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It is now well established that human-induced species extinctions and habitat degradation are currently occurring at unprecedented rates. To halt and reverse this decline, the international community adopted the Kunming–Montreal Global Biodiversity Framework (GBF), as part of the Kunming–Montreal Biodiversity Package, in December 2022. We clarify what this new framework means for conservation zoos and aquariums in their mission to prevent species extinction by highlighting areas of focus. We explain why it is necessary that conservation zoos and aquariums establish the appropriate mechanisms for contributing towards such a framework to help validate their role in the 21st Century. Conservation zoos and aquariums should be reassured that much of their work already fits within the GBF. However, the current mechanisms for individual zoos and aquariums to directly contribute to the implementation of the GBF mostly rely on close collaboration with individual national governments and/or are only possible at a national level. It is therefore critical that national, regional, and global zoo membership organisations take a leading role in championing the work of their members. Equally, adequately linking the efforts of zoos and aquariums to the national implementation of international instruments, such as the GBF, is imperative to ensure that these organizations’ contributions feed into the understanding we have of global progress towards the implementation of international instruments.

Background: Recognising acute stroke symptoms is crucial in providing timely treatment. However, evidence suggests that females often experience unique symptoms compared with males, resulting in delays to seeking medical attention and treatment. This systematic review and meta-analysis evaluated whether sex is associated with differences in acute stroke symptoms. Methods: Searches from 1946 to 7th September 2021 were carried out using MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and the Cochrane Library. Studies reporting acute stroke symptoms in adult females and males were eligible for inclusion. Eleven observational studies met the inclusion criteria. Methodological quality was assessed using the Newcastle–Ottawa scale (NOS). Data were meta-analysed using a random-effects model. Results: Compared with males, females had higher odds of experiencing headache (odds ratio [OR]: 1.27; 95% confidence interval [CI]: 1.01–1.59); change in level of consciousness (OR: 1.36; 95% CI: 1.13–1.63); fatigue (OR: 1.53; 95% CI: 1.04–2.25); and incontinence (OR: 1.44; 95% CI: 1.29–1.60). In contrast, females were at lower odds of experiencing trouble speaking (OR: 0.79; 95% CI: 0.64–0.96); trouble walking, loss of balance, or co-ordination (OR: 0.55; 95% CI: 0.39–0.76); and dizziness (OR: 0.77; 95% CI: 0.64–0.94) compared with males. No difference was found in confusion, difficulty understanding speech, trouble seeing in one or both eyes, mental status change, and nausea or vomiting. Discussion: Sex differences do exist in some acute stroke symptoms. At the same time, the overlap in symptoms between sexes was substantial. Healthcare professionals and public health campaigns should continue to promote classic symptoms of acute stroke, whilst taking into account the less common symptoms and the potential differences in symptoms experienced by females and males.

Despite virologic suppression, people living with HIV (PLWH) remain at risk for developing cognitive impairment, with aberrations in motor control being a predominant symptom leading to functional dependencies in later life. While the neuroanatomical bases of motor dysfunction have recently been illuminated, the underlying molecular processes remain poorly understood. Herein, we evaluate the predictive capacity of the mitochondrial redox environment on sensorimotor brain-behavior dynamics in 40 virally-suppressed PLWH and 40 demographically-matched controls using structural equation modeling. We used state-of-the-art approaches, including Seahorse Analyzer of mitochondrial function, electron paramagnetic resonance spectroscopy to measure superoxide levels, antioxidant activity assays and dynamic magnetoencephalographic imaging to quantify sensorimotor oscillatory dynamics. We observed differential modulation of sensorimotor brain-behavior relationships by superoxide and hydrogen peroxide-sensitive features of the redox environment in PLWH, while only superoxide-sensitive features were related to optimal oscillatory response profiles and better motor performance in controls. Moreover, these divergent pathways may be attributable to immediate, separable mechanisms of action within the redox environment seen in PLWH, as evidenced by mediation analyses. These findings suggest that mitochondrial redox parameters are important modulators of healthy and pathological oscillations in motor systems and behavior, serving as potential targets for remedying HIV-related cognitive-motor dysfunction in the future.

A primary goal of zoos is to educate their visitors about global conservation efforts. Studying visitors’ perceptions and attitudes towards captive and wild endangered species helps target conservation messaging. This is especially important in countries, such as Pakistan, where hunting and human–wildlife conflict pose the greatest threats to species. While there have been some studies about Pakistan’s rural communities’ perceptions, few studies have examined the perceptions of Pakistan’s zoo visitors. We present data from exit surveys (n = 304) collected at three of the largest zoos in Pakistan (Lahore: an established zoo, Peshawar: a newly built zoo, and Jungle Kingdom: a theme park and zoo). Zoo location was a significant predictor for a range of attitudes, suggesting that the way a zoo presents itself strongly impacts visitor perceptions. Perceptions of learning were influenced by high biodiversity appreciation but a low confidence in knowledge about animals. Support for keeping animals in captivity was most likely when animal welfare was perceived as good and amongst respondents who valued biodiversity. Zoo-goers, regardless of location, demonstrated high levels of interest in animals and environmental concerns. However, the primary visit motivator was spending time with family and friends.

