The impact of clinical genome sequencing in a global population with suspected rare genetic disease.

There is mounting evidence of the value of clinical genome sequencing (cGS) in individuals with suspected rare genetic disease (RGD), but cGS performance and impact on clinical care in a diverse population drawn from both high-income countries (HICs) and low- and middle-income countries (LMICs) has not been investigated. The iHope program, a philanthropic cGS initiative, established a network of 24 clinical sites in eight countries through which it provided cGS to individuals with signs or symptoms of an RGD and constrained access to molecular testing. A total of 1,004 individuals (median age, 6.5 years; 53.5% male) with diverse ancestral backgrounds (51.8% non-majority European) were assessed from June 2016 to September 2021. The diagnostic yield of cGS was 41.4% (416/1,004), with individuals from LMIC sites 1.7 times more likely to receive a positive test result compared to HIC sites (LMIC 56.5% [195/345] vs. HIC 33.5% [221/659], OR 2.6, 95% CI 1.9-3.4, p < 0.0001). A change in diagnostic evaluation occurred in 76.9% (514/668) of individuals. Change of management, inclusive of specialty referrals, imaging and testing, therapeutic interventions, and palliative care, was reported in 41.4% (285/694) of individuals, which increased to 69.2% (480/694) when genetic counseling and avoidance of additional testing were also included. Individuals from LMIC sites were as likely as their HIC counterparts to experience a change in diagnostic evaluation (OR 6.1, 95% CI 1.1-∞, p = 0.05) and change of management (OR 0.9, 95% CI 0.5-1.3, p = 0.49). Increased access to genomic testing may support diagnostic equity and the reduction of global health care disparities.

Reduced fire severity offers near-term buffer to climate-driven declines in conifer resilience across the western United States.

Increasing fire severity and warmer, drier postfire conditions are making forests in the western United States (West) vulnerable to ecological transformation. Yet, the relative importance of and interactions between these drivers of forest change remain unresolved, particularly over upcoming decades. Here, we assess how the interactive impacts of changing climate and wildfire activity influenced conifer regeneration after 334 wildfires, using a dataset of postfire conifer regeneration from 10,230 field plots. Our findings highlight declining regeneration capacity across the West over the past four decades for the eight dominant conifer species studied. Postfire regeneration is sensitive to high-severity fire, which limits seed availability, and postfire climate, which influences seedling establishment. In the near-term, projected differences in recruitment probability between low- and high-severity fire scenarios were larger than projected climate change impacts for most species, suggesting that reductions in fire severity, and resultant impacts on seed availability, could partially offset expected climate-driven declines in postfire regeneration. Across 40 to 42% of the study area, we project postfire conifer regeneration to be likely following low-severity but not high-severity fire under future climate scenarios (2031 to 2050). However, increasingly warm, dry climate conditions are projected to eventually outweigh the influence of fire severity and seed availability. The percent of the study area considered unlikely to experience conifer regeneration, regardless of fire severity, increased from 5% in 1981 to 2000 to 26 to 31% by mid-century, highlighting a limited time window over which management actions that reduce fire severity may effectively support postfire conifer regeneration.

A rural doctor's telehealth training program during the COVID-19 pandemic.

INTRODUCTION: In Australia, remote consultations have been used as an adjunct to traditional healthcare delivery during the COVID-19 pandemic using telephone and video techniques with an increase in the use of telephone consultations, and to a lesser extent video consultations, for management of patient conditions, assessment, treatment, monitoring and diagnosis. METHODS: To establish the needs of rural doctors for training in the provision of remote consultations, an online survey of members of the Australian College of Rural and Remote Medicine was undertaken. Subsequently an online scenario-based training program was designed to improve the competencies of members in providing these consultations. The outcomes of this program were analysed using pre- and post-intervention surveys, and qualitative analysis of session recordings. RESULTS: The program improved trainee confidence and competence in providing safe, quality remote consultations, particularly when using video technologies. Competencies in communication, history taking, physical online examination, clinical management and professionalism improved. Trainees adapted their practice because they were then able to manage potential issues, were more aware of the capabilities of telehealth technologies and could assist a health professional, such as a nurse or Aboriginal Health Worker (with the patient) to do an examination. Concerns remained about set-up time, technical quality, privacy, interaction with and examination of patients, and how to assess the severity of conditions. CONCLUSION: The outcomes of the program showed significant improvement in the levels of confidence and competencies required for providing remote consultations using telehealth services. A need remains to improve virtual interactions with patients, and to acquire better technology and financial support for remote consultations. In an environment where government is asking whether remote consultations are appropriate and clinically effective, these findings provide guidance from a professional group of experienced rural practitioners.

