The Caribbean and Mesoamerica Biogeochemical Isotope Overview (CAMBIO).

The Caribbean & Mesoamerica Biogeochemical Isotope Overview (CAMBIO) is an archaeological data community designed to integrate published biogeochemical data from the Caribbean, Mesoamerica, and southern Central America to address questions about dynamic interactions among humans, animals, and the environment in the region over the past 10,000 years. Here we present the CAMBIO human dataset, which consists of more than 16,000 isotopic measurements from human skeletal tissue samples (δ13C, δ15N, δ34S, δ18O, 87Sr/86Sr, 206/204Pb, 207/204Pb, 208/204Pb, 207/206Pb) from 290 archaeological sites dating between 7000 BC to modern times. The open-access dataset also includes detailed chronological, contextual, and laboratory/sample preparation information for each measurement. The collated data are deposited on the open-access CAMBIO data community via the Pandora Initiative data platform ( https://pandoradata.earth/organization/cambio ).

Effects of Aficamten on cardiac contractility in a feline translational model of hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is the most prevalent inherited cardiac disease in humans and cats and lacks efficacious pharmacologic interventions in the preclinical phase of disease. LV outflow tract obstruction (LVOTO) is commonly observed in HCM-affected patients and is a primary driver of heart failure symptoms and reduced quality of life. Novel small-molecule cardiac myosin inhibitors target actin-myosin interactions to alleviate overactive protein interactions. A prospective, randomized, controlled cross-over study was performed to evaluate pharmacodynamic effects of two doses (0.3 and 1 mg/kg) of a next-in-class cardiac myosin inhibitor, aficamten (CK-3773274, CK-274), on cardiac function in cats with the A31P MYBPC3 mutation and oHCM. Dose-dependent reductions in LV systolic function, LVOT pressure gradient, and isovolumetric relaxation times compared to baseline were observed. Promising beneficial effects of reduced systolic function warrant further studies of this next-in-class therapeutic to evaluate the benefit of long-term administration in this patient population.

Pharmacokinetics of a single dose of Aficamten (CK-274) on cardiac contractility in a A31P MYBPC3 hypertrophic cardiomyopathy cat model.

Hypertrophic cardiomyopathy (HCM) is the most prevalent cardiac disease in cats and lacks efficacious preclinical pharmacologic intervention, prompting investigation of novel therapies. Genetic mutations encoding sarcomeric proteins are implicated in the development of HCM and small molecule myosin inhibitors are an emerging class of therapeutics designed to target the interaction of actin and myosin to alleviate the detrimental effects of inappropriate contractile protein interactions. The purpose of this study was to characterize the pharmacodynamic effects of a single oral dose of the novel cardiac myosin inhibitor aficamten (CK-274) on cardiac function in purpose bred cats with naturally occurring A31P MYBPC3 mutation and a clinical diagnosis of HCM with left ventricular outflow tract obstruction (LVOTO). Five purpose bred cats were treated with aficamten (2 mg/kg) or vehicle and echocardiographic evaluations were performed at 0, 6, 24, and 48 h post-dosing. High dose aficamten (2 mg/kg) reduced left ventricular fractional shortening (LVFS%) by increasing the LV systolic internal dimension (LVIDs) and reduced isovolumic relaxation time (IVRT) compared with baseline without significant adverse effects. The marked reduction in systolic function and reduced IVRT coupled with an increased heart rate in treated cats, suggest a lower dose may be optimal. Further studies to determine optimal dosing of aficamten are indicated.

'We should have been told what would happen': Children's and parents' procedural knowledge levels and information-seeking behaviours when coming to hospital for a planned procedure.