Motor control requires the coordination of spatiotemporally precise neural oscillations in the beta and gamma range within the primary motor cortex (M1). Recent studies have shown that motor performance can be differentially modulated based on the spectral target of noninvasive transcranial alternating current stimulation (tACS), with gamma-frequency tACS improving motor performance. However, the spectral specificity for eliciting such improvements remains unknown. Herein, we derived the peak movement-related gamma frequency in 25 healthy adults using magnetoencephalography and a motor control paradigm. These individualized peak gamma frequencies were then used for personalized sessions of tACS. All participants completed 4 sessions of high-definition (HD)-tACS (sham, low-, peak-, and high-gamma frequency) over M1 for 20 min during the performance of sequential movements of varying complexity (e.g. tapping adjacent fingers or nonadjacent fingers). Our primary findings demonstrated that individualized tACS dosing over M1 leads to enhanced motor performance/learning (i.e. greatest reduction in time to complete motor sequences) compared to nonspecific gamma-tACS in humans, which suggests that personalized neuromodulation may be advantageous to optimize behavioral outcomes.

Physics-guided machine learning (PGML) offers a new approach to stability modeling during machining that leverages experimental data generated during the machining process while incorporating decades of theoretical process modeling efforts. This approach addresses specific limitations of machine learning models and physics-based models individually. Data-driven machine learning models are typically black box models that do not provide deep insight into the underlying physics and do not reflect physical constraints for the modeled system, sometimes yielding solutions that violate physical laws or operational constraints. In addition, acquiring the large amounts of manufacturing data needed for machine learning modeling can be costly. On the other hand, many physical processes are not completely understood by domain experts and have a high degree of uncertainty. Physics-based models must make simplifying assumptions that can compromise prediction accuracy. This research explores whether data generated by an uncertain physics-based milling stability model that is used to train a physics-guided machine learning stability model, and then updated with measured data, domain knowledge, and theory-based knowledge provides a useful approximation to the unknown true stability model for a specific set of factory operating conditions. Four novel strategies for updating the machine learning model with experimental data are explored. These updating strategies differ in their assumptions about and implementation of the type of physics-based knowledge included in the PGML model. Using a simulation experiment, these strategies achieve useful approximations of the underlying true stability model while reducing the number of experimental measurements required for model update.

Over 50 years ago, a marine estuary was converted to a wastewater stabilization basin for treatment of primarily pulp and paper effluent. As a result, the basin was immediately converted to a “freshwater” environment and subsequently accumulated a thin layer of black, organic-rich sediment containing varying amounts of dioxins and furans, metals, polycyclic aromatic hydrocarbons, and petroleum hydrocarbons. Previous studies on the site have shown that the majority of this contamination in the basin appears to have been contained within this black sediment layer and not migrated to any significant extent into the original underlying marine sediments. The purpose of this study is to examine sediment porewater chemistry changes that have occurred over 51 years of operation of the stabilization basin with the intent of better understanding why contamination has been minimal into the underlying natural marine sediments. Field and laboratory testing is presented to characterize the physical, chemical, and mineralogical sediments in the basin. Porewater chemistry profiles obtained from this work are then used in combination with a one-dimensional contaminant transport model to examine the role of diffusion, sorption, and upward groundwater flux in the porewater profiles found for the sediments.

To identify the clinical indicators of acute deterioration in residents and the factors that influence residential aged care facility staff's identification of these.Rapid review and narrative synthesis.The WHO and Cochrane Rapid Review Methods Group recommendations guided the review processes. CINAHL, Medline, PubMed, and the Cochrane Library were searched from 2000 to January 2022. Data related to clinical indicators of deterioration were categorized using the Airway, Breathing, Circulation, Disability, Exposure assessment framework, and factors influencing detection were grouped as consumer (resident and family), aged care workforce, and organization factors.Twenty publications were included of which 14 informed clinical indicators; nine highlighted factors that influence staff's identification of these and three informed both. Included article were collectively below moderate quality. Most clinical indicators were grouped into the 'Disability' category with altered level of consciousness, behavior, and pain identified most frequently. Few studies reported more traditional indicators of deterioration used in the general population - changes in vital signs. The most common factors influencing the detection of acute deterioration were organizational and workforce-related including resource, knowledge, and confidence deficits.Findings suggest subtle changes in resident's health status, rather than focusing primarily on physiologic parameters used in early warning tools for acute care settings, should be recognized and considered in the design of early warning tools for residential aged care facilities.Early warning tools sensitive to the unique needs of residents and support for aged care facility staff are recommended to improve the capacity of aged care facility care staff to identify and manage acute deterioration early to avoid hospitalization.

