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The millisecond pulsar PSR J1713$+$0747 is a high-priority target for pulsar timing array experiments due to its long-term timing stability, and bright, narrow pulse profile. In April 2021, PSR J1713$+$0747 underwent a significant profile change event, observed by several telescopes worldwide. Using the broad bandwidth and polarimetric fidelity of the Ultra-Wideband Low-frequency receiver on Murriyang, CSIRO’s Parkes radio telescope, we investigated the long-term spectro-polarimetric behaviour of this profile change in detail. We highlight the broad-bandwidth nature of the event, which exhibits frequency dependence that is inconsistent with cold-plasma propagation effects. We also find that spectral and temporal variations are stronger in one of the orthogonal polarisation modes than the other and observe mild variations ($\sim 3$ – $5\,\sigma$ significance) in circular polarisation above 1 400 MHz following the event. However, the linear polarisation position angle remained remarkably stable in the profile leading edge throughout the event. With over three years of data post-event, we find that the profile has not yet recovered back to its original state, indicating a long-term asymptotic recovery, or a potential reconfiguration of the pulsar’s magnetic field. These findings favour a magnetospheric origin of the profile change event over a line-of-sight propagation effect in the interstellar medium.
Paleontology provides insights into the history of the planet, from the origins of life billions of years ago to the biotic changes of the Recent. The scope of paleontological research is as vast as it is varied, and the field is constantly evolving. In an effort to identify “Big Questions” in paleontology, experts from around the world came together to build a list of priority questions the field can address in the years ahead. The 89 questions presented herein (grouped within 11 themes) represent contributions from nearly 200 international scientists. These questions touch on common themes including biodiversity drivers and patterns, integrating data types across spatiotemporal scales, applying paleontological data to contemporary biodiversity and climate issues, and effectively utilizing innovative methods and technology for new paleontological insights. In addition to these theoretical questions, discussions touch upon structural concerns within the field, advocating for an increased valuation of specimen-based research, protection of natural heritage sites, and the importance of collections infrastructure, along with a stronger emphasis on human diversity, equity, and inclusion. These questions offer a starting point—an initial nucleus of consensus that paleontologists can expand on—for engaging in discussions, securing funding, advocating for museums, and fostering continued growth in shared research directions.
Rationality is a fundamental pillar of Economics. It is however unclear if this assumption holds when decisions are made under stress. To answer this question, we design two laboratory experiments where we exogenously induce physiological stress in participants and test the consistency of their choices with economic rationality. In both experiments we induce stress with the Cold Pressor test and measure economic rationality by the consistency of participants’ choices with the Generalized Axiom of Revealed Preference (GARP). In the first experiment, participants delay the decision-making task for 20 min until the cortisol level peaks. We find significant differences in cortisol levels between the stressed group and the placebo group which, however, do not affect the consistency of choices with GARP. In a second experiment, we study the immediate effect of the stressor on rationality. Overall, results from the second experiment confirm that rationality is not impaired by the stressor. If anything, we observe that compared to the placebo group, participants are more consistent with rationality immediately after the stressor. Our findings provide strong empirical support for the robustness of the economic rationality assumption under physiological stress.
This study introduces the prostate cancer linear energy transfer sensitivity index (PCLSI) as a novel method to predict relative biological effectiveness (RBE) in prostate cancer using linear energy transfer (LET) in proton therapy based on screening for DNA repair mutations.
Materials and Methods:
Five prostate cancer cell lines with DNA repair mutations known to cause sensitivity to LET and DNA repair inhibitors were examined using published data. Relative Du145 LET sensitivity data were leveraged to deduce the LET equivalent of olaparib doses. The PCLSI model was built using three of the prostate cancer cell lines (LNCaP, 22Rv1 and Du145) with DNA mutation frequency from patient cohorts. The PCLSI model was compared against two established RBE models, McNamara and McMahon, for LET-optimized prostate cancer treatment plans.
Results:
The PCLSI model relies on the presence of eight DNA repair mutations: AR, ATM, BRCA1, BRCA2, CDH1, ETV1, PTEN and TP53, which are most likely to predict increased LET sensitivity and RBE in proton therapy. In the LET-optimized plan, the PCLSI model indicates that prostate cancer cells with these DNA repair mutations are more sensitive to increased LET than the McNamara and McMahon RBE models, with expected RBE increases ranging from 11%–33% at 2keV/µm.
