Bone health in women with premature ovarian insufficiency/early menopause: a 23-year longitudinal analysis.

STUDY QUESTION: What is the frequency of, and predictors for, osteoporosis, fractures, and osteoporosis management (investigation, treatment) in women with premature ovarian insufficiency (POI; menopause <40 years) and early menopause (EM; menopause 40-44years)? SUMMARY ANSWER: Over the 23-year follow-up duration, at a mean age of 68 years, women with POI/EM had higher osteoporosis/fracture risk and prevalence, higher osteoporosis screening and anti-osteoporosis medication use compared to women with usual age menopause; increasing age was predictive of increased risk of osteoporosis/fracture and menopause hormone therapy (MHT) prior to or at study entry (aged 45-50 years) was protective. WHAT IS KNOWN ALREADY: Women with POI/EM have increased risk of osteoporosis and fractures with limited data regarding risk factors for reduced bone density and fractures. Clinical guidelines recommend screening with dual X-ray absorptiometry (DXA) and treatment with MHT for most women with POI/EM to reduce osteoporosis and fracture risk; however, studies indicate gaps in osteoporosis knowledge, guideline uptake, and management adherence by clinicians and women. STUDY DESIGN, SIZE, DURATION: The Australian Longitudinal Study on Women's Health is a prospective longitudinal study of Australian women. This study uses the cohort of women born between 1946 and 1951, surveyed nine times between 1996 and 2019. Data from the Australian administrative health records, including hospital admissions data (fractures, osteoporosis), Medicare Benefits Schedule (DXA), and the Pharmaceutical Benefits Scheme (PBS; MHT, anti-osteoporosis medication, available only from 2002) were linked to survey data. PARTICIPANTS/MATERIALS, SETTING, METHODS: Survey respondents with self-reported age of menopause were included. POI/EM was defined as menopause <45 years. T-test or chi-square were used for comparisons at baseline (P < 0.05 indicates significance). Generalized estimating equations for panel data explored predictors for the longitudinal outcomes of osteoporosis, fractures, DXA rates, MHT use, and anti-osteoporosis medication (in women with osteoporosis/fracture, from Survey 4 onwards only). Univariable regression was performed, and variables retained where P < 0.2, to form the multivariable model, and bootstrapping with 100 repetitions at 95% sampling of the original dataset to ensure robustness of results. MAIN RESULTS AND THE ROLE OF CHANCE: Eight thousand six hundred and three women were included: 610 (7.1%) with POI/EM. Mean (SD) baseline age was 47.6 (1.45) years in the entire cohort and mean (SD) age of menopause was 38.2 (7.95) and 51.3 (3.04) years in women with POI/EM and usual age menopause, respectively (P < 0.001). Over the 23 years, of women with POI/EM, 303 (49.7%) had osteoporosis/fractures, 421 (69.0%) had DXA screening, 474 ever used MHT (77.7%), and 116 (39.1%) of those with osteoporosis/fractures used anti-osteoporosis medication. Of women with usual age menopause, 2929 (36.6%) had osteoporosis/fractures, 4920 (61.6%) had DXA screening, 4014 (50.2%) used MHT, and 964 (33.0%) of those with osteoporosis/fractures used anti-osteoporosis medication. Compared to women with menopause at age ≥45 years and after adjusting for other risk factors, women with POI/EM had increased risk of osteoporosis (odds ratio [OR] 1.37; 95% CI 1.07-1.77), fractures (OR 1.45; 1.15-1.81), DXA testing (OR 1.64; 1.42-1.90), MHT use (OR 6.87; 5.68-8.30), and anti-osteoporosis medication use (OR 1.50; 1.14-1.98). In women with POI/EM women, increasing age was associated with greater risk of osteoporosis/fracture (OR 1.09; 1.08-1.11), and MHT prior to or at study entry (aged 45-50 years), was protective (OR 0.65, 0.45-0.96). In women with POI/EM, age (OR 1.11; 1.10-1.12), fractures (OR 1.80, 1.38-2.34), current smoking (OR 0.60; 0.43-0.86), and inner (OR 0.68; 0.53-0.88) or outer regional (OR 0.63; 0.46-0.87) residential location were associated with DXA screening. In women with POI/EM, increasing age (OR 1.02; 1.01-1.02), and currently consuming alcohol (OR 1.17; 1.06-1.28), was associated with having ever used MHT. In the 299 women with POI/EM and osteoporosis/fractures, only 39.1% ever received treatment with an anti-osteoporosis medication. Increasing age (OR 1.07; 1.04-1.09) and lower BMI (OR 0.95; 0.92-0.98) were associated with greater likelihood of treatment with anti-osteoporosis medication. LIMITATIONS, REASONS FOR CAUTION: Survey data including age of menopause were self-reported by participants; fracture questions were not included in the 2001 survey, and location or level of trauma of self-reported fractures was not asked. Additional risk/protective factors such as vitamin D status, calcium intake, and exercise were not able to be included. Due to sample size, POI and EM were combined for all analyses, and we were unable to differentiate between causes of POI/EM. PBS data were only available from 2004, and hospital admissions data were state-based, with all of Australia were only available from 2007. WIDER IMPLICATIONS OF THE FINDINGS: This study supports previous literature indicating increased risk of osteoporosis and fractures in women with POI, and adds evidence for women with POI/EM, where there was a relative paucity of data. This is the first study to analyse a variety of clinical and demographic risk factors for osteoporosis and fractures in women with POI/EM, as well as analysing investigation and treatment rates. In these women, using MHT prior to or at study entry, aged 45-50 years, was protective for osteoporosis/fractures; however, having ever used MHT was not, highlighting the importance of early treatment with MHT in these women to preserve bone strength. Although women with POI/EM and osteoporosis or fractures were more likely to use anti-osteoporosis medications than those with usual age menopause, overall treatment rates are low at <40%, demonstrating a significant treatment gap that should be addressed to reduce future fracture risk. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by The Australian NHMRC Centre of Research Excellence Women's Health in Reproductive Life (CRE-WHIRL, project number APP1171592). A.R.J. is the recipient of a National Health and Medical Research Council post-graduate research scholarship (grant number 1169192). P.R.E. is supported by a National Health and Medical Research Council grant 1197958. P.R.E. reports grants paid to their institution from Amgen, Sanofi, and Alexion, honoraria from Amgen paid to their institution, and honoraria from Alexion and Kyowa-Kirin. TRIAL REGISTRATION NUMBER: N/A.