BackgroundAlternative approaches to syndromic management are needed to reduce rates of sexually transmitted infections (STIs) in resource-limited settings. We investigated the impact of point-of-care (POC) versus central laboratory–based testing on STI treatment initiation and STI adverse event (STI-AE) reporting.MethodsWe used Kaplan-Meier and Cox regression models to compare times to treatment initiation and STI-AE reporting among HVTN702 trial participants in South Africa. Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) were diagnosed POC at eThekwini clinic and in a central laboratory at Verulam/Isipingo clinics. All clinics used POC assays for Trichomonas vaginalis (TV) testing.ResultsAmong 959 women (median age, 23 [interquartile range, 21–26] years), median days (95% confidence interval [95%CI]) to NG/CT treatment initiation and NG/CT-AE reporting were 0.20 (.16–.25) and 0.24 (.19–.27) at eThekwini versus 14.22 (14.12–15.09) and 15.12 (13.22–21.24) at Verulam/Isipingo (all P < .001). Median days (95%CI) to TV treatment initiation and TV-AE reporting were 0.17 (.12–.27) and 0.25 (.20–.99) at eThekwini versus 0.18 (.15–.2) and 0.24 (.15–.99) at Verulam/Isipingo (all P > .05). Cox regression analysis revealed that NG/CT treatment initiation (adjusted hazard ratio [aHR], 39.62 [95%CI, 15.13–103.74]) and NG/CT-AE reporting (aHR, 3.38 [95%CI, 2.23–5.13]) occurred faster at eThekwini versus Verulam/Isipingo, while times to TV treatment initiation (aHR, 0.93 [95%CI, .59–1.48]) and TV-AE reporting (aHR, 1.38 [95%CI, .86–2.21]) were similar.ConclusionsPOC testing led to prompt STI management with potential therapeutic and prevention benefits, highlighting its utility as a diagnostic tool in resource-limited settings.

Students with extensive support needs (ESN) benefit from inclusion in general education settings with their same-age peers. Many teachers, however, report feeling overwhelmed and underprepared to effectively educate students with ESN within general education settings. To mitigate this, we must ensure that content related to the instruction and inclusion of students with ESN in general education settings is included in the introductory special education courses taken by preservice general education teachers, which we refer to as “SPED 101.” Our research team surveyed 302 instructors of SPED 101 courses in general education baccalaureate teacher preparation programs at institutions of higher education across the United States. Data suggest that most instructors cover content related to the instruction and the inclusion of students with ESN, although the extent to which content is addressed varies among instructors, indicating inconsistencies in course content, delivery, and instruction. Limitations, implications, and future research are discussed.

We report a case of alpelisib-induced uveitis. A 68-year-old female who had recently been given alpelisib for metastatic breast cancer presented with a 2-week history of bilateral worsening vision with a corresponding acute hypermetropic shift. Her unaided visual acuity was 6/60 in both eyes, with bilateral anterior uveitis, non-granulomatous keratic precipitates, posterior synechiae, and limited fundal view. There was also a mild iris bombe configuration, although the intraocular pressures were normal. Ocular ultrasound revealed bilateral uveal effusion, ciliary body congestion, dense vitreous cells, and exudative retinal detachments. These findings were also confirmed on multimodal imaging with widefield fundus photography (Optos) and optical coherence tomography. Based on the clinical features above, a diagnosis of alpelisib-induced panuveitis was diagnosed. She was then admitted and treated with a 3-day course of intravenous methylprednisolone and intensive topical steroids. Her clinical signs and symptoms started to improve, and she was discharged 4 days later. At 1 week of follow-up, her best-corrected visual acuity was 6/12 in both eyes, with broken posterior synechiae and resolution of exudative retinal detachments. This case highlights the importance of early ophthalmology involvement by the oncology team as oncology therapy can have potential unexpected ocular manifestations.

High-Performance Liquid Chromatography-Tandem Mass Spectrometry has emerged triumphant over the years as a reliable and high throughput clinical instrument to assess different metabolic irregularities. One of the latest applications of LC-MS/MS has been in the field of quantification of glucocorticoids, such as cortisol and cortisone from saliva, that can be an indicator of abnormalities such as Congenital Adrenal Hyperplasia (CAH), Cushing's Syndrome, and Addison's disease. We have developed and validated an LC-MS/MS-based assay for simultaneous detection of cortisol and cortisone in human saliva, which requires only 20 µL of sample, to measure cortisol across a 0.5 - 70 ng/mL range, and cortisone across a 1.2- 100 ng/mL range, respectively. The developed method exhibits linearity of R

Partial molar volumes of amino acids in their zwitterionic and molecular forms were calculated using molecular dynamics simulations of these systems in aqueous solutions. Calculations performed with the TIP4P, SPC (rigid and flexible), SPC/E, and polarizable water models showed that the choice of water model can have a significant impact on the calculated volumes. The effect of treatment of long-range electrostatic interactions on the calculated results was also investigated. The volumes obtained in simulations with a properly chosen water model fit well the experimental data for both molecular and zwitterionic forms of amino acids.