Children continue to be poorly prepared and informed about clinical procedures, despite increased evidence of the worth of preparation and the availability of information resources. This study used a concurrent mixed-methods approach to explore the information accessed by children and their parents before attending hospital for a procedure. Information was collected separately from 40 children (aged between 8 and 12 years) and their parents using a paper booklet to examine self-reported perceived procedural knowledge and information-seeking behaviours. Data were analysed using descriptive statistics and content analysis techniques. The findings indicate that many children (70%, n = 28) and their parents (65%, n = 26) have low procedural knowledge levels. The majority of children (85%, n = 36) reported not receiving or seeking information about their procedure, despite identifying a desire and preference for more information. This study shows a mismatch between the current provision of procedural information and children and parents' expectations that information will be provided directly to them by health professionals. In order for this 'information hole' to be filled, there needs to be a concerted effort to develop and systematically use meaningful information materials and for children and their parents to have the opportunity to discuss their procedural knowledge with health professionals.

Origins and spread of formal ceremonial complexes in the Olmec and Maya regions revealed by airborne lidar.

City plans symbolizing cosmologies have long been recognized as a defining element of Mesoamerican civilizations. The origins of formal spatial configurations are thus the key to understanding early civilizations in the region. Assessment of this issue, however, has been hindered by the lack of systematic studies of site plans over broad areas. Here, we report the identification of 478 formal rectangular and square complexes, probably dating from 1,050 to 400 BC, through a lidar (laser imaging, detection and ranging) survey across the Olmec region and the western Maya lowlands. Our analysis of lidar data also revealed that the earlier Olmec centre of San Lorenzo had a central rectangular space, which possibly provided the spatial template for later sites. This format was probably formalized and spread after the decline of San Lorenzo through intensive interaction across various regions. These observations highlight the legacy of San Lorenzo and the critical role of inter-regional interaction.

Reference intervals for radiographic, echocardiographic and N-terminal pro B-type natriuretic peptide values in healthy kittens.

OBJECTIVES: Assessment of heart size in kittens is important, and there is a need for reference intervals (RIs) to prevent misinterpretation of cardiomegaly in this patient population. The purpose of this study was to generate RIs for echocardiographic and radiographic quantification of cardiac size in healthy kittens. METHODS: In total, 88 kittens aged 6-16 weeks were enrolled in this study. Physical examination, and radiographic and echocardiographic evaluations were performed without sedation. Thoracic radiographs and echocardiographic images were measured to establish RIs for vertebral heart score (VHS), cardiac thoracic ratio (CTR) and multiple echocardiographic variables. N-terminal pro B-type natriuretic peptide (NT-proBNP) was measured. Statistical correlations between echocardiographic parameters and age, body weight and sex were all evaluated and RIs were generated. RESULTS: Low-grade heart murmurs were appreciated in 26/88 kittens (29.5%). Kittens had a median VHS of 9.5 vertebrae (95% RI 8.0-10.9) and a median CTR of 67.2% (95% RI 54.4-79.8%). Measured NT-proBNP levels were comparable to healthy adult cats with a median of 31 pmol/l (upper reference limit 75 pmol/l). Multiple moderate-to-strong correlations between body weight and age with various echocardiographic parameters were observed and allometric scaling was performed for body weight. RIs for echocardiographic parameters were generated based on patient weight using allometric scaling formulas. Tricuspid valve regurgitation was a common finding and was present in 37.5% (n = 33) of the kittens. CONCLUSIONS AND RELEVANCE: This study establishes RIs for thoracic radiograph assessment, echocardiography and cardiac biomarkers in kittens, which fills a critical gap in the veterinary literature. The VHS reported in this study is higher than previously reported for adult cats.

The Acceptability and Impact of the Xploro Digital Therapeutic Platform to Inform and Prepare Children for Planned Procedures in a Hospital: Before and After Evaluation Study.

