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Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).
Aims
We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.
Method
Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.
Results
Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD.
Conclusions
We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.
Employment and relationship are crucial for social integration. However, individuals with major psychiatric disorders often face challenges in these domains.
Aims
We investigated employment and relationship status changes among patients across the affective and psychotic spectrum – in comparison with healthy controls, examining whether diagnostic groups or functional levels influence these transitions.
Method
The sample from the longitudinal multicentric PsyCourse Study comprised 1260 patients with affective and psychotic spectrum disorders and 441 controls (mean age ± s.d., 39.91 ± 12.65 years; 48.9% female). Multistate models (Markov) were used to analyse transitions in employment and relationship status, focusing on transition intensities. Analyses contained multiple multistate models adjusted for age, gender, job or partner, diagnostic group and Global Assessment of Functioning (GAF) in different combinations to analyse the impact of the covariates on the hazard ratio of changing employment or relationship status.
Results
The clinical group had a higher hazard ratio of losing partner (hazard ratio 1.46, P < 0.001) and job (hazard ratio 4.18, P < 0.001) than the control group (corrected for age/gender). Compared with controls, clinical groups had a higher hazard of losing partner (affective group, hazard ratio 2.69, P = 0.003; psychotic group, hazard ratio 3.06, P = 0.001) and job (affective group, hazard ratio 3.43, P < 0.001; psychotic group, hazard ratio 4.11, P < 0.001). Adjusting for GAF, the hazard ratio of losing partner and job decreased in both clinical groups compared with controls.
Conclusion
Patients face an increased hazard of job loss and relationship dissolution compared with healthy controls, and this is partially conditioned by the diagnosis and functional level. These findings underscore a high demand for destigmatisation and support for individuals in managing their functional limitations.
To understand healthcare workers’ (HCWs) beliefs and practices toward blood culture (BCx) use.
Design:
Cross-sectional electronic survey and semi-structured interviews.
Setting:
Academic hospitals in the United States.
Participants:
HCWs involved in BCx ordering and collection in adult intensive care units (ICU) and wards.
Methods:
We administered an anonymous electronic survey to HCWs and conducted semi-structured interviews with unit staff and quality improvement (QI) leaders in these institutions to understand their perspectives regarding BCx stewardship between February and November 2023.
Results:
Of 314 HCWs who responded to the survey, most (67.4%) were physicians and were involved in BCx ordering (82.3%). Most survey respondents reported that clinicians had a low threshold to culture patients for fever (84.4%) and agreed they could safely reduce the number of BCx obtained in their units (65%). However, only half of them believed BCx was overused. Although most made BCx decisions as a team (74.1%), a minority reported these team discussions occurred daily (42.4%). A third of respondents reported not usually collecting the correct volume per BCx bottle, half were unaware of the improved sensitivity of 2 BCx sets, and most were unsure of the nationally recommended BCx contamination threshold (87.5%). Knowledge regarding the utility of BCx for common infections was limited.
Conclusions:
HCWs’ understanding of best collection practices and yield of BCx was limited.
The aim of this study was to determine whether there was a significant change in cardiac [123I]-metaiodobenzylguanidine uptake between baseline and follow-up in individuals with mild cognitive impairment with Lewy bodies (MCI-LB) who had normal baseline scans. Eight participants with a diagnosis of probable MCI-LB and a normal baseline scan consented to a follow-up scan between 2 and 4 years after baseline. All eight repeat scans remained normal; however, in three cases uptake decreased by more than 10%. The mean change in uptake between baseline and repeat was −5.2% (range: −23.8% to +7.0%). The interpolated mean annual change in uptake was −1.6%.
Carl Snyder was one of the most prominent US monetary economists of the 1920s and 1930s. His pioneering work on constructing the empirical counterparts of the terms in the equation of exchange led him to formulate a 4% monetary growth rule. Snyder is especially apposite because he was on the staff of the New York Federal Reserve Bank. Why, despite his pioneering empirical work and his position as an insider, did Snyder fail to effectively challenge the dominant real bills views of the Federal Reserve (Fed)? A short answer is that he did not possess a convincing version of the quantity theory that attributed the Great Depression to a contraction in the money stock produced by the Fed, as opposed to the dominant real bills view attributing it to the collapse of speculative excess.
