Strontium (87 Sr/86 Sr) isotope analysis of the Namu skeletal assemblage: A study of past human migration on Taumako, a Polynesian Outlier in the eastern Solomon Islands.

OBJECTIVES: This study aims to assess if inter-island mobility can be identified during the Namu period (ca. 1,510-1800 AD) using 87 Sr/86 Sr analysis of dental enamel for individuals from the Namu burial ground on Taumako Island in the eastern Solomon Island Chain. Historic evidence from this region suggests that females migrated between the Duff, Reef, and Santa Cruz islands for marriage purposes. We hypothesize that observable trends in migrational (87 Sr/86 Sr) and dietary (δ13 C and δ15 N) isotopes can reveal the relationship between demographic factors, social status, diet, and female mobility on Taumako. METHODS: This research analyzes enamel 87 Sr/86 Sr for 58 individuals in the Namu skeletal sample. The 87 Sr/86 Sr results were compared with published dietary isotope data (bone collagen and dentin δ13 C and δ15 N values) and type/number of grave goods to assess whether trends within the data may be related to sex, age, or burial wealth. RESULTS: The results show that females display significantly higher 87 Sr/86 Sr values compared to males. One young adult female displayed a 87 Sr/86 Sr value that was +2SD outside the mean for the sampled individuals. A linear mixed-effects model and principle components analysis of 87 Sr/86 Sr, δ13 C, and δ15 N values suggest that wealth, sex, and age-cohort membership have an observable influence on the isotopic variation for the Taumako population. CONCLUSION: We suggest that during the Namu period, Taumako was patrilocal and that some females migrated there from the nearby Santa Cruz and Reef islands. One female immigrated to Taumako from a geologically distinct region outside of the Duff, Reef, and Santa Cruz Island groups.

A mitochondrial genetic divergence proxy predicts the reproductive compatibility of mammalian hybrids.

Numerous pairs of evolutionarily divergent mammalian species have been shown to produce hybrid offspring. In some cases, F1 hybrids are able to produce F2s through matings with F1s. In other instances, the hybrids are only able to produce offspring themselves through backcrosses with a parent species owing to unisexual sterility (Haldane's Rule). Here, we explicitly tested whether genetic distance, computed from mitochondrial and nuclear genes, can be used as a proxy to predict the relative fertility of the hybrid offspring resulting from matings between species of terrestrial mammals. We assessed the proxy's predictive power using a well-characterized felid hybrid system, and applied it to modern and ancient hominins. Our results revealed a small overlap in mitochondrial genetic distance values that distinguish species pairs whose calculated distances fall within two categories: those whose hybrid offspring follow Haldane's Rule, and those whose hybrid F1 offspring can produce F2s. The strong correlation between genetic distance and hybrid fertility demonstrated here suggests that this proxy can be employed to predict whether the hybrid offspring of two mammalian species will follow Haldane's Rule.

Correction: Pharmacogenomic associations of adverse drug reactions in asthma: systematic review and research prioritization.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Pharmacogenomic associations of adverse drug reactions in asthma: systematic review and research prioritisation.

A systematic review of pharmacogenomic studies capturing adverse drug reactions (ADRs) related to asthma medications was undertaken, and a survey of Pharmacogenomics in Childhood Asthma (PiCA) consortia members was conducted. Studies were eligible if genetic polymorphisms were compared with suspected ADR(s) in a patient with asthma, as either a primary or secondary outcome. Five studies met the inclusion criteria. The ADRs and polymorphisms identified were change in lung function tests (rs1042713), adrenal suppression (rs591118), and decreased bone mineral density (rs6461639) and accretion (rs9896933, rs2074439). Two of these polymorphisms were replicated within the paper, but none had external replication. Priorities from PiCA consortia members (representing 15 institution in eight countries) for future studies were tachycardia (SABA/LABA), adrenal suppression/crisis and growth suppression (corticosteroids), sleep/behaviour disturbances (leukotriene receptor antagonists), and nausea and vomiting (theophylline). Future pharmacogenomic studies in asthma should collect relevant ADR data as well as markers of efficacy.

A multi-isotope, multi-tissue study of colonial origins and diet in New Zealand.

