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Network analysis (NA) conceptualizes psychiatric disorders as complex dynamic systems of mutually interacting symptoms. Major depressive disorder (MDD) is a heterogeneous clinical condition, and very few studies to date have assessed putative changes in its psychopathological network structure in response to antidepressant (AD) treatment.
In this randomized trial with adult depressed outpatients (n = 151), we estimated Gaussian graphical models among nine core MDD symptom-domains before and after 8 weeks of treatment with either escitalopram or desvenlafaxine. Networks were examined with the measures of cross-sectional and longitudinal structure and connectivity, centrality and predictability as well as stability and accuracy.
At baseline, the most connected MDD symptom-domains were fatigue–cognitive disturbance, whereas at week 8 they were depressed mood–suicidality. Overall, the most central MDD symptom-domains at baseline and week 8 were, respectively, fatigue and depressed mood; in contrast, the most peripheral symptom-domain across both timepoints was appetite/weight disturbance. Furthermore, the psychopathological network at week 8 was significantly more interconnected than at baseline, and they were also structurally dissimilar.
Our findings highlight the utility of focusing on the dynamic interaction between depressive symptoms to better understand how the treatment with ADs unfolds over time. In addition, depressed mood, fatigue, and cognitive/psychomotor disturbance seem to be central MDD symptoms that may be viable targets for novel, focused therapeutic interventions.
Lymphopenia is common in adults who have had a Fontan operation although its aetiology and clinical implications remain unknown. Previous work suggests an association between lymphopenia and both liver disease and splenomegaly. The objective of this study was to assess the prevalence of lymphopenia in adults with a Fontan circulation and evaluate its associations with risk factors and clinical outcomes. Using a retrospective cohort study design, we studied 73 adult Fontan patients (age 25.0 ± 8.4 years) who had a complete blood count and abdominal imaging performed. Patients with protein-losing enteropathy were excluded. Clinical data were extracted from hospital records. The mean white blood cell count was 6580 ± 220/ml with a mean lymphocyte count of 1223 ± 508/ml. Lymphopenia, defined as lymphocyte count <1000/ml, was present in 23 (32%) patients. Patients with lymphopenia had a lower total white blood cell count (5556 ± 2517 versus 7136 ± 1924/ml, p = 0.009) and a lower platelet count (162 ± 69 versus 208 ± 69 k/ml, p = 0.008). Lymphopenia was also associated with findings of portal hypertension, including splenomegaly (36 versus 14%, p = 0.04), varices (22 versus 6%, p = 0.04), and ascites (39 versus 14%, p = 0.02). Lymphopenia did not correlate with any cardiac imaging, haemodynamic or exercise testing variables. In conclusion, lymphopenia is common in adult Fontan patients and is associated with markers of portal hypertension. Larger studies are needed to better define the relationship between lymphopenia and clinical outcomes.
Late-life depression (LLD) is associated with poor social functioning. However, previous research uses bias-prone self-report scales to measure social functioning and a more objective measure is lacking. We tested a novel wearable device to measure speech that participants encounter as an indicator of social interaction.
Twenty nine participants with LLD and 29 age-matched controls wore a wrist-worn device continuously for seven days, which recorded their acoustic environment. Acoustic data were automatically analysed using deep learning models that had been developed and validated on an independent speech dataset. Total speech activity and the proportion of speech produced by the device wearer were both detected whilst maintaining participants' privacy. Participants underwent a neuropsychological test battery and clinical and self-report scales to measure severity of depression, general and social functioning.
Compared to controls, participants with LLD showed poorer self-reported social and general functioning. Total speech activity was much lower for participants with LLD than controls, with no overlap between groups. The proportion of speech produced by the participants was smaller for LLD than controls. In LLD, both speech measures correlated with attention and psychomotor speed performance but not with depression severity or self-reported social functioning.
