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We review the Pima County (Arizona) Health Department’s efforts to achieve equitable COVID-19 vaccine distribution in a county with a social vulnerability index of 0.88. We expedited vaccine distribution, focusing on equitable distribution, implementing a multi–point of dispensing approach, and using a periurban and rural strategy. Pima County has one of the highest vaccine distribution percentages among the highest social vulnerability index quartiles and is more than 10 percentage points ahead of other large counties in Arizona in vaccine uptake. (Am J Public Health. 2022;112(11):1560–1563. https://doi.org/10.2105/AJPH.2022.307040 )

A stablehand in his 20s presented with increasing dyspnoea on exertion and chest pain months after being kicked directly in the chest by a horse. Further investigations revealed severe isolated, primary tricuspid regurgitation due to partial avulsion of the anterior leaflet. Open surgical repair was successfully performed from which he recovered uneventfully with resolution of his symptoms and minimal residual tricuspid regurgitation. Although uncommon, blunt force trauma to the chest is becoming increasingly recognised as a rare cause of tricuspid regurgitation. Symptoms may be insidious, and a high index of suspicion is required to avoid missing the diagnosis.

Glycogen storage disease type Ia (GSD Ia) is the inherited deficiency of glucose-6-phosphatase (G6Pase), associated with life-threatening hypoglycemia and long-term complications, including hepatocellular carcinoma formation. Gene replacement therapy fails to stably reverse G6Pase deficiency. We attempted genome editing using two adeno-associated virus vectors, one that expressed Staphylococcus aureus Cas9 protein and a second containing a donor transgene encoding G6Pase, in a dog model for GSD Ia. We demonstrated donor transgene integration in the liver of three adult-treated dogs accompanied by stable G6Pase expression and correction of hypoglycemia during fasting. Two puppies with GSD Ia were treated by genome editing that achieved donor transgene integration in the liver. Integration frequency ranged from 0.5% to 1% for all dogs. In adult-treated dogs, anti-SaCas9 antibodies were detected before genome editing, reflecting prior exposure to S. aureus. Nuclease activity was low, as reflected by a low percentage of indel formation at the predicted site of SaCas9 cutting that indicated double-stranded breaks followed by non-homologous end-joining. Thus, genome editing can integrate a therapeutic transgene in the liver of a large animal model, either early or later in life, and further development is warranted to provide a more stable treatment for GSD Ia.

This article explores volatility from the perspective of hilsa fish in the Bengal Delta. The hilsa, known as ilish in Bengali, takes advantage of monsoonal hydrological dynamics in its life cycle. Today, hilsa are changing in response to anthropogenic activities, which attempt to stabilise delta landscapes in response to perceived volatility, but generate new volatilities that are felt and sensed corporeally by people who are entangled with hilsa lifeways. Interactions with a fisher, a cook, a scientist and an environmental activist during multi-sited ethnographic fieldwork in Bangladesh provide insights into how hilsa are experiencing and responding to spatial, material and temporal environmental transformations. Embodied understandings of hilsa lifeworlds gained through acts of fishing, cooking, dissecting and monitoring reveal the more-than-human reverberations of human-induced volatility.Résumé : Cet article analyse la volatilité du point de vue du poisson hilsa dans le delta du Bengale. Le hilsa, également connu sous le nom de ilish en bengali, exploite la dynamique hydraulogique de la mousson au cours de son cycle de vie. Aujourd’hui, on constate que le poisson hilsa a changé en réponse aux activités anthropique qui tentent de stabiliser l’espace du delta contre sa volatilité perçue. Cette action créé une nouvelle volatilité qui est perçu par les personnes vivant étroitement avec le poisson hilsa. L’étude est basée sur une ethnographie multisite et des interactions avec un pêcheur, un cuisinier, un scientifi que et un activiste écologique au Bangladesh, dont l’objectif était de comprendre comment les expériences avec et l’étude du hisla permettent de saisir les transformations de l’environnement à l’œuvre. Le savoir incorporé des rythmes de vie du hilsa à travers l’activité de pêche, de cuisine, de dissection ou de surveillance donne à voir les réverbérations sur le non-humain de la volatilité induite par l’homme.