OBJECTIVES: Colonial period New Zealand was lauded as a land of plenty, where colonists could improve their station in life and secure a future for their families. Our understanding of colonial experience, however, is often shaped by historical records which communicate a state-sponsored version of history. This study aims to reconstruct the lives of settlers using isotopic evidence from the colonial skeletons themselves. MATERIALS AND METHODS: We use skeletal remains from recently excavated colonial sites in Otago (South Island, New Zealand) to illustrate the information that can be gleaned from the isotopic analysis of individuals. We use 87 Sr/86 Sr to identify European settlers, and δ13 C and δ15 N from collagen and hair keratin, as well as dental enamel carbonate δ13 C to trace dietary change over their life-courses. RESULTS: Strontium isotope analysis shows that all adults in our sample are non-local. Dietary isotopes show that while most individuals had relatively consistent childhood diet, one individual with more rural origins likely had seasonal use of resources during childhood. While some members of the population seem to have increased their meat intake in the new colony most do not have clear evidence for this. DISCUSSION: We show the diversity of human experience in first-generation New Zealanders both prior to emigration and in the new colony. Despite colonial propaganda claiming that circumstances in New Zealand were improved for all settlers, we have little evidence for this, aside from among individuals of potentially high status.

Let's talk about stress, baby! Infant-feeding practices and stress in the ancient Atacama desert, Northern Chile.

AIMS AND OBJECTIVES: The transition to an agricultural economy is often presumed to involve an increase in female fertility related to changes in weaning practice. In particular, the availability of staple crops as complementary foods is hypothesized to allow earlier weaning in agricultural populations. In this study, our primary aim is to explore whether this model fits the agricultural transition in the Atacama Desert using incremental isotopic analysis. A secondary aim of this study is to identify isotopic patterns relating to weaning, and assess how these may be differentiated from those relating to early life stress. MATERIALS AND METHODS: We use incremental isotopic analysis of dentine to examine changes in δ15 N and δ13 C values from infancy and childhood in sites of the Arica region (n = 30). We compare individuals from pre-agricultural and agricultural phases to establish isotopic patterns and relate these patterns to maternal diet, weaning trajectory and physiological stress. RESULTS: We find that there is no evidence for systematic temporal or geographic variation in incremental isotopic results. Instead, results from all time periods are highly variable, with weaning completed between 1.5 and 3.5 years. Characteristics of the incremental profiles indicate that both in utero and postnatal stress were a common part of the infant experience in the Atacama. DISCUSSION: In the Atacama Desert it appears that the arrival of agricultural crops did not result in uniform shifts in weaning behavior. Instead, infant and child diet seems to have been dictated by the broad-spectrum diets of the mothers, perhaps as a way of mitigating the stresses of the harsh desert environment.

Using isotopic evidence to assess the impact of migration and the two-layer hypothesis in prehistoric Northeast Thailand.

OBJECTIVES: The nature of the agricultural transition in Southeast Asia has been a topic of some debate for archaeologists over the past decades. A prominent model, known as the two-layer hypothesis, states that indigenous hunter-gatherers were subsumed by the expansion of exotic Neolithic farmers into the area around 2000 BC. These farmers had ultimate origins in East Asia and brought rice and millet agriculture. Ban Non Wat is one of the few archaeological sites in Southeast Asia where this model can potentially be tested. The site is located in the Mun River valley of Northeast Thailand, and divided into 12 phases that span over 2,000 years, from about 1750 BC to the end of the Iron Age (ca. 500 AD). These phases exhibit successive cultural changes, and current interpretation of the site is of an early hunter-gatherer population, with agriculturalists immigrating into the later phases. METHODS: We analyzed strontium, oxygen, and carbon isotopes in tooth enamel from over 150 individuals, dating from the Neolithic to Iron Age, to assess extrinsic origins and differences in diet between early and later phases. RESULTS: We find evidence of dietary and cultural differences between groups at Ban Non Wat during its early occupation, but little evidence for immigration from distinct environments beyond the Khorat Plateau of Northeast Thailand. CONCLUSIONS: The lack of consistent isotopic differences between early and later Neolithic occupants at Ban Non Wat means that the site does not conclusively support the two-layer hypothesis.

