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To evaluate the quality of systemic antifungal prescribing in Australian hospitals using point-prevalence survey data from the Hospital National Antimicrobial Prescribing Survey (Hospital NAPS).
Methods:
Data were extracted from the Hospital NAPS dataset from January 2014 to December 2024. Systemic antifungal prescriptions were analyzed for antifungal use, guideline compliance, appropriateness, and reasons for inappropriateness according to the Hospital NAPS methodology. Demographic factors, hospital classifications, antifungals, and antifungal indication were compared.
Results:
A total of 7,830 systemic antifungal prescriptions from 372 healthcare facilities across all Australian states and territories were included. Overall 88.4% were guideline compliant and 92.3% of prescriptions were deemed appropriate. Fluconazole was the most commonly prescribed antifungal but had one of the lowest percentage appropriateness (88.4%). In contrast, mold-active azoles, echinocandins, and amphotericin B demonstrated appropriateness rates exceeding 90%. Prescriptions with approval through local antimicrobial stewardship (AMS) processes had significantly higher appropriateness than those without (95.9% vs. 82.9%, p < 0.001). Specialized facilities managing immunocompromised populations showed both higher antifungal use and higher prescribing quality compared to general acute public hospitals.
Conclusion:
This national evaluation highlights the overall high quality of systemic antifungal prescribing in Australian hospitals, reflecting the strength of AMS programs. However, variation across hospital types, specialties, and antifungal agents—particularly fluconazole—indicates opportunities for targeted stewardship interventions to further optimize antifungal use.
Objectives/Goals: Mathematical models of airborne virus transmission lack supporting field and clinical data such as viral aerosol emission rates and airborne infectious doses. Here, we aim to measure inhalation exposure to influenza aerosols in a room shared with persons with community-acquired influenza and estimate the infectious dose via inhalation. Methods/Study Population: We recruited healthy volunteer recipients and influenza donors with polymerase chain reaction (PCR)-confirmed community-acquired infection. On admission to a hotel quarantine, recipients provided sera to determine baseline immunity to influenza virus, and donor infections were confirmed by quantitative real-time polymerase chain reaction. Donors and recipients were housed in separate rooms and interacted in an “event room” with controlled ventilation (0.2 – 0.5 air changes/hour) and relative humidity (20–40%). We collected ambient bioaerosol exposure samples using NIOSH BC-251 samplers. Donors provided exhaled breath samples collected by a Gesundheit-II (G-II). We analyzed aerosol samples using dPCR and fluorescent focus assays for influenza A and sera by hemagglutinin inhibition assay (HAI) against donor viruses and vaccine strains. Results/Anticipated Results: Among two cohorts (24b and 24c), we exposed 11 recipients (mean age: 36; 55% female) to 5 donors (mean age: 21; 80% female) infected with influenza A H1N1 or H3N2. Eight G-II and two NIOSH bioaerosol samples (1–4 µm and ≥4 µm) were PCR positive. We cultured virus from one G-II sample. Based on previous literature, we hypothesized that ~50% of immunologically naïve people (HAI Discussion/Significance of Impact: We demonstrated that it is feasible to recruit donors with community-acquired influenza and expose recipients to measurable virus quantities under controlled conditions. However, baseline immunity was high among volunteers. Our work sets the stage for designing studies with increased sample sizes comprising immunologically naïve volunteers.
This work presents visual morphological and dynamical classifications for 637 spatially resolved galaxies, most of which are at intermediate redshift ($z\sim0.3$), in the Middle-Ages Galaxy Properties with Integral field spectroscopy (MAGPI) Survey. For each galaxy, we obtain a minimum of 11 independent visual classifications by knowledgeable classifiers. We use an extension of the standard Dawid-Skene bayesian model introducing classifier-specific confidence parameters and galaxy-specific difficulty parameters to quantify classifier confidence and infer reliable statistical confidence estimates. Selecting sub-samples of 86 bright ($r\lt20$ mag) high-confidence ($\gt0.98$) morphological classifications at redshifts ($0.2 \le z \le0.4$), we confirm the full range of morphological types is represented in MAGPI as intended in the survey design. Similarly, with a sub-sample of 82 bright high-confidence stellar kinematic classifications, we find that the rotating and non-rotating galaxies seen at low redshift are already in place at intermediate redshifts. We do not find evidence that the kinematic morphology–density relation seen at $z\sim0$ is established at $z\sim0.3$. We suggest that galaxies without obvious stellar rotation are dynamically pre-processed sometime before $z\sim0.3$ within lower mass groups before joining denser environments.