Heterozygous gain of function variants in a critical region of RNF13 cause congenital microcephaly, epileptic encephalopathy, blindness, and failure to thrive.

Missense variants in the RNF13 gene have been previously known to cause congenital microcephaly, epileptic encephalopathy, blindness, and failure to thrive through a gain-of-function disease mechanism. Here, we identify a nonsense variant, expected to result in protein truncation, in a similarly affected patient. We show that this nonsense variant, residing in the terminal exon, is likely to escape nonsense-mediated decay while removing a critical region for protein function, thus resulting in a gain-of-function effect. We review the literature and disease databases and identify several other affected individuals with overlapping phenotypes carrying distinct truncating variants in the terminal exon upstream of the putative critical region. Furthermore, we analyze truncating variants from the general population, namely, the Genome Aggregation Database (gnomAD), and provide additional evidence supporting our hypothesis, and ruling out haploinsufficiency as an alternative disease mechanism. In summary, our case report, literature review, and analysis of disease and population databases strongly support the hypothesis that heterozygous gain-of-function variants in a critical region of RNF13 cause congenital microcephaly, epileptic encephalopathy, blindness, and failure to thrive.

Which environmental sample type and statistical approach provides most information about metal exposure in young children from an urban setting?

Identification of sources and pathways is critical in minimizing exposure of young children to toxic materials. We monitored 108 children <5 years old 6-monthly for up to 5 years in a major urban setting. Samples (ñ7000) included interior handwipes (W1) and after exterior playing (W2), interior house dust (PD1) and day care dust (PD2) using petri dishes, exterior dust-fall accumulation, exterior dust sweepings, garden soil, blood and urine. Here we describe multi-element results to determine which sampling method and analysis of the data provide the most reliable indicators of metal exposure to young children. Samples were analysed by ICPMS for Ca, Cd, Cr, Cu, Fe, Mg, Mn, Ni, Pb, Ti, V and Zn. Pearson Correlations showed the highest number of significant correlations are for: W1 and W2, dust sweepings and soil. Mixed model analyses (MMA) for the blood levels as the dependent variable and environmental predictor variables showed the most consistent results were for W1, PD1 and sweepings. MMA to investigate the association between each metal (e.g. Ca) and the other 11 metals showed the largest numbers of significant relationships are for W1 and sweepings. Cluster analyses showed that the 'best' clusters in W1 and W2 are for Fe-Zn-Mg and Mn-Pb-Ni. For PD1 and PD2 the 'best' clusters were Fe-Zn-Mg, Cr-Ni-Ti, and Cu-Mn-Pb. Clusters for dust sweepings and soil are generally similar. Principal component analysis (PCA) loadings for W1 and PD1 accounted for >50% of the variance. Metals comprising loading 1 component for both sample types included Ca, Fe, Mg, and Mn. Overall cluster analyses provided more information than PCA loadings. In summary: The most suitable methods and analyses are MMA of W1 and sweepings, and cluster analyses of W1and PD1. Resuspension from outdoor surfaces and soils and deposition in the residences is a likely pathway for most metals.

Jet stream dynamics, hydroclimate, and fire in California from 1600 CE to present.

Moisture delivery in California is largely regulated by the strength and position of the North Pacific jet stream (NPJ), winter high-altitude winds that influence regional hydroclimate and forest fire during the following warm season. We use climate model simulations and paleoclimate data to reconstruct winter NPJ characteristics back to 1571 CE to identify the influence of NPJ behavior on moisture and forest fire extremes in California before and during the more recent period of fire suppression. Maximum zonal NPJ velocity is lower and northward shifted and has a larger latitudinal spread during presuppression dry and high-fire extremes. Conversely, maximum zonal NPJ is higher and southward shifted, with narrower latitudinal spread during wet and low-fire extremes. These NPJ, precipitation, and fire associations hold across pre-20th-century socioecological fire regimes, including Native American burning, postcontact disruption and native population decline, and intensification of forest use during the later 19th century. Precipitation extremes and NPJ behavior remain linked in the 20th and 21st centuries, but fire extremes become uncoupled due to fire suppression after 1900. Simulated future conditions in California include more wet-season moisture as rain (and less as snow), a longer fire season, and higher temperatures, leading to drier fire-season conditions independent of 21st-century precipitation changes. Assuming continuation of current fire management practices, thermodynamic warming is expected to override the dynamical influence of the NPJ on climate-fire relationships controlling fire extremes in California. Recent widespread fires in California in association with wet extremes may be early evidence of this change.

