Decentralized clinical trials (DCTs) have the potential to increase pace and reach of recruitment as well as to improve sample representation, compared to traditional in-person clinical trials. However, concerns linger regarding data integrity in DCTs due to threats of fraud and sampling bias. The purpose of this report is to describe two tools that we have developed and successfully implemented to combat these threats. Cheatblocker and QuotaConfig are two external modules that we have made publicly available within the REDCap data capture system to target fraud and sampling bias, respectively. We describe the modules, present two case examples in which we used the modules successfully, and discuss the potential impact of tools such as these on data integrity in DCTs. We situate this discussion within the broader landscape of translational science wherein we strive to improve research rigor and efficiency to maximize public health benefit.

Background: Infection is a common and highly morbid postoperative complication in victims of physical trauma. Current literature analyzing the infectious sequelae of physical trauma predominately comes from military data, where blast trauma, rather than blunt or penetrating trauma, is most common. The epidemiology and management of infectious sequelae of civilian trauma are poorly understood, as is perioperative antimicrobial management of trauma laparotomy. Methods: We performed a single-center retrospective chart review using data from University of Chicago’s electronic medical record (Epic) and the National Trauma Registry. Patients 16 years and older admitted for level 1-2 trauma who underwent laparotomy between 5/1/2018-3/18/2023 were included. Using informatics and manual chart review, we analyzed patient demographics, rates of infection, sites of infection, timing of infection from initial trauma event, and causative organisms. We compared patients based on mechanism of injury (blunt versus penetrating) and whether patients underwent damage control laparotomy (DCL)--where the abdomen is left in discontinuity after the initial laparotomy--or single laparotomy (SL). Results: 430 patients met criteria. The median age was 30. Patients were majority Black (80.9%) and male (80.9%). 80.5% of patients had penetrating trauma, of which 90% were gunshot wounds (GSW). 19.8% had blunt trauma, of which 89% were motor-vehicle crashes (MVC). 19 (4.4%) died during initial stabilization, 199 (46.3%) underwent single laparotomy, and 212 (49.3%) underwent DCL (Figure 1). Of patients that survived initial stabilization, 27 (6.6%) developed a bloodstream infection (BSI), of which 21 (77.8%) came from the DCL group (Figures 2, 3). 19% of BSI in the DCL group were caused by yeast. 30.7% of patients developed a culture-positive surgical site infection (SSI) or intra-abdominal infection (IAI), with a rate of 40.6% in the DCL group (Table 2). Yeast were isolated in 40.5% of patients with positive cultures, 86.3% of which were isolated in the DCL group, with an overall incidence of 20.8% in the entire DCL group. Median time from arrival to infection diagnosis was 11 days. Patients generally received empiric Piperacillin-tazobactam while the abdomen was in discontinuity. Conclusions: Infection in civilian trauma laparotomy often arises as SSI or IAI, and is most pronounced in the DCL population. Yeast represents an unexpectedly high proportion of causative organisms. Further research is required to assess whether yeast burden can be mitigated by either incorporating antifungal prophylaxis at time of initial laparotomy, or by shortening empiric post-laparotomy antibiotic courses.

Although depression can be transmitted across generations, less is known about how this cycle can be interrupted. This study examines whether the multilevel Fast Track intervention (clinicaltrials.gov, NCT01653535) disrupts intergenerational transmission of depression. Children at high risk for aggression were randomly assigned to a 10-year control group or intervention targeting parenting and children’s intrapersonal, interpersonal, and academic skills. The original sample included 891 first-generation (G1) participants who reported on their depression and their children’s (second-generation; G2) internalizing problems. At age 34, 374 G2 participants (n = 191 intervention, n = 183 control) reported on their and their children’s (third-generation; G3) emotional difficulties. Mediated path models showed that a cascading model where higher G1 depressive symptoms influence higher G2 childhood depressive symptoms, leading to higher G2 adulthood depressive symptoms, which in turn is connected with greater G3 emotional difficulties, emerged only in the control group. The Fast Track intervention disrupted the pathways from G1 depressive symptoms to G3 emotional difficulties, from G2 childhood depressive symptoms to G2 adulthood depressive symptoms, and from G2 adulthood depressive symptoms to G3 emotional difficulties, highlighting the importance of preventive interventions in altering developmental trajectories of psychopathology.