Tufts Clinical and Translational Science Institute (CTSI) developed an online self-paced course to address the gap identified in critical thinking skills related to peer-reviewed nutrition science publications. Initial engagement was low, prompting the launch of a quality improvement project utilizing Dissemination and Implementation (D&I) science principles to enhance participation. This report details the development and execution of the dissemination strategy, course promotion methods, and outcomes related to participant engagement and feedback.
Methods:
A dissemination plan was designed and implemented using the Value-Added Research Dissemination Framework and the Consolidated Framework for Implementation Research (CFIR). Dissemination efforts targeted registered dietitians and university nutrition program instructors, along with their students.
Results:
During the active dissemination period from January to May 2023, the cumulative numbers of learners increased from 23 to 118. Instructors from three nutrition degree programs found the course valuable, reporting that it introduced new content or reinforced existing material. Learner participation continued past the active dissemination period into 2024. Findings from the course evaluation survey provided insights to guide future course improvements.
Conclusion:
This project demonstrates the successful use of D&I frameworks to support the dissemination and implementation of educational innovations such as online learning initiatives.
Metabolic enzymes are the catalysts that drive the biochemical reactions essential for sustaining life. Many of these enzymes are tightly regulated by feedback mechanisms. To fully understand their roles and modulation, it is crucial to investigate the relationship between their structure, catalytic mechanism, and function. In this perspective, by using three examples from our studies on Mycobacterium tuberculosis (Mtb) isocitrate lyase and related proteins, we highlight how an integrated approach combining structural, activity, and biophysical data provides insights into their biological functions. These examples underscore the importance of employing fast-fail experiments at the early stages of a research project, emphasise the value of complementary techniques in validating findings, and demonstrate how in vitro data combined with chemical, biochemical, and physiological knowledge can lead to a broader understanding of metabolic adaptations in pathogenic bacteria. Finally, we address the unexplored questions in Mtb metabolism and discuss how we expand our approach to include microbiological and bioanalytical techniques to further our understanding. Such an integrated and interdisciplinary strategy has the potential to uncover novel regulatory mechanisms and identify new therapeutic opportunities for the eradication of tuberculosis. The approach can also be broadly applied to investigate other biochemical networks and complex biological systems.
Borderline personality disorder (BPD) is a debilitating condition characterized by pervasive instability across multiple major domains of functioning. The majority of persons with BPD engage in self-injury and up to 10% die by suicide – rendering persons with this condition at exceptionally elevated risk of comorbidity and premature mortality. Better characterization of clinical risk factors among persons with BPD who die by suicide is urgently needed.
Methods
We examined patterns of medical and psychiatric diagnoses (1580 to 1700 Phecodes) among persons with BPD who died by suicide (n = 379) via a large suicide death data resource and biobank. In phenotype-based phenome-wide association tests, we compared these individuals to three other groups: (1) persons who died by suicide without a history of BPD (n = 9468), (2) persons still living with a history of BPD diagnosis (n = 280), and (3) persons who died by suicide with a different personality disorder (other PD n = 589).
Results
Multivariable logistic regression models revealed that persons with BPD who died by suicide were more likely to present with co-occurring psychiatric diagnoses, and have a documented history of self-harm in the medical system prior to death, relative to suicides without BPD. Posttraumatic stress disorder was more elevated among those with BPD who died by suicide relative to the other PD group.
Conclusions
We found significant differences among persons with BPD who died by suicide and all other comparison groups. Such differences may be clinically informative for identifying high-risk subtypes and providing targeted intervention approaches.
Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an environmental endocrine disruptor and model AhR agonist, is linked to skeletal abnormalities, cardiac edema, stunted growth rate, altered metabolism, and neurobehavioral deficits. We have previously reported transgenerational reproductive outcomes of developmental TCDD exposure in adult zebrafish (Danio rerio), an NIH-validated model for developmental and generational toxicology. Using the same paradigm of sublethal TCDD exposure (50 pg/ml) at both 3 and 7 weeks post fertilization (wpf), we investigated several novel endpoints, including longitudinal morphometrics and anxiety-linked behavior, in fish exposed as juveniles. We also assessed developmental abnormalities and neurobehavior in their F1 larval offspring. TCDD exposure induced timepoint-dependent decreases in several craniofacial and trunk morphometrics across juvenile development. In early adulthood, however, only exposed males underwent a transient period of compensatory growth, ending between 7 and 12 months post fertilization (mpf). At 12 mpf, exposed adult fish of both sexes displayed increased exploratory behaviors in a novel tank test. The F1 offspring of parents exposed at both 3 and 7 wpf were hyperactive, but neurobehavioral outcomes diverged depending on parental exposure window. F1 exposure-lineage larvae had increased rates of edema and skeletal abnormalities, but fewer unhatched larvae compared to controls. Parent- and timepoint-specific effects of exposure on abnormality rate were also evaluated; these outcomes were considerably less severe. Our novel behavioral findings expand current knowledge of the long-term and intergenerational consequences of early-life TCDD exposure in a zebrafish model, in addition to delineating minor longitudinal morphometric changes in exposed fish and abnormalities in larval offspring.
Initial microbial colonization plays an important role in neonatal gut health. However, studies on gut microbial composition at birth are challenging, due to the limited access to accurate sampling. Here, we characterized the jejunal and ileal bacterial composition (epimural and luminal) of neonatal calves within 30 minutes after birth, and compared it with maternal (birth canal and rectum) and birth environments. RNA-based quantification along with amplicon sequencing revealed the colonization of active, dense (1.1–9.4 × 108 16S rRNA copy/g of sample), and diverse bacteria in the calf small intestine at birth. Pseudomonadaceae and Propionibacteriaceae dominated epimural communities, while Propionibacteriaceae, Prevotellaceae, Ruminococcaceae, and Lachnospiraceae dominated luminal communities. The composition of calf gut bacteria at birth was significantly different from maternal bacteria, especially for beneficial bifidobacteria. The bacterial communities of calf body habitats were similar to those of the birth environment, which was again divergent from gut microbiota. This study suggests an establishment of small intestinal-specific microbiota from birth, which is considerably deviated from maternal microbiota. In corollary, we further propose that small intestinal microbiota colonization could be mainly modulated by host selection.
This retrospective cohort study examined prosocial skills development in child welfare-involved children, how intimate partner violence (IPV) exposure explained heterogeneity in children’s trajectories of prosocial skill development, and the degree to which protective factors across children’s ecologies promoted prosocial skill development. Data were from 1,678 children from the National Survey of Child and Adolescent Well-being I, collected between 1999 and 2007. Cohort-sequential growth mixture models were estimated to identify patterns of prosocial skill development between the ages of 3 to 10 years. Four diverse pathways were identified, including two groups that started high (high subtle-decreasing; high decreasing-to-increasing) and two groups that started low (low stable; low increasing-to-decreasing). Children with prior history of child welfare involvement, preschool-age IPV exposure, school-age IPV exposure, or family income below the federal poverty level had higher odds of being in the high decreasing-to-increasing group compared with the high subtle-decreasing group. Children with a mother with greater than high school education or higher maternal responsiveness had higher odds of being in the low increasing-to-decreasing group compared with the low stable group. The importance of maternal responsiveness in fostering prosocial skill development underlines the need for further assessment and intervention. Recommendations for clinical assessment and parenting programs are provided.
Patients with Fontan failure are high-risk candidates for heart transplantation and other advanced therapies. Understanding the outcomes following initial heart failure consultation can help define appropriate timing of referral for advanced heart failure care.
Methods:
This is a survey study of heart failure providers seeing any Fontan patient for initial heart failure care. Part 1 of the survey captured data on clinical characteristics at the time of heart failure consultation, and Part 2, completed 30 days later, captured outcomes (death, transplant evaluation outcome, and other interventions). Patients were classified as “too late” (death or declined for transplant due to being too sick) and/or “care escalation” (ventricular assist device implanted, inotrope initiated, and/or listed for transplant), within 30 days. “Late referral” was defined as those referred too late and/or had care escalation.
