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Noether’s first theorem, in its modern form, does not establish a one-way explanatory arrow from symmetries to conservation laws, but such an arrow is widely assumed in discussions of the theorem in the physics and philosophy literature. It is argued here that there are pragmatic reasons for privileging symmetries, even if they do not strictly justify explanatory priority. To this end, some practical factors are adduced as to why Noether’s direct theorem seems to be more well-known and exploited than its converse, with special attention being given to the sometimes overlooked nature of Noether’s converse result and to its strengthened version due to Luis Martínez Alonso in 1979 and independently Peter Olver in 1986.
Humpback whales (Megaptera novaeangliae) exhibit maternally driven fidelity to feeding grounds, and yet occasionally occupy new areas. Humpback whale sightings and mortalities in the New York Bight apex (NYBA) have been increasing over the last decade, providing an opportunity to study this phenomenon in an urban habitat. Whales in this area overlap with human activities, including busy shipping traffic leading into the Port of New York and New Jersey. The site fidelity, population composition and demographics of individual whales were analysed to better inform management in this high-risk area. Whale watching and other opportunistic data collections were used to identify 101 individual humpback whales in the NYBA from spring through autumn, 2012–2018. Although mean occurrence was low (2.5 days), mean occupancy was 37.6 days, and 31.3% of whales returned from one year to the next. Individuals compared with other regional and ocean-basin-wide photo-identification catalogues (N = 52) were primarily resighted at other sites along the US East Coast, including the Gulf of Maine feeding ground. Sightings of mother-calf pairs were rare in the NYBA, suggesting that maternally directed fidelity may not be responsible for the presence of young whales in this area. Other factors including shifts in prey species distribution or changes in population structure more broadly should be investigated.
The primary objective of this study was to co-design and conduct a pilot evaluation of a novel, immersive virtual reality (VR) experience for procedural pain and anxiety in an Australian healthcare setting. The secondary objective was to identify key parameters that can facilitate the development and implementation of VR experiences in clinical practice.
A qualitative, Design Box method was selected for co-design. It was used with adult burns survivors and adolescents and young adults (AYAs) with cancer, and healthcare professionals from these fields to identify the practical and design parameters required for the application of VR technology within the clinical setting. Results informed the development of the VR experience that was evaluated by consumers and healthcare professionals, who completed qualitative surveys. Thematic analysis was conducted on co-design notes and survey data.
Procedural pain and management was a challenge for both cohorts, but particularly the burns cohort. Anxiety was significant challenge for both cohorts. Boredom and quality of life was a significant challenge, particularly for the AYA oncology cohort. These results informed the development of “A Wanderers Tale,” an Australiana-themed, gaze-controlled VR application for Oculus Quest platforms. Thematic analysis results suggest that cultural preferences, procedural contexts of use, and agency through customization and interaction are three parameters to consider when creating or selecting VR experiences for application in health.
Significance of results
This work describes a novel method for the use VR as an adjuvant pain management tool in patients with burns and cancer. The VR experience may provide a culturally, practice and procedure-appropriate tool in comparable settings of care. The study also describes interdisciplinary co-design and evaluation approaches that can help maximize the use of VR to improve healthcare approaches that address clinical challenges in pain, anxiety, and quality of life for patients while in hospital.