We present the serendipitous radio-continuum discovery of a likely Galactic supernova remnant (SNR) G305.4–2.2. This object displays a remarkable circular symmetry in shape, making it one of the most circular Galactic SNRs known. Nicknamed Teleios due to its symmetry, it was detected in the new Australian Square Kilometre Array Pathfinder (ASKAP) Evolutionary Map of the Universe (EMU) radio–continuum images with an angular size of 1 320$^{\prime\prime}$$\times$1 260$^{\prime\prime}$ and PA = 0$^\circ$. While there is a hint of possible H$\alpha$ and gamma-ray emission, Teleios is exclusively seen at radio–continuum frequencies. Interestingly, Teleios is not only almost perfectly symmetric, but it also has one of the lowest surface brightnesses discovered among Galactic SNRs and a steep spectral index of $\alpha$=–0.6$\pm$0.3. Our best estimates from Hi studies and the $\Sigma$–D relation place Teleios as a type Ia SNR at a distance of either $\sim$2.2 kpc (near-side) or $\sim$7.7 kpc (far-side). This indicates two possible scenarios, either a young (under 1 000 yr) or a somewhat older SNR (over 10 000 yr). With a corresponding diameter of 14/48 pc, our evolutionary studies place Teleios at the either early or late Sedov phase, depending on the distance/diameter estimate. However, our modelling also predicts X-ray emission, which we do not see in the present generation of eROSITA images. We also explored a type Iax explosion scenario that would point to a much closer distance of $\lt$1 kpc and Teleios size of only $\sim$3.3 pc, which would be similar to the only known type Iax remnant SN1181. Unfortunately, all examined scenarios have their challenges, and no definitive Supernova (SN) origin type can be established at this stage. Remarkably, Teleios has retained its symmetrical shape as it aged even to such a diameter, suggesting expansion into a rarefied and isotropic ambient medium. The low radio surface brightness and the lack of pronounced polarisation can be explained by a high level of ambient rotation measure (RM), with the largest RM being observed at Teleios’s centre.

Aims: A handful of studies argue that ED treatment would benefit from a network analysis of social influences, particularly in girls and young women pressured by socio-culturally prescribed beauty standards, and reinforced by peers and family. The study’s aim was to investigate the impact of social network density on a person’s acquisition, perpetuation, and recovery from an eating disorder (ED). It was hypothesized that one’s connectedness within dense social networks of others with EDs would increase the likelihood of an ED diagnosis and resistance to treatment and recovery.

Methods: One thousand participants, largely from North America and Europe, completed an online survey of ED social networks. Respondents were asked whether they had an ED diagnosis, and if so, the diagnosis/typology, whether they knew others with an ED, whether they were in recovery, and, if so, the extent of social supports. Indices and latent structural equation model (SEM) variables were constructed from respondents’ identification of siblings, peers, friends, parents, other relatives, spouses, and neighbours with an ED. Similar indices were constructed for others identified as supportive of recovery. Social media influence was measured by asking if pro-anorexic or recovery websites were viewed. Data were analysed using bivariate statistics and Lavaan’s SEM R program.

Results: Social network density (knowing others with EDs) was highly predictive of ED diagnosis, including multiple EDs. Internet media was equally impactful. Same-sex siblings and peers had the greatest influence, exceeding parents or other relatives/friends. Networks of supportive others were highly predictive of recovery, outweighing negative ED models and media.

Conclusion: Our results were highly revealing of dense networks of family and peer models of EDs as well as supportive networks for recovery. The density/richness of social networks of others with an ED was highly predictive of an ED diagnosis, particularly of multiple EDs. Same-sex peers and siblings with an ED were especially strong influences. “Rich” day-to-day networks of multiple social contacts with EDs were associated with multiple ED diagnoses. Media appeared to complement these social contacts. However, only dense networks of supportive others were significantly predictive of recovery. Effective ED treatment requires a careful consideration of social influences who may model ED attitudes and behaviours; same-sex siblings and peers are especially critical. ED treatment and recovery might be compromised if these significant others model and reinforce a patient’s ED attitudes and behaviours.