Results:
Between 7/2020 and 7/2022, 77 Fontan patients (52% inpatient) had an initial heart failure consultation. Ten per cent were referred too late (6 were too sick for heart transplantation with one subsequent death, and two others died without heart transplantation evaluation, within 30 days), and 36% had care escalation (21 listed ± 5 ventricular assist device implanted ± 6 inotrope initiated). Overall, 42% were late referrals. Heart failure consultation < 1 year after Fontan surgery was strongly associated with late referral (OR 6.2, 95% CI 1.8–21.5, p=0.004).
Conclusions:
Over 40% of Fontan patients seen for an initial heart failure consultation were late referrals, with 10% dying or being declined for transplant within a month of consultation. Earlier referral, particularly for those with heart failure soon after Fontan surgery, should be encouraged.
Accumulating evidence shows associations between rapid eating and overweight. Modifying eating rate might be a potential weight management strategy without imposing additional dietary restrictions. A comprehensive understanding of factors associated with eating speed will help with designing effective interventions. The aim of this review was to synthesise the current state of knowledge on the factors associated with eating rate. The socio-ecological model (SEM) was utilised to scaffold the identified factors. A comprehensive literature search of eleven databases was conducted to identify factors associated with eating rate. The 104 studies that met the inclusion criteria were heterogeneous in design and methods of eating rate measurement. We identified thirty-nine factors that were independently linked to eating speed and mapped them onto the individual, social and environmental levels of the SEM. The majority of the reported factors pertained to the individual characteristics (n = 20) including demographics, cognitive/psychological factors and habitual food oral processing behaviours. Social factors (n = 11) included eating companions, social and cultural norms, and family structure. Environmental factors (n = 8) included food texture and presentation, methods of consumption or background sounds. Measures of body weight, food form and characteristics, food oral processing behaviours and gender, age and ethnicity were the most researched and consistent factors associated with eating rate. A number of other novel and underresearched factors emerged, but these require replication and further research. We highlight directions for further research in this space and potential evidence-based candidates for interventions targeting eating rate.
The Maser Monitoring Organisation is a collection of researchers exploring the use of time-variable maser emission in the investigation of astrophysical phenomena. The forward directed aspects of research primarily involve using maser emission as a tool to investigate star formation. Simultaneously, these activities have deepened knowledge of maser emission itself in addition to uncovering previously unknown maser transitions. Thus a feedback loop is created where both the knowledge of astrophysical phenomena and the utilised tools of investigation themselves are iteratively sharpened. The project goals are open-ended and constantly evolving, however, the reliance on radio observatory maser monitoring campaigns persists as the fundamental enabler of research activities within the group.
Recently, remarkable progress has been made in understanding the formation of high mass stars. Observations provided direct evidence that massive young stellar objects (MYSOs), analogously to low-mass ones, form via disk-mediated accretion accompanied by episodic accretion bursts, possibly caused by disk fragmentation. In the case of MYSOs, the mechanism theoretically provides a means to overcome radiation pressure, but in practice it is poorly studied - only three accretion bursts in MYSOs have been caught in action to date. A significant contribution to the development of the theory has been made with the study of masers, which have proven to be a powerful tool for locating “bursting” MYSOs. This overview focuses on the exceptional role that masers play in the search and study of accretion bursts in massive protostars.
The modern Nile delta developed in the Middle and Late Holocene, and at its most northern-central point is situated at the Burullus Lagoon, which is environmentally diverse, including salt marshes, mudflats, and sand plains, and separated from a sea by a sand barrier overtopped with high sand dunes. The lagoon has been fed since the Middle Holocene by the Sebennitic branch of the Nile and marine intrusions through the Bughaz inlet. A sediment core (BO-1) was collected at the northeastern shore of the lagoon and sampled at centennial scale resolution in order to reconstruct the development of the lagoon. The results show that an initial and limited lagoon had developed at the end of the Early Holocene, but after a dry period ca. 7.2 cal ka BP it has been progressively transformed into a marshy area, with occasional inflows of sea water. Lower water level and higher salinity of the Burullus Lagoon at 6.0–5.5 and 4.8–4.2 cal ka BP reflected droughts in the Nile catchment. Thereafter, the river reactivated in the Burullus Lagoon area, and since 2.8 cal ka BP was accompanied by occasional inflows of sea water. Since ca. 0.8 cal ka BP, increased fluvial activity occurred in this part of the Nile delta, which terminated after construction of the Aswan dams in the twentieth century.