OBJECTIVES/GOALS: We aimed to determine if GLP-1 receptor agonists exert beneficial effects on surrogate measures of cardiovascular function independently of weight loss. Our objective was to compare the outcomes between GLP-1 receptor agonist treatment versus a similar drug without cardiovascular benefit versus weight loss through diet alone. METHODS/STUDY POPULATION: We enrolled 88 individuals with obesity (BMI â‰¥ 30kg/m2) and pre-diabetes and randomized them in a 2:1:1 ratio to 14 weeks of the GLP-1 receptor agonist liraglutide, the dipeptidyl peptidase-4 inhibitor sitagliptin, or hypocaloric diet. Sitagliptin blocks degradation of endogenous GLP-1 but does not cause weight loss or lower adverse cardiovascular outcomes. Treatment was double-blinded and placebo-controlled for drug, and unblinded for diet. Primary endpoints were flow-mediated dilation (FMD) to assess endothelial vasodilatory function, and plasminogen activator inhibitor-1 (PAI-1) to assess endothelial fibrinolytic function. We used a general linear model for each outcome and included gender as a covariate for FMD. Baseline characteristics were similar. Mean age was 50, with 32% men and 13% black. RESULTS/ANTICIPATED RESULTS: At 14 weeks, diet and liraglutide caused weight loss (diet -4.3 Â± 3.2 kg, P<0.01; liraglutide -2.7 Â± 3.2, P<0.01), while sitagliptin did not (-0.7 Â± 2.0, P=0.17). Diet did not improve FMD at 14 weeks compared to baseline (+0.9%, 95% CI [-1.5, 3.3], P=0.46). FMD tended to increase after liraglutide and sitagliptin but was not significant (liraglutide +1.2 [-0.3, 2.8], P=0.12; sitagliptin +1.6 [-0.6, 3.8], P=0.15). Given that liraglutide and sitagliptin work through the same GLP-1 pathway, we combined the liraglutide and sitagliptin groups for overall effect on FMD, which was significantly improved from baseline (+1.4 [0.1, 2.8], P=0.04). Diet and liraglutide improved PAI-1 at 14 weeks (diet -4.4U/mL, [-8.5, -0.2], P=0.04; liraglutide -3.4 [-6.0, -0.7], P=0.01), while sitagliptin did not (-1.4 [-5.1, 2.3], P=0.46). DISCUSSION/SIGNIFICANCE: Activation of the GLP-1 pathway by liraglutide or sitagliptin improves FMD independent of weight loss, while PAI-1 improvement is weight-loss dependent and is only seen after liraglutide or diet. Our study suggests the cardiovascular benefit of liraglutide may be due to combined improvements in endothelial vasodilatory and fibrinolytic function.
Children with CHD are at risk for psychosocial and neurodevelopmental difficulties, as well as lapses in care during their transition from paediatric to adult CHD providers. The American Heart Association and American Academy of Pediatrics released guidelines for best practices in the neurodevelopmental and transitional care for children with CHD in 2012 and 2011, respectively. CHD providers from 48 (42.1% response rate) geographically diverse cardiac clinics completed a 31-item electronic survey designed to assess the cardiac teams’ consistency with neurodevelopmental evaluation and management recommendations, consultation/liaison patterns for psychosocial services, and procedures regarding transitional services for emerging adults. Responses suggest most cardiac teams refer patients to psychosocial services as needed, and 39.6% of teams screen for psychosocial distress. CHD providers at 66.7% of cardiac clinics reported a formal neurodevelopmental programme/clinic. Nearly half of cardiac teams conduct routine neurodevelopmental evaluations, most frequently occurring at 9 months of age. Less than 10% of cardiac clinics have resources to meet the American Heart Association and American Academy of Pediatrics 2012 neurodevelopmental evaluation and management guidelines. Formal paediatric to adult CHD transition programmes were reported at 70.8% of cardiac clinics and were associated with younger ages of transition to adult CHD care. Care practices varied across the 48 represented cardiac clinics, indicating inconsistent practices for patients with CHD. Barriers and facilitators to the provision of care for children in these areas were reported and are presented. More support is needed for cardiac clinics to continue improvements in psychosocial, neurodevelopmental, and transitional care services.
COVID-19 is a major health threat around the world causing hundreds of millions of infections and millions of deaths. There is a pressing global need for effective therapies. We hypothesized that leukotriene inhibitors (LTIs), that have been shown to lower IL6 and IL8 levels, may have a protective effect in patients with COVID-19.
In this retrospective controlled cohort study, we compared death rates in COVID-19 patients who were taking a LTI with those who were not taking an LTI. We used the Department of Veterans Affairs (VA) Corporate Data Warehouse (CDW) to create a cohort of COVID-19-positive patients and tracked their use of LTIs between November 1, 2019 and November 11, 2021.