DNAscan: personal computer compatible NGS analysis, annotation and visualisation.

BACKGROUND: Next Generation Sequencing (NGS) is a commonly used technology for studying the genetic basis of biological processes and it underpins the aspirations of precision medicine. However, there are significant challenges when dealing with NGS data. Firstly, a huge number of bioinformatics tools for a wide range of uses exist, therefore it is challenging to design an analysis pipeline. Secondly, NGS analysis is computationally intensive, requiring expensive infrastructure, and many medical and research centres do not have adequate high performance computing facilities and cloud computing is not always an option due to privacy and ownership issues. Finally, the interpretation of the results is not trivial and most available pipelines lack the utilities to favour this crucial step. RESULTS: We have therefore developed a fast and efficient bioinformatics pipeline that allows for the analysis of DNA sequencing data, while requiring little computational effort and memory usage. DNAscan can analyse a whole exome sequencing sample in 1 h and a 40x whole genome sequencing sample in 13 h, on a midrange computer. The pipeline can look for single nucleotide variants, small indels, structural variants, repeat expansions and viral genetic material (or any other organism). Its results are annotated using a customisable variety of databases and are available for an on-the-fly visualisation with a local deployment of the gene.iobio platform. DNAscan is implemented in Python. Its code and documentation are available on GitHub: https://github.com/KHP-Informatics/DNAscan . Instructions for an easy and fast deployment with Docker and Singularity are also provided on GitHub. CONCLUSIONS: DNAscan is an extremely fast and computationally efficient pipeline for analysis, visualization and interpretation of NGS data. It is designed to provide a powerful and easy-to-use tool for applications in biomedical research and diagnostic medicine, at minimal computational cost. Its comprehensive approach will maximise the potential audience of users, bringing such analyses within the reach of non-specialist laboratories, and those from centres with limited funding available.

The effects of the neonicotinoid imidacloprid on gene expression and DNA methylation in the buff-tailed bumblebee Bombus terrestris.