Changes in fire behavior caused by fire exclusion and fuel build-up vary with topography in California montane forests, USA.

Wildfire sizes and proportions burned with high severity effects are increasing in seasonally dry forests, especially in the western USA. A critical need in efforts to restore or maintain these forest ecosystems is to determine where fuel build-up caused by fire exclusion reaches thresholds that compromise resilience to fire. Empirical studies identifying drivers of fire severity patterns in actual wildfires can be confounded by co-variation of vegetation and topography and the stochastic effects of weather and rarely consider long-term changes in fuel caused by fire exclusion. To overcome these limitations, we used a spatially explicit fire model (FlamMap) to compare potential fire behavior by topographic position in Lassen Volcanic National Park (LAVO), California, a large (43,000 ha), mountainous, unlogged landscape with extensive historical and contemporary fuels data. Fuel loads were uniformly distributed and incrementally increased across the landscape, meaning variation in fire behavior within each simulation was due to topography and among simulations, to fuels. We analyzed changes in fire line intensity (FLI) and crown fire potential as surface and canopy fuels increased from historical to contemporary levels and with percentile and actual wildfire weather conditions. Sensitivity to the influence of fuel build-up on fire behavior varied by topographic position. Steep slopes and ridges were most sensitive. At lower surface fuel loads, under pre-exclusion and contemporary canopy conditions, fire behavior was comparable and remained surface-type. As fuels increased, FLI and passive crown fire increased on steep slopes and ridgetops but remained largely unchanged on gentle slopes. Topographic variability in fire behavior was greatest with intermediate fuels. At higher surface fuel loads, under contemporary canopy fuels, passive crown fire dominated all topographic positions. With LAVO's current surface fuels, the area with potential for passive crown fire during actual fire weather increased from 6% pre-exclusion to 34% due to canopy fuel build-up. For topographically diverse landscapes, the results highlight where contemporary fire characteristics are most likely to deviate from historical patterns and may help managers prioritize locations for prescribed burning and managed wildfire to increase fire resilience in fuel rich landscapes.

Public and manager perceptions about prescribed fire in the Mid-Atlantic, United States.

Firescapes of the Mid-Atlantic are understudied compared to other ecosystems in the United States, and little is known about the acceptance of prescribed fire as a forest management tool. Yet, this region harbors high levels of wildland-urban interface (WUI), has a close intermingling of land ownerships, and reflects substantial regional heterogeneity in burning histories and fire hazards. As prescribed fire is increasingly applied in the Mid-Atlantic as a critical tool to meet various land management objectives, research is needed to help managers understand community perceptions of prescribed fire implementation. Through intercept surveys of forest recreationists and online surveys of fire managers, this study investigates perceptions about prescribed fire use in the Mid-Atlantic, in addition to the critical contributing factors of public support toward prescribed fires. Two states, Pennsylvania and New Jersey, were selected as case studies to explore regional differences in social perception due to their contrasts in fire history, policy, management objectives, and social exposure. Our results show moderate social awareness of local prescribed fires, moderate to high familiarity with prescribed burning, high agency trust, and strong community support toward prescribed fires. However, the perceived concerns and benefits differed between managers and forest recreationists and between recreationists from Pennsylvania and New Jersey. The factors influencing the support of prescribed burning practices included forest management beliefs, concern about prescribed fire effects, familiarity with prescribed fires as a forest management tool, and awareness of local prescribed fires. Collectively, these results highlighted needs in public outreach to strengthen education, build broader community awareness, engage critical stakeholder groups such as forest recreationists, and re-align public outreach messages based on community-level concerns and perceived benefits. Additionally, it will be vital for the scientific community to help monitor critical shifts in forest value orientations and fill in significant research gaps regarding prescribed fire benefits.