Comparing Walker's (2008) skull trait sex estimation standard to proteomic sex estimation for a group of South Asian individuals.

This research assesses the potential for misidentification of sex in individuals of South Asian ancestry using the Walker (2008) morphological skull sex estimation standard [1]. Chromosomal sex was assessed using proteomic analysis targeting sex chromosome-specific amylogenic peptides. Results showed that the Walker method produced incorrect classification for 36.7 % of individuals. Overwhelmingly, those incorrectly assigned were chromosomally male. Misidentification was due to males within the group having lower trait scores (i.e., more gracile traits) than the standard would predict. There was also a high level of overlap in trait scores between male and females indicating reduced expression of sexual dimorphism. The use of established multivariate statistical techniques improved accuracy of sex estimation in some cases, but larger osteological data sets from South Asian individuals are required to develop population-specific standards. We suggest that peptide analysis may provide a useful tool for the forensic anthropologist when assessing sex in populations without population specific osteological standards.

Multispecies bacterial invasion of human host cells.

Urinary tract infection (UTI), one of the most common bacterial infections worldwide, is a typical example of an infection that is often polymicrobial in nature. While the overall infection course is known on a macroscale, bacterial behavior is not fully understood at the cellular level and bacterial pathophysiology during multispecies infection is not well characterized. Here, using clinically relevant bacteria, human epithelial bladder cells and human urine, we establish co-infection models combined with high resolution imaging to compare single- and multi-species bladder cell invasion events in three common uropathogens: uropathogenic Escherichia coli (UPEC), Klebsiella pneumoniae and Enterococcus faecalis. While all three species invaded the bladder cells, under flow conditions the Gram-positive E. faecalis was significantly less invasive compared to the Gram-negative UPEC and K. pneumoniae. When introduced simultaneously during an infection experiment, all three bacterial species sometimes invaded the same bladder cell, at differing frequencies suggesting complex interactions between bacterial species and bladder cells. Inside host cells, we observed encasement of E. faecalis colonies specifically by UPEC. During subsequent dispersal from the host cells, only the Gram-negative bacteria underwent infection-related filamentation (IRF). Taken together, our data suggest that bacterial multispecies invasions of single bladder cells are frequent and support earlier studies showing intraspecies cooperation on a biochemical level during UTI.

A Comparison of Sound Production Treatment and Metrical Pacing Therapy for Apraxia of Speech: A Single-Case Experimental Design.

PURPOSE: The purpose of this investigation was to compare the effects of two specific treatment protocols for acquired apraxia of speech (AOS): Sound Production Treatment (SPT) and Metrical Pacing Therapy (MPT), and to examine changes in communicative participation. METHOD: Four speakers with chronic AOS and aphasia were each administered SPT and MPT in a replicated crossover design (ABACA/ACABA) with nonconcurrent multiple baselines across participants and behaviors. Treatment outcomes were compared with respect to whole word correctness (WWC) for treated and untreated multisyllabic word targets. Speech intelligibility was assessed using the Chapel Hill Multilingual Intelligibility Test, and communicative participation was measured using the Communicative Participation Item Bank at baseline, washout, and follow-up phases. RESULTS: Three of the four participants experienced statistically significant improvements in WWC with SPT, and three of the four participants with MPT. Based on a priori criteria, three participants demonstrated relatively greater benefit from SPT and one participant demonstrated relatively greater benefit from MPT. There were measurable improvements in intelligibility following SPT for three of the four participants. Only one participant in this investigation reported a significant change in communicative participation, and only following MPT. CONCLUSIONS: This study demonstrated that individuals in the chronic stages of AOS can benefit from both SPT and MPT, corroborating prior research on articulatory kinematic and rate and/or rhythm control treatment approaches. It contributes a comparison of two protocols for AOS with respect to whole word targets, intelligibility, and individual self-report of communicative participation changes. More participants showed a relative advantage of SPT over MPT. One individual reported communicative participation improvement after MPT. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.23971929.

For children admitted to hospital, what interventions improve medication safety on ward rounds? A systematic review.