Background: Motor control requires a reciprocal volley between somatosensory and motor systems, with somatosensory feedback being essential for the online updating of motor commands to achieve behavioral outcomes. However, this dynamic interplay among sensorimotor brain systems serving motor control remains poorly understood. Methods: To address this, we designed a novel somatosensory entrainment-movement task, which 25 adults completed during magnetoencephalography (MEG). Specifically, participants completed a quasi-paced finger-tapping paradigm while subthreshold electrical stimulation was applied to the right median nerve at a sensorimotor-relevant frequency (15 Hz) and during a second condition where no electrical stimulation was applied. The MEG data were transformed into the time-frequency domain and imaged by using a beamformer to evaluate the effect of somatosensory feedback (i.e., entrainment) on movement-related oscillations and motor performance at the single trial level. Results: Our results indicated spectrally specific reductions in movement-related oscillatory power (i.e., theta, gamma) during 15 Hz stimulation in the contralateral motor cortex during motor execution. In addition, we observed robust cross-frequency coupling within the motor cortex and further, stronger theta-gamma coupling was predictive of faster reaction times, irrespective of condition (i.e., stim vs. no stim). Finally, in the presence of electrical stimulation, cross-frequency coupling of movement-related oscillations was reduced, and the stronger the entrained neuronal populations (i.e., increased oscillatory power) were before movement onset, the weaker the inherent theta-gamma coupling became in the motor cortex. Discussion: This novel exogenous manipulation paradigm provides key insights on how the somatosensory system modulates the motor cortical oscillations required for volitional movement in the normative sensorimotor system.

A temporal graph with lifetime L is a sequence of L graphs $$G_1, \ldots ,G_L$$ G 1 , … , G L , called layers, all of which have the same vertex set V but can have different edge sets. The underlying graph is the graph with vertex set V that contains all the edges that appear in at least one layer. The temporal graph is always connected if each layer is a connected graph, and it is k-edge-deficient if each layer contains all except at most k edges of the underlying graph. For a given start vertex s, a temporal exploration is a temporal walk that starts at s, traverses at most one edge in each layer, and visits all vertices of the temporal graph. We show that always-connected, k-edge-deficient temporal graphs with sufficient lifetime can always be explored in $$O(kn \log n)$$ O ( k n log n ) time steps. We also construct always-connected, k-edge-deficient temporal graphs for which any exploration requires $$\varOmega (n \log k)$$ Ω ( n log k ) time steps. For always-connected, 1-edge-deficient temporal graphs, we show that O(n) time steps suffice for temporal exploration.

The current study examined the effects of a shared reading instructional package on the receptive identification of English sight vocabulary in multilingual learner students with extensive support needs. Two participants received the intervention, one in a face-to-face format and one in a videoconferencing format (due to the COVID-19 pandemic). To establish experimental control, the researchers used a multiple probe design with conditions across word sets and replicated across participants. Results showed both students met criterion on word sets as a result of the intervention. Considerations in interpreting the results for classroom implementation and future research are discussed.

Accelerated global warming is directly related to greenhouse gas (GHG) emissions. In order to achieve international and national set targets on reducing GHG emissions, paediatricians should aim to decrease GHG emissions associated with paediatric care, when this is not in conflict with patient outcomes. In this article, we review literature on practical ways to encourage environmentally sustainable paediatric care and identify areas where more evidence is required. Finally, we introduce readers to the principles of sustainable healthcare which may be used to help guide further efforts to reduce the environmental impact of paediatric care.

Introduction: Inflammatory breast cancer (IBC) is an aggressive form of breast cancer with a poorly characterized immune microenvironment. Methods: We used a five-colour multiplex immunofluorescence panel, including CD68, CD4, CD8, CD20, and FOXP3 for immune microenvironment profiling in 93 treatment-naïve IBC samples. Results: Lower grade tumours were characterized by decreased CD4+ cells but increased accumulation of FOXP3+ cells. Increased CD20+ cells correlated with better response to neoadjuvant chemotherapy and increased CD4+ cells infiltration correlated with better overall survival. Pairwise analysis revealed that both ER+ and triple-negative breast cancer were characterized by co-infiltration of CD20 + cells with CD68+ and CD4+ cells, whereas co-infiltration of CD8+ and CD68+ cells was only observed in HER2+ IBC. Co-infiltration of CD20+, CD8+, CD4+, and FOXP3+ cells, and co-existence of CD68+ with FOXP3+ cells correlated with better therapeutic responses, while resistant tumours were characterized by co-accumulation of CD4+, CD8+, FOXP3+, and CD68+ cells and co-expression of CD68+ and CD20+ cells. In a Cox regression model, response to therapy was the most significant factor associated with improved patient survival. Conclusion: Those results reveal a complex unique pattern of distribution of immune cell subtypes in IBC and provide an important basis for detailed characterization of molecular pathways that govern the formation of IBC immune landscape and potential for immunotherapy.

Background People with severe mental illness have a higher rate of premature death than the general population, largely due to primary care preventable diseases. There has been little research on the health profile of this population attending Australian general practices. Methods In this nationwide cross-sectional study, MedicineInsight data for adult patients regularly attending general practices in 2018 were analysed to estimate the prevalence of schizophrenia or bipolar disorders (SBD) and investigate the health profile of people with SBD compared with other patients. Multilevel models clustered by practice (n = 565) and patient, and practice characteristics were created. Results The prevalence of recorded SBD was 1.91% (95% CI = 1.88%–1.94%) among the 618 849 patients included. Patients with recorded SBD were more likely than other patients to have records of health risk factors, particularly smoking (aOR = 3.8, 95% CI = 3.6–3.9) and substance use (aOR = 5.9, 95% CI = 5.6–6.3), and higher probabilities of comorbidities including cardiovascular diseases (aOR = 1.3, 95% CI = 1.2–1.4), cancer (aOR = 1.1, 95% CI = 1.0–1.2), diabetes mellitus type 2 (aOR = 2.2, 95% CI = 2.0–2.3), chronic kidney diseases (aOR = 1.7, 95% CI = 1.5–2.0), chronic liver diseases (aOR = 3.3, 95% CI = 2.6–4.0) and chronic respiratory diseases (aOR = 1.7, 95% CI = 1.7–1.8). Conclusions The higher prevalence of health risk factors and comorbidities among patients with recorded SBD underscores the need for proactive health risk monitoring and preventive care to address this health inequity.