Precipitation alters the CO2 effect on water-use efficiency of temperate forests.

Increasing water-use efficiency (WUE), the ratio of carbon gain to water loss, is a key mechanism that enhances carbon uptake by terrestrial vegetation under rising atmospheric CO2 (ca ). Existing theory and empirical evidence suggest a proportional WUE increase in response to rising ca as plants maintain a relatively constant ratio between the leaf intercellular (ci ) and ambient (ca ) partial CO2 pressure (ci /ca ). This has been hypothesized as the main driver of the strengthening of the terrestrial carbon sink over the recent decades. However, proportionality may not characterize CO2 effects on WUE on longer time-scales and the role of climate in modulating these effects is uncertain. Here, we evaluate long-term WUE responses to ca and climate from 1901 to 2012 CE by reconstructing intrinsic WUE (iWUE, the ratio of photosynthesis to stomatal conductance) using carbon isotopes in tree rings across temperate forests in the northeastern USA. We show that iWUE increased steadily from 1901 to 1975 CE but remained constant thereafter despite continuously rising ca . This finding is consistent with a passive physiological response to ca and coincides with a shift to significantly wetter conditions across the region. Tree physiology was driven by summer moisture at multi-decadal time-scales and did not maintain a constant ci /ca in response to rising ca indicating that a point was reached where rising CO2 had a diminishing effect on tree iWUE. Our results challenge the mechanism, magnitude, and persistence of CO2 's effect on iWUE with significant implications for projections of terrestrial productivity under a changing climate.

Genetic diagnoses in epilepsy: The impact of dynamic exome analysis in a pediatric cohort.

OBJECTIVE: We evaluated the yield of systematic analysis and/or reanalysis of whole exome sequencing (WES) data from a cohort of well-phenotyped pediatric patients with epilepsy and suspected but previously undetermined genetic etiology. METHODS: We identified and phenotyped 125 participants with pediatric epilepsy. Etiology was unexplained at the time of enrollment despite clinical testing, which included chromosomal microarray (57 patients), epilepsy gene panel (n = 48), both (n = 28), or WES (n = 8). Clinical epilepsy diagnoses included developmental and epileptic encephalopathy (DEE), febrile infection-related epilepsy syndrome, Rasmussen encephalitis, and other focal and generalized epilepsies. We analyzed WES data and compared the yield in participants with and without prior clinical genetic testing. RESULTS: Overall, we identified pathogenic or likely pathogenic variants in 40% (50/125) of our study participants. Nine patients with DEE had genetic variants in recently published genes that had not been recognized as epilepsy-related at the time of clinical testing (FGF12, GABBR1, GABBR2, ITPA, KAT6A, PTPN23, RHOBTB2, SATB2), and eight patients had genetic variants in candidate epilepsy genes (CAMTA1, FAT3, GABRA6, HUWE1, PTCHD1). Ninety participants had concomitant or subsequent clinical genetic testing, which was ultimately explanatory for 26% (23/90). Of the 67 participants whose molecular diagnoses were "unsolved" through clinical genetic testing, we identified pathogenic or likely pathogenic variants in 17 (25%). SIGNIFICANCE: Our data argue for early consideration of WES with iterative reanalysis for patients with epilepsy, particularly those with DEE or epilepsy with intellectual disability. Rigorous analysis of WES data of well-phenotyped patients with epilepsy leads to a broader understanding of gene-specific phenotypic spectra as well as candidate disease gene identification. We illustrate the dynamic nature of genetic diagnosis over time, with analysis and in some cases reanalysis of exome data leading to the identification of disease-associated variants among participants with previously nondiagnostic results from a variety of clinical testing strategies.

Dietary zinc, calcium and nickel are associated with lower childhood blood lead levels.