A large proportion of jockeys report symptoms associated with mental health difficulties (MHDs), yet most do not seek help from professional mental health support services. Due to the paucity of literature in this field, this study sought to explore jockeys’ barriers to, and facilitators of, help-seeking for MHDs. Twelve jockeys participated in semistructured interviews, subsequently analyzed via reflexive thematic analysis. Barriers to help-seeking included the negative perceptions of others (stigma and career implications), cultural norms (masculinity and self-reliance), and low mental health literacy (not knowing where to seek help, minimization of MHDs, negative perceptions of treatment, and recognizing symptoms). Facilitators to help-seeking included education (exposure to psychological support at a younger age), social support (from professionals, jockeys, family, and friends), and media campaigns (high-profile disclosures from jockeys). Findings are consistent with barrier and facilitator studies among general and athletic populations. Applied recommendations and future research considerations are presented throughout the manuscript.

War in Europe has transformed the global geopolitical landscape and Russia has weaponised its commodities. Europe’s energy market is now out of control. Europe will never rely on Russia for anything again. But, can Europe live with no gas supply from Russia at all? This has had far-reaching consequences for the global liquefied natural gas (LNG) industry. Volatility and sky-high prices are now an enormous risk to gas demand. Long hailed the ‘transition fuel’. Record gas prices pose a dilemma for governments who must balance climate change goals with mounting energy security concerns. Affordability is particularly pressing in the booming Asian markets that are underpinning much of the next wave of supply. It is in these markets that gas should play a critical role to facilitate the power sector transition from coal to renewables. In addition, about half of gas demand is in non-power sectors, contributing as industrial feedstock and heating fuel. In many of these sectors, gas simply cannot be replaced by renewables, and despite all eyes on Europe for now, the longer-term LNG story will remain centred around Asia. In this paper, Wood Mackenzie will argue that Asian gas demand can rebound and will remain robust as new supply emerges, reinforcing the longevity of LNG investments. But the race is on. Australian LNG must reduce its emissions and ensure contractual attractiveness to remain competitive against a wave of new low-cost, low-emission projects that are rapidly moving forwards around the world.

Objective The annual American College of Medical Informatics (ACMI) symposium focused discussion on the national public health information systems (PHIS) infrastructure to support public health goals. The objective of this article is to present the strengths, weaknesses, threats, and opportunities (SWOT) identified by public health and informatics leaders in attendance. Materials and Methods The Symposium provided a venue for experts in biomedical informatics and public health to brainstorm, identify, and discuss top PHIS challenges. Two conceptual frameworks, SWOT and the Informatics Stack, guided discussion and were used to organize factors and themes identified through a qualitative approach. Results A total of 57 unique factors related to the current PHIS were identified, including 9 strengths, 22 weaknesses, 14 opportunities, and 14 threats, which were consolidated into 22 themes according to the Stack. Most themes (68%) clustered at the top of the Stack. Three overarching opportunities were especially prominent: (1) addressing the needs for sustainable funding, (2) leveraging existing infrastructure and processes for information exchange and system development that meets public health goals, and (3) preparing the public health workforce to benefit from available resources. Discussion The PHIS is unarguably overdue for a strategically designed, technology-enabled, information infrastructure for delivering day-to-day essential public health services and to respond effectively to public health emergencies. Conclusion Most of the themes identified concerned context, people, and processes rather than technical elements. We recommend that public health leadership consider the possible actions and leverage informatics expertise as we collectively prepare for the future.

Background Recurrent miscarriage is defined as three recurrent first trimester pregnancy losses. The Tender Loving Care Clinic is a specialist clinic for women during the first trimester of a pregnancy following recurrent miscarriages. This study's aim was to review cases of those who attended the tender loving care clinic for antenatal care. Methods A retrospective chart review was conducted using anonymous data, collected from the electronic records of women who attended the clinic over a 1-year period. Results A total of 103 women attended the clinic during the study period. The majority (90.3%) were prescribed medication while attending. Pregnancy outcomes for women attending the clinic were good; 69.2% of women went on to have a live birth. Conclusions Pregnancy outcomes following recurrent miscarriages are reassuring with supportive antenatal care. This review highlights the importance of psychological care and reassurance in a pregnancy following recurrent miscarriages.