Individuals at risk for bipolar disorder (BD) have a wide range of genetic and non-genetic risk factors, like a positive family history of BD or (sub)threshold affective symptoms. Yet, it is unclear whether these individuals at risk and those diagnosed with BD share similar gray matter brain alterations.
Methods:
In 410 male and female participants aged 17–35 years, we compared gray matter volume (3T MRI) between individuals at risk for BD (as assessed using the EPIbipolar scale; n = 208), patients with a DSM-IV-TR diagnosis of BD (n = 87), and healthy controls (n = 115) using voxel-based morphometry in SPM12/CAT12. We applied conjunction analyses to identify similarities in gray matter volume alterations in individuals at risk and BD patients, relative to healthy controls. We also performed exploratory whole-brain analyses to identify differences in gray matter volume among groups. ComBat was used to harmonize imaging data from seven sites.
Results:
Both individuals at risk and BD patients showed larger volumes in the right putamen than healthy controls. Furthermore, individuals at risk had smaller volumes in the right inferior occipital gyrus, and BD patients had larger volumes in the left precuneus, compared to healthy controls. These findings were independent of course of illness (number of lifetime manic and depressive episodes, number of hospitalizations), comorbid diagnoses (major depressive disorder, attention-deficit hyperactivity disorder, anxiety disorder, eating disorder), familial risk, current disease severity (global functioning, remission status), and current medication intake.
Conclusions:
Our findings indicate that alterations in the right putamen might constitute a vulnerability marker for BD.
OBJECTIVES/GOALS: 48,000,000 people in the U.S. have hearing loss, negatively impacting quality of life and work. Unveiling axon guidance for auditory type II spiral ganglia neurons (SGNs) will aid development of new therapies. I study the role of Eph/Ephrin and planar cell polarity (PCP) signaling during type II SGN turning and outer hair cell (OHC) innervation. METHODS/STUDY POPULATION: This quantitative study was conducted on Efna3 and Vangl2 null mice possessing Neurog1CreERT2 and R26RtdTomato mutations. Spontaneous Cre activity within the Neurogenin1CreERT2 line causes recombination and expression of fluorescent Rosa26 Reporter (R26R)tdTomatoin a restricted number of SGNs, including type IIs. Together, these lines permit SGN sparse labeling. Immunostaining and confocal imaging were used to analyze dsRed in Efna3 and Vangl2 mice and quantify type II SGN turning. In combination, Imaris 3D renderings were used to quantify type II SGN turning, branching, navigation features and temporal effects of EPHRIN-A3-Fc on type IIs via cochlear cultures (a gain-of-function manipulation). For both sexes, 5-6 cochleae per genotype were analyzed and compared by t-test to wildtype (WT) controls. RESULTS/ANTICIPATED RESULTS: Efna3 nulls showed a small rise in type II SGNs incorrectly turning toward the apex at an error rate of 16.0% compared to WTs (n=6; p=0.05). P0 Efna3 nulls had reduced branch number compared to WTs, 4.1 and 7.2, respectively (n=129; p=<0.0001), suggesting EPHRIN-A3 acts as a positive growth cue. In cochlear cultures, EPHRIN-A3-Fc led to type II SGN collapse at E15.5, indicating a repulsive function. However, at P0, EPHRIN-A3-Fc treatment led to type II SGNs with elevated branch numbers compared to Control-Fc treatment: 18.1 and 11.4, respectively (n=116; p=<0.0001). This indicates a positive growth function. At E16.5, EPHRIN-A3 protein immunoreactivity on Deiters’ and pillar cells appears reduced in Vangl2 nulls compared to WT cochleae, suggesting that EPHRIN-A3 acts downstream of PCP signaling. DISCUSSION/SIGNIFICANCE: Results suggest that Eph/Ephrin signaling acts downstream of PCP signaling to mediate type II SGN guidance and EPHRIN-A3 switches its mode of activation. The clinical implications of these findings are that therapeutics targeting EPHRIN-A3 and/or VANGL2 in their given pathways could stimulate new OHC innervation following auditory damage.