The potential mitigation of elevated blood lead (PbB) levels with nutrient intake remains debatable. A comprehensive review by Kordas (2017) concluded that careful examination of the links between nutrition (nutritional status, nutrients, diet) and lead (Pb) exposure revealed limited and tenuous evidence. We have measured 20 elements including calcium (Ca), chromium (Cr), copper (Cu), iron (Fe), magnesium (Mg), manganese (Mn), nickel (Ni), zinc (Zn), and Pb from 6-day duplicate diets of 108 young children over a 5-year period and expressed these as intakes per body weight. Bivariate analyses showed a weak positive association between the Pb content in the diets of the participants and the level of Pb in their blood, as might be expected. Weak, but negative, associations occurred between the other elements in the diet and PbB. The associations for Ca, Mg, Ni and Zn were statistically significant for both subject-based (between subjects) and within-subject effects: that is, as the levels of elements in diet increased, the PbB level decreased. The largest percentage of variance of PbB in the context of the bivariate model accounted for was 4.23% for Zn, followed by Ca (3.91%) and Fe (2.20%). Supplementary analyses indicated that the between- and within-subject effects did not vary with the age at which participants entered the study, or with the levels of elements at their first measurement. A multivariable analysis using Weighted Quantile Sum Regressions showed that a weighted composite comprised of all the dietary elements had a significant association with PbB when adjusted for Pb in the diet and other covariates and also when adjusted for Pb in house dust; the latter was found to have the strongest association with PbB in earlier analyses. The highest weights were for Ca (0.29), Ni (0.27) and Zn (0.22); these results are generally consistent with those from the mixed model analyses.

Socioecological transitions trigger fire regime shifts and modulate fire-climate interactions in the Sierra Nevada, USA, 1600-2015 CE.

Large wildfires in California cause significant socioecological impacts, and half of the federal funds for fire suppression are spent each year in California. Future fire activity is projected to increase with climate change, but predictions are uncertain because humans can modulate or even override climatic effects on fire activity. Here we test the hypothesis that changes in socioecological systems from the Native American to the current period drove shifts in fire activity and modulated fire-climate relationships in the Sierra Nevada. We developed a 415-y record (1600-2015 CE) of fire activity by merging a tree-ring-based record of Sierra Nevada fire history with a 20th-century record based on annual area burned. Large shifts in the fire record corresponded with socioecological change, and not climate change, and socioecological conditions amplified and buffered fire response to climate. Fire activity was highest and fire-climate relationships were strongest after Native American depopulation-following mission establishment (ca. 1775 CE)-reduced the self-limiting effect of Native American burns on fire spread. With the Gold Rush and Euro-American settlement (ca. 1865 CE), fire activity declined, and the strong multidecadal relationship between temperature and fire decayed and then disappeared after implementation of fire suppression (ca. 1904 CE). The amplification and buffering of fire-climate relationships by humans underscores the need for parameterizing thresholds of human- vs. climate-driven fire activity to improve the skill and value of fire-climate models for addressing the increasing fire risk in California.

Collaboration Between Medical Professionals: Special Interest Groups in the Brazilian Telemedicine University Network (RUTE).

Background and Introduction: In Brazil, the Telemedicine University Network (RUTE) initiative promotes collaboration between university hospitals, teaching hospitals, health professionals, and students using information and communication technology infrastructure to support special interest groups (SIGs) in health care. Health professionals in institutions belonging to RUTE plan a program of video conferences and/or web conferences to discuss specific themes. This article presents the results of an analysis of collaboration in these SIGs. Materials and Methods: This study uses descriptive statistical analysis and visualization of data contained in management reports provided by RUTE national coordinators for the period between 2007 and 2016 to evaluate the extent of participation in SIGs between institutions associated with RUTE. In this data visualization, we employ concepts from social network theory. Results: The analysis identified the most influential institutions as measured by social network theory metrics. A small number of institutions were found to have many participating SIGs, but most had only a few participating institutions (more than 130 institutions have only one participating SIG). Over the study period, a significant quantitative growth in collaboration occurred, increasing from 21 institutions and 92 participating SIGs in 2007 to 380 institutions and 1,912 participating SIGs in 2016. Conclusion: The growth in collaboration within the network indicates increasing interest and participation in telehealth initiatives in Brazil.

Lead exposure in young children over a 5-year period from urban environments using alternative exposure measures with the US EPA IEUBK model - A trial.