OBJECTIVE: Every year, medication errors harm children in hospitals. Ward rounds are a unique opportunity to bring information together and plan management. There is a need to understand what strategies can improve medication safety on ward rounds. We systematically reviewed published interventions to improve prescribing and safety of medicines on ward rounds. DESIGN: Systematic review of randomised controlled trials and observational studies. SETTING: Studies examining inpatient ward rounds. PATIENTS: Children and young people aged between 0 and 18 years old. INTERVENTIONS: Any intervention or combination of interventions implemented that alters how paediatric ward rounds review inpatient medications. MAIN OUTCOME MEASURE: Primary outcome was improvement in medication safety on paediatric ward rounds. This included reduction in prescribing error rates, healthcare professionals' opinions on prescribing and improvement in documentation on ward rounds. RESULTS: Three studies were eligible for review. One examined the use of an acrostic, one the use of a checklist, and the other a use of a specific prescribing ward round involving a clinical pharmacist and doctor. None of the papers considered weight-based errors or demonstrated reductions in clinical harm. Reductions in prescribing errors were noted by the different interventions. CONCLUSIONS: There are limited data on interventions to improve medication safety in paediatric ward rounds, with all published data being small scale, either quality improvement or audits, and locally derived/delivered. Good-quality interventional or robust quality improvement studies are required to improve medication safety on ward rounds. PROSPERO REGISTRATION NUMBER: CRD42022340201.

Impact of indoor environment on children's pulmonary health.

INTRODUCTION: A child's living environment has a significant impact on their respiratory health, with exposure to poor indoor air quality (IAQ) contributing to potentially lifelong respiratory morbidity. These effects occur throughout childhood, from the antenatal period through to adolescence. Children are particularly susceptible to the effects of environmental insults, and children living in socioeconomic deprivation globally are more likely to breathe air both indoors and outdoors, which poses an acute and long-term risk to their health. Adult respiratory health is, at least in part, determined by exposures and respiratory system development in childhood, starting in utero. AREAS COVERED: This narrative review will discuss, from a global perspective, what contributes to poor IAQ in the child's home and school environment and the impact that indoor air pollution exposure has on respiratory health throughout the different stages of childhood. EXPERT OPINION: All children have the right to a living and educational environment without the threat of pollution affecting their health. Action is needed at multiple levels to address this pressing issue to improve lifelong respiratory health. Such action should incorporate a child's rights-based approach, empowering children, and their families, to have access to clean air to breathe in their living environment.

Somatic mutations in facial skin from countries of contrasting skin cancer risk.

The incidence of keratinocyte cancer (basal cell and squamous cell carcinomas of the skin) is 17-fold lower in Singapore than the UK1-3, despite Singapore receiving 2-3 times more ultraviolet (UV) radiation4,5. Aging skin contains somatic mutant clones from which such cancers develop6,7. We hypothesized that differences in keratinocyte cancer incidence may be reflected in the normal skin mutational landscape. Here we show that, compared to Singapore, aging facial skin from populations in the UK has a fourfold greater mutational burden, a predominant UV mutational signature, increased copy number aberrations and increased mutant TP53 selection. These features are shared by keratinocyte cancers from high-incidence and low-incidence populations8-13. In Singaporean skin, most mutations result from cell-intrinsic processes; mutant NOTCH1 and NOTCH2 are more strongly selected than in the UK. Aging skin in a high-incidence country has multiple features convergent with cancer that are not found in a low-risk country. These differences may reflect germline variation in UV-protective genes.

Validation of colorectal cancer surgery data from administrative data sources.

BACKGROUND: Surgery is the primary treatment for colorectal cancer for both curative and palliative intent. Availability of high quality surgery data is essential for assessing many aspects of the quality of colorectal cancer care. The objective of this study was to determine the quality of different administrative data sources in identifying surgery for colorectal cancer with respect to completeness and accuracy. METHODS: All residents in Alberta, Canada who were diagnosed with invasive colorectal cancer in years 2000-2005 were identified from the Alberta Cancer Registry and included in the study. Surgery data for these patients were obtained from the Cancer Registry (which collects the date of surgery for which the primary tumor was removed) and compared to surgery data obtained from two different administrative data sources: Physician Billing and Hospital Inpatient data. Sensitivity, specificity, positive predictive value, negative predictive value and observed agreement were calculated compared to the Cancer Registry data. RESULTS: The Physician Billing data alone or combined with Hospital Inpatient data demonstrated equally high sensitivity (97% for both) and observed agreement with the Cancer Registry data (93% for both) for identifying surgeries. The Hospital Inpatient data, however, had the highest specificity (80%). The positive predictive value varied by disease stage and across data sources for stage IV (99% for stages I-III and 83-89% for stage IV), the specificity is better for colon cancer surgeries (72-85%) than for rectal cancer surgeries (60-73%); validation measures did not vary over time. CONCLUSION: Physician Billing data identify the colorectal cancer surgery more completely than Hospital Inpatient data although both sources have a high level of completeness.

