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Antenatal corticosteroids are given to pregnant people at risk of preterm birth to reduce newborn morbidity, including respiratory distress syndrome. However, there has been concern surrounding potential adverse effects on subsequent generations. Animal studies have demonstrated endocrine and metabolic changes in those exposed to corticosteroids in utero (F1) and in the second generation (F2). We aimed to assess the effects of parental antenatal corticosteroid exposure on health of the second generation (F2) of Auckland Steroid Trial (AST) participants. In the AST, women (F0) expected to birth between 24 and 36 weeks’ gestation were randomised to betamethasone or placebo. When their children (F1) were 50 years old, they and their children (F2) were followed up with a self-report questionnaire and data linkage. The primary outcome for this analysis was body mass index (BMI) z-score in the F2 generation. Secondary outcomes included respiratory, cardiovascular, neurodevelopmental, mental and general health, and social outcomes. Of the 213 F2 participants, 144 had BMI data available. There was no difference in BMI z-score between participants whose parent was exposed to betamethasone versus placebo (mean (SD) 0.63 (1.45), N = 77 vs 0.41 (1.28), N = 67, adjusted mean difference (95% confidence interval) = 0.16 (-0.37, 0.69)). There was no evidence of a difference in rates of overweight, diabetes, respiratory disease, cardiometabolic risk factors, neurodevelopmental difficulties, mental health difficulties and social outcomes between parental betamethasone versus placebo exposure groups, but confidence intervals were wide. These findings are reassuring regarding the intergenerational safety of antenatal corticosteroids.
Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.
Methods
T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).
Results
PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (pcorrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (pcorrected = .001).
Conclusions
PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.
Paediatric ventricular assist device patients, including those with single ventricle anatomy, are increasingly managed outside of the ICU. We used retrospective chart review of our single centre experience to quantify adverse event rates and ICU readmissions for 22 complex paediatric patients on ventricular assist device support (15 two ventricles, 7 single ventricle) after floor transfer. The median age was 1.65 years. The majority utilised the Berlin EXCOR (17, 77.3%). There were 9 ICU readmissions with median length of stay of 2 days. Adverse events were noted in 9 patients (41%), with infection being most common (1.8 events per patient year). There were no deaths. Single ventricle patients had a higher proportion of ICU readmission and adverse events. ICU readmission rates were low, and adverse event rates were comparable to published rates suggesting ventricular assist device patients can be safely managed on the floor.
This paper studies the problem of scaling ordinal categorical data observed over two or more sets of categories measuring a single characteristic. Scaling is obtained by solving a constrained entropy model which finds the most probable values of the scales given the data. A Kullback-Leibler statistic is generated which operationalizes a measure for the strength of consistency among the sets of categories. A variety of data of two and three sets of categories are analyzed using the entropy approach.
The Duke Activity Status Index is used to assess an individual patient’s perception of their fitness abilities. It has been validated and shown to predict actual fitness in adults but has been studied less in the paediatric population, specifically those with heart disease. This study aims to assess if the Duke Activity Status Index is associated with measured markers of physical fitness in adolescents and young adults with heart disease.
Methods:
This retrospective single-centre cohort study includes patients who completed a minimum of 12 weeks of cardiac rehabilitation between 2016 and 2022. Cardiac rehabilitation outcomes included physical, performance, and psychosocial measures. A comparison between serial testing was performed using a paired t-test. Univariable and multivariable analyses for Duke Activity Status Index were performed. Data are reported as median [interquartile range].
Results:
Of the 118 participants (20 years-old [13.9–22.5], 53% male), 33 (28%) completed at least 12 weeks of cardiac rehabilitation. Median peak oxygen consumption was 60.1% predicted [49–72.8%], and Duke Activity Status Index was 32.6 [21.5–48.8]. On Pearson’s correlation assessing the Duke Activity Status Index, there were significant associations with % predicted peak oxygen consumption (r = 0.49, p < 0.0001), 6-minute walk distance (r = 0.45, p < 0.0001), Duke Activity Status Index metabolic equivalents (r = 0.45, p < 0.0001), and dominant hand grip (r = 0.48, p < 0.0001). In multivariable analysis, the % predicted peak oxygen consumption (r = 0.40, p = 0.005) and dominant hand grip (r = 0.37, p = 0.005) remained statistically significant.
Conclusions:
Duke Activity Status Index is associated with measures of physical fitness in paediatric and young adults with heart disease who complete a cardiac rehabilitation program.