The US Environmental Protection Agency (EPA) Integrated Exposure Uptake Biokinetic (IEUBK) model has been widely used to predict blood lead (PbB) levels in children especially around industrial sites. Exposure variables have strongly focussed on the major contribution of lead (Pb) in soil and interior dust to total intake and, in many studies, site-specific data for air, water, diet and measured PbB were not available. We have applied the IEUBK model to a comprehensive data set, including measured PbB, for 108 children monitored over a 5-year period in Sydney, New South Wales, Australia. To use this data set, we have substituted available data (with or without modification) for standard inputs as needed. For example, as an alternative measure for soil Pb concentration (µg/g), we have substituted exterior dust sweepings Pb concentration (µg/g). As alternative measures for interior dust Pb concentration (µg/g) we have used 1) 30-day cumulative petri dish deposition data (PDD) (as µg Pb/m2/30days), or 2) hand wipe data (as µg Pb/hand). For comparison, simulations were also undertaken with estimates of dust Pb concentration derived from a prior regression of dust Pb concentration (µg/g) on dust Pb loading (µg/ft2) as concentration is the unit specified for the Model. Simulations for each subject using observed data aggregated over the 5-year interval of the study, the most usual application of the IEUBK model, showed using Wilcoxon tests that there was a significant difference between the observed values and the values predicted by the Model containing soil with hand wipes (p < 0.001), and soil and PDD (p = 0.026) but not those for the other two sets of predictors, based on sweepings and PDD or sweepings and wipes. Overall, simulations of the Model using alternative exposure measures of petri dish dust (and possibly hand wipes) instead of vacuum cleaner dust and dust sweepings instead of soil provide predicted PbB which are generally consistent with each other and observed values. The predicted geometric mean PbBs were 2.17 ( ± 1.24) µg/dL for soil with PDD, 1.95 ( ± 1.17) µg/dL for soil with hand wipes, 2.36 ( ± 1.75) µg/dL for sweepings with PDD, and 2.15 ( ± 1.69) for sweepings with hand wipes. These results are in good agreement with the observed geometric mean PbB of 2.46 ( ± 0.99) µg/dL. In contrast to all other IEUBK model studies to our knowledge, we have stratified the data over the age ranges from 1 to 5 years. The median of the predicted values was lower than that for the observed values for every combination of age and set of measures; in some cases, the difference was statistically significant. The differences between observed and predicted PbB tended to be greatest for the soil plus wipes measure and for the oldest age group. Use of 'default dust' values calculated from the site-specific soil values, a common application of the IEUBK model, results in predicted PbB about 22% (range 0 to 52%) higher than those from soil with PDD data sets. Geometric mean contributions estimated from the Model to total Pb intake for a child aged 1-2 years was 0.09% for air, 42% for diet, 5.3% for water and 42% for soil and dust. Our results indicate that it is feasible to use alternative measures of soil and dust exposure to provide reliable predictions of PbB in urban environments.

A simple lead dust fall method predicts children's blood lead level: New evidence from Australia.

We have measured dust fall accumulation in petri dishes (PDD) collected 6 monthly from inside residences in Sydney urban area, New South Wales, Australia as part of a 5-year longitudinal study to determine environmental associations, including soil. with blood lead (PbB) levels. The Pb loading in the dishes (n = 706) had geometric means (GM) of 24µg/m2/30d, a median value of 22µg/m2/30d with a range from 0.2 to 11,390µg/m2/30d. Observed geometric mean PbB was 2.4µg/dL at ages 2-3 years. Regression analyses showed a statistically significant relationship between predicted PbB and PDD. The predicted PbB values from dust in our study are consistent with similar analyses from the US in which floor dust was collected by wipes. Predicted PbB values from PDD indicate that an increase in PDD of about 100µg/m2/30d would increase PbB by about 1.5µg/dL or a doubling PbB at the low levels currently observed in many countries. Predicted PbB values from soil indicate that a change from 0 to 1000mg Pb/kg results in an increase of 1.7µg/dL in PbB, consistent with earlier investigations. Blood Pb levels can be predicted from dust fall accumulation (and soil) in cases where blood sampling is not always possible, especially in young children. Petri dish loading data could provide an alternative or complementary "action level" at about 100µg Pb/m2/30 days, similar to the suggested level of about 110µg Pb/m2 for surface wipes, for use in monitoring activities such as housing rehabilitation, demolition or soil resuspension.

Revisiting mobilisation of skeletal lead during pregnancy based on monthly sampling and cord/maternal blood lead relationships confirm placental transfer of lead.