Conclusions:
The PCLSI model predicts increasing RBE as a function of LET in the presence of certain genetic mutations. The integration of LET-optimized proton therapy and genetic mutation profiling could be a significant step toward the use of individualized medicine to improve outcomes using RBE escalation without the potential toxicity of physical dose escalation.
Milk is a fundamental food matrix that is widely consumed. Milk fat is important for producing dairy products such as butter, cream, cheese and whole milk powder. Aside from flavour, it has been linked to human health and its chemistry can be modulated by various means towards a more healthy fatty acid profile. Industry and stakeholders have different interests in milk fat, based on specific policies which reflect the type of research and funding initiatives currently performed in different countries. This position paper summarizes the current state-of-the-art with regards to milk fat research and industry as well as stakeholder initiatives, and then highlights new developments based on information gathered from North America (United States and Mexico), Europe (United Kingdom, Spain, Italy, and Finland), Africa (Egypt), Asia (China and Bangladesh) and Oceania (New Zealand). South America is an important contributor to the dairy industry but will not be considered here and thus this paper must be considered cross-continental rather than global. This manuscript intends to show a wide ‘picture’ of milk fat from different angles in different parts of the globe.
Educational attainment (EduA) is correlated with life outcomes, and EduA itself is influenced by both cognitive and non-cognitive factors. A recent study performed a ‘genome-wide association study (GWAS) by subtraction,’ subtracting genetic effects for cognitive performance from an educational attainment GWAS to create orthogonal ‘cognitive’ and ‘non-cognitive’ factors. These cognitive and non-cognitive factors showed associations with behavioral health outcomes in adults; however, whether these correlations are present during childhood is unclear.
Methods
Using data from up to 5517 youth (ages 9–11) of European ancestry from the ongoing Adolescent Brain Cognitive DevelopmentSM Study, we examined associations between polygenic scores (PGS) for cognitive and non-cognitive factors and cognition, risk tolerance, decision-making & personality, substance initiation, psychopathology, and brain structure (e.g. volume, fractional anisotropy [FA]). Within-sibling analyses estimated whether observed genetic associations may be consistent with direct genetic effects.
Results
Both PGSs were associated with greater cognition and lower impulsivity, drive, and severity of psychotic-like experiences. The cognitive PGS was also associated with greater risk tolerance, increased odds of choosing delayed reward, and decreased likelihood of ADHD and bipolar disorder; the non-cognitive PGS was associated with lack of perseverance and reward responsiveness. Cognitive PGS were more strongly associated with larger regional cortical volumes; non-cognitive PGS were more strongly associated with higher FA. All associations were characterized by small effects.
Conclusions
While the small sizes of these associations suggest that they are not effective for prediction within individuals, cognitive and non-cognitive PGS show unique associations with phenotypes in childhood at the population level.
Penicillin allergy delabeling may benefit antimicrobial stewardship (AS). Cost of initial penicillin treatments following risk-stratified inpatient delabeling were compared to two hypothetical treatment regimens if delabeling had not occurred: (1) AS-guided and (2) Common Treatment. Penicillin allergy delabeling improved antimicrobial spectrum index, was cost-neutral, and averted unnecessary penicillin desensitizations.
This study documents several correlations observed during the first run of the plasma wakefield acceleration experiment E300 conducted at FACET-II, using a single drive electron bunch. The established correlations include those between the measured maximum energy loss of the drive electron beam and the integrated betatron X-ray signal, the calculated total beam energy deposited in the plasma and the integrated X-ray signal, among three visible light emission measuring cameras and between the visible plasma light and X-ray signal. The integrated X-ray signal correlates almost linearly with both the maximum energy loss of the drive beam and the energy deposited into the plasma, demonstrating its usability as a measure of energy transfer from the drive beam to the plasma. Visible plasma light is found to be a useful indicator of the presence of a wake at three locations that overall are two metres apart. Despite the complex dynamics and vastly different time scales, the X-ray radiation from the drive bunch and visible light emission from the plasma may prove to be effective non-invasive diagnostics for monitoring the energy transfer from the beam to the plasma in future high-repetition-rate experiments.