Neonicotinoids are effective insecticides used on many important arable and horticultural crops. They are nicotinic acetylcholine receptor agonists which disrupt the function of insect neurons and cause paralysis and death. In addition to direct mortality, there are numerous sublethal effects of low doses of neonicotinoids on bees. We hypothesize that some of these large array of effects could be a consequence of epigenetic changes in bees induced by neonicotinoids. We compared whole methylome (BS-seq) and RNA-seq libraries of the brains of buff-tailed bumblebee Bombus terrestris workers exposed to field-realistic doses of the neonicotinoid imidacloprid to libraries from control workers. We found numerous genes which show differential expression between neonicotinoid-treated bees and control bees, but no differentially methylated cytosines in any context. We found CpG methylation to be focused mainly in exons and associated with highly expressed genes. We discuss the implications of our results for future legislation.

Development of the MapMe intervention body image scales of known weight status for 4-5 and 10-11 year old children.

Background: Parents tend to visually assess children to determine their weight status and typically underestimate child body size. A visual tool may aid parents to more accurately assess child weight status and so support strategies to reduce childhood overweight. Body image scales (BIS) are visual images of people ranging from underweight to overweight but none exist for children based on UK criteria. Our aim was to develop sex- and age-specific BIS for children, based on British growth reference (UK90) criteria. Methods: BIS were developed using 3D surface body scans of children, their associated weight status using UK90 criteria from height and weight measurements, and qualitative work with parents and health professionals. Results: Height, weight and 3D body scans were collected (211: 4-5 years; 177: 10-11 years). Overall, 12 qualitative sessions were held with 37 participants. Four BIS (4-5-year-old girls and boys, 10-11-year-old girls and boys) were developed. Conclusions: This study has created the first sex- and age-specific BIS, based on UK90 criteria. The BIS have potential for use in child overweight prevention and management strategies, and in future research. This study also provides a protocol for the development of further BIS appropriate to other age groups and ethnicities.

Mothers' perceptions of child weight status and the subsequent weight gain of their children: a population-based longitudinal study.

BACKGROUND: There is a plethora of cross-sectional work on maternal perceptions of child weight status showing that mothers typically do not classify their overweight child as being overweight according to commonly used clinical criteria. Awareness of overweight in their child is regarded as an important prerequisite for mothers to initiate appropriate action. The gap in the literature is determining whether, if mothers do classify their overweight child's weight status correctly, this is associated with a positive outcome for the child's body mass index (BMI) at a later stage. OBJECTIVE: To explore longitudinal perceptions of child weight status from mothers of a contemporary population-based birth cohort (Gateshead Millennium Study) and relationships of these perceptions with future child weight gain. METHODS: Data collected in the same cohort at 7, 12 and 15 years of age: mothers' responses to two items concerning their child's body size; child's and mother's BMI; pubertal maturation; demographic information. RESULTS: Mothers' perceptions of whether their child was overweight did not change markedly over time. Child BMI was the only significant predictor of mothers' classification of overweight status, and it was only at the extreme end of the overweight range and in the obese range that mothers reliably described their child as overweight. Even when mothers did appropriately classify their child as overweight at an earlier stage, this was not related to relatively lower child BMI a few years later. CONCLUSIONS: Mothers tend to classify their child as overweight in only more extreme cases. It is an important finding that no beneficial impact was shown on later child BMI in overweight children whose mothers classified their child's weight status as overweight at an earlier stage.

Human leucocyte antigen-adverse drug reaction associations: from a perspective of ethnicity.

Whilst immune-mediated adverse drug reactions (ADRs) are rare, they are potentially life-threatening and present a major problem for clinicians. The underlying mechanisms that cause ADRs are not fully understood although genomewide association studies (GWAS) and case-control investigations have associated human leucocyte antigen (HLA) alleles as risk factors. There is evidence that a patient's ethnic background can have an impact on their risk of developing an ADR. This review summarizes the evidence related to HLA alleles and ADRs with particular focus on patient ethnicity. Our analysis indicated that many of the alleles which have been associated with ADRs are found at higher frequencies in Asian populations. The data also showed that many of the alleles that are reported to be statistically significantly associated with ADRs are in linkage disequilibrium with each other and that they form haplotypes specific to certain ethnicities indicating at least some of the allele associations may not be causal.

Altered gene expression in the dorsolateral prefrontal cortex of individuals with schizophrenia.