Lead (Pb) can be released from the maternal skeleton during pregnancy and lactation and transferred to the infant. Most support for this hypothesis comes from blood Pb (PbB) studies involving limited sampling during pregnancy, the maximum usually being five samplings, including at delivery. We provide longitudinal data for PbB concentrations and Pb isotopic ratios for three cohorts of pregnant females (n = 31), two of which are based on monthly sampling and the other on quarterly sampling. We also provide data for samples collected post-partum. The data are compared with changes observed in a matched, by country and age, non-pregnant control cohort (n = 5). The monthly data illustrate the variability between subjects, which is also apparent when the data are compared on a trimester basis. Mixed model analyses showed that, in the third trimester, the mean PbB level was significantly lower for women (n = 10) who took a calcium (Ca) supplement (PbB 1.6 µg/dL) than those whose Ca intake was low (low-Ca cohort; n = 15; PbB 2.5 µg/dL) because low Ca means more mobilisation is required for homoeostasis so that more Pb was mobilised from the skeleton. For women who took the supplement, post-partum PbB levels were significantly higher than those in the other periods (2.7 vs 1.4-1.6 µg/dL). For women in the low-Ca cohort, PbB levels were higher at post-partum than in pre-pregnancy and in the first and second trimesters (3.1 vs 1.8 µg/dL), while the levels in the third trimester were higher than those in the first and second trimesters. Importantly, the increase in PbB during gestation was delayed until the third trimester in the Ca-supplemented cohort compared with the low-Ca cohort. Regression analysis showed that the changes over trimester were very similar for PbB and the (206)Pb/(204)Pb ratio providing convincing evidence for extra mobilisation of Pb from the maternal skeleton during pregnancy and lactation. Isotopic ratios in the cord blood samples were similar to those in the maternal blood samples taken prior to parturition with an R (2) 0.94 for the migrant subjects and R (2) 0.74 for Australian subjects for (206)Pb/(204)Pb ratios, supporting the concept of placental transfer of mobilised skeletal stores of Pb.

Transitioning a home telehealth project into a sustainable, large-scale service: a qualitative study.

BACKGROUND: This study was a component of the Flinders Telehealth in the Home project, which tested adding home telehealth to existing rehabilitation, palliative care and geriatric outreach services. Due to the known difficulty of transitioning telehealth projects services, a qualitative study was conducted to produce a preferred implementation approach for sustainable and large-scale operations, and a process model that offers practical advice for achieving this goal. METHODS: Initially, semi-structured interviews were conducted with senior clinicians, health service managers and policy makers, and a thematic analysis of the interview transcripts was undertaken to identify the range of options for ongoing operations, plus the factors affecting sustainability. Subsequently, the interviewees and other decision makers attended a deliberative forum in which participants were asked to select a preferred model for future implementation. Finally, all data from the study was synthesised by the researchers to produce a process model. RESULTS: 19 interviews with senior clinicians, managers, and service development staff were conducted, finding strong support for home telehealth but a wide diversity of views on governance, models of clinical care, technical infrastructure operations, and data management. The deliberative forum worked through these options and recommended a collaborative consortium approach for large-scale implementation. The process model proposes that the key factor for large-scale implementation is leadership support, which is enabled by 1) showing solutions to the problems of service demand, budgetary pressure and the relationship between hospital and primary care, 2) demonstrating how home telehealth aligns with health service policies, and 3) achieving clinician acceptance through providing evidence of benefit and developing new models of clinical care. Two key actions to enable change were marketing telehealth to patients, clinicians and policy-makers, and building a community of practice. CONCLUSIONS: The implementation of home telehealth services is still in an early stage. Change agents and a community of practice can contribute by marketing telehealth, demonstrating policy alignment and providing potential solutions for difficult health services problems. This should assist health leaders to move from trials to large-scale services.

Factors predicting adherence to risk management behaviors of women at increased risk for developing lymphedema.

