Opportunities for primary health care: a qualitative study of perinatal health and wellbeing during bushfire crises.

BACKGROUND: During the summer of 2019/2020, Australia experienced a catastrophic wildfire season that affected nearly 80% of Australians either directly or indirectly. The impacts of climate crisis on perinatal health have only recently begun to receive attention. The objective of this study was to understand experiences of perinatal women during the bushfire and smoke events of 2019-2020 regarding health, health care, and public health messaging. METHODS: Semistructured interviews were conducted by phone or web conferencing platforms with 43 participants living in the south-east of Australia who were either pregnant or who had recently had a baby during the 2019/2020 fires. RESULTS: The health impacts on participants of the fires, associated smoke, and evacuations for some, were both physical and psychological. Many participants sought information regarding how to protect their own health and that of their unborn/recently born children, but reported this difficult to find. CONCLUSIONS: Pregnant women and new mothers exposed to bushfire events are a risk group for adverse physical and psychological outcomes. At the time of the 2019/2020 Australian bushfires, exposed women could not easily access evidence-based information to mitigate this risk. Family practitioners are well placed to provide pregnant women and new mothers with this sought-after information, but they need to be prepared well in advance of future similar events.

Obstetric and perinatal outcomes for women with pre-existing diabetes in rural compared to metropolitan settings in Victoria, Australia.

BACKGROUND: Pre-existing diabetes in pregnancy is associated with an increased risk of complications. Likewise, living in rural, regional and remote Victoria, Australia, is also associated with poorer health outcomes. There is a gap in the literature with regard to whether Victorian women with pre-existing diabetes experience a greater risk of adverse pregnancy outcomes compared to their metropolitan counterparts. AIM: Our objective is to compare obstetric and perinatal outcomes for women with pre-existing diabetes delivering in rural vs metropolitan hospitals in Victoria, Australia. MATERIALS AND METHODS: Retrospective population-based study using routinely collected state-based data of singleton births to women with type 1 and type 2 diabetes who delivered in metropolitan (n = 3233) and rural hospitals (n = 693) in Victoria, Australia, between 2006-2015. Pearson's χ2 test, Fisher's exact test and MannWhitney U-test were used to compare obstetric and perinatal outcomes between metropolitan and rural locations. RESULTS: Delivery in a rural hospital was associated with higher rates of stillbirth (2.3% vs 1.1%, P = 0.027), macrosomia (25.9% vs 16.9%, P < 0.001), shoulder dystocia (8.4% vs 3.5%, P < 0.001) and admission to the neonatal intensive care unit/special care nursery (73.2% vs 59.3%, P < 0.001). Smoking (18.0% vs 8.9%, P < 0.001), overweight/obesity (P = 0.047) and socioeconomic disadvantage (P < 0.001) were more common in rural women. CONCLUSIONS: Women with pre-existing diabetes who deliver in rural hospitals experience a greater risk of adverse perinatal outcomes and present with increased maternal risk factors. These results suggest a need to improve care for women with pre-existing diabetes in rural Victoria.

Effect of tobacco smoking on outcomes after left ventricular assist device implantation.

Despite the well-established correlation between the tobacco use and cardiovascular disease, little is known about postoperative outcomes following the left ventricular assist device (LVAD) implantation. We aimed to elucidate the effect of tobacco smoking on post-LVAD implant outcomes. Patients who received LVADs from 2013 to 2018 were retrospectively characterized as current, former, or never smokers at the time of implant. We examined 1-year survival, total hospital readmissions, and specific hospital readmissions for LVAD-related adverse events based on patient's smoking status. Of the enrolled patients (n = 292), 55% were former smokers, 33% were never smokers, and 11% were current smokers. The majority of patients were African-American (48%) with a median age of 58 years. Never smokers were younger and less likely to be Caucasian compared to former or current smokers (P < .05, for both). The category of former smokers had statistically comparable total readmission rates with never smokers (2.49 vs. 2.13 event/year), whereas current smokers had significantly higher rates compared to never smokers (2.81 events/year, P < .05), with odds ratio 2.12 (95% CI = 1.35-3.32) adjusted for age and Caucasian race for >5 times of total readmissions per year. The rates of driveline infection, stroke, and hemolysis were statistically comparable between the never smokers and former smokers, while current smokers had significantly higher rates compared to never smokers (P < .05 for all).

