, 95% CI, 0.59–1.03 p = 0.077). A prior history of depression was associated with higher BDI-II scores at 3 and 12 months (3 months OR 2.15, 95% CI, 1.42–3.24 p = <0.001; 12 months OR 1.89, 95% CI, 1.24–2.87 p = 0.003). We did not observe an association between preadmission history of depression and cognitive performance at either 3 or 12 months (3 months beta coefficient −0.04, 95% CI, −2.70–2.62 p = 0.97; 12 months 1.5, 95% CI, −1.26–4.26 p = 0.28).
Conclusion:
Patients with a depression history prior to ICU stay exhibit a greater severity of depressive symptoms in the year after hospitalization.
The GaLactic and Extragalactic All-sky Murchison Widefield Array (GLEAM) is a radio continuum survey at 76–227 MHz of the entire southern sky (Declination
$<\!{+}30^{\circ}$
) with an angular resolution of
${\approx}2$
arcmin. In this paper, we combine GLEAM data with optical spectroscopy from the 6dF Galaxy Survey to construct a sample of 1 590 local (median
$z \approx 0.064$
) radio sources with
$S_{200\,\mathrm{MHz}} > 55$
mJy across an area of
${\approx}16\,700\,\mathrm{deg}^{2}$
. From the optical spectra, we identify the dominant physical process responsible for the radio emission from each galaxy: 73% are fuelled by an active galactic nucleus (AGN) and 27% by star formation. We present the local radio luminosity function for AGN and star-forming (SF) galaxies at 200 MHz and characterise the typical radio spectra of these two populations between 76 MHz and
${\sim}1$
GHz. For the AGN, the median spectral index between 200 MHz and
${\sim}1$
GHz,
$\alpha_{\mathrm{high}}$
, is
$-0.600 \pm 0.010$
(where
$S \propto \nu^{\alpha}$
) and the median spectral index within the GLEAM band,
$\alpha_{\mathrm{low}}$
, is
$-0.704 \pm 0.011$
. For the SF galaxies, the median value of
$\alpha_{\mathrm{high}}$
is
$-0.650 \pm 0.010$
and the median value of
$\alpha_{\mathrm{low}}$
is
$-0.596 \pm 0.015$
. Among the AGN population, flat-spectrum sources are more common at lower radio luminosity, suggesting the existence of a significant population of weak radio AGN that remain core-dominated even at low frequencies. However, around 4% of local radio AGN have ultra-steep radio spectra at low frequencies (
$\alpha_{\mathrm{low}} < -1.2$
). These ultra-steep-spectrum sources span a wide range in radio luminosity, and further work is needed to clarify their nature.
Diagnosis of CHD substantially affects parent mental health and family functioning, thereby influencing child neurodevelopmental and psychosocial outcomes. Recognition of the need to proactively support parent mental health and family functioning following cardiac diagnosis to promote psychosocial adaptation has increased substantially over recent years. However, significant gaps in knowledge remain and families continue to report critical unmet psychosocial needs. The Parent Mental Health and Family Functioning Working Group of the Cardiac Neurodevelopmental Outcome Collaborative was formed in 2018 through support from an R13 grant from the National Heart, Lung, and Blood Institute to identify significant knowledge gaps related to parent mental health and family functioning, as well as critical questions that must be answered to further knowledge, policy, care, and outcomes. Conceptually driven investigations are needed to identify parent mental health and family functioning factors with the strongest influence on child outcomes, to obtain a deeper understanding of the biomarkers associated with these factors, and to better understand how parent mental health and family functioning influence child outcomes over time. Investigations are also needed to develop, test, and implement sustainable models of mental health screening and assessment, as well as effective interventions to optimise parent mental health and family functioning to promote psychosocial adaptation. The critical questions and investigations outlined in this paper provide a roadmap for future research to close gaps in knowledge, improve care, and promote positive outcomes for families of children with CHD.