The underlying pathology of schizophrenia (SZ) is likely as heterogeneous as its symptomatology. A variety of cortical and subcortical regions, including the prefrontal cortex, have been implicated in its pathology, and a number of genes have been identified as risk factors for disease development. We used in situ hybridization (ISH) to examine the expression of 58 genes in the dorsolateral prefrontal cortex (DLPFC, comprised of Brodmann areas 9 and 46) from 19 individuals with a premorbid diagnosis of SZ and 33 control individuals. Genes were selected based on: (1) previous identification as risk factors for SZ; (2) cell type markers or (3) laminar markers. Cell density and staining intensity were compared in the DLPFC, as well as separately in Brodmann areas 9 and 46. The expression patterns of a variety of genes, many of which are associated with the GABAergic system, were altered in SZ when compared with controls. Additional genes, including C8orf79 and NR4A2, showed alterations in cell density or staining intensity between the groups, highlighting the need for additional studies. Alterations were, with only a few exceptions, limited to Brodmann area 9, suggesting regional specificity of pathology in the DLPFC. Our results agree with previous studies on the GABAergic involvement in SZ, and suggest that areas 9 and 46 may be differentially affected in the disease. This study also highlights additional genes that may be altered in SZ, and indicates that these potentially interesting genes can be identified by ISH and high-throughput image analysis techniques.

An assessment of the doses received by members of the public in Japan following the nuclear accident at Fukushima Daiichi nuclear power plant.

The earthquake and tsunami on 11 March 2011, centred off the east coast of Japan, caused considerable destruction and substantial loss of life along large swathes of the Japanese coastline. The tsunami damaged the Fukushima Daiichi nuclear power plant (NPP), resulting in prolonged releases of radioactive material into the environment. This paper assesses the doses received by members of the public in Japan. The assessment is based on an estimated source term and atmospheric dispersion modelling rather than monitoring data. It is evident from this assessment that across the majority of Japan the estimates of dose are very low, for example they are estimated to be less than the annual average dose from natural background radiation in Japan. Even in the regions local to Fukushima Daiichi NPP (and not affected by any form of evacuation) the maximum lifetime effective dose is estimated to be well below the cumulative natural background dose over the same period. The impact of the urgent countermeasures on the estimates of dose was considered. And the relative contribution to dose from the range of exposure pathways and radionuclides were evaluated. Analysis of estimated doses focused on the geographic irregularity and the impact of the meteorological conditions. For example the dose to an infant's thyroid received over the first year was estimated to be greater in Hirono than in the non-evacuated region of Naraha, despite Hirono being further from the release location. A number of factors were identified and thought to contribute towards this outcome, including the local wind pattern which resulted in the recirculation of part of the release. The non-uniform nature of dose estimates strengthens the case for evaluations based on dispersion modelling.

Microencapsulation of gallium-indium (Ga-In) liquid metal for self-healing applications.

Microcapsules containing a liquid metal alloy core of gallium-indium (Ga-In) are prepared via in situ urea-formaldehyde (UF) microencapsulation. The capsule size, shape, thermal properties, and shell wall thickness are investigated. We prepare ellipsoidal capsules with major and minor diameter aspect ratios ranging from 1.64 to 1.08 and with major diameters ranging from 245 µm to 3 µm. We observe that as the capsule major diameter decreases, the aspect ratio approaches 1. The thermal properties of the prepared microcapsules are investigated by thermogravimetric (TGA) and differential scanning calorimetry (DSC). Microcapsules are shown to survive incorporation into an epoxy matrix and to trigger via mechanical damage to the cured matrix. Microcapsules containing liquid metal cores may have diverse applications ranging from self-healing to contrast enhancement or the demonstration of mechano-adaptive circuitry.

16(th) IHIW: extending the number of resources and bioinformatics analysis for the investigation of HLA rare alleles.

Continuing a project presented at the 15th International HLA and Immunogenetics Workshop (IHIWS) on the rarity of HLA alleles, we sought to expand the number of data sources and bioinformatics tools available in the Allele Frequencies Net Database website (AFND, www.allelefrequencies.net). In this 16th IHIWS Rare Alleles project, HLA alleles described in the latest IMGT/HLA Database (release 3.8.0) were queried against different sources including data from registries (stem cell) and from 74 different laboratories around the world. We demonstrated that approximately 40% of the alleles officially named in the IMGT/HLA Database have been reported only once across all different sources. To facilitate the large-scale analysis of rare alleles, we have produced an online tool called the Rare Allele Detector that simplifies the detection of alleles that are considered to be 'very rare', 'rare' or 'frequent'. Tools and associated data can be accessed via the www.allelefrequencies.net website.