Toddlers imitate prosocial demonstrations in bystander but not transgressor contexts.

Although prosocial abilities are associated with a wide range of healthy outcomes, few studies have experimentally examined socialization practices that may cause increased prosocial responding. The purpose of this study was to investigate conditions under which 2- and 3-year-old children can acquire prosocial behaviors through imitation. In Study 1 (N = 53), toddlers in the experimental condition watched a video of an adult comfort a woman in distress by performing a novel prosocial action without depicting how the woman was hurt. Parents then pretended they hurt their own finger and feigned distress. Children in the experimental condition were more likely to imitate the novel action relative to two control groups: (a) children who did not watch the video but witnessed a distressed parent, and (b) children who watched the video but witnessed parents engage in a neutral interaction. Thus, in a bystander context where children witnessed parent distress, toddlers imitated a general demonstration of how to respond prosocially to distress and applied this information to a specific distress scenario. In Study 2 (N = 54), the procedures were identical to those in the first study except that children were led to believe that they had transgressed to cause parent distress. In a transgressor context, children in the experimental condition were not more likely to imitate the prosocial behavior relative to children in either control group. These studies demonstrate that whether or not children have caused a victim's distress greatly affects their ability to apply a socially learned prosocial behavior, possibly due to self-conscious emotions such as guilt and shame.

Pregnancy outcomes for women with pre-pregnancy diabetes mellitus in Australian populations, rural and metropolitan: A review.

BACKGROUND: Historically, pre-pregnancy diabetes (PPDM) is a recognised risk factor for poor pregnancy outcome. Co-existing pathology and adverse social determinants including rural-metropolitan inequities in health and healthcare access may confer additional risks. Multidisciplinary care before, during and after pregnancy can improve outcomes for women with PPDM and their infants. The extent to which rural Australian women and their families share in improved outcomes is unknown. We aimed to summarise maternal characteristics and pregnancy outcomes for women with PPDM, including women in rural settings and examine applications of existing clinical guidelines to rural Australian practice. METHODS: We sought English language population and cohort studies about PPDM using Medline, Embase, PubMed, Australian epidemiological and international clinical practice guidelines. RESULTS: Women with PPDM are changing: older, more obese, of lower parity, less likely to smoke, more likely to have type 2 rather than type 1 diabetes and shorter duration of PPDM. Women with PPDM continue to experience excess adverse pregnancy outcomes, including maternal morbidity, complicated birth, perinatal loss, congenital anomalies and mother-infant separation. On face value, clinical guidelines appear relevant to women living in rural settings but there are only a few, conflicting outcome studies for rural women with PPDM. CONCLUSIONS: PPDM is changing. A significant minority live in rural locations, and although perinatal mortality/morbidity seems to be improving, it is unclear if this is also true for rural women due to a lack of recent Australian studies. Further research is necessary to achieve excellence everywhere for women with PPDM and their babies.

Disruption of amyloid precursor protein ubiquitination selectively increases amyloid ß (Aß) 40 levels via presenilin 2-mediated cleavage.

Amyloid plaques, a neuropathological hallmark of Alzheimer's disease, are largely composed of amyloid ß (Aß) peptide, derived from cleavage of amyloid precursor protein (APP) by ß- and γ-secretases. The endosome is increasingly recognized as an important crossroad for APP and these secretases, with major implications for APP processing and amyloidogenesis. Among various post-translational modifications affecting APP accumulation, ubiquitination of cytodomain lysines may represent a key signal controlling APP endosomal sorting. Here, we show that substitution of APP C-terminal lysines with arginine disrupts APP ubiquitination and that an increase in the number of substituted lysines tends to increase APP metabolism. An APP mutant lacking all C-terminal lysines underwent the most pronounced increase in processing, leading to accumulation of both secreted and intracellular Aß40. Artificial APP ubiquitination with rapalog-mediated proximity inducers reduced Aß40 generation. A lack of APP C-terminal lysines caused APP redistribution from endosomal intraluminal vesicles (ILVs) to the endosomal limiting membrane, with a subsequent decrease in APP C-terminal fragment (CTF) content in secreted exosomes, but had minimal effects on APP lysosomal degradation. Both the increases in secreted and intracellular Aß40 were abolished by depletion of presenilin 2 (PSEN2), recently shown to be enriched on the endosomal limiting membrane compared with PSEN1. Our findings demonstrate that ubiquitin can act as a signal at five cytodomain-located lysines for endosomal sorting of APP. They further suggest that disruption of APP endosomal sorting reduces its sequestration in ILVs and results in PSEN2-mediated processing of a larger pool of APP-CTF on the endosomal membrane.