Existing systematic reviews have suggested mixed effects of the Covid pandemic on the mental health of children and young people. Those with pre-existing mental health and neurodevelopmental conditions have been suggested to be disproportionately affected, but this has not been meta-analysed. Most reviews of studies in clinical populations to date only include cross-sectional studies during the first lockdown or longitudinal cohorts up to early 2021, which limits our understanding of causality and long-term effects. To our knowledge, this is the first systematic review and meta-analysis to examine the longitudinal impact of the pandemic on the mental health of children and young people with pre-existing mental health and neurodevelopmental conditions.
Objectives
To compare 1) mental health pre versus during Covid, and 2) mental health during Covid.
Methods
Medline, Embase, APA PsycInfo, and Global Health databases were searched up to August 2023. Longitudinal studies reporting mental health outcomes in children and young people (≤18 years old) with pre-Covid mental health and/or neurodevelopmental conditions were included. Cohorts were deemed eligible if children and young people were diagnosed using a diagnostic assessment, scored above clinical threshold on validated measures, or attended mental health services pre-Covid. Outcomes included internalising, externalising, and other symptoms. Studies were narratively synthesised by symptom category and meta-analyses performed where number of studies reporting the same outcomes were sufficient (≥5).
Results
6,083 records were identified and 21 studies (N=2,617) were included. These widely differed in country, setting, diagnosis, outcome, and timepoints under study. The narrative synthesis highlighted mixed findings in mental health changes during the pandemic for all three symptom categories showing increases, reductions, and no changes. Only studies reporting changes in internalising symptoms pre- versus during the pandemic were in sufficient number to be amenable to meta-analysis.
Conclusions
Our findings suggest the pandemic’s impact on the mental health of children and young people with pre-existing mental health and neurodevelopmental conditions were complex and varied. We highlight an urgent need for longitudinal Covid research on long-term mental health outcomes in this vulnerable group. Understanding risk factors and longitudinal trajectories is warranted to guide clinical practice and policy.
Background: Duchenne muscular dystrophy (DMD) is caused by DMD gene mutations. Delandistrogene moxeparvovec is an investigational gene transfer therapy, developed to address the underlying cause of DMD. We report findings from Part 1 (52 weeks) of the two-part EMBARK trial (NCT05096221). Methods: Key inclusion criteria: Ambulatory patients aged ≥4-<8 years with a confirmed DMD mutation within exons 18–79 (inclusive); North Star Ambulatory Assessment (NSAA) score >16 and <29 at screening. Eligible patients were randomized 1:1 to intravenous delandistrogene moxeparvovec (1.33×1014 vg/kg) or placebo. The primary endpoint was change from baseline in NSAA total score to Week 52. Results: At Week 52 (n=125), the primary endpoint did not reach statistical significance, although there was a nominal difference in change from baseline in NSAA total score in the delandistrogene moxeparvovec (2.6, n=63) versus placebo groups (1.9, n=61). Key secondary endpoints (time to rise, micro-dystrophin expression, 10-meter walk/run) demonstrated treatment benefit in both age groups (4-5 and 6-7 years; p<0.05).There were no new safety signals, reinforcing the favorable and manageable safety profile observed to date. Conclusions: Based on the totality of functional assessments including the timed function tests, treatment with delandistrogene moxeparvovec indicates beneficial modification of disease trajectory.
Artificial Intelligence (AI) is reshaping the world as we know it, impacting all aspects of modern society, basically due to the advances in computer power, data availability and AI algorithms. The dairy sector is also on the move, from the exponential growth in AI research, to ready to use AI-based products, this new evolution to Dairy 4.0 represents a potential ‘game-changer’ for the dairy sector, to confront challenges regarding sustainability, welfare, and profitability. This research reflection explores the possible impact of AI, discusses the main drivers in the field and describes its origins, challenges, and opportunities. Further, we present a multidimensional vision considering factors that are not commonly considered in dairy research, such as geopolitical aspects and legal regulations that can have an impact on the application of AI in the dairy sector. This is just the beginning of the third tide of AI, and a future is still ahead. For now, the current advances in AI at on-farm level seem limited and based on the revised data, we believe that AI can be a ‘game-changer’ only if it is integrated with other components of Dairy 4.0 (such as robotics) and is fully adopted by dairy farmers.