In Australia, policy makers demand school leaders focus on raising student achievement levels when planning and implementing a school improvement (SI) plan. This paper explores the SI process for two Australian primary schools deemed to be underperforming and underwent a priority school support review (PSSR). In this study, 2 principals and members of their leadership team and 10 teachers across 2 schools were interviewed to explore how they experienced the PSSR process at different stages of the review process. Two assistant regional directors assigned to supporting the two schools during the PSSR process were also interviewed. The findings suggested that initially, school principals wondered how a PSSR would impact the morale of teaching staff already working hard to support student outcomes. However, as the schools progressed through the process, the principals’ perspectives shifted to see the PSSR as a valuable process for building leadership and teacher capacity and improving student outcomes.

Mathematical problem solving has been identified as one foundational area of mathematics for all students but is an area of weakness for students with disabilities. This investigation sought to determine the effects of peer-delivered schema-based instruction on the mathematical problem solving of the change problem type with four middle school students with extensive support needs using a single-case multiple-probe-across-participants design. We also wanted to determine if same-age peer tutors who received behavior skills training could deliver the academic instruction with fidelity. Students and peer tutors were representative of diverse backgrounds. Results showed a functional relation between peer-delivered modified schema-based instruction and students’ acquisition and maintenance of mathematical word problem–solving skills, and strong effect sizes were found. Peer tutors were able to provide instruction with high levels of fidelity across the study. Social validity data showed that all participants benefited from the peer-delivered instruction.

Objectives Health policy and funding initiatives have addressed increasing workloads in general practice through the deployment of clinicians from different disciplinary backgrounds. This study examines how general practices in England operate with increasingly diverse groups of practitioners. Methods Five general practices were selected for maximum variation of the duration and diversity of skill-mix in their workforce. Individual interviews were recorded with management and administrative staff and different types of practitioner. Patient surveys and focus groups gathered patients’ perspectives of consulting with different practitioners. Researchers collaborated during coding and thematic analysis of transcripts of audio recordings. Results The introduction of a wide range of practitioners required significant changes in how practices dealt with patients requesting treatment, and these changes were not necessarily straightforward. The matching of patients with practitioners required effective categorization of health care patients’ reported problem(s) and an understanding of practitioners’ capabilities. We identified individual and organizational responses that could minimize the impact on patients, practitioners and practices of imperfections in the matching process. Conclusions The processes underpinning the redistribution of tasks from GPs to non-GP practitioners are complex. As practitioner employment under the Primary Care Network contracts continues to increase, it is not clear how the necessarily fine-grained adjustments will be made for practitioners working across multiple practices.

Ocular coloboma arises from genetic or environmental perturbations that inhibit optic fissure (OF) fusion during early eye development. Despite high genetic heterogeneity, 70% to 85% of patients remain molecularly undiagnosed. In this study, we have identified new potential causative genes using cross-species comparative meta-analysis.Evolutionarily conserved differentially expressed genes were identified through in silico analysis, with in situ hybridization, gene knockdown, and rescue performed to confirm spatiotemporal gene expression and phenotype. Interrogation of the 100,000 Genomes Project for putative pathogenic variants was performed.Nine conserved differentially expressed genes between zebrafish and mouse were identified. Expression of zebrafish ank3a, bmpr1ba/b, cdh4, and pdgfaa was localized to the OF, periocular mesenchyme cells, or ciliary marginal zone, regions traversed by the OF. Knockdown of ank3, bmpr1b, and pdgfaa revealed a coloboma and/or microphthalmia phenotype. Novel pathogenic variants in ANK3, BMPR1B, PDGFRA, and CDH4 were identified in 8 unrelated coloboma families. We showed BMPR1B rescued the knockdown phenotype but variant messenger RNAs failed, providing evidence of pathogenicity.We show the utility of cross-species meta-analysis to identify several novel coloboma disease-causing genes. There is a potential to increase the diagnostic yield for new and unsolved patients while adding to our understanding of the genetic basis of OF morphogenesis.

International journal of earth sciences (2022). doi:10.1007/s00531-022-02174-5, Published by Springer, Berlin ; Heidelberg

Acetone and butanone were seen to emit blue light around 450 nm when excited in the green by a high intensity pulsed laser. The pathway of this anti-Stokes emission is believed to be multiphoton absorption followed by phosphorescence, with emission being observed in the samples at cryogenic temperatures below their melting point and not seen from either ketone in their cold liquid state. Given the widespread nature of these simple ketones in off-world bodies and their potential importance as an organic resource for Space Resource Utilization, signals which enable the identification and tracing of these materials are of use in applications from remote sensing and mapping to monitoring during extraction processes. While the excitation process has a low efficiency, the ability to use visible light for sensing of these targets has advantages over UV sources, such as the wider availability of high-powered lasers which could be utilized.