Type of iconicity influences children's comprehension of gesture.

Children produce iconic gestures conveying action information earlier than the ones conveying attribute information (Özçaliskan, Gentner, & Goldin-Meadow, 2014). In this study, we ask whether children's comprehension of iconic gestures follows a similar pattern, also with earlier comprehension of iconic gestures conveying action. Children, ages 2-4years, were presented with 12 minimally-informative speech+iconic gesture combinations, conveying either an action (e.g., open palm flapping as if bird flying) or an attribute (e.g., fingers spread as if bird's wings) associated with a referent. They were asked to choose the correct match for each gesture in a forced-choice task. Our results showed that children could identify the referent of an iconic gesture conveying characteristic action earlier (age 2) than the referent of an iconic gesture conveying characteristic attribute (age 3). Overall, our study identifies ages 2-3 as important in the development of comprehension of iconic co-speech gestures, and indicates that the comprehension of iconic gestures with action meanings is easier than, and may even precede, the comprehension of iconic gestures with attribute meanings.

Do Children Understand Iconic Gestures About Events as Early as Iconic Gestures About Entities?

Children can understand iconic co-speech gestures that characterize entities by age 3 (Stanfield et al. in J Child Lang 40(2):1-10, 2014; e.g., "I'm drinking" [Formula: see text] tilting hand in C-shape to mouth as if holding a glass). In this study, we ask whether children understand co-speech gestures that characterize events as early as they do so for entities, and if so, whether their understanding is influenced by the patterns of gesture production in their native language. We examined this question by studying native English speaking 3- to 4 year-old children and adults as they completed an iconic co-speech gesture comprehension task involving motion events across two studies. Our results showed that children understood iconic co-speech gestures about events at age 4, marking comprehension of gestures about events one year later than gestures about entities. Our findings also showed that native gesture production patterns influenced children's comprehension of gestures characterizing such events, with better comprehension for gestures that follow language-specific patterns compared to the ones that do not follow such patterns-particularly for manner of motion. Overall, these results highlight early emerging abilities in gesture comprehension about motion events.

Yield of screening echocardiograms during pediatric follow-up in survivors treated with anthracyclines and cardiotoxic radiation.

BACKGROUND: Guidelines published by the Children's Oncology Group recommend screening echocardiograms for childhood cancer survivors exposed to anthracyclines and/or cardiotoxic radiation. This study aims to assess risk factors for cardiac late effects while evaluating the overall yield of screening echocardiograms. PROCEDURE: Demographics, exposures, and echocardiogram results were abstracted from the medical records of survivors diagnosed at ≤ 21 years old and ≥ 2 years off therapy who were exposed to anthracyclines and/or potentially cardiotoxic radiotherapy. Descriptive statistics and logistic regressions were performed and the yield of screening echocardiograms was calculated. RESULTS: Of 853 patients, 1,728 screening echocardiograms were performed, and 37 patients had an abnormal echocardiogram (overall yield 2.1%). Yields were only somewhat higher in more frequently screened patients. Risk factors for an abnormal result included anthracycline dose of ≥300 mg/m2 (adjusted odds ratio [aOR] 3.1; 95% confidence interval [CI]: 1.3-7.2; P < 0.01) with a synergist relationship in patients who also received radiation doses ≥30 Gy (aOR 7.0; 95% CI: 1.6-31.9; P = 0.01), as well as autologous bone marrow transplant (OR 3.3; 95% CI: 1.3-8.5; P = 0.01). Sex, race, age at diagnosis, and cyclophosphamide exposure were not statistically significant risk factors, and no patient receiving <100 mg/m2 anthracycline dose without concomitant radiation had an abnormal echocardiogram. CONCLUSIONS: Dose-dependent and synergist anthracycline and cardiotoxic radiotherapy risks for developing cardiomyopathy were confirmed. However, previously identified risk factors including female sex, black race, and early age at diagnosis were not replicated in this cohort. The yields showed weak correlation across frequency categories. Echocardiographic screening recommendations for low-risk pediatric patients may warrant re-evaluation.

