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Objectives/Goals: We describe the prevalence of individuals with household exposure to SARS-CoV-2, who subsequently report symptoms consistent with COVID-19, while having PCR results persistently negative for SARS-CoV-2 (S[+]/P[-]). We assess whether paired serology can assist in identifying the true infection status of such individuals. Methods/Study Population: In a multicenter household transmission study, index patients with SARS-CoV-2 were identified and enrolled together with their household contacts within 1 week of index’s illness onset. For 10 consecutive days, enrolled individuals provided daily symptom diaries and nasal specimens for polymerase chain reaction (PCR). Contacts were categorized into 4 groups based on presence of symptoms (S[+/-]) and PCR positivity (P[+/-]). Acute and convalescent blood specimens from these individuals (30 days apart) were subjected to quantitative serologic analysis for SARS-CoV-2 anti-nucleocapsid, spike, and receptor-binding domain antibodies. The antibody change in S[+]/P[-] individuals was assessed by thresholds derived from receiver operating characteristic (ROC) analysis of S[+]/P[+] (infected) versusS[-]/P[-] (uninfected). Results/Anticipated Results: Among 1,433 contacts, 67% had ≥1 SARS-CoV-2 PCR[+] result, while 33% remained PCR[-]. Among the latter, 55% (n = 263) reported symptoms for at least 1 day, most commonly congestion (63%), fatigue (63%), headache (62%), cough (59%), and sore throat (50%). A history of both previous infection and vaccination was present in 37% of S[+]/P[-] individuals, 38% of S[-]/P[-], and 21% of S[+]/P[+] (P<0.05). Vaccination alone was present in 37%, 41%, and 52%, respectively. ROC analyses of paired serologic testing of S[+]/P[+] (n = 354) vs. S[-]/P[-] (n = 103) individuals found anti-nucleocapsid data had the highest area under the curve (0.87). Based on the 30-day antibody change, 6.9% of S[+]/P[-] individuals demonstrated an increased convalescent antibody signal, although a similar seroresponse in 7.8% of the S[-]/P[-] group was observed. Discussion/Significance of Impact: Reporting respiratory symptoms was common among household contacts with persistent PCR[-] results. Paired serology analyses found similar seroresponses between S[+]/P[-] and S[-]/P[-] individuals. The symptomatic-but-PCR-negative phenomenon, while frequent, is unlikely attributable to true SARS-CoV-2 infections that go missed by PCR.
Turbulent mixing in a supercritical CO$_2$ shear layer is examined using both experimental and numerical methods. Boundary conditions are selected to focus on the rarely studied near-critical regime, where thermophysical properties vary nonlinearly with respect to temperature and pressure. Experimental results are obtained via Raman spectroscopy and shadowgraphy, while numerical results are obtained via direct numerical simulation. The shear layer growth rate is found to be 0.2. Additionally, density profiles indicate a relaxation of density gradients between the mixed fluid and heavy fluid as the flow evolves downstream, which runs counter to existing supercritical shear layer data in the literature. The computational results identify significant anisotropy in the turbulence in the shear layer, which is discussed in terms of the development of regions of high density gradient magnitude. The Reynolds-averaged enstrophy budget at various streamwise locations indicates no significant dilatational or baroclinic contribution within the shear layer.
Preventing neonatal calf diarrhea (NCD) and bovine respiratory disease (BRD) in cow–calf herds is essential to optimizing calfhood health. Disease control can prevent morbidity and mortality; however, evidence concerning the effectiveness of practices to achieve this is limited. The objective of this systematic review was to assess and summarize the evidence on the effectiveness of management practices to prevent calf morbidity and mortality from NCD and BRD in beef cow–calf herds. The population of interest was preweaned beef calves. The outcomes were calf morbidity and mortality caused by NCD and BRD. Only studies reporting naturally occurring diseases were included. Seventeen studies were deemed relevant, 6 studies of which were controlled trials or randomized controlled trials (RCTs), and 11 were observational studies. Most management practices had some evidence to support their use; however, the certainty of the findings was low to very low. Most of the practices were shown to impact both NCD and BRD. Yet, the different levels of consistency in the directionality of the findings suggest that some outcomes are more affected by some practices than others. More well-designed RCTs and cohort studies are required to provide reliable estimates to support recommended practices for cow–calf herds.