Effect of table tilt on ligamentum flavum length measured using ultrasonography in pregnant women*.

The purpose of this study was to assess whether applying dorsal table tilt to a seated parturient positioned for neuraxial anaesthesia (i.e. facing laterally with her legs over the side of the table) increased the size of the target area for the neuraxial needle. We performed lumbar ultrasonography on 20 pregnant women with the table level (0°) and tilted 8° and 15° dorsally. For each position, the size of the 'target area', defined as the visible length of the ligamentum flavum in the longitudinal paramedian view, and the interlaminar distance, were measured at the L3-4 interspace. There were significant increases in the mean (SD) size of the target area with increasing table tilt (10.7 (1.3) mm at 0°, 11.5 (1.3) mm at 8° and 12.2 (1.7) mm at 15°; p < 0.0001). Interlaminar distances were not significantly increased. These data show that using dorsal table tilt in obstetric patients increases the target area for neuraxial needles. Additional research is required to assess whether this eases the placement of neuraxial needles in clinical practice.

Mothers' judgements about their child's weight: distinguishing facts from values.

BACKGROUND: Mothers' responses to questionnaire items assessing their child's weight status typically do not correspond to conventional clinical classifications based on body mass index (BMI). From this observation health professionals infer that mothers do not recognize overweight in their child. But the questions used have generally confounded factual judgements with values, so it is not clear whether the mothers are making factual errors, or differ from professionals in their values. METHODS: Cross-sectional study of population-based birth cohort at 6-8 years and their mothers (n = 540). An objective BMI matching task was used to determine the accuracy of mothers' recognition of their child's weight. Mothers matched their child to sex- and age-specific images of children of known BMI ranging from very thin to obese, and chose a descriptor of their child's weight of the kind used in previous research. RESULTS: Mothers tended to underestimate their child's BMI on the matching task. Matching errors significantly predicted mothers' description of their child's weight; those who overestimated their child's BMI on the matching task were more likely to say their child was overweight, while those who underestimated it were less likely to, independently of their child's actual BMI. CONCLUSIONS: Educational programmes aimed at parents of young primary school children need to address separately the factual and the evaluative components of their assessment of child weight.

Widespread aneuploidy revealed by DNA microarray expression profiling.

Expression profiling using DNA microarrays holds great promise for a variety of research applications, including the systematic characterization of genes discovered by sequencing projects. To demonstrate the general usefulness of this approach, we recently obtained expression profiles for nearly 300 Saccharomyces cerevisiae deletion mutants. Approximately 8% of the mutants profiled exhibited chromosome-wide expression biases, leading to spurious correlations among profiles. Competitive hybridization of genomic DNA from the mutant strains and their isogenic parental wild-type strains showed they were aneuploid for whole chromosomes or chromosomal segments. Expression profile data published by several other laboratories also suggest the use of aneuploid strains. In five separate cases, the extra chromosome harboured a close homologue of the deleted gene; in two cases, a clear growth advantage for cells acquiring the extra chromosome was demonstrated. Our results have implications for interpreting whole-genome expression data, particularly from cells known to suffer genomic instability, such as malignant or immortalized cells.

Multidrug-resistant OXA-48/CTX-M-15 Klebsiella pneumoniae cluster in a COVID-19 intensive care unit: salient lessons for infection prevention and control during the COVID-19 pandemic.