Adding sound to theory of mind: Comparing children's development of mental-state understanding in the auditory and visual realms.

Theory of mind (ToM) gradually develops during the preschool years. Measures of ToM usually target visual experience, but auditory experiences also provide valuable social information. Given differences between the visual and auditory modalities (e.g., sights persist, sounds fade) and the important role environmental input plays in social-cognitive development, we asked whether modality might influence the progression of ToM development. The current study expands Wellman and Liu's ToM scale (2004) by testing 66 preschoolers using five standard visual ToM tasks and five newly crafted auditory ToM tasks. Age and gender effects were found, with 4- and 5-year-olds demonstrating greater ToM abilities than 3-year-olds and girls passing more tasks than boys; there was no significant effect of modality. Both visual and auditory tasks formed a scalable set. These results indicate that there is considerable consistency in when children are able to use visual and auditory inputs to reason about various aspects of others' mental states.

Analysis of Risk Factors for Abnormal Pulmonary Function in Pediatric Cancer Survivors.

BACKGROUND: Childhood cancer survivors are at increased risk for pulmonary-related morbidity and mortality. The Children's Oncology Group Long-Term Follow-Up (COG-LTFU) guidelines recommend pulmonary function testing after treatment with bleomycin, busulfan, carmustine, lomustine, thoracic radiation, bone marrow transplant, or pulmonary surgery. The aim of this analysis was to determine the prevalence of pulmonary function abnormalities in a pediatric survivor cohort. PROCEDURE: Patients ≥5 years old seen in our survivor clinic with at least one exposure outlined by COG-LFTU Guidelines were included. Original pulmonary function test (PFT) results were obtained and blindly reinterpreted by a single reviewer. Demographic, diagnosis, treatment factors, and clinical and/or patient-reported symptoms of cough, wheeze, and/or dyspnea were abstracted from their medical record. RESULTS: Overall, 143 (63.3%) survivors had PFT results available; 55.2% were male, 49.7% were white, and the mean age was 14.1 ± 4.8 years. Abnormal PFTs were found in 65.0% (n = 93) with 21.0% having multiple abnormalities. Specifically, 41.3% had hyperinflation, 25.9% had obstructive, and 13.3% had restrictive disease. Patients diagnosed at <5 years were more likely to have a pulmonary abnormality (P = 0.04); a majority of those diagnosed <5 years underwent pulmonary surgery or thoracic radiation. Regardless of the presence of a PFT abnormality, more than 80% of survivors were asymptomatic (82.9% vs.81.5%; P-value = 0.54). CONCLUSIONS: Almost two-thirds of survivors screened per the COG-LTFU Guidelines had an abnormal PFT but a majority reported no clinical symptoms. Hyperinflation was the most prevalent abnormality.

Chimpanzees play the ultimatum game.

Is the sense of fairness uniquely human? Human reactions to reward division are often studied by means of the ultimatum game, in which both partners need to agree on a distribution for both to receive rewards. Humans typically offer generous portions of the reward to their partner, a tendency our close primate relatives have thus far failed to show in experiments. Here we tested chimpanzees (Pan troglodytes) and human children on a modified ultimatum game. One individual chose between two tokens that, with their partner's cooperation, could be exchanged for rewards. One token offered equal rewards to both players, whereas the other token favored the chooser. Both apes and children responded like humans typically do. If their partner's cooperation was required, they split the rewards equally. However, with passive partners--a situation akin to the so-called dictator game--they preferred the selfish option. Thus, humans and chimpanzees show similar preferences regarding reward division, suggesting a long evolutionary history to the human sense of fairness.

Extending serum half-life of albumin by engineering neonatal Fc receptor (FcRn) binding.