This chapter focuses on constitutional disharmony as central to forging constitutional identity by looking at the place of Black citizenship prior to the Civil War. While there are powerful arguments that the Constitution could be seen as antislavery, even while it allowed for slavery to persist where it already existed, those who were antislavery did not give much thought to the place of Blacks within the constitutional order—particularly not to the question of Black citizenship. It was, rather, events such as the second Missouri Crisis of 1821 that forced the issue of Black citizenship onto the polity. Events forced constitutional actors to wrestle with questions that were not clear, or easily answered, by way of constitutional text. This chapter offers an important contrast to more prevalent approaches – to either originalism or moral readings – that too often try to dissolve constitutional disharmony.
A system-in-package for a wideband digital radar, in D-band, requires broadband, high-gain antennas combined with broadband chip-to-package and package-to-printed circuit board (PCB) interconnects. This paper demonstrates a wideband, low-loss quasi-coaxial signal transition, and a novel electric split ring resonator (eSRR)-based antenna-in-package (AiP) with a modified reflector concept, for improved gain, in embedded wafer level ball grid array (eWLB) technology. A complete chip-to-package-to-PCB interconnect is also demonstrated by combining the quasi-coaxial transition with a chip-to-package interconnect. The quasi-coaxial signal transition has the largest impedance bandwidth among ball grid array-based quasi-coaxial signal transitions. For the modified reflector concept, a horn-shaped cavity is micromachined in the PCB substrate and remetallized with aerosol-jet printing, placing the reflector 0.25λ from the antenna. The antenna gain is improved with up to 5.3 dB. The AiP with the horn-shaped reflector is the single element with the highest gain, in eWLB technology, above 100 GHz.
An ab initio theoretical approach has been used to calculate optimized geometries and the relative energies of various compositional arrangements in structures of dioctahedral smectites based on models consisting of two unit-cells. These calculations indicate that the energy differences between structures having vacancies in sites with cis- or trans-OH coordination are small and that their relative energies vary with the chemical nature of the substitutions. For example, a cis-OH coordination for the vacancy was the most stable when the interlayer charge originated from substitution of Al for Si in the tetrahedral sheet, whereas the trans-coordination was the more stable for most cases of substitution in the octahedral sheet, an exception being Fe(II) for Al where the cis-OH coordination was favored. It seems likely, therefore, that long-range structural disorder will be a common phenomenon in natural phyllosilicate specimens.
Anterior temporal lobectomy is a common surgical approach for medication-resistant temporal lobe epilepsy (TLE). Prior studies have shown inconsistent findings regarding the utility of presurgical intracarotid sodium amobarbital testing (IAT; also known as Wada test) and neuroimaging in predicting postoperative seizure control. In the present study, we evaluated the predictive utility of IAT, as well as structural magnetic resonance imaging (MRI) and positron emission tomography (PET), on long-term (3-years) seizure outcome following surgery for TLE.
Participants and Methods:
Patients consisted of 107 adults (mean age=38.6, SD=12.2; mean education=13.3 years, SD=2.0; female=47.7%; White=100%) with TLE (mean epilepsy duration =23.0 years, SD=15.7; left TLE surgery=50.5%). We examined whether demographic, clinical (side of resection, resection type [selective vs. non-selective], hemisphere of language dominance, epilepsy duration), and presurgical studies (normal vs. abnormal MRI, normal vs. abnormal PET, correctly lateralizing vs. incorrectly lateralizing IAT) were associated with absolute (cross-sectional) seizure outcome (i.e., freedom vs. recurrence) with a series of chi-squared and t-tests. Additionally, we determined whether presurgical evaluations predicted time to seizure recurrence (longitudinal outcome) over a three-year period with univariate Cox regression models, and we compared survival curves with Mantel-Cox (log rank) tests.