Although mania is the hallmark symptom of bipolar I disorder (BD-I), most patients initially present for treatment with depressive symptoms. Misdiagnosis of BD-I as major depressive disorder (MDD) is common, potentially resulting in poor outcomes and inappropriate antidepressant monotherapy treatment. Screening patients with depressive symptoms is a practical strategy to help healthcare providers (HCPs) identify when additional assessment for BD-I is warranted. The new 6-item Rapid Mood Screener (RMS) is a pragmatic patient-reported BD-I screening tool that relies on easily understood terminology to screen for manic symptoms and other BD-I features in <2 minutes. The RMS was validated in an observational study in patients with clinically confirmed BD-I (n=67) or MDD (n=72). When 4 or more items were endorsed (“yes”), the sensitivity of the RMS for identifying patients with BP-I was 0.88 and specificity was 0.80; positive and negative predictive values were 0.80 and 0.88, respectively. To more thoroughly understand screening tool use among HCPs, a 10-minute survey was conducted.
Methods
A nationwide sample of HCPs (N=200) was selected using multiple HCP panels; HCPs were asked to describe their opinions/current use of screening tools, assess the RMS, and evaluate the RMS versus the widely recognized Mood Disorder Questionnaire (MDQ). Results were reported by grouped specialties (primary care physicians, general nurse practitioners [NPs]/physician assistants [PAs], psychiatrists, and psychiatric NPs/PAs). Included HCPs were in practice <30 years, spent at least 75% of their time in clinical practice, saw at least 10 patients with depression per month, and diagnosed MDD or BD in at least 1 patient per month. Findings were reported using descriptive statistics; statistical significance was reported at the 95% confidence interval.
Results
Among HCPs, 82% used a tool to screen for MDD, while 32% used a tool for BD. Screening tool attributes considered to be of the greatest value included sensitivity (68%), easy to answer questions (66%), specificity (65%), confidence in results (64%), and practicality (62%). Of HCPs familiar with screening tools, 70% thought the RMS was at least somewhat better than other screening tools. Most HCPs were aware of the MDQ (85%), but only 29% reported current use. Most HCPs (81%) preferred the RMS to the MDQ, and the RMS significantly outperformed the MDQ across valued attributes; 76% reported that they were likely to use the RMS to screen new patients with depressive symptoms. A total of 84% said the RMS would have a positive impact on their practice, with 46% saying they would screen more patients for bipolar disorder.
Discussion
The RMS was viewed positively by HCPs who participated in a brief survey. A large percentage of respondents preferred the RMS over the MDQ and indicated that they would use it in their practice. Collectively, responses indicated that the RMS is likely to have a positive impact on screening behavior.
People with CHD are at increased risk for executive functioning deficits. Meta-analyses of these measures in CHD patients compared to healthy controls have not been reported.
Objective:
To examine differences in executive functions in individuals with CHD compared to healthy controls.
Data sources:
We performed a systematic review of publications from 1 January, 1986 to 15 June, 2020 indexed in PubMed, CINAHL, EMBASE, PsycInfo, Web of Science, and the Cochrane Library.
Study selection:
Inclusion criteria were (1) studies containing at least one executive function measure; (2) participants were over the age of three.
Data extraction:
Data extraction and quality assessment were performed independently by two authors. We used a shifting unit-of-analysis approach and pooled data using a random effects model.
Results:
The search yielded 61,217 results. Twenty-eight studies met criteria. A total of 7789 people with CHD were compared with 8187 healthy controls. We found the following standardised mean differences: −0.628 (−0.726, −0.531) for cognitive flexibility and set shifting, −0.469 (−0.606, −0.333) for inhibition, −0.369 (−0.466, −0.273) for working memory, −0.334 (−0.546, −0.121) for planning/problem solving, −0.361 (−0.576, −0.147) for summary measures, and −0.444 (−0.614, −0.274) for reporter-based measures (p < 0.001).
Limitations:
Our analysis consisted of cross-sectional and observational studies. We could not quantify the effect of collinearity.
Conclusions:
Individuals with CHD appear to have at least moderate deficits in executive functions. Given the growing population of people with CHD, more attention should be devoted to identifying executive dysfunction in this vulnerable group.