Rather than centering technology, we need to view tools as raw materials that students can use strategically to build mathematical knowledge.

We present detailed monitoring data across a five-country randomized trial of phone-based targeted tutoring–one of the largest multicountry replication efforts in education to date. We study an approach shown to work in Botswana and replicated in India, Kenya, Nepal, the Philippines, and Uganda. While the existing literature often finds diminishing effects as proof-of-concept studies are replicated and scaled, we find the opposite: implementation fidelity (the degree of targeted educational instruction) improves across replications and over time. This demonstrates that replication is not intractable; rather, equipped with mechanisms to learn from experience, organizational “learning curves” can enable effective replication and scale-up.

With the increasing appreciation for sex as a biological variable and the inclusion of female mice in research, it is important to understand the influence of the estrous cycle on physiological function. Sex hormones are known to modulate vascular function, but the effects of the mouse estrous cycle phase on arterial stiffness, endothelial function, and arterial estrogen receptor expression remain unknown. In 23 female C57BL/6 mice (6 mo of age), we determined the estrous cycle stage via vaginal cytology and plasma hormone concentrations. Aortic stiffness, assessed by pulse wave velocity, was lower during the estrus phase compared with diestrus. In ex vivo assessment of isolated pressurized mesenteric and posterior cerebral arteries, the responses to acetylcholine, insulin, and sodium nitroprusside, as well as nitric oxide-mediated dilation, were not different between estrous cycle phases. In the aorta, expression of phosphorylated estrogen receptor-α was higher for mice in estrus compared with mice in proestrus. In the cerebral arteries, gene expression for estrogen receptor-β (

The challenge of eradicating leukemia in patients with acute myelogenous leukemia (AML) after initial cytoreduction has motivated modern efforts to combine synergistic active modalities including immunotherapy. Recently, the ETCTN/CTEP 10026 study tested the combination of the DNA methyltransferase inhibitor decitabine together with the immune checkpoint inhibitor ipilimumab for AML/myelodysplastic syndrome (MDS) either after allogeneic hematopoietic stem cell transplantation (HSCT) or in the HSCT-naïve setting. Integrative transcriptome-based analysis of 304 961 individual marrow-infiltrating cells for 18 of 48 subjects treated on study revealed the strong association of response with a high baseline ratio of T to AML cells. Clinical responses were predominantly driven by decitabine-induced cytoreduction. Evidence of immune activation was only apparent after ipilimumab exposure, which altered CD4+ T-cell gene expression, in line with ongoing T-cell differentiation and increased frequency of marrow-infiltrating regulatory T cells. For post-HSCT samples, relapse could be attributed to insufficient clearing of malignant clones in progenitor cell populations. In contrast to AML/MDS bone marrow, the transcriptomes of leukemia cutis samples from patients with durable remission after ipilimumab monotherapy showed evidence of increased infiltration with antigen-experienced resident memory T cells and higher expression of CTLA-4 and FOXP3. Altogether, activity of combined decitabine and ipilimumab is impacted by cellular expression states within the microenvironmental niche of leukemic cells. The inadequate elimination of leukemic progenitors mandates urgent development of novel approaches for targeting these cell populations to generate long-lasting responses. This trial was registered at www.clinicaltrials.gov as #NCT02890329.

Background Our study addressed the diagnostic performance of the Atellica® IM High-Sensitivity Troponin I (hs-cTnI) assay for the rapid rule-out of myocardial infarction (MI) using a single hs-cTnI measurement at presentation in patients presenting to a US emergency department (ED). Methods This was a prospective, observational, cohort study of consecutive ED patients with suspected acute coronary syndrome, using 12-lead electrocardiogram and serial hs-cTnI measurements ordered on clinical indication (SAFETY, NCT04280926). ST-segment elevation MI patients were excluded. The optimal threshold required a sensitivity ≥99% and a negative predictive value (NPV) ≥99.5% for MI during index hospitalization as primary outcome. Type 1 MI (T1MI), myocardial injury, and 30-day adverse events were considered secondary outcomes. Event adjudications were established using the hs-cTnI assay used in clinical care. Results In 1171 patients, MI occurred in 97 patients (8.3%), 78.3% of which were type 2 MI. The optimal rule out hs-cTnI threshold was Conclusions A single hs-cTnI measurement strategy enabled the rapid identification of patients at low risk of MI and 30-day adverse events, allowing potential discharge early after ED presentation. Clinicaltrials.gov Registration number NCT04280926.