A major challenge for the therapeutic use of many peptides and proteins is their short circulatory half-life. Albumin has an extended serum half-life of 3 weeks because of its size and FcRn-mediated recycling that prevents intracellular degradation, properties shared with IgG antibodies. Engineering the strictly pH-dependent IgG-FcRn interaction is known to extend IgG half-life. However, this principle has not been extensively explored for albumin. We have engineered human albumin by introducing single point mutations in the C-terminal end that generated a panel of variants with greatly improved affinities for FcRn. One variant (K573P) with 12-fold improved affinity showed extended serum half-life in normal mice, mice transgenic for human FcRn, and cynomolgus monkeys. Importantly, favorable binding to FcRn was maintained when a single-chain fragment variable antibody was genetically fused to either the N- or the C-terminal end. The engineered albumin variants may be attractive for improving the serum half-life of biopharmaceuticals.

The effects of hydroxyurea and bone marrow transplant on Anti-Müllerian hormone (AMH) levels in females with sickle cell anemia.

Gonadal hypofunction is described in male and female patients with sickle cell anemia (SCA) after bone marrow transplant (BMT) and in males treated with hydroxyurea (HU). Anti-Müllerian hormone (AMH) is a serum marker of ovarian reserve. This study describes AMH and follicle-stimulating hormone (FSH) levels in female SCA subjects treated with supportive care (SCA-SC), HU (SCA-HU) and BMT (SCA-BMT). SCA (SS/Sß(0)) subjects not on HU, on HU and status-post BMT, ages 10-21 years were recruited. SCA-HU subjects were treated with HU ≥ 20 mg/kg for ≥ 12 consecutive months. SCA-BMT subjects had received busulfan and cyclophosphamide. Serum AMH and random FSH levels were obtained. Diminished ovarian reserve (DOR) was defined as AMH level <5th percentile for age-matched controls. Subjects also with FSH >40 IU/L were classified as having premature ovarian insufficiency (POI). 14 SCA-SC (14.5 ± 2.7 years), 33 SCA-HU (14.4 ± 2.4 years) and 9 SCA-BMT (14.3 ± 2.7 years) females were included. AMH was undetectable in all SCA-BMT subjects and <5th percentile in 24% of SCA-HU subjects. FSH was menopausal (>40 IU/L) in 88.9% of SCA-BMT subjects. All SCA-BMT subjects and 24% of subjects on HU had DOR; 89% of SCA-BMT subjects had POI. AMH and FSH may be useful tools in assessing ovarian reserve and function.

Social learning promotes understanding of the physical world: Preschool children's imitation of weight sorting.

We investigated whether social learning, specifically imitation, can advance preschoolers' understanding of weight. Preschoolers were randomly assigned to experimental and control groups. The experimental group saw an adult intentionally categorize an array of four visually identical objects based on weight. Then, children's weight-based sorting of the objects was evaluated. To test generalization, children were presented with novel objects (differing in shape, color, and weight from the original ones) and not shown what to do with them. Results indicate that 48-month-olds learned to sort by weight via observing the adult's demonstration of categorization and that children generalized weight sorting to novel objects. This shows that children imitate at a more abstract level than merely motor actions. They learn and imitate generalizable rules. 36-month-olds did not succeed on this weight sorting task. Children's cognitive development constrains what children learn through social observation and imitation.

Prospective memory in children and chimpanzees.

Prospective memory (PM) involves remembering to do something at a specific time in the future. Here, we investigate the beginnings of this ability in young children (3-year-olds; Homo sapiens) and chimpanzees (Pan troglodytes) using an analogous task. Subjects were given a choice between two toys (children) or two food items (chimpanzees). The selected item was delivered immediately, whereas the unselected item was hidden in an opaque container. After completing an ongoing quantity discrimination task, subjects could request the hidden item by asking for it (children) or by pointing to the container and identifying the item on a symbol board (chimpanzees). Children and chimpanzees showed evidence of prospective-like memory in this task, as evidenced by successful retrieval of the item at the end of the task, sometimes spontaneously with no prompting from the experimenter. These findings contribute to our understanding of PM from an ontogenetic and comparative perspective.