In this paper, we describe the system design and capabilities of the Australian Square Kilometre Array Pathfinder (ASKAP) radio telescope at the conclusion of its construction project and commencement of science operations. ASKAP is one of the first radio telescopes to deploy phased array feed (PAF) technology on a large scale, giving it an instantaneous field of view that covers $31\,\textrm{deg}^{2}$ at $800\,\textrm{MHz}$. As a two-dimensional array of 36$\times$12 m antennas, with baselines ranging from 22 m to 6 km, ASKAP also has excellent snapshot imaging capability and 10 arcsec resolution. This, combined with 288 MHz of instantaneous bandwidth and a unique third axis of rotation on each antenna, gives ASKAP the capability to create high dynamic range images of large sky areas very quickly. It is an excellent telescope for surveys between 700 and $1800\,\textrm{MHz}$ and is expected to facilitate great advances in our understanding of galaxy formation, cosmology, and radio transients while opening new parameter space for discovery of the unknown.
Antisaccade tasks can be used to index cognitive control processes, e.g. attention, behavioral inhibition, working memory, and goal maintenance in people with brain disorders. Though diagnoses of schizophrenia (SZ), schizoaffective (SAD), and bipolar I with psychosis (BDP) are typically considered to be distinct entities, previous work shows patterns of cognitive deficits differing in degree, rather than in kind, across these syndromes.
Methods
Large samples of individuals with psychotic disorders were recruited through the Bipolar-Schizophrenia Network on Intermediate Phenotypes 2 (B-SNIP2) study. Anti- and pro-saccade task performances were evaluated in 189 people with SZ, 185 people with SAD, 96 people with BDP, and 279 healthy comparison participants. Logistic functions were fitted to each group's antisaccade speed-performance tradeoff patterns.
Results
Psychosis groups had higher antisaccade error rates than the healthy group, with SZ and SAD participants committing 2 times as many errors, and BDP participants committing 1.5 times as many errors. Latencies on correctly performed antisaccade trials in SZ and SAD were longer than in healthy participants, although error trial latencies were preserved. Parameters of speed-performance tradeoff functions indicated that compared to the healthy group, SZ and SAD groups had optimal performance characterized by more errors, as well as less benefit from prolonged response latencies. Prosaccade metrics did not differ between groups.
Conclusions
With basic prosaccade mechanisms intact, the higher speed-performance tradeoff cost for antisaccade performance in psychosis cases indicates a deficit that is specific to the higher-order cognitive aspects of saccade generation.
To evaluate age-related differences in the independent/combined association of added sugar intake from soda and body adiposity with hyperuricaemia in gender-stratified US adults.
Design:
Consumption of added sugar from soda was calculated from 24-h dietary interviews and categorised into none, regular and excessive consumption. Hyperuricaemia was defined as serum uric acid levels >417 mmol/l in men and >357 mmol/l in women. Multiple regression models with interaction terms and logistic models adjusted for covariates were conducted under survey-data modules.
Setting:
National Health and Nutrition Examination Survey during 2007–2016.
Participants:
15 338 adults without gout, failing kidneys, an estimated glomerular filtration rate < 30 or diabetes were selected.
Results:
The age-stratified prevalence rate of hyperuricaemia was 18·8–20·4 % in males and 6·8–17·3 % in females. Hyperuricaemia prevalence of approximately 50 % was observed in young and middle age males who consumed excessive added sugar from soda. Excessive added sugar intake was observed to be associated with 1·5- to 2·0-fold and 2·0- to 2·3-fold increased risk of the probability of hyperuricaemia in young and middle age males and middle age females, respectively. Study participants, regardless of age or gender, who were obese and consumed excessive added sugar from soda had the highest risk of having hyperuricaemia.
Conclusions:
Our study revealed that the association between hyperuricaemia and consumption of excessive added sugar from soda may vary by age and gender. Obese adults who consumed excessive added sugar from soda had the highest risk of hyperuricaemia, a finding that was found across all age-specific groups for both genders.