Large theropod dinosaurs are often reconstructed with their marginal dentition exposed because of the enormous size of their teeth and their phylogenetic association to crocodylians. We tested this hypothesis using a multiproxy approach. Regressions of skull length and tooth size for a range of theropods and extant varanid lizards confirm that complete coverage of theropod dinosaur teeth with extraoral tissues (gingiva and labial scales) is both plausible and consistent with patterns observed in living ziphodont amniotes. Analyses of dental histology from crocodylians and theropod dinosaurs, including Tyrannosaurus rex , further indicate that the most likely condition was complete coverage of the marginal dentition with extraoral tissue when the mouth was closed. This changes our perceptions about the appearance and oral configuration of these iconic predators and has broad implications for our interpretations of other terrestrial animals with large teeth.

BackgroundThis study aimed to estimate the direct healthcare cost burden of acute chest pain attendances presenting to ambulance in Victoria, Australia, and to identify key cost drivers especially among low-risk patients.MethodsState-wide population-based cohort study of consecutive adult patients attended by ambulance for acute chest pain with individual linkage to emergency and hospital admission data in Victoria, Australia (1 January 2015–30 June 2019). Direct healthcare costs, adjusted for inflation to 2020–2021 ($A), were estimated for each component of care using a casemix funding method.ResultsFrom 241 627 ambulance attendances for chest pain during the study period, mean chest pain episode cost was $6284, and total annual costs were estimated at $337.4 million ($68 per capita per annum). Total annual costs increased across the period ($310.5 million in 2015 vs $384.5 million in 2019), while mean episode costs remained stable. Cardiovascular conditions (25% of presentations) were the most expensive (mean $11 523, total annual $148.7 million), while a non-specific pain diagnosis (49% of presentations) was the least expensive (mean $3836, total annual $93.4 million). Patients classified as being at low risk of myocardial infarction, mortality or hospital admission (Early Chest pain Admission, Myocardial infarction, and Mortality (ECAMM) score) represented 31%–57% of the cohort, with total annual costs estimated at $60.6 million–$135.4 million, depending on the score cut-off used.ConclusionsTotal annual costs for acute chest pain presentations are increasing, and a significant proportion of the cost burden relates to low-risk patients and non-specific pain. These data highlight the need to improve the cost-efficiency of chest pain care pathways.

The COVID-19 pandemic exposed multiple weaknesses in the nation’s public health system. Therefore, the American College of Medical Informatics selected “Rebuilding the Nation's Public Health Informatics Infrastructure” as the theme for its annual symposium. Experts in biomedical informatics and public health discussed strategies to strengthen the US public health information infrastructure through policy, education, research, and development. This article summarizes policy recommendations for the biomedical informatics community postpandemic. First, the nation must perceive the health data infrastructure to be a matter of national security. The nation must further invest significantly more in its health data infrastructure. Investments should include the education and training of the public health workforce as informaticians in this domain are currently limited. Finally, investments should strengthen and expand health data utilities that increasingly play a critical role in exchanging information across public health and healthcare organizations.

Apophenia is the tendency to falsely detect meaningful relationships and may indicate susceptibility to more extreme expressions on the psychotic spectrum. This pilot investigated the fragmented ambiguous object task (FAOT), a new measure designed to assess apophenia behaviorally in a sample of adolescents with and without mood disorders using an image recognition task. Our primary hypothesis was that increased image recognition would be associated with PID-5 psychoticism. Participants were 33 (79% female) adolescents with (n = 18) and without (n = 15) mood disorders. Consistent with predictions, increased recognition of ambiguous images correlated positively with psychoticism. There was also moderate evidence for long-term stability of FAOT apophenia scores over time (mean interval of approximately 10 months). These findings offer preliminary evidence that the FAOT may be reflective of underlying psychoticism in our target population.