BACKGROUND: There is increasing interest in finding novel approaches to improve the preparation of children for hospital procedures such as surgery, x-rays, and blood tests. Well-prepared and informed children have better outcomes (less procedural anxiety and higher satisfaction). A digital therapeutic (DTx) platform (Xploro) was developed with children to provide health information through gamification, serious games, a chatbot, and an augmented reality avatar. OBJECTIVE: This before and after evaluation study aims to assess the acceptability of the Xploro DTx and examine its impact on children and their parent's procedural knowledge, procedural anxiety, and reported experiences when attending a hospital for a planned procedure. METHODS: We used a mixed methods design with quantitative measures and qualitative data collected sequentially from a group of children who received standard hospital information (before group) and a group of children who received the DTx intervention (after group). Participants were children aged between 8 and 14 years and their parents who attended a hospital for a planned clinical procedure at a children's hospital in North West England. Children and their parents completed self-report measures (perceived knowledge, procedural anxiety, procedural satisfaction, and procedural involvement) at baseline, preprocedure, and postprocedure. RESULTS: A total of 80 children (n=40 standard care group and n=40 intervention group) and their parents participated in the study; the children were aged between 8 and 14 years (average 10.4, SD 2.27 years) and were attending a hospital for a range of procedures. The children in the intervention group reported significantly lower levels of procedural anxiety before the procedure than those in the standard group (two-tailed t63.64=2.740; P=.008). The children in the intervention group also felt more involved in their procedure than those in the standard group (t75=-2.238; P=.03). The children in the intervention group also reported significantly higher levels of perceived procedural knowledge preprocedure (t59.98=-4.892; P=.001) than those in the standard group. As for parents, those with access to the Xploro intervention reported significantly lower levels of procedural anxiety preprocedure than those who did not (t68.51=1.985; P=.05). During the semistructured write and tell interviews, children stated that they enjoyed using the intervention, it was fun and easy to use, and they felt that it had positively influenced their experiences of coming to the hospital for a procedure. CONCLUSIONS: This study has shown that the DTx platform, Xploro, has a positive impact on children attending a hospital for a procedure by reducing levels of procedural anxiety. The children and parents in the intervention group described Xploro as improving their experiences and being easy and fun to use.

Development of plasma and whole blood taurine reference ranges and identification of dietary features associated with taurine deficiency and dilated cardiomyopathy in golden retrievers: A prospective, observational study.

INTRODUCTION: A surge in Food and Drug Administration (FDA) consumer complaints identified concerns that legume-rich, grain-free diets were associated with nutritionally-mediated dilated cardiomyopathy (DCM). Golden retrievers represent the most reported breed affected by this condition and previous studies documented the disease is responsive to dietary change and taurine supplementation. Although dietary findings across cases are compelling, prospective studies with control groups are lacking. The role of diet in developing taurine deficiency and echocardiographic changes consistent with DCM in healthy dogs is unknown. OBJECTIVES: We hypothesized that golden retrievers eating non-traditional diets are at a higher risk of having taurine deficiency and nutritionally-mediated DCM compared with those eating traditional commercial diets. We aimed to compare taurine concentrations and echocardiographic indices of systolic function between golden retrievers in each diet group and elucidate associations between diet and these variables. Additionally, we aimed to generate breed-specific reference intervals for whole blood and plasma taurine concentrations. ANIMALS: 86 golden retrievers. METHODS: Golden retrievers eating traditional or non-traditional diets were evaluated and diet history, taurine concentrations and echocardiographic data were collected. Dietary features, taurine concentrations and echocardiographic findings were compared between diet groups. Relative risks were calculated for the likelihood of echocardiographic abnormalities and taurine deficiency in each diet group. Breed-specific reference intervals were constructed for taurine concentrations in dogs from the traditional diet group. RESULTS: Golden retrievers eating non-traditional diets had significantly lower taurine concentrations and more frequent systolic dysfunction. Breed specific reference intervals are higher than previously reported across breeds. CONCLUSIONS: Non-traditional diets, which were typically grain-free and contained legumes in this study, were significantly associated with and have increased relative risk for the identification of taurine deficiency and echocardiographic abnormalities consistent with nutritionally-mediated DCM. These findings were identifiable in the absence of clinical signs and support the findings of multiple previous studies and the ongoing FDA investigation.