Mild traumatic brain injury (mTBI) is common in children. Long-term cognitive and behavioral outcomes as well as underlying structural brain alterations following pediatric mTBI have yet to be determined. In addition, the effect of age-at-injury on long-term outcomes is largely unknown.
Methods
Children with a history of mTBI (n = 406; Mage = 10 years, SDage = 0.63 years) who participated in the Adolescent Brain Cognitive Development (ABCD) study were matched (1:2 ratio) with typically developing children (TDC; n = 812) and orthopedic injury (OI) controls (n = 812). Task-based executive functioning, parent-rated executive functioning and emotion-regulation, and self-reported impulsivity were assessed cross-sectionally. Regression models were used to examine the effect of mTBI on these domains. The effect of age-at-injury was assessed by comparing children with their first mTBI at either 0-3, 4-7, or 8-10 years to the respective matched TDC controls. Fractional anisotropy (FA) and mean diffusivity (MD), both MRI-based measures of white matter microstructure, were compared between children with mTBI and controls.
Results
Children with a history of mTBI displayed higher parent-rated executive dysfunction, higher impulsivity, and poorer self-regulation compared to both control groups. At closer investigation, these differences to TDC were only present in one respective age-at-injury group. No alterations were found in task-based executive functioning or white matter microstructure.
Conclusions
Findings suggest that everyday executive function, impulsivity, and emotion-regulation are affected years after pediatric mTBI. Outcomes were specific to the age at which the injury occurred, suggesting that functioning is differently affected by pediatric mTBI during vulnerable periods. Groups did not differ in white matter microstructure.
To cope with homonegativity-generated stress, gay, bisexual and other men who have sex with men (GBM) use more mental health services (MHS) compared with heterosexual men. Most previous research on MHS among GBM uses data from largely white HIV-negative samples. Using an intersectionality-based approach, we evaluated the concomitant impact of racialization and HIV stigma on MHS use among GBM, through the mediating role of perceived discrimination (PD).
Methods
We used baseline data from 2371 GBM enrolled in the Engage cohort study, collected between 2017 and 2019, in Montreal, Toronto and Vancouver, using respondent-driven sampling. The exposure was GBM groups: Group 1 (n = 1376): white HIV-negative; Group 2 (n = 327): white living with HIV; Group 3 (n = 577): racialized as non-white HIV-negative; Group 4 (n = 91): racialized as non-white living with HIV. The mediator was interpersonal PD scores measured using the Everyday Discrimination Scale (5-item version). The outcome was MHS use (yes/no) in the prior 6 months. We fit a three-way decomposition of causal mediation effects utilizing the imputation method for natural effect models. We obtained odds ratios (ORs) for pure direct effect (PDE, unmediated effect), pure indirect effect (PIE, mediated effect), mediated interaction effect (MIE, effect due to interaction between the exposure and mediator) and total effect (TE, overall effect). Analyses controlled for age, chronic mental health condition, Canadian citizenship, being cisgender and city of enrolment.
Results
Mean PD scores were highest for racialized HIV-negative GBM (10.3, SD: 5.0) and lowest for white HIV-negative GBM (8.4, SD: 3.9). MHS use was highest in white GBM living with HIV (GBMHIV) (40.4%) and lowest in racialized HIV-negative GBM (26.9%). Compared with white HIV-negative GBM, white GBMHIV had higher TE (OR: 1.71; 95% CI: 1.27, 2.29) and PDE (OR: 1.68; 95% CI: 1.27, 2.24), and racialized HIV-negative GBM had higher PIE (OR: 1.09; 95% CI: 1.02, 1.17). Effects for racialized GBMHIV did not significantly differ from those of white HIV-negative GBM. MIEs across all groups were comparable.
Conclusions
Higher MHS use was observed among white GBMHIV compared with white HIV-negative GBM. PD positively mediated MHS use only among racialized HIV-negative GBM. MHS may need to take into account the intersecting impact of homonegativity, racism and HIV stigma on the mental health of GBM.