The degree to which suicide risk aggregates in US families is unknown. The authors aimed to determine the familial risk of suicide in Utah, and tested whether familial risk varies based on the characteristics of the suicides and their relatives.
Methods
A population-based sample of 12 160 suicides from 1904 to 2014 were identified from the Utah Population Database and matched 1:5 to controls based on sex and age using at-risk sampling. All first through third- and fifth-degree relatives of suicide probands and controls were identified (N = 13 480 122). The familial risk of suicide was estimated based on hazard ratios (HR) from an unsupervised Cox regression model in a unified framework. Moderation by sex of the proband or relative and age of the proband at time of suicide (<25 v. ⩾25 years) was examined.
Results
Significantly elevated HRs were observed in first- (HR 3.45; 95% CI 3.12–3.82) through fifth-degree relatives (HR 1.07; 95% CI 1.02–1.12) of suicide probands. Among first-degree relatives of female suicide probands, the HR of suicide was 6.99 (95% CI 3.99–12.25) in mothers, 6.39 in sisters (95% CI 3.78–10.82), and 5.65 (95% CI 3.38–9.44) in daughters. The HR in first-degree relatives of suicide probands under 25 years at death was 4.29 (95% CI 3.49–5.26).
Conclusions
Elevated familial suicide risk in relatives of female and younger suicide probands suggests that there are unique risk groups to which prevention efforts should be directed – namely suicidal young adults and women with a strong family history of suicide.
Competition agency guidelines, policy statements and related advocacy activities are an important vehicle for policy expression across the full spectrum of anti-competitive practices and for the guidance of firms in determining their market conduct. They are also, often, a revealing window into the thinking of agency officials and professional staff regarding the problems they are grappling with, thus providing an empirical foundation for mapping the trends and evolution of such policy thinking across diverse jurisdictions and over time. An early, influential example of such guidelines was the Merger Guidelines adopted by the US Department of Justice in 1968,1 which embodied and set out clearly the structure-conduct-performance paradigm of industrial organization and competition policy analysis that was prevalent at the time.
Controlled clinical trials (CCTs) have traditionally been limited to urban academic clinical centers. Implementation of CCTs in rural setting is challenged by lack of resources, the inexperience of patient care team members in CCT conductance and workflow interruption, and global inexperience with remote data monitoring.
Methods:
We report our experience during the coronavirus disease 2019 (COVID-19) pandemic in activating through remote monitoring a multicenter clinical trial (the Study of Efficacy and Safety of Canakinumab Treatment for cytokine release syndrome (CRS) in Participants with COVID-19-induced Pneumonia [CAN-COVID] trial, ClinicalTrials.gov Identifier: NCT04362813) at a rural satellite hospital, the VCU Health Community Memorial Hospital (VCU-CMH) in South Hill, VA, that is part of the larger VCU Health network, with the lead institution being VCU Health Medical College of Virginia Hospital (VCU-MCV), Richmond, VA. We used the local resources at the facility and remote guidance and oversight from the VCU-MCV resources using a closed-loop communication network. Investigational pharmacy, pathology, and nursing were essential to operate the work in coordination with the lead institution.
Results:
Fifty-one patients with COVID-19 were enrolled from May to August 2020, 35 (69%) at VCU-MCV, and 16 (31%) at VCU-CMH. Among the patients enrolled at VCU-CMH, 37.5% were female, 62.5% Black, and had a median age of 60 (interquartile range 56–68) years.
Conclusion:
Local decentralization of this trial in our experience gave rural patients access to a novel treatment and also accelerated enrollment and more diverse participants’ representative of the target population.
We investigated how Central Swedish-speaking four to eleven-year-old children acquire the prosodic marking of narrow focus, compared to adult controls. Three measurements were analysed: placement of the prominence-marking high tone (prominence H), pitch range effects of the prominence H, and word duration. Subject-verb-object sentences were elicited in sentence-medial and sentence-final focus conditions via a semi-spontaneous elicitation task. The children largely performed in an adult-like manner already at four to five: they predominantly added prominence H to focal words and avoided this tone post-focally in both sentence-medial and sentence-final position. The placement or avoidance of prominence H had largely the same effects on pitch range for children and adults. Finally, the four to eight-year-olds also increased the duration of the focal word, similar to adults. Hence, Central Swedish-speaking children master the use of prosody for focus marking at an earlier age, compared to children acquiring a West Germanic language.