Calves sold at weaning are the main source of income for cow–calf operations, and their survival should be a priority. Given this, the effective use of management practices for pregnant dams and calves to prevent calf mortality is essential; however, decision-makers often do not have access to information about the effectiveness of many management practices. A systematic review was conducted to summarize the evidence of the effectiveness of biosecurity, vaccination, colostrum management, breeding and calving season management, and nutritional management practices for preventing preweaned beef calf mortality. The population of interest was preweaned beef calves from birth until at least 3 months of age. The outcome of interest was general preweaning calf mortality with stillbirths excluded. Eleven studies were deemed relevant. Ten were observational cross-sectional studies, and one was a randomized controlled trial (RCT). The practices that were statistically significantly associated with calf mortality were intervening with colostrum in case a calf had not nursed from its dam or was assisted at calving, timing and length of the calving season, and injecting selenium and vitamin E at birth. More well-executed RCTs and cohort studies are needed to provide evidence of effectiveness and help support implementation of recommended practices in herds.
This paper examines South–South security cooperation and regional organisations (ROs) in Africa. Much of the literature on peace and conflict in Africa has focused on ROs and the African Peace and Security Architecture (APSA). Guided by the mantra ‘African solutions to African problems’, these organisations have facilitated several instances of African-led security cooperation. Yet ROs have limited agency and capacity, are institutionally rigid, and are often donor-dependent. As a result, ad hoc security initiatives such as the G5 Sahel and Accra Initiative – our case studies – are on the rise. While such initiatives are better adapted to local context and feature higher levels of autonomy (relative to APSA), we critique this view by showing how donors pressure and trap African governments facing transnational security threats into ad hoc initiatives. These initiatives transform into ‘zombified’ security institutions that rarely live up to the elevated expectations of African and Western stakeholders. This creates a paradox for debates around African agency in security affairs: ad hoc initiatives lock African states into security frameworks that do not respond to their needs but also facilitate the pursuit of donor funding, reassert the national scale of sovereignty, and incentivise new forms of bilateral security cooperation.
The International Society for Twin Studies (ISTS) held its 19th scientific congress in Assisi, Italy, from September 26 to 28, 2024. This prestigious event, which was the seventh joint meeting with the World Congress on Twin Pregnancy, brought together researchers from various fields, including psychology, biology and medicine. Representatives from ICOMBO (the International Consortium of Multiple Birth Organisations), which supports multiple-birth families worldwide, were also in attendance. Many twin researchers consider this event to be the highlight of their professional year, as it brings together experts and parents alike to discuss the latest advancements in twin studies.
Peripheral inflammatory markers, including serum interleukin 6 (IL-6), are associated with depression, but less is known about how these markers associate with depression at different stages of the life course.
Methods
We examined the associations between serum IL-6 levels at baseline and subsequent depression symptom trajectories in two longitudinal cohorts: ALSPAC (age 10–28 years; N = 4,835) and UK Biobank (39–86 years; N = 39,613) using multilevel growth curve modeling. Models were adjusted for sex, BMI, and socioeconomic factors. Depressive symptoms were measured using the Short Moods and Feelings Questionnaire in ALSPAC (max time points = 11) and the Patient Health Questionnaire-2 in UK Biobank (max time points = 8).
Results
Higher baseline IL-6 was associated with worse depression symptom trajectories in both cohorts (largest effect size: 0.046 [ALSPAC, age 16 years]). These associations were stronger in the younger ALSPAC cohort, where additionally higher IL-6 levels at age 9 years was associated with worse depression symptoms trajectories in females compared to males. Weaker sex differences were observed in the older cohort, UK Biobank. However, statistically significant associations (pFDR <0.05) were of smaller effect sizes, typical of large cohort studies.
Conclusions
These findings suggest that systemic inflammation may influence the severity and course of depressive symptoms across the life course, which is apparent regardless of age and differences in measures and number of time points between these large, population-based cohorts.