The poor environmental stability of natural anthocyanin hinders its usefulness in various functional applications. The objectives of the present study were to enhance the environmental stability of anthocyanin extracted from Lycium ruthenicum by mixing it with montmorillonite to form an organic/inorganic hybrid pigment, and then to synthesize allochroic biodegradable composite films by incorporating the hybrid pigment into sodium alginate and test them for potential applications in food testing and packaging. The results of X-ray diffraction, Fourier-transform infrared spectroscopy, and use of the Brunauer–Emmett–Teller method and zeta potential demonstrated that anthocyanin was both adsorbed on the surface and intercalated into the interlayer of montmorillonite via host–guest interaction, and the hybrid pigments obtained allowed good, reversible, acid/base behavior after exposure to HCl and NH3 atmospheres. The composite films containing hybrid pigments had good mechanical properties due to the uniform dispersion of the pigments in a sodium alginate substrate and the formation of hydrogen bonds between them. Interestingly, the composite films also exhibited reversible acidichromism. The as-prepared hybrid pigments in composite films could, therefore, serve simultaneously as a reinforced material and as a smart coloring agent for a polymer substrate.
We present the third data release from the Parkes Pulsar Timing Array (PPTA) project. The release contains observations of 32 pulsars obtained using the 64-m Parkes ‘Murriyang’ radio telescope. The data span is up to 18 yr with a typical cadence of 3 weeks. This data release is formed by combining an updated version of our second data release with $\sim$3 yr of more recent data primarily obtained using an ultra-wide-bandwidth receiver system that operates between 704 and 4032 MHz. We provide calibrated pulse profiles, flux density dynamic spectra, pulse times of arrival, and initial pulsar timing models. We describe methods for processing such wide-bandwidth observations and compare this data release with our previous release.
The target backsheath field acceleration mechanism is one of the main mechanisms of laser-driven proton acceleration (LDPA) and strongly depends on the comprehensive performance of the ultrashort ultra-intense lasers used as the driving sources. The successful use of the SG-II Peta-watt (SG-II PW) laser facility for LDPA and its applications in radiographic diagnoses have been manifested by the good performance of the SG-II PW facility. Recently, the SG-II PW laser facility has undergone extensive maintenance and a comprehensive technical upgrade in terms of the seed source, laser contrast and terminal focus. LDPA experiments were performed using the maintained SG-II PW laser beam, and the highest cutoff energy of the proton beam was obviously increased. Accordingly, a double-film target structure was used, and the maximum cutoff energy of the proton beam was up to 70 MeV. These results demonstrate that the comprehensive performance of the SG-II PW laser facility was improved significantly.
Patients with major depressive disorder (MDD) with acute suicidal ideation or behavior (MDSI) require immediate intervention. Though oral antidepressants can be effective at reducing depressive symptoms, they can take 4–6 weeks to reach full effect.
Objectives
This study aimed to identify unmet needs in the treatment of patients with MDSI, specifically exploring the potential clinical benefits of rapid reduction of depressive symptoms.
Methods
A Delphi panel consisting of practicing psychiatrists (n=12) from the US, Canada and EU was conducted between December 2020–June 2021. Panelists were screened to ensure they had sufficient experience with managing patients with MDD and MDSI. Panelists completed two survey rounds, and a virtual consensus meeting.
Results
This research confirmed current unmet needs in the treatment of patients with MDSI.
Hopelessness, functional impairment, worsening of MDD symptoms, recurrent hospitalization and higher risk of suicide attempt were considered as key consequences of the slow onset of action of oral antidepressants.
Treatment with rapid acting antidepressant was anticipated by panelists to provide short-term benefit such as rapid reduction of core MDD symptoms which may contribute to shorter hospital stays and improved patient engagement/compliance, allowing for earlier interventions and improved patient outcomes. For long-term benefits, panelists agreed that improved daily functioning and increased trust/confidence in treatment options, constitute key benefits of rapid-acting treatments
Conclusions
There is need for rapid-acting treatments which may help address key unmet needs and provide clinically meaningful benefits driven by the rapid relief of depressive symptoms particularly in patients with MDSI.
Disclosure
SB, ED, KJ, MO’H, QZ, MM, MH, SR, JA and DZ are employees of Janssen and hold stock in Johnson & Johnson Inc. AN is currently employed by Neurocrine Biosciences Inc. RP is an employee of Adelphi Values PROVE hired by Janssen.