ON SEPTEMBER 23, 1904 a new adaptation of Frank Wedekind's Erdgeist premiered at the Neues Theater in Berlin, directed by Max Reinhardt. The production starred Gertrud Eysoldt in the lead as Lulu and, contributing to its novelty, it featured Wedekind himself as the Tierbändiger (animal tamer) in the prologue. At the beginning of the play, Wedekind stepped out from behind the curtain dressed in an iconic ringmaster's costume to deliver the opening lines (figure 3.1):
Walk in! Into the menagerie,
You proud gents, you boisterous women,
With hot desire, and cold dread,
To see the soulless creature,
Tamed by human genius.
The poetic monologue rehearses a well-established opposition between animal and man, who is made master by his intellect and soul. The animal's subjugation on display promises to affirm man's superiority. The Berliner Morgenpost reports that Wedekind “praised the beasts of his circus, all of which he commanded, and introduced a delectable rarity, a poisonous snake: Ms. Eysoldt was carried onto the stage in the pierrot costume of the first act.” The Tierbändiger continues: “She was made to incite calamity / to lure, to seduce, to poison— / to murder without anyone feeling a thing.” To demonstrate his lack of fear and his complete mastery over the deadly creature, he then scratches under her chin like a house pet as he calls her “my sweet beast” (ibid.).
With the overt equation that Wedekind draws between the figure of Lulu and animal predators in the dramatic prologue to Erdgeist it is fitting that reviews of the 1904 stage production also used zoomorphic rhetoric. Critics wrote about “Ms. Eysoldt the all-conquering snake,” or the “snake-woman in the guise of Lulu-Eysoldt.” They praised Eysoldt's performance in the role, to which she brought her “her snake-like grace [Schlangengrazie].” For others, Eysoldt's Lulu was perhaps too convincing and too naturally assimilated. A reviewer for the Volkszeitung comments: “With what uncanny naturalness she plays this snake in human form, this woman, who without conscious reflection coldly steps over the corpses of the men who worship her, and in the end drives the only man who ever loved her to ruin and fires a pistol at him.”
“THE PROBLEM OF the actor has disquieted me the longest,” Friedrich Nietzsche confessed in 1887. In the expanded, second edition of Die fröhliche Wissenschaft (The Gay Science) he addresses this concern in §361, “On the Problem of the Actor.” He wonders whether the actor might give him access to the “dangerous conception of ‘artist’” (ibid.) that preoccupies him throughout the book. For Nietzsche, the actor comprises: “Falsity with good conscience; delight in dissimulation breaking forth as power, pushing aside, overflowing, and sometimes extinguishing the so-called ‘character’ (Charakter); the inner longing for a role and mask, for an appearance (Schein)” (ibid.). Establishing the actor as a problem, Nietzsche foregrounds his concern with the relationship between Charakter, that is selfhood or one's very being, and Schein, appearance, or more specifically in this case, performance. Not surprisingly, Nietzsche is also interested in how performance enables individuals to attain power. While he first frames the problem of the actor in relation to modern man generally, moreover, the question becomes more urgent when he ties the propensity for acting to those who should not be powerful: lower-class men, Jews, and, most essentially, women. Concluding §361 he asks: “If we consider the whole history of women, are they not obliged first of all, and above all to be actresses?” (ibid., 226). Nietzsche's problem of the actor thus becomes the problem of the actress.
This book borrows its title from Nietzsche; however, he was certainly not the only modern thinker to contemplate the problem of the actress or to find it disquieting. In the late nineteenth and early twentieth centuries, when the so-called Frauenfrage (woman question) was among the most pressing matters of the age, across the broadest spectrum of modern German and Austrian culture and thought the actress emerged as a recurring, powerful, and highly complex figure. Female performers captured public interest on and off the stage. Actresses featured prominently in modernist literary works across genres. Painters and writers frequently chose actresses as their muses, portraying them in and out of character (figure Many artists, authors, and other public figures had significant including Corinth, August Renoir, and Franz von Stuck, who produced numerous studies of the actress.