Background: Pituitary adenomas are treated with endoscopic surgery, while stereotactic radiosurgery addresses complex cases. Our study highlights AI’s role in accurate segmentation, improving treatment planning workflow efficiency Methods: In a retrospective study at Na Homolce Hospital (January 2010 to October 2022), SRS for pituitary adenomas was analyzed. Data were split 80:20 for training and validation. Using nnU-net, a medical image segmentation tool, a model predicted precise tumor, optic nerve, and pituitary gland segmentation. Accuracy was evaluated quantitatively with Dice similarity coefficient and qualitatively by human experts. The study explored the impact of tumor volume and hormonal activity status on segmentation accuracy. Results: The study comprised 582 and 146 patients in training and validation sets, respectively. The model achieved Dice similarity coefficients of 83.1% (tumor), 62.9% (normal gland), and 78.0% (optic nerve). Expert assessments deemed 41% directly applicable, 31.5% needing minor adjustments, and 27.4% unsuitable for clinical use. Larger tumor volume and non-functioning adenomas correlated with higher accuracy. Including T2 weighted scans improved DSC for optic nerve and normal gland. Conclusions: The study showcases deep learning’s potential in automating pituitary adenoma segmentation from MRI data, particularly excelling in large, hormonally inactive macroadenomas. Encourages collaborative use with clinicians for improved neurosurgical patient care.
The Island Pacific, and especially Papua New Guinea (PNG), occupies an important place in Australia’s international relations. In part this flows from geographical proximity and historical linkages, and considerations of security, trade, and investment. But in addition the Island Pacific is perhaps the only part of the world in which Australia can hope to exercise a significant influence over events, and in which it is generally regarded by the international community as having a responsibility for promoting political stability and economic progress. Australia’s regional responsibility was explicitly recognised in the 1997 foreign policy White Paper, In the National Interest. Yet while the importance of the region is often recognised in the rhetoric of public statements, and concretely in levels of development assistance and defence cooperation, mention of the Pacific frequently comes only at the end of foreign policy and defence analyses, and it is difficult to discern a coherent, long-term policy framework in Australia’s dealings with the Pacific Island states.
The crystal structure of a natural, ordered IIb-4 triclinic clinochlore has been refined in space group C1̄ from 4282 unique X-ray intensity measurements of which 3833 are greater than 3 times the statistical counting error (3σ). Unit cell parameters are a = 5.3262(6) Å; b = 9.226(1) Å; c = 14.334(3) Å; α = 90.56(2)°; β = 97.47(2)°; and γ = 89.979(9)°, which represents the greatest deviation from mono-clinic symmetry yet recorded for a triclinic chlorite. The final weighted R is 0.059 for reflections with I > 3σ and 0.064 for all reflections. The chemical formula is (Mg0.966Fe0.034)MI(Mg0.962Fe0.038)M22(Si2.96Al1.04)O10 (OH)2(Mg0.996Fe0.004)M32(Al0.841FeIII0.102Cr0.004Ti0.004)M4(OH)6, which is consistent with electron microprobe (EMP), wet chemical analyses, Mössbauer spectroscopy and X-ray structure refinement. The high degree of ordering of the divalent versus trivalent octahedral cations in the interlayer is noteworthy, with FeIII and Al in M4 and virtually no Fe in M3. In the 2:1 layer, M1 and M2 each contain similar amounts of Fe. The 2 tetrahedral sites have nearly identical mean oxygen distances and volumes, and thus show no evidence of long-range cation ordering.
A mathematical model for the effect of the spatial variation of the local evaporative flux on the evaporation of and deposition from a thin pinned particle-laden sessile droplet is formulated and solved. We then analyse the behaviour for a one-parameter family of local evaporative fluxes with the free parameter $n \, (>-1)$ that exhibits qualitatively different behaviours mimicking those that can be obtained by, for example, surrounding the droplet with a bath of fluid or using a mask with one or more holes in it to achieve a desired pattern of evaporation enhancement and/or suppression. We show that when $-1< n<1$ (including the special cases $n=-1/2$ of diffusion-limited evaporation into an unbounded atmosphere and $n=0$ of spatially uniform evaporation), all of the particles are eventually advected to the contact line, and so the final deposit is a ring deposit at the contact line, whereas when $n>1$ all of the particles are eventually advected to the centre of the droplet, and so the final deposit is at the centre of the droplet. In particular, the present work demonstrates that a singular (or even a non-zero) evaporative flux at the contact line is not an essential requirement for the formation of a ring deposit. In addition, we calculate the paths of the particles when diffusion is slower than both axial and radial advection, and show that in this regime all of the particles are captured by the descending free surface before eventually being deposited onto the substrate.