BACKGROUND: Wards caring for COVID-19 patients, including intensive care units (ICUs), have an important focus on preventing transmission of SARS-CoV-2 to other patients and healthcare workers. AIM: To describe an outbreak of carbapenemase-producing Enterobacterales (CPE) in a COVID-19 ICU and to discuss key infection control measures enabling prompt termination of the cluster. METHODS: CPE were isolated from clinical specimens and screening swabs from intensive care patients with COVID-19 disease and from environmental screening. Whole-genome sequencing analysis was instrumental in informing phylogenetic relationships. FINDINGS: Seven clinical isolates and one environmental carbapenemase-producing Klebsiella pneumoniae isolate - all carrying OXA-48, CTX-M-15 and outer membrane porin mutations in ompK35/ompK36 - were identified with ≤1 single nucleotide polymorphism difference, indicative of clonality. A bundle of infection control interventions including careful adherence with contact precautions and hand hygiene, twice weekly screening for multidrug-resistant organisms, strict antimicrobial stewardship, and enhanced cleaning protocols promptly terminated the outbreak. CONCLUSION: Prolonged use of personal protective equipment is common with donning and doffing stations at the ward entrance, leaving healthcare workers prone to reduced hand hygiene practices between patients. Minimizing transmission of pathogens other than SARS-CoV-2 by careful adherence to normal contact precautions including hand hygiene, even during high patient contact manoeuvres, is critical to prevent outbreaks of multidrug-resistant organisms. Appropriate antimicrobial stewardship and screening for multidrug-resistant organisms must also be maintained throughout surge periods to prevent medium-term escalation in antimicrobial resistance rates. Whole-genome sequencing is highly informative for multidrug-resistant Enterobacterales surveillance strategies.

Parental perceptions of weight status in children: the Gateshead Millennium Study.

OBJECTIVES: To investigate parents' perceptions of weight status in children and to explore parental understanding of and attitudes to childhood overweight. DESIGN: Questionnaires and focus groups within a longitudinal study. SUBJECTS: 536 parents of Gateshead Millennium Study children, of which 27 attended six focus groups. MAIN OUTCOME MEASURES: Parents' perception of their child's weight status according to actual weight status as defined by International Obesity Taskforce (IOTF) cutoffs. Focus group outcomes included parental awareness of childhood overweight nationally and parental approaches to identifying overweight children. RESULTS: The sensitivity of parents recognising if their child was overweight was 0.31. Prevalence of child overweight was underestimated: 7.3% of children were perceived as 'overweight' or 'very overweight' by their parents, 23.7% were identified as overweight or obese using IOTF criteria. 69.3% of parents of overweight or obese children identified their child as being of 'normal' weight. During focus groups parents demonstrated an awareness of childhood overweight being a problem nationally but their understanding of how it is defined was limited. Parents used alternative approaches to objective measures when identifying overweight in children such as visual assessments and comparisons with other children. Such approaches relied heavily on extreme and exceptional cases as a reference point. The apparent lack of relevance of childhood overweight to their child's school or own community along with scepticism towards both media messages and clinical measures commonly emerged as grounds for failing to engage with the issue at a personal level. CONCLUSION: Parents' ability to identify when their child was overweight according to standard criteria was limited. Parents did not understand, use or trust clinical measures and used alternative approaches primarily reliant on extreme cases. Such approaches underpinned their reasoning for remaining detached from the issue. This study highlights the need to identify methods of improving parental recognition of and engagement with the problem of childhood overweight.

When do mothers think their child is overweight?

OBJECTIVE: To quantify how overweight children have to be for their mothers to classify them as overweight and to express concern about future overweight, and to investigate the adiposity cues in children that mothers respond to. DESIGN: Cross-sectional. SUBJECTS: A total of 531 children from the Gateshead Millennium Study cohort at 6-8 years and their mothers. MEASUREMENTS: In the mother: responses to two questions concerning the child's adiposity; height; weight; educational qualifications; and economic status. In the child: height; weight; waist circumference; skinfold thicknesses; bioelectrical impedance; and bone frame measurements. RESULTS: The body mass index (BMI) at which half the mothers classify their child as overweight was 21.3 (in the obese range for children of this age). The BMI at which half the mothers were concerned about their child becoming overweight in the future was 17.1 (below the overweight range). Waist circumference and skinfolds contributed most to mothers' responses. Although BMI and fat scores were important predictors individually, they did not contribute independently once waist circumference and skinfolds (their most visible manifestations) were included in the regression equations. Mothers were less likely to classify girls as overweight. Mothers with higher BMIs were less likely to classify their child as overweight, but were more likely to be concerned about future overweight. CONCLUSION: Health promotion efforts directed at parents of young primary school children might better capitalise on their concern about future overweight in their child than on current weight status, and focus on mothers' response to more visible characteristics than the BMI.

The role of soil in the contribution of food and feed.