The Maya Preclassic to Classic transition observed through faunal trends from Ceibal, Guatemala.

It is well known that the development of the ancient Maya civilization had significant and long-lasting impacts on the environment. This study assesses a large collection of faunal remains (>35,000 specimens) recovered over a span of several kilometers in and around the archaeological site of Ceibal, Guatemala, in order to determine whether the composition of animal resources was continuous throughout the site's history between 1000 BC and AD 1200, or whether there were any changes that could be attributed to sociopolitical or environmental causes. Results show a steep uniform decline in the number of freshwater mollusks across the site that occurred during the Preclassic to Classic transition, when large region-wide political changes, including the development of more complex and centralized political organization, took place throughout the Maya region. Evidence of species introductions (e.g., turkeys from central Mexico and possibly the Dermatemys river turtle from the Isthmus of Tehuantepec) and variations in resource exchange (e.g. marine shells) over time indicate that Ceibal was one of likely many communities involved in long-distance animal exchange networks. The results of the faunal analysis at Ceibal show how the ancient Maya had a complex and ever-changing relationship with the local wildlife, with outcomes that can still be observed in the environment today.

Cats with thermal burn injuries from California wildfires show echocardiographic evidence of myocardial thickening and intracardiac thrombi.

Recent increases in the prevalence and severity of wildfires in some regions have resulted in an increased frequency of veterinary burn patients. Few studies exist regarding diagnostics and management of burn wounds in veterinary patients and current knowledge is extrapolated from human literature and research models. Post-burn cardiac injury is a common finding and predictor of mortality in human patients and echocardiography is an important tool in monitoring response to therapy and predicting outcome. We describe the notable findings from cats naturally exposed to California wildfires in 2017 and 2018. Domestic cats (n = 51) sustaining burn injuries from the Tubbs (2017) and Camp (2018) wildfires were prospectively enrolled and serial echocardiograms and cardiac troponin I evaluations were performed. Echocardiograms of affected cats revealed a high prevalence of myocardial thickening (18/51) and spontaneous echocardiographic contrast and thrombi formation (16/51). Forty-two cats survived to discharge and 6 died or were euthanized due to a possible cardiac cause. For the first time, we describe cardiovascular and coagulation effects of thermal burn and smoke inhalation in cats. Further studies in veterinary burn victims are warranted and serve as a translational research opportunity for uncovering novel disease mechanisms and therapies.

'If I knew what was going to happen, it wouldn't worry me so much': Children's, parents' and health professionals' perspectives on information for children undergoing a procedure.

Children undergoing procedures such as blood tests and X-rays experience less anxiety and upset if they are well prepared and informed. Currently the provision of information about procedures can be ad hoc and there are barriers to children understanding this information. This study explored the perspectives of 32 children undergoing procedures (aged between 8 and 12 years), 27 parents and 19 health professionals on the provision of preparatory information to children. Qualitative interviews, prompted by visual images, were thematically analysed. The three themes, 'accessing information', 'understanding information' and 'using information', resonated with the central tenets of health literacy. Children reported mainly accessing information second-hand through their parents and demonstrated misconceptions about their procedure. Children identified that procedural information would help them to know what was going to happen and enable them to feel less worried and scared about their procedure. This study highlights that children can have low levels of health literacy in relation to a planned procedure. Their health literacy in this context is heavily influenced by the adults (parents and health professionals) around them. There needs to be further work conducted, informed directly by children, to improve the health literacy of children attending hospital for planned procedures.

Echocardiographic quantitation of left heart size and function in 122 healthy dogs: A prospective study proposing reference intervals and assessing repeatability.