OBJECTIVES/GOALS: Supported by the State of Alabama, the Alabama Genomic Health Initiative (AGHI) is aimed at preventing and treating common conditions with a genetic basis. This joint UAB Medicine-HudsonAlpha Institute for Biotechnology effort provides genomic testing, interpretation, and counseling free of charge to residents in each of Alabama’s 67 counties. METHODS/STUDY POPULATION: Launched in 2017, as a state-wide population cohort, AGHI (1.0) enrolled 6,331 Alabamians and returned individual risk of disease(s) related to the ACMG SF v2.0 medically actionable genes. In 2021, the cohort was expanded to include a primary care cohort. AGHI (2.0) has enrolled 750 primary care patients, returning individual risk of disease(s) related to the ACMG SF v3.1 gene list and pre-emptive pharmacogenetics (PGx) to guide medication therapy. Genotyping is done on the Illumina Global Diversity Array with Sanger sequencing to confirm likely pathogenic / pathogenic variants in medically actionable genes and CYP2D6 copy number variants using Taqman assays, resulting in a CLIA-grade report. Disease risk results are returned by genetic counselors and Pharmacogenetics results are returned by Pharmacists. RESULTS/ANTICIPATED RESULTS: We have engaged a statewide community (>7000 participants), returning 94 disease risk genetic reports and 500 PGx reports. Disease risk reports include increased predisposition to cancers (n=38), cardiac diseases (n=33), metabolic (n=12), other (n=11). 100% of participants harbor an actionable PGx variant, 70% are on medication with PGx guidance, 48% harbor PGx variants and are taking medications affected. In 10% of participants, pharmacists sent an active alert to the provider to consider/ recommend alternative medication. Most commonly impacted medications included antidepressants, NSAIDS, proton-pump inhibitors and tramadol. To enable the EMR integration of genomic information, we have developed an automated transfer of reports into the EMR with Genetics Reports and PGx reports viewable in Cerner. DISCUSSION/SIGNIFICANCE: We share our experience on pre-emptive implementation of genetic risk and pharmacogenetic actionability at a population and clinic level. Both patients and providers are actively engaged, providing feedback to refine the return of results. Real time alerts with guidance at the time of prescription are needed to ensure future actionability and value.
Having a sense of calling toward one's work has key benefits for both the employee and the employer. Yet, little is known about whether and what kind of work climate facilitates employees' senses of calling, hindering efforts toward positive changes from managers and organizations. This research introduces the concept of ‘career calling climate’ and describes the development of a scale (i.e., Career Calling Climate Scale) to measure the level of support that a work unit provides for its employees' pursuit of a calling. We established the scale's validity and reliability using survey responses from participants of various occupations and age. To provide evidence of its predictive validity, we examined career calling climate's relation with career callings using a sample of 189 healthcare employees nested in 34 work units. Results suggested that career calling climate predicted individuals' career callings. Implications for theory and practice are discussed.
In this paper we re-describe Trichuris muris based on morphological data following isolation from two commensal rodent species, Mus musculus from Mexico and Rattus rattus from Argentina. Furthermore, we provide a molecular characterization based on mitochondrial (cytochrome c oxidase subunit 1 mitochondrial gene) and nuclear (internal transcribed spacer 2 region) markers in order to support the taxonomic identification of the studied specimens of T. muris from M. musculus. We distinguished T. muris from 29 species of Trichuris found in American rodents based on morphological and biometrical features, such as the presence of a spicular tube, length of spicule, size of proximal and distal cloacal tube and non-protrusive vulva. We suggest that spicular tube patterns can be used to classify Trichuris species in three groups. Considering that the diagnosis among the species of this genus is mainly based on morphometry, this proposal represents a relevant contribution. We provide molecular studies on two markers, making this the first contribution for T. muris in the Americas. This study makes an important contribution to the integrative taxonomy of cosmopolitan nematode species, and its correct determination from the parasitological study of commensal rodents.
The title of this volume applies the increasingly popular concept of the Anthropocene1 to what have come to be known as environmental human rights (EHRs) (Knox et al., 2018; May, 2020; May & Daly, 2014, 2019). At its core, the Anthropocene reflects the idea that the human and non-human elements of the earth system have become so completely intertwined that no change can occur in one without impact on the other (Young et al., 2017). This new state of affairs imposes upon us a responsibility our species has never faced – that of determining both own our fate and the fate of all living things, and the role that law plays in the mix of environmental law and governance (Kotzé, 2017). However, with great responsibility sometimes comes great opportunity. If every environmental challenge is now also a human challenge, it may be that human interests and the interests of the non-human (or, more-than-human) environment are gradually converging (Baber & Bartlett, 2015). If so, then the protection of human rights may afford new opportunities to protect the environment (and vice versa). It remains to be seen whether we are astute enough to recognise those opportunities and take advantage of them.
The Anthropocene won’t be ignored but doesn’t care if it is. Headlines tumble out one after another, revealing disaster in every part of our environment: one day we learn that eight million tons of plastic are put into the world’s oceans every year, and as we try to comprehend the magnitude of that, we hear about the seemingly intractable air pollution in the world’s largest cities (UN, 2020, 2021). And then there’s climate change, which is raising global temperatures, warming and acidifying oceans, melting glaciers and ice caps, and wreaking havoc on weather patterns. June 2021 was the hottest month in recorded history. The Anthropocene is here and it is us, human rights be damned.
As the chapters of this book recount, the last few decades have witnessed increasing communion between the fields of environmental law and human rights. Traditionally, the field of environmental law serves to achieve desired ecological conditions, such as clean air, water, and land and is captured by more than 500 international agreements, many of the world’s constitutions, and in countless laws and regulations and local ordinances around the world. Human rights, on the other hand, serve to advance desired human conditions, including civil rights such as voting and socioeconomic rights such as health or education, again through a combination of international, regional, and municipal legal pproaches. Yet what work can the legal order do to address the Anthropocene?