PURPOSE: Lymphedema affects 20-30% of women following breast cancer treatment. However, even when women are informed, they do not necessarily adhere to recommended lymphedema self-management regimens. Utilizing the Cognitive-Social Health Information Processing framework, we assessed the cognitive and emotional factors influencing adherence to lymphedema risk management. METHODS: Women with breast cancer who had undergone breast and lymph node surgery were recruited through the Fox Chase Cancer Center breast clinic. Participants (N = 103) completed measures of lymphedema-related perceived risk, beliefs and expectancies, distress, self-regulatory ability to manage distress, knowledge, and adherence to risk management behaviors. They then received the American Cancer Society publication "Lymphedema: What Every Woman with Breast Cancer Should Know." Cognitive and affective variables were reassessed at 6 and 12 months post-baseline. RESULTS: Maximum likelihood multilevel model analyses indicated that overall adherence increased over time, with significant differences between baseline and 6- and 12-month assessments. Adherence to wearing gloves was significantly lower than that for all other behaviors except electric razor use. Distress significantly decreased, and knowledge significantly increased, over time. Greater knowledge, higher self-efficacy to enact behaviors, lower distress, and higher self-regulatory ability to manage distress were associated with increased adherence. CONCLUSIONS: Women who understand lymphedema risk management and feel confident in managing this risk are more likely to adhere to recommended strategies. These factors should be rigorously assessed as part of routine care to ensure that women have the self-efficacy to seek treatment and the self-regulatory skills to manage distress, which may undermine attempts to seek medical assistance.

Tomato Seed Coat Permeability to Selected Carbon Nanomaterials and Enhancement of Germination and Seedling Growth.

Seed coat permeability was examined using a model that tested the effects of soaking tomato (Solanum lycopersicon) seeds in combination with carbon-based nanomaterials (CBNMs) and ultrasonic irradiation (US). Penetration of seed coats to the embryo by CBNMs, as well as CBNMs effects on seed germination and seedling growth, was examined. Two CBNMs, C60(OH)20 (fullerol) and multiwalled nanotubes (MWNTs), were applied at 50 mg/L, and treatment exposure ranged from 0 to 60 minutes. Bright field, fluorescence, and electron microscopy and micro-Raman spectroscopy provided corroborating evidence that neither CBNM was able to penetrate the seed coat. The restriction of nanomaterial (NM) uptake was attributed to the semipermeable layer located at the innermost layer of the seed coat adjacent to the endosperm. Seed treatments using US at 30 or 60 minutes in the presence of MWNTs physically disrupted the seed coat; however, the integrity of the semipermeable layer was not impaired. The germination percentage and seedling length and weight were enhanced in the presence of MWNTs but were not altered by C60(OH)20. The combined exposure of seeds to NMs and US provided insight into the nanoparticle-seed interaction and may serve as a delivery system for enhancing seed germination and early seedling growth.

Antioxidant supplements reduced oxidative stress and stabilized liver function tests but did not reduce inflammation in a randomized controlled trial in obese children and adolescents.

Oxidative stress and low-grade systemic inflammation may contribute to the pathogenesis of obesity-induced comorbidities, including nonalcoholic fatty liver disease. Increasing intake of dietary antioxidants might be beneficial, but there are few data in obese children. To examine the effect of antioxidant supplementation on biomarkers of oxidative stress, inflammation, and liver function, we randomly assigned overweight or obese children and adolescents (n = 44; mean ± SD age: 12.7 ± 1.5 y) participating in a lifestyle modification program to a 4-mo intervention with daily antioxidants (vitamin E, 400 IU; vitamin C, 500 mg; selenium, 50 µg) or placebo. We measured anthropometrics, antioxidant status, oxidative stress (F(2)-isoprostanes, F(2)-isoprostane metabolites), inflammation, liver enzymes, fasting insulin and glucose, and lipid profile at baseline and endpoint. There was a significant treatment effect of antioxidant supplementation on antioxidant status [α-tocopherol, ß = 23.2 (95% CI: 18.0, 28.4); ascorbic acid, ß = 70.6 (95% CI: 51.7, 89.4); selenium, ß = 0.07 (95% CI: 0.01, 0.12)] and oxidative stress [8-iso-prostaglandin F2α, ß = -0.11 (95% CI: -0.19, -0.02)] but not on any of the inflammatory markers measured. There was a significant treatment effect on alanine aminotransferase [ß = -0.13 (95% CI: -0.23, -0.03)], a trend toward a significant effect on aspartate aminotransferase [ß = -0.04 (95% CI: -0.09, 0.01)], and no significant effect on γ-glutamyltransferase [ß = -0.03 (95% CI: -0.11, 0.06)]. In summary, antioxidant supplementation for 4 mo improved antioxidant-oxidant balance and modestly improved liver function tests; however, it did not reduce markers of systemic inflammation despite significant baseline correlations between oxidative stress and inflammation. The study was registered at clinicaltrials.gov as NCT01316081.