We aimed to assess the effectiveness of a single dose of the Ad26.COV2.S vaccine (JohnsonJohnson) in health-care workers in South Africa during two waves of the South African COVID-19 epidemic.In the single-arm, open-label, phase 3B implementation Sisonke study, health-care workers aged 18 years and older were invited for vaccination at one of 122 vaccination sites nationally. Participants received a single dose of 5 × 10Between Feb 17 and May 17, 2021, 477 102 health-care workers were enrolled and vaccinated, of whom 357 401 (74·9%) were female and 119 701 (25·1%) were male, with a median age of 42·0 years (33·0-51·0). 215 813 vaccinated individuals were matched with 215 813 unvaccinated individuals. As of data cutoff (July 17, 2021), vaccine effectiveness derived from the total matched cohort was 83% (95% CI 75-89) to prevent COVID-19-related deaths, 75% (69-82) to prevent COVID-19-related hospital admissions requiring critical or intensive care, and 67% (62-71) to prevent COVID-19-related hospitalisations. The vaccine effectiveness for all three outcomes were consistent across scheme A and scheme B. The vaccine effectiveness was maintained in older health-care workers and those with comorbidities including HIV infection. During the course of the study, the beta (B.1.351) and then the delta (B.1.617.2) SARS-CoV-2 variants of concerns were dominant, and vaccine effectiveness remained consistent (for scheme A plus B vaccine effectiveness against COVID-19-related hospital admission during beta wave was 62% [95% CI 42-76] and during delta wave was 67% [62-71], and vaccine effectiveness against COVID-19-related death during beta wave was 86% [57-100] and during delta wave was 82% [74-89]).The single-dose Ad26.COV2.S vaccine shows effectiveness against severe COVID-19 disease and COVID-19-related death after vaccination, and against both beta and delta variants, providing real-world evidence for its use globally.National Treasury of South Africa, the National Department of Health, Solidarity Response Fund NPC, The MichaelSusan Dell Foundation, The Elma Vaccines and Immunization Foundation, and the BillMelinda Gates Foundation.

Introduction: The coronavirus pandemic changed the way urology education was delivered. At Dalhousie University, third-year medical students (clinical clerks) undergoing a two-week urology elective had the historic in-person seminars changed to virtual seminars with pre-recorded lectures by staff. The academic abilities of the clerks were measured via a standardized written exam and clinical score assigned by a staff preceptor. This study aimed to measure the impact of virtual education on student performance. Methods: Clerk clinical and exam scores have been recorded since 2014. The in-person seminar (pre-COVID) cohort included students from January 2014 to March 2020 (n=109), while the virtual seminar (post-COVID) cohort was recorded from April 2020 to August 2022 (n=60). Independent T-test was used to compare clinical, exam, and total scores between the pre-COVID student groups after ensuring normality. Results: Students in the virtual seminar group (mean ± standard deviation 88.69±6.50%) performed better than the in-person seminar student groups (86.32±6.33%) in terms of clinical performance gradings (p=0.02). There was no statistically significant difference in written exam scores between the in-person seminar and virtual seminar cohorts (77.34±10.94% vs. 78.75±11.37%, p=0.43). Cumulative scores were higher for virtual seminar student groups vs. in-person seminar cohort (86.70±5.40% vs. 84.52±5.44%, p=0.01). Conclusions: Clinical clerks undergoing virtual education during a two-week urology elective had improved clinical and cumulative score performances when compared to the in-personal seminar cohort; virtual seminars did not statistically negatively impact exam scores.

The global COVID-19 pandemic brought considerable public and policy attention to the field of infectious disease modelling. A major hurdle that modellers must overcome, particularly when models are used to develop policy, is quantifying the uncertainty in a model’s predictions. By including the most recent available data in a model, the quality of its predictions can be improved and uncertainties reduced. This paper adapts an existing, large-scale, individual-based COVID-19 model to explore the benefits of updating the model in pseudo-real time. We use Approximate Bayesian Computation (ABC) to dynamically recalibrate the model’s parameter values as new data emerge. ABC offers advantages over alternative calibration methods by providing information about the uncertainty associated with particular parameter values and the resulting COVID-19 predictions through posterior distributions. Analysing such distributions is crucial in fully understanding a model and its outputs. We find that forecasts of future disease infection rates are improved substantially by incorporating up-to-date observations and that the uncertainty in forecasts drops considerably in later simulation windows (as the model is provided with additional data). This is an important outcome because the uncertainty in model predictions is often overlooked when models are used in policy.