With wide-field phased array feed technology, the Australian Square Kilometre Array Pathfinder (ASKAP) is ideally suited to search for seemingly rare radio transient sources that are difficult to discover previous-generation narrow-field telescopes. The Commensal Real-time ASKAP Fast Transient (CRAFT) Survey Science Project has developed instrumentation to continuously search for fast radio transients (duration $\lesssim$ 1 s) with ASKAP, with a particular focus on finding and localising fast radio bursts (FRBs). Since 2018, the CRAFT survey has been searching for FRBs and other fast transients by incoherently adding the intensities received by individual ASKAP antennas, and then correcting for the impact of frequency dispersion on these short-duration signals in the resultant incoherent sum (ICS) in real time. This low-latency detection enables the triggering of voltage buffers, which facilitates the localisation of the transient source and the study of spectro-polarimetric properties at high time resolution. Here we report the sample of 43 FRBs discovered in this CRAFT/ICS survey to date. This includes 22 FRBs that had not previously been reported: 16 FRBs localised by ASKAP to $\lesssim 1$ arcsec and 6 FRBs localised to $\sim 10$ arcmin. Of the new arcsecond-localised FRBs, we have identified and characterised host galaxies (and measured redshifts) for 11. The median of all 30 measured host redshifts from the survey to date is $z=0.23$. We summarise results from the searches, in particular those contributing to our understanding of the burst progenitors and emission mechanisms, and on the use of bursts as probes of intervening media. We conclude by foreshadowing future FRB surveys with ASKAP using a coherent detection system that is currently being commissioned. This will increase the burst detection rate by a factor of approximately ten and also the distance to which ASKAP can localise FRBs.
Early conceptions of humanity’s relationship with God were patterned after human social hierarchies. The original meaning of "worship" is indicative of such conceptions. But these early views don’t do justice to the true greatness of God. The book of Psalms and many of the prophets of Israel insist that God doesn’t require gifts or rituals, but rather moral conduct from humans. This shift in our conception of humanity’s relationship with God requires a corresponding shift in our conception of what worship should be.
Managing clinical trials is a complex process requiring careful integration of human, technology, compliance, and operations for success. We collaborated with experts to develop a multi-axial Clinical Trials Management Ecosystem (CTME) maturity model (MM) to help institutions identify best practices for CTME capabilities.
Methods:
A working group of research informaticists was established. An online session on maturity models was hosted, followed by a review of the candidate domain axes and finalization of the axes. Next, maturity level attributes were defined for min/max levels (level 1 and level 5) for each axis of the CTME MM, followed by the intermediate levels. A REDCap survey comprising the model’s statements was then created, and a subset of working group members tested the model by completing it at their respective institutions. The finalized survey was distributed to all working group members.
Results:
We developed a CTME MM comprising five maturity levels across 11 axes: study management, regulatory and audit management, financial management, investigational product management, subject identification and recruitment, subject management, data, reporting analytics & dashboard, system integration and interfaces, staff training & personnel management, and organizational maturity and culture. Informaticists at 22 Clinical and Translational Science Award hubs and one other organization self-assessed their institutional CTME maturity. Respondents reported relatively high maturity for study management and investigational product management. The reporting analytics & dashboard axis was the least mature.
Conclusion:
The CTME MM provides a framework to research organizations to evaluate their current clinical trials management maturity across 11 axes and identify areas for future growth.
If being asked to give to charity stimulates an emotional response, like empathy, that makes giving difficult to resist, a natural self-control mechanism might be to avoid being asked in the first place. We replicate a result from a field experiment that points to the role of empathy in giving. We conduct an experiment in a large superstore in which we solicit donations to charity and randomly allow shoppers the opportunity to avoid solicitation by using the other door. We find the rate of avoidance by store entrants to be 8.9 %. However, we also find that the avoidance effect disappears in very cold weather, suggesting that avoidance behavior is sensitive to its cost.
Syncope is common among pediatric patients and is rarely pathologic. The mechanisms for symptoms during exercise are less well understood than the resting mechanisms. Additionally, inert gas rebreathing analysis, a non-invasive examination of haemodynamics including cardiac output, has not previously been studied in youth with neurocardiogenic syncope.
Methods:
This was a retrospective (2017–2023), single-center cohort study in pediatric patients ≤ 21 years with prior peri-exertional syncope evaluated with echocardiography and cardiopulmonary exercise testing with inert gas rebreathing analysis performed on the same day. Patients with and without symptoms during or immediately following exercise were noted.