Using this device, LLD was associated with lower levels of speech than controls and speech activity was related to psychomotor retardation. We have demonstrated that speech activity measured by wearable technology differentiated LLD from controls with high precision and, in this study, provided an objective measure of an aspect of real-world social functioning in LLD.
The personality traits of neuroticism, openness, and conscientiousness are relevant factors for cognitive aging outcomes. The present study examined how these traits were associated with cognitive abilities and corresponding resting-state functional connectivity (RSFC) of the default mode network (DMN) in an older and predominantly minority sample. A sample of 58 cognitively unimpaired, largely African-American, older adults (M age = 68.28 ± 8.33) completed a standard RSFC magnetic resonance imaging sequence, a Big Five measure of personality, and delayed memory, Stroop, and verbal fluency tasks. Personality trait associations of within-network connectivity of the posterior cingulate cortex (PCC), a hub of the DMN, were examined using a seed-based approach. Trait scores were regressed on cognitive performance (delayed memory for neuroticism, Stroop for conscientiousness, and verbal fluency for openness). Greater openness predicted greater verbal fluency and greater RSFC between the PCC and eight clusters, including the medial prefrontal cortex, left middle frontal gyrus, and precuneus. Greater PCC–precuneus connectivity predicted greater verbal fluency. Neuroticism and conscientiousness did not significantly predict either cognitive performance or RSFC. Although requiring replication and elaboration, the results implicate openness as a contributing factor to cognitive aging via concomitant cognitive performance and connectivity within cortical hubs of the DMN and add to the sparse literature on these variables in a diverse group of older adults.
Tranexamic acid (TXA) is an antifibrinolytic agent shown to reduce morbidity and mortality in hemorrhagic shock. It has potential use in prehospital and wilderness medicine; however, in these environments, TXA is likely to be exposed to fluctuating and extreme temperatures. If TXA degrades under these conditions, this may reduce antifibrinolytic effects.
This study sought to determine if repetitive temperature derangement causes degradation of TXA.
Experimental samples underwent either seven days of freeze/thaw or heating cycles and then were analyzed via mass spectrometry for degradation of TXA. An internal standard was used for comparison between experimental samples and controls. These samples were compared to room temperature controls to determine if fluctuating extreme temperatures cause degradation of TXA.
The coefficient of variability of ratios of TXA to internal standard within each group (room temperature, freeze, and heated) was less than five percent. An independent t-test was performed on freeze/thaw versus control samples (t = 2.77; P = .17) and heated versus control samples (t = 2.77; P = .722) demonstrating no difference between the groups.
These results suggest that TXA remains stable despite repeated exposure to extreme temperatures and does not significantly degrade. These findings support the stability of TXA and its use in extreme environments.
Declining sea ice is expected to change the Arctic's physical and biological systems in ways that are difficult to predict. This study used stable isotope compositions (δ13C and δ15N) of archaeological, historic, and modern Pacific walrus (Odobenus rosmarus divergens) bone collagen to investigate the impacts of changing sea ice conditions on walrus diet during the last ~4000 yr. An index of past sea ice conditions was generated using dinocyst-based reconstructions from three locations in the northeastern Chukchi Sea. Archaeological walrus samples were assigned to intervals of high and low sea ice, and δ13C and δ15N were compared across ice states. Mean δ13C and δ15N values were similar for archaeological walruses from intervals of high and low sea ice; however, variability among walruses was greater during low-ice intervals, possibly indicating decreased availability of preferred prey. Overall, sea ice conditions were not a primary driver of changes in walrus diet. The diet of modern walruses was not consistent with archaeological low sea ice intervals. Rather, the low average trophic position of modern walruses (primarily driven by males), with little variability among individuals, suggests that trophic changes to this Arctic ecosystem are still underway or are unprecedented in the last ~4000 yr.