Deprescribing montelukast in children with asthma: a systematic review.

BACKGROUND: National and international asthma guidelines recommend adjusting asthma treatment based on levels of control, yet no guidance is given regarding the stepping-down of montelukast in children and young people (CYP). OBJECTIVE: To systematically review evidence regarding deprescribing montelukast in CYP with established asthma. DESIGN: Systematic review. DATA SOURCES: Embase, Medline, PubMed and CINAHL were searched up to October 2020. STUDY SELECTION: Eligible studies contained patients aged 0-18 years with a diagnosis of asthma, who had been administering montelukast before it was withdrawn. All reasons for withdrawal were included. RESULTS: The search identified 197 papers. After deduplication, five papers were included (three randomised control studies and two cohort studies). Four studies observed the impact of montelukast withdrawal for 2 weeks, and one study for 8 weeks. The impact of withdrawal was measured in the studies using a combination of lung tests (eg, forced expiratory volume in 1 s (FEV1), fractional exhaled nitric oxide (FeNO)), asthma scoring methods and exercise challenges. Of the 17 domains in the Core Outcome Set for Clinical Trials in Childhood Asthma, eight outcomes were measured in at least one of the five studies, with all five studies measuring the outcome of 'Lung Function'. No significant differences were found between the montelukast and placebo groups following montelukast withdrawal. Significant differences between the comparator points within the test group were found in nine outcomes across four studies; FEV1/forced vital capacity, FEV1, forced expiratory flows (25%-75%), asthma score (study specific), maximum % fall in FEV1 and time to recovery (post exercise) significantly decreased whereas FEV1/bronchodilator response, FeNO and eNO significantly increased. CONCLUSION: Only limited, contradictory and short-term effects of deprescribing montelukast in CYP with established asthma are presented in literature. Definitive studies determining clinical stability, and impact of deprescribing montelukast in CYP are imperative to improve the safety of asthma treatment in CYP. PROSPERO REGISTRATION NUMBER: CRD42020213971.

Pharmacogenomics and asthma treatment: acceptability to children, families and healthcare professionals.

BACKGROUND: Evidence supporting personalised treatment for asthma based on an individual's genetics is mounting. The views of children and young people (CYP), parents and healthcare professionals (HCPs) about this evolution of clinical care are not known. METHODS: A pilot prospective questionnaire-based study was undertaken of CYP with asthma, their parents and HCPs at a secondary/tertiary children's hospital in the UK. RESULTS: Fifty-nine questionnaires were distributed and 50 returned (response rate 84.7%), comprising 26 CYP (10 were 5-11 years, 11 were 12-15 years and 5 were 16-18 years old), 13 parents and 11 HCPs. For all types of data, personal information was ranked as the 'most important' (n=19, 47.5%) and 'most private' (n=16, 40%), but with considerable variation across groups. Within health data, allergies were rated as 'most important' (n=12, 30.8%), and mental health records the 'most private' (n=21, 53.8%), again with variation across groups. A 'personalised genetic asthma plan' was acceptable to the majority overall (n=40, 80.0%). With regard to sharing CYP's genetic data, 23 (46%) of participants were happy for unconditional sharing between HCPs, and 23 (46%) agreed to sharing solely in relation to the CYP's asthma management. Forty-two (84.0%) of participants felt CYP should be informed about genetic data being shared, and the majority felt this should commence by 12 years of age. CONCLUSION: The use of genetic information to guide management of asthma in CYP is largely acceptable to CYP, parents/guardians and HCPs. However, there are key differences between the opinions of CYP, parents and HCPs.