Objective: The aim of this study was to examine the relationship between obesity and risk of stillbirth among pregnant women with obesity in the United States, with a focus on racial and ethnic disparities. Study Design: We conducted a retrospective cross-sectional analysis of birth and fetal data from the 2014-2019 National Vital Statistics System (N=14,938,384 total births), to examine associations of maternal body mass index (BMI) and risk of stillbirth. Cox proportional-hazards regression model was used to compute adjusted hazard ratios (HR) as a measure of risk of stillbirth in relation to maternal BMI. Results: The stillbirth rate was 6.70 per 1,000 births among women with a pre-pregnancy obesity, while the stillbirth rate among women with a normal (non-obese) pre-pregnancy BMI was 3.85 per 1,000 births. The risk of stillbirth was greater among women with obesity compared to women without obesity (HR 1.39; 95% CI: 1.37-1.41). Compared to Non-Hispanic (NH) Whites, women identifying as NH-other (HR 1.66; 95% CI: 1.61-1.72) and NH-Black (HR 1.31; 95% CI: 1.26-1.35) were at higher risk of stillbirth, while Hispanic women had a decreased likelihood of stillbirth (HR 0.38; 95% CI: 0.37-0.40). Conclusion: Obesity is a modifiable risk factor for stillbirth. Public health awareness campaigns and strategies targeting weight management in women of reproductive age and racial/ethnic populations at highest risk for stillbirth are needed.

Ethylene Oxide (EtO) is a colorless, flammable gas at room temperature, produced by the catalytic oxidation of ethylene. EtO is widely used by medical sterilization facilities to clean medical supplies and equipment. Recent epidemiological studies showed that EtO is a more potent carcinogen than previously documented, leading the Environmental Protection Agency (EPA) to update, in December 2016, the inhalation unit risk estimate for EtO. This resulted in the identification of EtO as a potential health concern in several areas across the US, including the state of Utah. The geography surrounding Salt Lake Valley creates a bowl; ideal for collecting air pollution emissions. The region often experiences inversion episodes which inhibit vertical mixing and cause an accumulation of air pollutants, leading to unhealthy pollution levels. Using the EPA's dispersion modeling software, AERMOD, this study estimated EtO concentrations through facility stack and fugitive emissions modeling results. These values were compared with those of canister-based concentrations from ambient air samples taken near a medical device sterilization facility in the Salt Lake Valley. Stainless steel, whole-air passivated canisters were used to collect 24-hour ambient concentration samples of EtO. Eight locations surrounding a Salt Lake Valley medical device sterilization facility and four background sites were chosen to measure the ambient concentrations. Accounting for potential atmospheric impacts on EtO, measurements were sampled in winter 2022 (January-March) and summer 2022 (July-September). The modeled EtO concentrations were adjusted to account for background values associated with the winter or summer data. Then the two methodologies were compared using a Wilcoxon Sign-ranked, paired test. The statistical analysis resulted in six of the eight sample locations surrounding the sterilization facility being significantly different when comparing canister-based measurements of ambient EtO to modeled estimates. Canister-based measurements taken at sites one, three, and four were statistically greater than the modeled estimates, while sites two, five, and seven were statistically less than the modeled estimates. Also, the summer background value calculated was almost 2.5 times greater than the winter. The results do not suggest whether one method is more or less conservative than the other. In conclusion, the five of the closest sites and site seven were statistically different when comparing measured and modeled ambient concentrations of EtO. The comparison results do not clearly indicate if a correction factor could be derived for future human exposure to cancer risk assessment modeling. However, it is reasonable that the closer to the sterilization facility, the more total EtO exposure will be realized.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic fatty liver disease worldwide, particularly in obese and type 2 diabetic individuals. Currently, there are no therapies for NAFLD that have been approved by the US Food and Drug Administration. Herein, we examine the rationale for using ω3 polyunsaturated fatty acids (PUFAs) in NAFLD therapy. This focus is based on the finding that NAFLD severity is associated with a reduction of hepatic C20–22 ω3 PUFAs. Because C20–22 ω3 PUFAs are pleiotropic regulators of cell function, loss of C20–22 ω3 PUFAs has the potential to significantly impact hepatic function. We describe NAFLD prevalence and pathophysiology as well as current NAFLD therapies. We also present evidence from clinical and preclinical studies that evaluated the capacity of C20–22 ω3 PUFAs to treat NAFLD. Given the clinical and preclinical evidence, dietary C20–22 ω3 PUFA supplementation has the potential to decrease human NAFLD severity by reducing hepatosteatosis and liver injury. Expected final online publication date for the Annual Review of Nutrition, Volume 43 is August 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

To safeguard nature, we must understand the drivers of biodiversity loss. Time-delayed biodiversity responses to environmental changes (ecological lags) are often absent from models of biodiversity change, despite their well-documented existence. We quantify how lagged responses to climate and land-use change have influenced mammal and bird populations around the world, while incorporating effects of direct exploitation and conservation interventions. Ecological lag duration varies between drivers, vertebrate classes and body size groupings—e.g. lags linked to climate-change impacts are 13 years for small birds, rising to 40 years for larger species. Past warming and land conversion generally combine to predict population declines; however, such conditions are associated with population increases for small mammals. Positive effects of management ( > +4% annually for large mammals) and protected areas ( > +6% annually for large birds) on population trends contrast with the negative impact of exploitation ( < −7% annually for birds), highlighting the need to promote sustainable use. Model projections suggest a future with winners (e.g. large birds) and losers (e.g. medium-sized birds), with current/recent environmental change substantially influencing abundance trends to 2050. Without urgent action, including effective conservation interventions and promoting sustainable use, ambitious targets to stop declines by 2030 may already be slipping out of reach.

PDF file - 108 KB, This file provides additional details on methods and protocols.