OBJECTIVES/SPECIFIC AIMS: To longitudinally track emerging research collaborations and assess their development and productivity. METHODS/STUDY POPULATION: In four administrations (2011, 2013, 2015, 2017), all full- and part-time University of Rochester Medical Center faculty received an email invitation to complete a research collaborators survey. Respondents indicated whether they were involved in research, and if involved in research, identified collaborators from a drop-down list of investigators in the institution. Space was provided for write-ins. Full- and part-time status, faculty rank, and departmental affiliation was associated with each investigator. Grant data were obtained from a grant management database maintained by the institution’s Office of Research and Project Administration. Grant data included all submissions (funded and not funded), award number, award effective data, award final expiration date, funding amounts, principal investigator and co-investigators. Using Mathematica SNA software, for each year we identified collaborator dyads (including their characteristics such as inter/intradepartmental; investigator characteristics) and networks (e.g. size, density). RESULTS/ANTICIPATED RESULTS: On average, 1800 (range 1730-2034) full- and part-time faculty received email invitations to complete the survey. An average of 403 respondents (range 385-441) completed the survey each administration. While the response rate seems low, the survey was distributed to every faculty member regardless of their primary appointment. Thus it included a large number of individuals whose role is exclusively clinical. Grant data included 4429 awards received between 2011 and 2018, involving 1395 investigators as principal or co-investigators. Survey respondents naming collaborators ranged from 233 to 280 (average 257) with 1594 to 2265 (average 1988) collaborations named each year. Overall density increased from.0204 in 2011 to.0342 in 2017. Density within the group of female investigators increased from.0219 in 2011 to.0412 in 2017. Within the group of male investigators, density increase from.0226 to.0333 in the same time span. Analysis by rank, changes over time and those with grant funding is underway. DISCUSSION/SIGNIFICANCE OF IMPACT: This methodology captured a consistent number of collaborations over an 8 year period. Analyses reveal network growth over time and of increasing heterogeneity (by gender). Analyzing research networks overtime provides an important metric to assess how research networks evolve and devolve and the characteristics of those that grow or stagnate. Further these analyses can demonstrate the impact of support provided to networks or teams by the CTSI, department or other institutional mechanism.
During the past two decades, it has been amply documented that neuropsychiatric disorders (NPDs) disproportionately account for burden of illness attributable to chronic non-communicable medical disorders globally. It is also likely that human capital costs attributable to NPDs will disproportionately increase as a consequence of population aging and beneficial risk factor modification of other common and chronic medical disorders (e.g., cardiovascular disease). Notwithstanding the availability of multiple modalities of antidepressant treatment, relatively few studies in psychiatry have primarily sought to determine whether improving cognitive function in MDD improves patient reported outcomes (PROs) and/or is cost effective. The mediational relevance of cognition in MDD potentially extrapolates to all NPDs, indicating that screening for, measuring, preventing, and treating cognitive deficits in psychiatry is not only a primary therapeutic target, but also should be conceptualized as a transdiagnostic domain to be considered regardless of patient age and/or differential diagnosis.
The target article addresses increased food-seeking behaviors in times of instability, particularly in passerines. We note that food instability might have intergenerational effects on birds: Nutritional stress during development affects song-learning abilities, associating parental foraging with offspring sexual selection. We explore the implications of these compounding selection pressures on food-seeking motivation during breeding, as well as the hormonal underpinnings of these behaviors.
Field identification of ST-elevation myocardial infarction (STEMI) and advanced hospital notification decreases first-medical-contact-to-balloon (FMC2B) time. A recent study in this system found that electrocardiogram (ECG) transmission following a STEMI alert was frequently unsuccessful.
Instituting weekly test ECG transmissions from paramedic units to the hospital would increase successful transmission of ECGs and decrease FMC2B and door-to-balloon (D2B) times.