Results:
Demographic and clinical variables (including type [selective vs. whole lobectomy] and side of resection) were not associated with seizure outcome. No associations were found among the presurgical variables. Presurgical MRI was not associated with cross-sectional (OR=1.5, p=.557, 95% CI=0.4-5.7) or longitudinal (HR=1.2, p=.641, 95% CI=0.4-3.9) seizure outcome. Normal PET scan (OR= 4.8, p=.045, 95% CI=1.0-24.3) and IAT incorrectly lateralizing to seizure focus (OR=3.9, p=.018, 95% CI=1.2-12.9) were associated with higher odds of seizure recurrence. Furthermore, normal PET scan (HR=3.6, p=.028, 95% CI =1.0-13.5) and incorrectly lateralized IAT (HR= 2.8, p=.012, 95% CI=1.2-7.0) were presurgical predictors of earlier seizure recurrence within three years of TLE surgery. Log rank tests indicated that survival functions were significantly different between patients with normal vs. abnormal PET and incorrectly vs. correctly lateralizing IAT such that these had seizure relapse five and seven months earlier on average (respectively).
Conclusions:
Presurgical normal PET scan and incorrectly lateralizing IAT were associated with increased risk of post-surgical seizure recurrence and shorter time-to-seizure relapse.
In July 2021, Public Health Wales received two notifications of salmonella gastroenteritis. Both cases has attended the same barbecue to celebrate Eid al–Adha, two days earlier. Additional cases attending the same barbecue were found and an outbreak investigation was initiated. The barbecue was attended by a North African community’s social network. On same day, smaller lunches were held in three homes in the social network. Many people attended both a lunch and the barbecue. Cases were defined as someone with an epidemiological link to the barbecue and/or lunches with diarrhoea and/or vomiting with date of onset following these events. We undertook a cohort study of 36 people attending the barbecue and/or lunch, and a nested case-control study using Firth logistic regression. A communication campaign, sensitive towards different cultural practices, was developed in collaboration with the affected community. Consumption of a traditional raw liver dish, ‘marrara’, at the barbecue was the likely vehicle for infection (Firth logistic regression, aOR: 49.99, 95%CI 1.71–1461.54, p = 0.02). Meat and offal came from two local butchers (same supplier) and samples yielded identical whole genome sequences as cases. Future outbreak investigations should be relevant to the community affected by considering dishes beyond those found in routine questionnaires.
Land expansion by existing smallholder farmers (SHFs), aka stepping-up, is a major pathway to the rise of medium-scale farmers (MSFs) in Africa. In this paper, we investigate if and how armed conflicts constrain the ability of SHFs to transition to MSFs. We find that increased conflict intensity reduces the likelihood that a SHF will expand to a larger scale, especially for farmers who rely mostly on farm incomes, rather than off-farm incomes, for their livelihoods. These findings uphold other evidence that peace and stability influence private investment, including land-based investments, that are associated with economic transformation.
The European Congenital Heart Surgeons Association (ECHSA) Congenital Database (CD) is the second largest clinical pediatric and congenital cardiac surgical database in the world and the largest in Europe, where various smaller national or regional databases exist. Despite the dramatic increase in interventional cardiology procedures over recent years, only scattered national or regional databases of such procedures exist in Europe. Most importantly, no congenital cardiac database exists in the world that seamlessly combines both surgical and interventional cardiology data on an international level; therefore, the outcomes of surgical and interventional procedures performed on the same or similar patients cannot easily be tracked, assessed, and analyzed. In order to fill this important gap in our capability to gather and analyze information on our common patients, ECHSA and The Association for European Paediatric and Congenital Cardiology (AEPC) have embarked on a collaborative effort to expand the ECHSA-CD with a new module designed to capture data about interventional cardiology procedures. The purpose of this manuscript is to describe the concept, the structure, and the function of the new AEPC Interventional Cardiology Part of the ECHSA-CD, as well as the potentially valuable synergies provided by the shared interventional and surgical analyses of outcomes of patients. The new AEPC Interventional Cardiology Part of the ECHSA-CD will allow centers to have access to robust surgical and transcatheter outcome data from their own center, as well as robust national and international aggregate outcome data for benchmarking. Each contributing center or department will have access to their own data, as well as aggregate data from the AEPC Interventional Cardiology Part of the ECHSA-CD. The new AEPC Interventional Cardiology Part of the ECHSA-CD will allow cardiology centers to have access to aggregate cardiology data, just as surgical centers already have access to aggregate surgical data. Comparison of surgical and catheter interventional outcomes could potentially strengthen decision processes. A study of the wealth of information collected in the database could potentially also contribute toward improved early and late survival, as well as enhanced quality of life of patients with pediatric and/or congenital heart disease treated with surgery and interventional cardiac catheterization across Europe and the world.