Results:
Of the 101 patients (15.2 ± 2.3 years; 31% male), there were 22 patients with symptoms during exercise testing or recovery. Resting echocardiography stroke volume correlated with resting (r = 0.53, p < 0.0001) and peak stroke volume (r = 0.32, p = 0.009) by inert gas rebreathing and with peak oxygen pulse (r = 0.61, p < 0.0001). Patients with syncopal symptoms peri-exercise had lower left ventricular end-diastolic volume (Z-score –1.2 ± 1.3 vs. –0.36 ± 1.3, p = 0.01) and end-systolic volume (Z-score –1.0 ± 1.4 vs. −0.1 ± 1.1, p = 0.001) by echocardiography, lower percent predicted peak oxygen pulse during exercise (95.5 ± 14.0 vs. 104.6 ± 18.5%, p = 0.04), and slower post-exercise heart rate recovery (31.0 ± 12.7 vs. 37.8 ± 13.2 bpm, p = 0.03).
Discussion:
Among youth with a history of peri-exertional syncope, those who become syncopal with exercise testing have lower left ventricular volumes at rest, decreased peak oxygen pulse, and slower heart rate recovery after exercise than those who remain asymptomatic. Peak oxygen pulse and resting stroke volume on inert gas rebreathing are associated with stroke volume on echocardiogram.
We examine the energy distribution of the fast radio burst (FRB) population using a well-defined sample of 63 FRBs from the Australian Square Kilometre Array Pathfinder (ASKAP) radio telescope, 28 of which are localised to a host galaxy. We apply the luminosity-volume ($V/V_{\mathrm{max}}$) test to examine the distribution of these transient sources, accounting for cosmological and instrumental effects, and determine the energy distribution for the sampled population over the redshift range $0.01 \lesssim z \lesssim 1.02$. We find the distribution between $10^{23}$ and $10^{26}$ J Hz$^{-1}$ to be consistent with both a pure power-law with differential slope $\gamma=-1.96 \pm 0.15$, and a Schechter function with $\gamma = -1.82 \pm 0.12$ and downturn energy $E_\mathrm{max} \sim 6.3 \, \times 10^{25}$ J Hz$^{-1}$. We identify systematic effects which currently limit our ability to probe the luminosity function outside this range and give a prescription for their treatment. Finally, we find that with the current dataset, we are unable to distinguish between the evolutionary and spectral models considered in this work.
This chapter reviews research on a contemporary form of prejudice – aversive racism – and considers the important role of implicit bias in the subtle expressions of discrimination associated with aversive racism. Aversive racism characterizes the racial attitudes of a substantial portion of well-intentioned people who genuinely endorse egalitarian values and believe that they are not prejudiced but at the same time possess automatically activated, often nonconscious, negative feelings and beliefs about members of another group. Our focus in this chapter is on the bias of White Americans toward Black Americans, but we also discuss relevant findings in other intergroup contexts. We emphasize the importance of considering, jointly, both explicit and implicit biases for understanding subtle, and potentially unintentional, expressions of discrimination. The chapter concludes by discussing how research on aversive racism and implicit bias has been mutually informative and suggests specific promising directions for future work.
Fast radio burst (FRB) science primarily revolves around two facets: the origin of these bursts and their use in cosmological studies. This work follows from previous redshift–dispersion measure (z–DM) analyses in which we model instrumental biases and simultaneously fit population parameters and cosmological parameters to the observed population of FRBs. This sheds light on both the progenitors of FRBs and cosmological questions. Previously, we have completed similar analyses with data from the Australian Square Kilometer Array Pathfinder (ASKAP) and the Murriyang (Parkes) Multibeam system. In this manuscript, we use 119 FRBs with 29 associated redshifts by additionally modelling the Deep Synoptic Array (DSA) and the Five-hundred-metre Aperture Spherical radio Telescope (FAST). We also invoke a Markov chain Monte Carlo (MCMC) sampler and implement uncertainty in the Galactic DM contributions. The latter leads to larger uncertainties in derived model parameters than previous estimates despite the additional data and indicate that precise measurements of DM$_\textrm{ISM}$ will be important in the future. We provide refined constraints on FRB population parameters and derive a new constraint on the minimum FRB energy of log $E_{\mathrm{min}}$(erg)=39.47$^{+0.54}_{-1.28}$ which is significantly higher than bursts detected from strong repeaters. This result likely indicates a low-energy turnover in the luminosity function or may alternatively suggest that strong repeaters have a different luminosity function to single bursts. We also predict that FAST will detect 25–41% of their FRBs at $z \gtrsim 2$ and DSA will detect 2–12% of their FRBs at $z \gtrsim 1$.