Triple-negative breast cancers (TNBC) have an aggressive phenotype with a relatively high rate of recurrence and poor overall survival. To date, there is no approved targeted therapy for TNBCs. Aurora kinases act as regulators of mammalian cell division. They are important for cell-cycle progression and are frequently overexpressed or mutated in human tumors, including breast cancer. In this study, we investigated the therapeutic potential of targeting Aurora kinases in preclinical models of human breast cancers using a pan-inhibitor of Aurora kinases, AS703569. In vitro, AS703569 was tested in 15 human breast cancer cell lines. TNBC cell lines were more sensitive to AS703569 than were other types of breast cancer cells. Inhibition of proliferation was associated with cell-cycle arrest, aneuploidy, and apoptosis. In vivo, AS703569 administered alone significantly inhibited tumor growth in seven of 11 patient-derived breast cancer xenografts. Treatment with AS703569 was associated with a decrease of phospho-histone H3 expression. Finally, AS703569 combined to doxorubicin–cyclophosphamide significantly inhibited in vivo tumor recurrence, suggesting that Aurora kinase inhibitors could be used both in monotherapy and in combination settings. In conclusion, these data indicate that targeting Aurora kinases could represent a new effective approach for TNBC treatment. Mol Cancer Ther; 11(12); 2693–703. ©2012 AACR.

Adoptive T-cell transfer therapy is an FDA- approved treatment for leukemia that relies on the ex vivo expansion and reinfusion of a patient's immune cells, which can be engineered with a chimeric antigen receptor (CAR) for more efficient tumor recognition. Type 17 T cells, controlled transcriptionally by RORγ, have been reported to mediate potent antitumor effects superior to those observed with conventionally expanded T cells. Here, we demonstrate that addition of a synthetic, small-molecule RORγ agonist during ex vivo expansion potentiates the antitumor activity of human Th17 and Tc17 cells redirected with a CAR. Likewise, ex vivo use of this agonist bolstered the antitumor properties of murine tumor-specific CD4+ and CD8+ T cells. Expansion in the presence of the RORγ agonist enhanced IL17A production without compromising IFNγ secretion in vitro. In vivo, cytokine neutralization studies revealed that IFNγ and IL17A were required to regress murine melanoma tumors. The enhanced antitumor effect of RORγ agonist treatment was associated with recovery of more donor T cells in the tumor and spleen; these cells produced elevated levels of cytokines months after infusion and expressed markers of long-lived stem and central memory cells such as Tcf7 and CD62L. Conversely, untreated cells mainly exhibited effector phenotypes in the tumor. Cured mice previously treated with agonist-primed T cells were protected from tumor rechallenge. Collectively, our work reveals that in vitro treatment with a RORγ agonist generates potent antitumor Type 17 effector cells that persist as long-lived memory cells in vivo.Significance: RORγ agonists can be used in vitro during T-cell expansion to enhance the efficacy of adoptive cell therapy (e.g., CAR-T) and to provide long-term protection against tumors.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/14/3888/F1.large.jpg. Cancer Res; 78(14); 3888–98. ©2018 AACR.

Supplementary Figure S1 shows that RORgamma agonist treatment does not impact the transduction efficiency of CAR virus. Supplementary Figure S2 shows that RORgamma agonist treatment increases IL-17A secretion from TRP-1 Th0 and Th17 cells. Included in Supplementary Figure S3 are spaghetti plots showing data of individual mice used in main Figure 3 and survival curves of TRP-1 Th17 transferred mice. Supplementary Figure S4 presents bar graphs of memory markers. Graphs in Supplementary Figure S5 showing eradication of primary tumors by Type 17 T cells and the frequency of donor cells after third tumor challenge supplement the data described in Figure 7. Supplementary Figure S6 shows that after adoptive cell transfer, RORgamma agonist primed donor T cells contain fewer Treg cells and express lower levels of PD-1.

BackgroundCannabis is the most widely used illicit drug in the United States and is often associated with changes in attention function, which may ultimately impact numerous other cognitive faculties (e.g. memory, executive function). Importantly, despite the increasing rates of cannabis use and widespread legalization in the United States, the neural mechanisms underlying attentional dysfunction in chronic users are poorly understood.MethodsWe used magnetoencephalography (MEG) and a modified Posner cueing task in 21 regular cannabis users and 32 demographically matched non-user controls. MEG data were imaged in the time−frequency domain using a beamformer and peak voxel time series were extracted to quantify the oscillatory dynamics underlying use-related aberrations in attentional reorienting, as well as the impact on spontaneous neural activity immediately preceding stimulus onset.ResultsBehavioral performance on the task (e.g. reaction time) was similar between regular cannabis users and non-user controls. However, the neural data indicated robust theta-band synchronizations across a distributed network during attentional reorienting, with activity in the bilateral inferior frontal gyri being markedly stronger in users relative to controls (p's < 0.036). Additionally, we observed significantly reduced spontaneous theta activity across this distributed network during the pre-stimulus baseline in cannabis users relative to controls (p's < 0.020).ConclusionsDespite similar performance on the task, we observed specific alterations in the neural dynamics serving attentional reorienting in regular cannabis users compared to controls. These data suggest that regular cannabis users may employ compensatory processing in the prefrontal cortices to efficiently reorient their attention relative to non-user controls.