Objectives/Goals: This study tests how fiber microstructural integrity and myelination levels within the cingulum connectome are associated with information processing speed (IPS) in relapsing-remitting multiple sclerosis (RRMS). We investigate the functional impact of structural coherence, myelin content, and white matter hyperintensities (WMH) load on IPS. Methods/Study Population: Data from 63 RRMS and 25 healthy controls (HC) were used. We hypothesize that the structural integrity of the cingulum bundle and its structural network – or connectome – is distinctly associated with IPS function in people with RRMS (vs. HC) due to myelin-related plasticity across the wiring. Using diffusion spectrum imaging and high-resolution tract segmentation, we constructed individualized white matter connectomes. Diffusion quantitative anisotropy (QA) and myelin fractions (MWF) were used to quantify structural coherence and myelination. WMH load was measured with T2-FLAIR imaging. Bayesian–Pearson correlations, mixed-linear, and moderation models explored how fiber-specific QA, MWF, and WMH load relate to IPS function in RRMS, as measured by Symbol Digit Modalities Test (SDMT). Results/Anticipated Results: We theorize that (1) QA in the cingulum connectome correlates with SDMT performance dimensionally, indicating that structural coherence in the white matter supports IPS function among both groups; (2) increased myelination will strengthen the positive association between QA and SDMT scores, suggesting that connectome-specific myelin content facilitates IPS; (3) conversely, WMH load within the cingulum connectome is expected to inversely correlate with SDMT scores, reflecting the detrimental impact of lesion burden on IPS function; (4) myelination in specialized tracts within the cingulum connectome play a compensatory role to support IPS function in the RRMS group. These investigations can offer a mechanistic clue to potential neuroplastic targets for cognitive interventions in MS. Discussion/Significance of Impact: By linking white matter integrity to cognitive function at the connectome level, this study can support neuroregenerative strategies to mitigate cognitive burden in RRMS. Our findings may advance understanding of how structural coherence, tract myelination, and WMH affect IPS, shaping personalized prognostic and therapeutic interventions.

We present a re-discovery of G278.94+1.35a as possibly one of the largest known Galactic supernova remnants (SNRs) – that we name Diprotodon. While previously established as a Galactic SNR, Diprotodon is visible in our new Evolutionary Map of the Universe (EMU) and GaLactic and Extragalactic All-sky MWA (GLEAM) radio continuum images at an angular size of $3{{{{.\!^\circ}}}}33\times3{{{{.\!^\circ}}}}23$, much larger than previously measured. At the previously suggested distance of 2.7 kpc, this implies a diameter of 157$\times$152 pc. This size would qualify Diprotodon as the largest known SNR and pushes our estimates of SNR sizes to the upper limits. We investigate the environment in which the SNR is located and examine various scenarios that might explain such a large and relatively bright SNR appearance. We find that Diprotodon is most likely at a much closer distance of $\sim$1 kpc, implying its diameter is 58$\times$56 pc and it is in the radiative evolutionary phase. We also present a new Fermi-LAT data analysis that confirms the angular extent of the SNR in gamma rays. The origin of the high-energy emission remains somewhat puzzling, and the scenarios we explore reveal new puzzles, given this unexpected and unique observation of a seemingly evolved SNR having a hard GeV spectrum with no breaks. We explore both leptonic and hadronic scenarios, as well as the possibility that the high-energy emission arises from the leftover particle population of a historic pulsar wind nebula.

Evidence-based insertion and maintenance bundles are effective in reducing the incidence of central line-associated bloodstream infections (CLABSI) in intensive care unit (ICU) settings. We studied the adoption and compliance of CLABSI prevention bundle programs and CLABSI rates in ICUs in a large network of acute care hospitals across Canada.