This was a natural experiment of consecutive patients with field-identified STEMI transported to a single percutaneous coronary intervention (PCI)-capable hospital in a regional STEMI system before and after implementation of scheduled test ECG transmissions. In November 2014, paramedic units began weekly test transmissions. The mobile intensive care nurse (MICN) confirmed the transmission, or if not received, contacted the paramedic unit and the department’s nurse educator to identify and resolve the problem. Per system-wide protocol, paramedics transmit all ECGs with interpretation of STEMI. Receiving hospitals submit patient data to a single registry as part of ongoing system quality improvement. The frequency of successful ECG transmission and time to intervention (FMC2B and D2B times) in the 18 months following implementation was compared to the 10 months prior. Post-implementation, the time the ECG transmission was received was also collected to determine the transmission gap time (time from ECG acquisition to ECG transmission received) and the advanced notification time (time from ECG transmission received to patient arrival).
There were 388 patients with field ECG interpretations of STEMI, 131 pre-intervention and 257 post-intervention. The frequency of successful transmission post-intervention was 73% compared to 64% prior; risk difference (RD)=9%; 95% CI, 1-18%. In the post-intervention period, the median FMC2B time was 79 minutes (inter-quartile range [IQR]=68-102) versus 86 minutes (IQR=71-108) pre-intervention (P=.3) and the median D2B time was 59 minutes (IQR=44-74) versus 60 minutes (IQR=53-88) pre-intervention (P=.2). The median transmission gap was three minutes (IQR=1-8) and median advanced notification time was 16 minutes (IQR=10-25).
Implementation of weekly test ECG transmissions was associated with improvement in successful real-time transmissions from field to hospital, which provided a median advanced notification time of 16 minutes, but no decrease in FMC2B or D2B times.
The re-emergence of debates on the decolonisation of knowledge has revived interest in the National Question, which began over a century ago and remains unresolved. Tensions that were suppressed and hidden in the past are now being openly debated. Despite this, the goal of one united nation living prosperously under a constitutional democracy remains elusive. This edited volume examines the way in which various strands of left thought have addressed the National Question, especially during the apartheid years, and goes on to discuss its relevance for South Africa today and in the future. Instead of imposing a particular understanding of the National Question, the editors identified a number of political traditions and allowed contributors the freedom to define the question as they believed appropriate – in other words, to explain what they thought was the Unresolved National Question. This has resulted in a rich tapestry of interweaving perceptions. The volume is structured in two parts. The first examines four foundational traditions: Marxism-Leninism (the Colonialism of a Special Type thesis); the Congress tradition; the Trotskyist tradition; and Africanism. The second part explores the various shifts in the debate from the 1960s onwards, and includes chapters on Afrikaner nationalism, ethnic issues, black consciousness, feminism, workerism and constitutionalism. The editors hope that by revisiting the debates not popularly known among the scholarly mainstream, this volume will become a catalyst for an enriched debate on our identity and our future.
We evaluated the extent to which providing training and technical assistance to early childcare centre (ECC) directors, faculty and staff in the implementation of evidence-based nutrition strategies improved the nutrition contexts, policies and practices of ECC serving racially and ethnically diverse, low-income children in Broward County, Florida, USA. The nutrition strategies targeted snack and beverage policies and practices, consistent with Caring for Our Children National Standards.
We used the nutrition observation and document review portions of the Environment and Policy Assessment and Observation (EPAO) instrument to observe ECC as part of a one-group pre-test/post-test evaluation design.
ECC located within areas of high rates of poverty, diabetes, minority representation and unhealthy food index in Broward County, Florida, USA.
Eighteen ECC enrolled, mean 112·9 (sd 53·4) children aged 2–5 years; 12·3 (sd 7·2) staff members; and 10·2 (sd 4·6) children per staff member at each centre.
We found significant improvements in centres’ overall nutrition contexts, as measured by total EPAO nutrition scores (P=0·01). ECC made specific significant gains within written nutrition policies (P=0·03) and nutrition training and education (P=0·01).
Our findings support training ECC directors, faculty and staff in evidence-based nutrition strategies to improve the nutrition policies and practices of ECC serving racially and ethnically diverse children from low-income families. The intervention resulted in improvements in some nutrition policies and practices, but not others. There remains a need to further develop the evaluation base involving the effectiveness of policy and practice interventions within ECC serving children in high-need areas.