ADDRESSING THE “particular allure that the actress has always exercised over the world of men,” Heinrich Stümcke foregrounds an affinity between authors and actresses, writing: “It is precisely the poet who sees in the actress a corporeal embodiment of his dreams, the shaper of his wishes and hopes [die Gestalterin seiner Wünsche und Hoffnungen].” Here Stümcke offers a conflicted dynamic in the actress-author relationship. On the one hand, he presents the actress as a passive carrier, a body animated by the author's imagination. On the other, he attributes to the actress a semi-agentic status by combining the active feminine noun Gestalterin and the genitive seiner, which assigns creative agency to the poet. In the next sentence he further suggests: “yet another thing about [the actress] has tingling allure: the knowledge that the beloved woman is the object of the wishes and desires of countless hundreds, who powerlessly bounce off of her like arrows fired too short” (ibid., 101–2). Foregrounding the actress as an object of desire and implying the author's exclusive right to that object, he formalizes active-passive, subject-object positions in the author-actress relationship. In doing so, he also summons the centuries-old fantasy of artist and muse in its gender-specific relational, aesthetic, and erotic dimensions.
Stümcke was not wrong to identify a notable affinity between authors and actresses at the turn of the century. Several modernist writers had significant personal relationships—sibling bonds, friendships, affairs, marriages—with one or more actress-muses. Arthur Schnitzler, Frank Wedekind, and Heinrich Mann are among the most prominent. Dramatic authors were, not surprisingly, particularly apt to have close affiliation with actresses. They often collaborated with theater directors and companies on new productions of their work and thus had frequent contact and at times intensive working relationships with the actresses who performed in their plays. Ties to a prominent author or artist could also be advantageous to an actress. The connection could lead to roles in stage productions, contracts with desirable theater companies, and contact with other important artists and public figures. The partnership could be mutually beneficial, defined by respect and co-productive creative exchange. Some authors jealously guarded their protégées, however, at times even preventing them from performing in plays by other authors.
IN THE EARLY TWENTIETH CENTURY, the magazine Das Theater published a survey on the question, “Sollen Künstlerinnen heiraten?” (Should Female Artists Marry?). Numerous actresses responded to the poll with differing opinions on the matter. One answered: “In principle I say no; because the greatest sphere of the married woman, being a mother and housewife, is unfortunately very difficult to fulfill” (ibid.). Similar replies outlined the demanding work schedule of the career, concluding that between rehearsals and performances, sewing costumes, and frequent travel, actresses had little time for life outside of the theater. Some flatly denied the possibility for a woman to be an actress, a wife, and a mother. Yet others refuted this claim with personal experience: “I can also say completely objectively that I am a very good housewife, which proves that the artistic career and the domestic can be combined very well” (ibid.). Still others argued that marriage and motherhood were in fact essential to expanding the actress's repertoire. “Stage performers should marry,” Else Wassermann (of the Deutsches Theater) wrote, “because in order to represent the character of many kinds of beings truly, the artist must be familiar with love and sorrow, joy and grief in her own life” (ibid.).
Answering the seemingly straightforward question that the survey posed, the women who responded revealed the complex sociocultural circumstances and a field of ideas encapsulated in the recurring juxtaposition of actress as woman and woman as actress. In Julius Bab and Heinrich Stümcke's two studies of Die Frau als Schauspielerin and in other texts from the period a paradox emerges in simultaneous claims that women are naturally actresses, and that being an actress goes against woman's natural instinct as wife and mother. Bab summarizes the contrast, writing: “While many alluring and compelling possibilities bring woman to the art of acting, just as many deep-seated inhibitions remain and make ‘woman as actress’ into a problematic nature” (FaS, 39). In almost every respect, working actresses did not conform to normative cultural expectations for German women at the turn of the twentieth century; yet Heinrich Mann would assert through one of his dramatic characters: “the quintessential woman is above all the actress.”