Today, there are an increasing number of procedures requiring moderate and deep sedation being performed outside the surgical suite. As a result, qualified non-anesthesia providers are administering varying levels of sedation to patients for a variety of diagnostic, therapeutic, and/or surgical procedures. Practitioners should provide patients with the benefits of sedation and/or analgesia while minimizing the associated risks. To do so, providers should understand the pharmacology of the agents being administered as well as the role of pharmacologic antagonists for opioids and benzodiazepines. Today’s practitioners are equipped with an abundance of versatile sedative agents that can be used alone and in combination. Furthermore, combinations of sedative and analgesics should be administered as appropriate for the procedure being performed and the condition of the patient. Policies and standards regarding administration of sedation and analgesia by non-anesthesia providers are addressed elsewhere in the book. This chapter focuses on the pharmacology of the drugs most used to provide moderate and deep sedation and their available reversal agents.
Inappropriate diagnosis and treatment of urinary tract infections (UTIs) contribute to antibiotic overuse. The Inappropriate Diagnosis of UTI (ID-UTI) measure uses a standard definition of asymptomatic bacteriuria (ASB) and was validated in large hospitals. Critical access hospitals (CAHs) have different resources which may make ASB stewardship challenging. To address this inequity, we adapted the ID-UTI metric for use in CAHs and assessed the adapted measure’s feasibility, validity, and reliability.
Design:
Retrospective observational study
Participants:
10 CAHs
Methods:
From October 2022 to July 2023, CAHs submitted clinical information for adults admitted or discharged from the emergency department who received antibiotics for a positive urine culture. Feasibility of case submission was assessed as the number of CAHs achieving the goal of 59 cases. Validity (sensitivity/specificity) and reliability of the ID-UTI definition were assessed by dual-physician review of a random sample of submitted cases.
Results:
Among 10 CAHs able to participate throughout the study period, only 40% (4/10) submitted >59 cases (goal); an additional 3 submitted >35 cases (secondary goal). Per the ID-UTI metric, 28% (16/58) of cases were ASB. Compared to physician review, the ID-UTI metric had 100% specificity (ie all cases called ASB were ASB on clinical review) but poor sensitivity (48.5%; ie did not identify all ASB cases). Measure reliability was high (93% [54/58] agreement).
Conclusions:
Similar to measure performance in non-CAHs, the ID-UTI measure had high reliability and specificity—all cases identified as ASB were considered ASB—but poor sensitivity. Though feasible for a subset of CAHs, barriers remain.
Weight loss results in obligatory reductions in energy expenditure (EE) due to loss of metabolically active fat-free mass (FFM). This is accompanied by adaptive reductions (i.e. adaptive thermogenesis) designed to restore energy balance while in an energy crisis. While the ‘3500-kcal rule’ is used to advise weight loss in clinical practice, the assumption that EE remains constant during energy restriction results in a large overestimation of weight loss. Thus, this work proposes a novel method of weight-loss prediction to more accurately account for the dynamic trajectory of EE. A mathematical model of weight loss was developed using ordinary differential equations relying on simple self-reported inputs of weight and energy intake to predict weight loss over a specified time. The model subdivides total daily EE into resting EE, physical activity EE, and diet-induced thermogenesis, modelling obligatory and adaptive changes in each compartment independently. The proposed model was tested and refined using commercial weight-loss data from participants enrolled on a very low-energy total-diet replacement programme (LighterLife UK, Essex). Mathematical modelling predicted post-intervention weight loss within 0.75% (1.07 kg) of that observed in females with overweight or obesity. Short-term weight loss was consistently underestimated, likely due to considerable FFM reductions reported on the onset of weight loss. The best model agreement was observed from 6 to 9 weeks where the predicted end-weight was within 0.35 kg of that observed. The proposed mathematical model simulated rapid weight loss with reasonable accuracy. Incorporated terms for energy partitioning and adaptive thermogenesis allow us to easily account for dynamic changes in EE, supporting the potential use of such a model in clinical practice.