Of the 1,677,595 cohort of patients tested for COVID-19, 189,195 patients tested positive for COVID-19. Forty thousand seven hundred one were admitted. 38,184 had an oxygen requirement and 1214 were taking an LTI. The use of dexamethasone plus a LTI in hospital showed a survival advantage of 13.5% (CI: 0.23%–26.7%; p < 0.01) in patients presenting with a minimal O2Sat of 50% or less. For patients with an O2Sat of <60 and <50% if they were on LTIs as outpatients, continuing the LTI led to a 14.4% and 22.25 survival advantage if they were continued on the medication as inpatients.
When combined dexamethasone and LTIs provided a mortality benefit in COVID-19 patients presenting with an O2 saturations <50%. The LTI cohort had lower markers of inflammation and cytokine storm.
Online peer support platforms have been shown to provide a supportive space that can enhance social connectedness and personal empowerment. Some studies have analysed forum messages, showing that users describe a range of advantages, and some disadvantages to their use. However, the direct examination of users’ experiences of such platforms is rare and may be particularly informative for enhancing their helpfulness. This study aimed to understand users’ experiences of the Support, Hope and Recovery Online Network (SHaRON), an online cognitive behavioural therapy-based peer support platform for adults with mild to moderate anxiety or depression. Platform users (n = 88) completed a survey on their use of different platform features, feelings about using the platform, and overall experience. Responses were analysed descriptively and using thematic analysis. Results indicated that most features were generally well used, with the exception of private messaging. Many participants described feeling well supported and finding the information and resources helpful; the majority of recent users (81%) rated it as helpful overall. However, some participants described feeling uncomfortable about posting messages, and others did not find the platform helpful and gave suggestions for improvements. Around half had not used the platform in the past 3 months, for different reasons including feeling better or forgetting about it. Some described that simply knowing it was there was helpful, even without regular use. The findings highlight what is arguably a broader range of user experiences than observed in previous studies, which may have important implications for the enhancement of SHaRON and other platforms.
Key learning aims
(1) To understand what an online peer support platform is and how this can be used to support users’ mental health.
(2) To learn how users described their experience of the SHaRON platform.
(3) To understand the benefits that online peer support may provide.
(4) To consider what users found helpful and unhelpful, and how this might inform the further development of these platforms.
Castration of male piglets in the United States is conducted without analgesics because no Food and Drug Administration (FDA) approved products are labeled for pain control in swine. The absence of approved products is primarily due to a wide variation in how pain is measured in suckling piglets and the lack of validated pain-specific outcomes individually indistinct from other biological responses, such as general stress or inflammation responses with cortisol. Simply put, to measure pain mitigation, measurement of pain must be specific, quantifiable, and defined. Therefore, given the need for mitigating castration pain, a consortium of researchers, veterinarians, industry, and regulatory agencies was formed to identify potential animal-based outcomes and develop a methodology, based on the known scientific research, to measure pain and the efficacy of mitigation strategies. The outcome-based measures included physiological, neuroendocrine, behavioral, and production parameters. Ultimately, this consortium aims to provide a validated multimodal methodology to demonstrate analgesic drug efficacy for piglet castration.
Measurable outcomes were selected based on published studies suggesting their validity, reliability, and sensitivity for the direct or indirect measurement of pain associated with surgical castration in piglets. Outcomes to be considered are observation of pain behaviors (i.e. ethogram defined behaviors and piglet grimace scale), gait parameters measured with a pressure mat, infrared thermography of skin temperature of the cranium and periphery of the eye, and blood biomarkers. Other measures include body weight and mortality rate.
This standardized measurement of the outcome variable's primary goal is to facilitate consistency and rigor by developing a research methodology utilizing endpoints that are well-defined and reliably measure pain in piglets. The resulting methodology will facilitate and guide the evaluation of the effectiveness of comprehensive analgesic interventions for 3- to 5-day-old piglets following surgical castration.