BACKGROUND: Broadly applicable reference intervals (RIs) for measurements of left atrial (LA) and left ventricular (LV) size and function generated prospectively using statistically appropriate methods are limited. OBJECTIVES: To generate body size-independent RIs for linear, area, and volume measurements of LA size and LV size and function. ANIMALS: Healthy adult dogs (n = 122) of variable size and somatotype. METHODS: Prospective study. All dogs underwent an echocardiogram performed by the same examiner. Effects of body weight, sex, age, and heart rate were evaluated by regression and correlation analyses. Scaling exponents and prediction intervals were generated for linear measurements using the allometric equation. After normalization to body weight, 95% RIs were determined using nonparametric methods with 2.5 and 97.5 percentiles serving as the lower and upper limits (each with 90% confidence intervals), respectively. RESULTS: Linear LA and LV measurements were strongly correlated (R2 ≥ 0.79) with body weight. Scaling exponents were close to the expected 1/3 (0.299-0.392). Prediction intervals for linear measurements of LV chamber size were considerably narrower than previously reported. Weak correlations (r = -0.42 to -0.50) among LV fractional shortening, fractional area change, and ejection fraction and body weight were identified. No other meaningful relationships were identified between the measurements and sex, age, and heart rate. CONCLUSIONS AND CLINICAL IMPORTANCE: Body size-independent RIs for several linear, area, and volume measurements of LA and LV size and function were generated prospectively from a large and diverse reference population and are available for clinical use.

The information needs of children having clinical procedures in hospital: Will it hurt? Will I feel scared? What can I do to stay calm?

BACKGROUND: Children often have unmet information needs when attending hospital, and this can cause them anxiety and uncertainty. If children are prepared and informed about what will happen during a procedure, they tend to have a better experience. Finding out what children want to know before they attend hospital for procedures could provide significant benefits for children, their families, and healthcare professionals. This study set out to investigate children's perspectives of what information is important and valuable to know before attending hospital for a planned procedure. METHODS: A "write and tell" activity sheet underpinned a semistructured qualitative interview with children attending hospital for a planned procedure. The interview focussed on the information children thought was important to know before a procedure. Data were analysed using content analysis techniques. RESULTS: One hundred six children aged between 8 and 12 years old participated in the interviews. The children identified 616 pieces of information they thought would be of value to children attending hospital for procedures. These were inductively coded into three types of information: procedural, sensory, and self-regulation. Children want to know detailed procedural and sensory information to actively construct a script of a procedure and then build on this with information about specific strategies to help them cope with and self-regulate the situation. CONCLUSION: This study has identified three types of information children recognize as important in preprocedural preparation. Children construct an understanding of a planned procedure through actively scaffolding procedural, sensory, and self-regulation information.

Earliest isotopic evidence in the Maya region for animal management and long-distance trade at the site of Ceibal, Guatemala.

This study uses a multiisotope (carbon, nitrogen, oxygen, and strontium) approach to examine early animal management in the Maya region. An analysis of faunal specimens across almost 2,000 years (1000 BC to AD 950) at the site of Ceibal, Guatemala, reveals the earliest evidence for live-traded dogs and possible captive-reared taxa in the Americas. These animals may have been procured for ceremonial functions based on their location in the monumental site core, suggesting that animal management and trade began in the Maya area to promote special events, activities that were critical in the development of state society. Isotopic evidence for animal captivity at Ceibal reveals that animal management played a greater role in Maya communities than previously believed.

The Newcomer Health Clinic in Nova Scotia: A Beacon Clinic to Support the Health Needs of the Refugee Population.

Refugees tend to have greater vulnerability compared to the general population reporting greater need for physical, emotional, or dental problems compared to the general population. Despite the importance of creating strong primary care supports for these patients, it has been demonstrated that there is a significant gap in accessing primary care providers who are willing to accept the refugee population. These have resulted in bottlenecks in the transition or bridge clinics and have left patients orphaned without a primary care provider. This in turn results in higher use of emergency service and other unnecessary costs to the healthcare system. Currently there are few studies that have explored these challenges from primary care provider perspectives and very few to none from patient perspectives. A novel collaborative implementation initiative in primary healthcare (PHC) is seeking to improve primary medical care for the refugee population by creating a globally recommended transition or beacon clinic to support care needs of new arrivals and transitions to primary care providers. We discuss the innovative elements of the clinic model in this paper.