The anesthesia workstation, commonly referred to as the “anesthesia machine,” is a complex and very specialized piece of equipment that is relatively unique in medical practice. It is, in essence, a device to control the delivery of medical gases to patients, including oxygen, air, nitrous oxide, and volatile anesthetics, along with a specialized ventilator adapted to operating room conditions. The safe use of the anesthesia workstation requires proper training, preuse checkout, and continuous monitoring of its function. The medical literature is replete with examples of patient harm from inappropriate use of the anesthesia workstation and from mechanical or electrical failure of its components. Additionally, volatile anesthetics, while valuable in medical practice, have a very low therapeutic index and manifest severe, and even fatal, side effects when administered improperly. Finally, many patients under general anesthesia are paralyzed for surgery and ventilated through an endotracheal tube. Their safety is completely dependent on the anesthesia professional’s use of the anesthesia workstation to deliver breathing gases, remove carbon dioxide from exhaled gas, and precise administration of volatile anesthetics.
Individuals with bipolar disorder are commonly correctly diagnosed a decade after symptom onset. Machine learning techniques may aid in early recognition and reduce the disease burden. As both individuals at risk and those with a manifest disease display structural brain markers, structural magnetic resonance imaging may provide relevant classification features.
Methods
Following a pre-registered protocol, we trained linear support vector machine (SVM) to classify individuals according to their estimated risk for bipolar disorder using regional cortical thickness of help-seeking individuals from seven study sites (N = 276). We estimated the risk using three state-of-the-art assessment instruments (BPSS-P, BARS, EPIbipolar).
Results
For BPSS-P, SVM achieved a fair performance of Cohen's κ of 0.235 (95% CI 0.11–0.361) and a balanced accuracy of 63.1% (95% CI 55.9–70.3) in the 10-fold cross-validation. In the leave-one-site-out cross-validation, the model performed with a Cohen's κ of 0.128 (95% CI −0.069 to 0.325) and a balanced accuracy of 56.2% (95% CI 44.6–67.8). BARS and EPIbipolar could not be predicted. In post hoc analyses, regional surface area, subcortical volumes as well as hyperparameter optimization did not improve the performance.
Conclusions
Individuals at risk for bipolar disorder, as assessed by BPSS-P, display brain structural alterations that can be detected using machine learning. The achieved performance is comparable to previous studies which attempted to classify patients with manifest disease and healthy controls. Unlike previous studies of bipolar risk, our multicenter design permitted a leave-one-site-out cross-validation. Whole-brain cortical thickness seems to be superior to other structural brain features.
George Angohiatok (pronounced ‘ano-HI-tok’) is a keen observer of Arctic landscapes, animals, and peoples. Raised on the land by his parents and grandparents in the western Canadian Arctic, George talks easily about his deep appreciation for the land and his significant concerns for the future of the Arctic and Inuit. George shares his observations of changes to the physical and social environments – changes he calls overwhelming – through richly detailed personal narratives. In the conversations presented in this chapter, George deftly weaves together changes to both settings, and illustrates the importance of considering our two worlds holistically. George’s story and words are transcribed here with minimal interruption from the other authors. Conventional academic reflections on methodology and literature are found within George’s story and afterwards.