Background: Medulloblastoma (MB) is the most common solid malignant pediatric brain neoplasm. Group 3 (G3) MB, particularly MYC amplified G3 MB, is the most aggressive subgroup with the highest frequency of children presenting with metastatic disease, and is associated with a poor prognosis. To further our understanding of the role of MSI1 in MYC amplified G3 MB, we performed an unbiased integrative analysis of eCLIP binding sites, with changes observed at the transcriptome, the translatome, and the proteome after shMSI1 inhibition. Methods: Primary human pediatric MBs, SU_MB002 and HD-MB03 were kind gifts from Dr. Yoon-Jae Cho (Harvard, MS) and Dr. Till Milde (Heidelberg) and cultured for in vitro and in vivo experiments. eCLIP, RNA-seq, Polysome-seq, and TMT-MS were completed as previously described. Results:MSI1 is overexpressed in G3 MB. shRNA Msi1 interference resulted in a reduction in tumour burden conferring a survival advantage to mice injected with shMSI1 G3MB cells. Robust ranked multiomic analysis (RRA) identified an unconventional gene set directly perturbed by MSI1 in G3 MB. Conclusions: Our robust unbiased integrative analysis revealed a distinct role for MSI1 in the maintenance of the stem cell state in G3 MB through post-transcriptional modification of multiple pathways including identification of unconventional targets such as HIPK1.
This study aimed to investigate whether children with cochlear implants received the recommended vaccinations according to New Zealand national immunisation guidelines and to report the incidence of meningitis in this population after intervention.
A retrospective review of the vaccination coverage of paediatric patients receiving cochlear implants between 2005 and 2019 was performed.
Data were collected on 203 children. Evidence of immunisation against Haemophilus influenza B was documented in 94.1 per cent of this cohort and 21.2 per cent received the seasonal influenza vaccine. The pneumococcal conjugate vaccine was fully administered in 81.8 per cent of children; however, only 16.9 per cent of eligible children had received the pneumococcal polysaccharide vaccine. There was marked improvement in compliance to the pneumococcal conjugate vaccine once it became fully funded for cochlear implant patients.
Despite established guidelines, the paediatric vaccination rates were less than expected. Work is in progress to address this.
Exercise has been found to be important in maintaining neurocognitive health. However, the effect of exercise intensity level remains relatively underexplored. Thus, to test the hypothesis that self-paced high-intensity exercise and cardiorespiratory fitness (peak aerobic capacity; VO2peak) increase grey matter (GM) volume, we examined the effect of a 6-month exercise intervention on frontal lobe GM regions that support the executive functions in older adults.
Ninety-eight cognitively normal participants (age = 69.06 ± 5.2 years; n = 54 female) were randomised into either a self-paced high- or moderate-intensity cycle-based exercise intervention group, or a no-intervention control group. Participants underwent magnetic resonance imaging and fitness assessment pre-intervention, immediately post-intervention, and 12-months post-intervention.
The intervention was found to increase fitness in the exercise groups, as compared with the control group (F = 9.88, p = <0.001). Changes in pre-to-post-intervention fitness were associated with increased volume in the right frontal lobe (β = 0.29, p = 0.036, r = 0.27), right supplementary motor area (β = 0.30, p = 0.031, r = 0.29), and both right (β = 0.32, p = 0.034, r = 0.30) and left gyrus rectus (β = 0.30, p = 0.037, r = 0.29) for intervention, but not control participants. No differences in volume were observed across groups.
At an aggregate level, six months of self-paced high- or moderate-intensity exercise did not increase frontal GM volume. However, experimentally-induced changes in individual cardiorespiratory fitness was positively associated with frontal GM volume in our sample of older adults. These results provide evidence of individual variability in exercise-induced fitness on brain structure.