Soils play a critical role in the production of food and feed for a growing global population. Here, we review global patterns in soil characteristics, agricultural production and the fate of embedded soil nutrients. Nitrogen- and organic-rich soils supported the highest crop yields, yet the efficiency of nutrient utilization was concentrated in regions with lower crop productivity and lower rates of chemical fertilizer inputs. Globally, soil resources were concentrated in animal feed, resulting in large inefficiencies in nutrient utilization and losses from the food system. Intercontinental transport of soil-derived nutrients displaced millions of tonnes of nitrogen and phosphorus annually, much of which was ultimately concentrated in urban waste streams. Approximately 40% of the global agricultural land area was in small farms providing over 50% of the world's food and feed needs but yield gaps and economic constraints limit the ability to intensify production on these lands. To better use and protect soil resources in the global food system, policies and actions should encourage shifts to more nutrient-efficient diets, strategic intensification and technological improvement, restoration and maintenance of soil fertility and stability, and enhanced resilience in the face of global change. This article is part of the theme issue 'The role of soils in delivering Nature's Contributions to People'.

A Thermodynamic Model for Interpreting Tryptophan Excitation-Energy-Dependent Fluorescence Spectra Provides Insight Into Protein Conformational Sampling and Stability.

It is now over 30 years since Demchenko and Ladokhin first posited the potential of the tryptophan red edge excitation shift (REES) effect to capture information on protein molecular dynamics. While there have been many key efforts in the intervening years, a biophysical thermodynamic model to quantify the relationship between the REES effect and protein flexibility has been lacking. Without such a model the full potential of the REES effect cannot be realized. Here, we present a thermodynamic model of the tryptophan REES effect that captures information on protein conformational flexibility, even with proteins containing multiple tryptophan residues. Our study incorporates exemplars at every scale, from tryptophan in solution, single tryptophan peptides, to multitryptophan proteins, with examples including a structurally disordered peptide, de novo designed enzyme, human regulatory protein, therapeutic monoclonal antibodies in active commercial development, and a mesophilic and hyperthermophilic enzyme. Combined, our model and data suggest a route forward for the experimental measurement of the protein REES effect and point to the potential for integrating biomolecular simulation with experimental data to yield novel insights.

Chloroplast transformation in Chlamydomonas with high velocity microprojectiles.

Bombardment of three mutants of the chloroplast atpB gene of Chlamydomonas reinhardtii with high-velocity tungsten microprojectiles that were coated with cloned chloroplast DNA carrying the wild-type gene permanently restored the photosynthetic capacity of the algae. In most transformants of one of the mutants, a fragment with a 2.5-kilobase deletion was restored to normal size by a homologous replacement event; in about 25 percent of the transformants the restored restriction fragment was 50 to 100 base pairs smaller or larger than that of wild type. About one-fourth of the transformants of this mutant contained unintegrated donor plasmid when first examined. This plasmid persisted in four different transformants after 65 cell generations of continuous liquid culture but was lost from all transformants maintained on plates of selective medium. The restored wild-type atpB gene remains in all transformants as an integral part of the chloroplast genome and is expressed and inherited normally.

Effect of annealing temperatures on the secondary re-crystallization of extruded PM2000 steel bar.

The ferritic oxide dispersion-strengthened alloy PM2000 is an ideal candidate for high-temperature applications as it contains uniform nano-oxide dispersoids, which act as pinning points to obstruct dislocation and grain boundary motion and therefore impart excellent creep resistance. The development of the microstructure during re-crystallization of oxide dispersion-strengthened alloys has been discussed by a number of authors, but the precise mechanism of secondary re-crystallization still remains uncertain. Hence, this work is aimed at investigating the re-crystallization behaviour of extruded PM2000 bar for different annealing temperatures, using electron backscatter diffraction, in particular, to determine grain orientations, grain boundary misorientation angles, etc. The results show that the as-extruded bar microstructure comprises both low-angle grain boundaries pinned by oxide particles and high-angle boundaries that will have inherent boundary mobility to allow boundary migration. In addition, dynamical re-crystallization was found in the outer region of the non-heat-treated PM2000 bar, which suggested that deformation heterogeneities can be introduced during thermo-mechanical processing that enhance the nucleation of re-crystallization. Subsequent heat treatments promote and stimulate secondary re-crystallization, giving rise to large grains with few sub-grain boundaries.