We describe a new low-frequency wideband radio survey of the southern sky. Observations covering 72–231 MHz and Declinations south of $+30^\circ$ have been performed with the Murchison Widefield Array “extended” Phase II configuration over 2018–2020 and will be processed to form data products including continuum and polarisation images and mosaics, multi-frequency catalogues, transient search data, and ionospheric measurements. From a pilot field described in this work, we publish an initial data release covering 1,447$\mathrm{deg}^2$ over $4\,\mathrm{h}\leq \mathrm{RA}\leq 13\,\mathrm{h}$, $-32.7^\circ \leq \mathrm{Dec} \leq -20.7^\circ$. We process twenty frequency bands sampling 72–231 MHz, with a resolution of 2′–45′′, and produce a wideband source-finding image across 170–231 MHz with a root mean square noise of $1.27\pm0.15\,\mathrm{mJy\,beam}^{-1}$. Source-finding yields 78,967 components, of which 71,320 are fitted spectrally. The catalogue has a completeness of 98% at ${{\sim}}50\,\mathrm{mJy}$, and a reliability of 98.2% at $5\sigma$ rising to 99.7% at $7\sigma$. A catalogue is available from Vizier; images are made available via the PASA datastore, AAO Data Central, and SkyView. This is the first in a series of data releases from the GLEAM-X survey.
The great demographic pressure brings tremendous volume of beef demand. The key to solve this problem is the growth and development of Chinese cattle. In order to find molecular markers conducive to the growth and development of Chinese cattle, sequencing was used to determine the position of copy number variations (CNVs), bioinformatics analysis was used to predict the function of ZNF146 gene, real-time fluorescent quantitative polymerase chain reaction (qPCR) was used for CNV genotyping and one-way analysis of variance was used for association analysis. The results showed that there exists CNV in Chr 18: 47225201-47229600 (5.0.1 version) of ZNF146 gene through the early sequencing results in the laboratory and predicted ZNF146 gene was expressed in liver, skeletal muscle and breast cells, and was amplified or overexpressed in pancreatic cancer, which promoted the development of tumour through bioinformatics. Therefore, it is predicted that ZNF146 gene affects the proliferation of muscle cells, and then affects the growth and development of cattle. Furthermore, CNV genotyping of ZNF146 gene was three types (deletion type, normal type and duplication type) by Real-time fluorescent quantitative PCR (qPCR). The association analysis results showed that ZNF146-CNV was significantly correlated with rump length of Qinchuan cattle, hucklebone width of Jiaxian red cattle and heart girth of Yunling cattle. From the above results, ZNF146-CNV had a significant effect on growth traits, which provided an important candidate molecular marker for growth and development of Chinese cattle.
We investigated the prospective associations between meat consumption and CVD and whether these relationships differ by dietary quality among African American (AA) adults.
Design:
Baseline diet was assessed with a regionally specific FFQ. Unprocessed red meat included beef and pork (120 g/serving); processed meat included sausage, luncheon meats and cured meat products (50 g/serving). Incident total CVD, CHD, stroke and heart failure were assessed annually over 9·8 years of follow-up. We characterised dietary quality using a modified Healthy Eating Index-2010 score (m-HEI), excluding meat contributions.
Setting:
Jackson, MS, USA.
Participants:
AA adults (n 3242, aged 55 y, 66 % female).
Results:
Mean total, unprocessed red and processed meat intakes were 5·7 ± 3·5, 2·3 ± 1·8 and 3·3 ± 2·7 servings/week, respectively. Mostly, null associations were observed between meat categories and CVD or subtypes. However, greater intake of unprocessed red meat (three servings/week) was associated with significantly elevated risk of stroke (hazard ratio = 1·43 (CI: 1·07,1·90)). With the exception of a more positive association between unprocessed meat consumption and stroke among individuals in m-HEI Tertile 2, the strength of associations between meat consumption categories and CVD outcomes did not differ by m-HEI tertile. In formal tests, m-HEI did not significantly modify meat–CVD associations.
Conclusions:
In this cohort of AA adults, total and processed meat were not associated with CVD outcomes, with the exception that unprocessed red meat was related to greater stroke risk. Dietary quality did not modfiy these associations. Research is needed in similar cohorts with longer follow-up and greater meat consumption to replicate these findings.