A chloroacetamide herbicide by application timing factorial experiment was conducted in 2017 and 2018 in Mississippi to investigate chloroacetamide use in a dicamba-based Palmer amaranth management program in cotton production. Herbicides used were S-metolachlor or acetochlor, and application timings were preemergence, preemergence followed by (fb) early postemergence, preemergence fb late postemergence, early postemergence alone, late postemergence alone, and early postemergence fb late postemergence. Dicamba was included in all preemergence applications, and dicamba plus glyphosate was included with all postemergence applications. Differences in cotton and weed response due to chloroacetamide type were minimal, and cotton injury at 14 d after late postemergence application was less than 10% for all application timings. Late-season weed control was reduced up to 30% and 53% if chloroacetamide application occurred preemergence or late postemergence only, respectively. Late-season weed densities were minimized if multiple applications were used instead of a single application. Cotton height was reduced by up to 23% if a single application was made late postemergence relative to other application timings. Chloroacetamide application at any timing except preemergence alone minimized late-season weed biomass. Yield was maximized by any treatment involving multiple applications or early postemergence alone, whereas applications preemergence or late postemergence alone resulted in up to 56% and 27% yield losses, respectively. While no yield loss was reported by delaying the first of sequential applications until early postemergence, forgoing a preemergence application is not advisable given the multiple factors that may delay timely postemergence applications such as inclement weather.
We present the data and initial results from the first pilot survey of the Evolutionary Map of the Universe (EMU), observed at 944 MHz with the Australian Square Kilometre Array Pathfinder (ASKAP) telescope. The survey covers
of an area covered by the Dark Energy Survey, reaching a depth of 25–30
rms at a spatial resolution of
11–18 arcsec, resulting in a catalogue of
220 000 sources, of which
180 000 are single-component sources. Here we present the catalogue of single-component sources, together with (where available) optical and infrared cross-identifications, classifications, and redshifts. This survey explores a new region of parameter space compared to previous surveys. Specifically, the EMU Pilot Survey has a high density of sources, and also a high sensitivity to low surface brightness emission. These properties result in the detection of types of sources that were rarely seen in or absent from previous surveys. We present some of these new results here.
Changes in climate and fire regime have long been recognized as drivers of the postglacial vegetation history of Yellowstone National Park, but the effects of locally dramatic hydrothermal activity are poorly known. Multi-proxy records from Goose Lake have been used to describe the history of Lower Geyser Basin where modern hydrothermal activity is widespread. From 10,300 cal yr BP to 3800 cal yr BP, thermal waters discharged into the lake, as evidenced by the deposition of arsenic-rich sediment, fluorite mud, and relatively high δ13Csediment values. Partially thermal conditions affected the limnobiotic composition, but prevailing climate, fire regime, and rhyolitic substrate maintained Pinus contorta forest in the basin, as found throughout the region. At 3800 cal yr BP, thermal water discharge into Goose Lake ceased, as evidenced by a shift in sediment geochemistry and limnobiota. Pollen and charcoal data indicate concurrent grassland development with limited fuel biomass and less fire activity, despite late Holocene climate conditions that were conducive to expanded forest cover. The shift in hydrothermal activity at Goose Lake and establishment of the treeless geyser basin may have been the result of a tectonic event or change in hydroclimate. This record illustrates the complex interactions of geology and climate that govern the development of an active hydrothermal geo-ecosystem.
The Critically Endangered Chapman's pygmy chameleon Rhampholeon chapmanorum is endemic to the low elevation rainforest of the Malawi Hills in southern Malawi. Much of this forest has been converted to agriculture and it was uncertain whether chameleon populations have persisted. We used current and historical satellite imagery to identify remaining forest patches and assess deforestation. We then surveyed forest patches for the presence of this chameleon, and assessed its genetic diversity and structure. We estimated that 80% of the forest has been destroyed since 1984, although we found extant populations of the chameleon in each of the patches surveyed. Differentiation of genetic structure was strong between populations, suggesting that gene flow has been impaired. Genetic diversity was not low, but this could be the result of a temporal lag as well as lack of sensitivity in the mitochondrial marker used. Overall, the impact of forest loss is assumed to have led to a large demographic decline, with forest fragmentation preventing gene flow.
Healthcare personnel with severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection were interviewed to describe activities and practices in and outside the workplace. Among 2,625 healthcare personnel, workplace-related factors that may increase infection risk were more common among nursing-home personnel than hospital personnel, whereas selected factors outside the workplace were more common among hospital personnel.
This chapter discusses critical issues involved in the interpretation of the Corinthian correspondence, with special attention to various responses to Paul and his claims to apostolic authority, to different understandings of the resurrection in the early church, and to the collection for the saints in Jerusalem and its significance for interpreting Paul’s larger ministry.