Due to the high number of road traffic accidents with acute injuries and fatalities–particularly in Mass Casualty Incidents (MCI) in low-resource urban sub-Saharan African cities–research was undertaken to create an evidence-based algorithm that could be used to assess and geospatially link EMS needs in Kumasi, Ghana, to trauma resources. Our examination showed that non-MCI fatalities was approximately 2.5%, however, MCI fatalities were found to be 1.8 times higher–at 4.3%, indicating significant opportunities in the planning, preparedness, care, and transport among MCI patient management.
Therefore, several studies (funded through Fulbright-Fogarty and Fulbright Specialist programs), supported the development of the A-E-M-S (Assess-EOP-Map-Simulate) Medical Mass Casualty Algorithm that began networking accident ‘hotspots’ to existing trauma-level capabilities and surge capacity competencies in eight specified Kumasi hospitals. This low-cost response model promises to be an innovative alternative to long-term infrastructure development and high-priced resource distributions. Use of GIS and UAV drones allowed response systems to geospatially locate, classify, shift, and/or augment resources as needed in conjunction with hotspots.
Method:
Sample sizes were averaged at 295 for all patients' ages, with only a sample size of 292 for adults at 95% confidence intervals, and a standard deviation of 0.5. A total of 300 road-traffic accident victims were collected at KATH A&E in February-May, 2017, utilizing handheld devices by four researchers 24/7 daily.
Results:
Our examination showed that non-MCI fatalities were approximately 2.5%, however, MCI fatalities were found to be 1.8 times higher–at 4.3%, indicating significant opportunities in the planning, preparedness, care, and transport among MCI patient management.
Conclusion:
To date–and in partnership with Kwame Nkrumah University of Science and Technology, Komfo Anokye Teaching Hospital, Ghana Medical Council, Health Services, National Disaster Management Organization, and others–over 306 Ghanaian healthcare providers from 80 different facilities have been trained in the AEMS program.
OBJECTIVES/GOALS: 30,000,000 people in the U.S. have hearing loss, negatively impacting quality of life and work. Understanding auditory axon guidance for spiral ganglia neurons (SGNs) will aid development of new therapies. I study role of Eph/Ephrin signaling in mediating type II SGN turning events, and how planar cell polarity (PCP) signaling modulates this process. METHODS/STUDY POPULATION: This quantitative study was conducted on Efna3 and Vangl2 null mice possessing Neurog1CreERT2 and R26RtdTomato mutations. Spontaneous Cre activity within the Neurogenin 1 CreERT2 line causes recombination and expression of fluorescent Rosa26 Reporter (R26R)tdTomato in a restricted number of SGNs, including type IIs. Together these lines permit SGN sparse labeling. Bulk-labeling was used for Efna3;Vangl2 double knockout (DKO) mutants. Immunostaining and confocal imaging was used to analyze dsRed in Efna3; Vangl2 and NF-200 in DKOs to quantify type II SGN turning. In combination, 3D rendering in Imaris software was used to quantify type II SGN turning, branching and other growth and navigation characteristics. 5-6 cochleae per genotype were analyzed and compared by t-test to wildtype controls. RESULTS/ANTICIPATED RESULTS: EPHRIN-A3 is expressed on the membranes of outer pillar and Deiters’cells of the cochlear epithelium. Efna3 nulls showed a small rise in type II SGNs incorrectly turning toward the apex at an error frequency of 16.9% compared to controls (n=6; p=0.05). Efna3 nulls had reduced branch number/fiber compared to controls, 4.14 and 7.22, respectively (n=129; p DISCUSSION/SIGNIFICANCE: Our results suggest that Eph/Ephrin signaling acts parallel of PCP signaling to mediate type II SGN guidance during development. The clinical implications of these findings are that therapeutics targeting EPHRIN-A3 and/or VANGL2 in this pathway could stimulate new outer hair cell innervation by type II SGNs following auditory damage.