Gambling primates: reactions to a modified Iowa Gambling Task in humans, chimpanzees and capuchin monkeys.

Humans will, at times, act against their own economic self-interest, for example, in gambling situations. To explore the evolutionary roots of this behavior, we modified a traditional human gambling task, the Iowa Gambling Task (IGT), for use with chimpanzees, capuchin monkeys and humans. We expanded the traditional task to include two additional payoff structures to fully elucidate the ways in which these primate species respond to differing reward distributions versus overall quantities of rewards, a component often missing in the existing literature. We found that while all three species respond as typical humans do in the standard IGT payoff structure, species and individual differences emerge in our new payoff structures. Specifically, when variance avoidance and reward maximization conflicted, roughly equivalent numbers of apes maximized their rewards and avoided variance, indicating that the traditional payoff structure of the IGT is insufficient to disentangle these competing strategies. Capuchin monkeys showed little consistency in their choices. To determine whether this was a true species difference or an effect of task presentation, we replicated the experiment but increased the intertrial interval. In this case, several capuchin monkeys followed a reward maximization strategy, while chimpanzees retained the same strategy they had used previously. This suggests that individual differences in strategies for interacting with variance and reward maximization are present in apes, but not in capuchin monkeys. The primate gambling task presented here is a useful methodology for disentangling strategies of variance avoidance and reward maximization.

Child-directed action promotes 2-year-olds' imitation.

Children are voracious learners and adults are ubiquitous teachers. This project investigated whether the special infant-directed action modifications parents use when teaching their children (called "motionese" by Brand et al., Developmental Science, 2002, Vol. 5, pp. 72-83) improves 2-year-olds' imitation. Children saw an adult perform a series of acts on four novel objects using either an infant-directed style (including larger range of motion and enhanced boundary marking) or an adult-directed style. Children's imitation of the acts was higher in the infant-directed condition relative to the adult-directed condition, and both types of demonstration increased imitation relative to baseline (no demonstration). We propose that motionese provides information about actions, objects, and intentionality, thereby enhancing toddlers' observational learning.

How early do children understand gesture-speech combinations with iconic gestures?

Children understand gesture+speech combinations in which a deictic gesture adds new information to the accompanying speech by age 1;6 (Morford & Goldin-Meadow, 1992; 'push'+point at ball). This study explores how early children understand gesture+speech combinations in which an iconic gesture conveys additional information not found in the accompanying speech (e.g., 'read'+BOOK gesture). Our analysis of two- to four-year-old children's responses in a gesture+speech comprehension task showed that children grasp the meaning of iconic co-speech gestures by age three and continue to improve their understanding with age. Overall, our study highlights the important role gesture plays in language comprehension as children learn to unpack increasingly complex communications addressed to them at the early ages.

2012 Update on global prevention of folic acid-preventable spina bifida and anencephaly.

BACKGROUND: Folic acid was proven in 1991 to prevent most cases of spina bifida and anencephaly. In 2008, less than 10% of folic acid-preventable spina bifida and anencephaly (FAPSBA) was prevented through folic acid fortification programs. This study updates the global estimates of the proportion of FAPSBA prevented with various types of folic acid fortification as of 2012. METHODS: For each country, we estimated the annual birth prevalence of FAPSBA and the daily amount of folic acid consumed from mandatory folic acid fortification programs. Assuming in Model I (our original Bell and Oakley model) that it required 400 µg, and in Model II (a new model), 200 µg of folic acid daily for total prevention of FAPSBA, we estimated the percentage of FAPSBA being prevented in each country by fortification. RESULTS: Using the original model, we estimate that 15% of FAPSBA is being prevented in 2012, compared with 2006 (6.8%) and 2008 (9.1%). We estimate in our new model that 25% of FAPSBA is being prevented. CONCLUSION: We estimate an increasing prevention of FAPSBA in the world through folic acid fortification, yet the pace is slow. Our new model estimates that only 25% prevention and reminds us that there remains a lot of work to do in countries that do not implement mandatory fortification, which is key to achieving global and total prevention. If we are to prevent all FAPSBA, there is an urgent need to build the global political will to find sufficient resources to aid in this effort.