Lead (Pb) Isotope Baselines for Studies of Ancient Human Migration and Trade in the Maya Region.

We examined the potential use of lead (Pb) isotopes to source archaeological materials from the Maya region of Mesoamerica. The main objectives were to determine if: 1) geologic terrains throughout the Maya area exhibit distinct lead isotope ratios (206Pb/204Pb, 207Pb/204Pb, and 208Pb/204Pb), and 2) a combination of lead and strontium ratios can enhance sourcing procedures in the Mesoamerica region. We analyzed 60 rock samples for lead isotope ratios and a representative subset of samples for lead, uranium, and thorium concentrations across the Maya region, including the Northern Lowlands of the Mexican Yucatan Peninsula, the Southern Lowlands of Guatemala and Belize, the Volcanic Highlands, the Belizean Maya Mountains, and the Metamorphic Province/Motagua Valley. Although there is some overlap within certain sub-regions, particularly the geologically diverse Metamorphic Province, lead isotopes can be used to distinguish between the Northern Lowlands, the Southern Lowlands, and the Volcanic Highlands. The distinct lead isotope ratios in the sub-regions are related to the geology of the Maya area, exhibiting a general trend in the lowlands of geologically younger rocks in the north to older rocks in the south, and Cenozoic volcanic rocks in the southern highlands. Combined with other sourcing techniques such as strontium (87Sr/86Sr) and oxygen (δ18O), a regional baseline for lead isotope ratios can contribute to the development of lead isoscapes in the Maya area, and may help to distinguish among geographic sub-regions at a finer scale than has been previously possible. These isotope baselines will provide archaeologists with an additional tool to track the origin and movement of ancient humans and artifacts across this important region.

Isolation of endothelial colony-forming cells from blood samples collected from the jugular and cephalic veins of healthy adult horses.

OBJECTIVE To evaluate optimal isolation of endothelial colony-forming cells (ECFCs) from peripheral blood of horses. SAMPLE Jugular and cephalic venous blood samples from 17 adult horses. PROCEDURES Each blood sample was divided; isolation was performed with whole blood adherence (WBA) and density gradient centrifugation (DGC). Isolated cells were characterized by uptake of 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate-labeled acetylated low-density lipoprotein (DiI-Ac-LDL), vascular tubule formation, and expression of endothelial (CD34, CD105, vascular endothelial growth factor receptor-2, and von Willebrand factor) and hematopoietic (CD14) cell markers by use of indirect immunofluorescence assay (IFA) and flow cytometry. RESULTS Colonies with cobblestone morphology were isolated from 15 of 17 horses. Blood collected from the cephalic vein yielded colonies significantly more often (14/17 horses) than did blood collected from the jugular vein (8/17 horses). Of 14 cephalic blood samples with colonies, 13 were obtained with DGC and 8 with WBA. Of 8 jugular blood samples with colonies, 8 were obtained with DGC and 4 with WBA. Colony frequency (colonies per milliliter of blood) was significantly higher for cephalic blood samples and samples isolated with DGC. Cells formed vascular tubules, had uptake of DiI-Ac-LDL, and expressed endothelial markers by use of IFA and flow cytometry, which confirmed their identity as ECFCs. CONCLUSIONS AND CLINICAL RELEVANCE Maximum yield of ECFCs was obtained for blood samples collected from both the jugular and cephalic veins and use of DGC to isolate cells. Consistent yield of ECFCs from peripheral blood of horses will enable studies to evaluate diagnostic and therapeutic uses.