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.

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.

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.

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'.

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.

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.

A remotely triggered fast neutron detection instrument based on a plastic organic scintillator.

A detector system for the characterization of radiation fields of both fast neutrons and γ rays is described comprising of a gated photomultiplier tube (PMT), an EJ299-33 solid organic scintillator detector, and an external trigger circuit. The objective of this development was to conceive a means by which the PMT in such a system can be actuated remotely during the high-intensity bursts of pulsed γ-ray contamination that can arise during active interrogation procedures. The system is used to detect neutrons and γ rays using established pulse-shape discrimination (PSD) techniques. The gating circuit enables the PMT to be switched off remotely. This is compatible with use during intense radiation transients to avoid saturation and the disruption of the operation of the PMT during the burst. Data are presented in the form of pulse-height spectra and PSD scatter plots for the system triggered with a strobed light source. These confirm that the gain of the system and the throughput for both triggered and un-triggered scenarios are as expected, given the duty cycle of the stimulating radiation. This demonstrates that the triggering function does not perturb the system response of the detector.

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.

Plasma REST: a novel candidate biomarker of Alzheimer's disease is modified by psychological intervention in an at-risk population.

The repressor element 1-silencing transcription (REST) factor is a key regulator of the aging brain's stress response. It is reduced in conditions of stress and Alzheimer's disease (AD), which suggests that increasing REST may be neuroprotective. REST can be measured peripherally in blood plasma. Our study aimed to (1) examine plasma REST levels in relation to clinical and biological markers of neurodegeneration and (2) alter plasma REST levels through a stress-reduction intervention-mindfulness training. In study 1, REST levels were compared across the following four well-characterized groups: healthy elderly (n=65), mild cognitive impairment who remained stable (stable MCI, n=36), MCI who later converted to dementia (converter MCI, n=29) and AD (n=65) from the AddNeuroMed cohort. REST levels declined with increasing severity of risk and impairment (healthy elderly>stable MCI>converter MCI>AD, F=6.35, P<0.001). REST levels were also positively associated with magnetic resonance imaging-based hippocampal and entorhinal atrophy and other putative blood-based biomarkers of AD (Ps<0.05). In study 2, REST was measured in 81 older adults with psychiatric risk factors for AD before and after a mindfulness-based stress reduction intervention or an education-based placebo intervention. Mindfulness-based training caused an increase in REST compared with the placebo intervention (F=8.57, P=0.006), and increased REST was associated with a reduction in psychiatric symptoms associated with stress and AD risk (Ps<0.02). Our data confirm plasma REST associations with clinical severity and neurodegeneration, and originally, that REST is modifiable by a psychological intervention with clinical benefit.

Review: Placental adaptations to the presence of maternal asthma during pregnancy.

Asthma is a highly prevalent chronic medical condition affecting an estimated 12% of pregnant, women each year, with prevalence of asthma greatest (up to 16%) among the socially disadvantaged. Maternal asthma is associated with significant perinatal morbidity and mortality including preterm births, neonatal hospitalisations and low birthweight outcomes each year. We have identified that the placenta adapts to the presence of chronic, maternal asthma during pregnancy in a sex specific manner that may confer sex differences in fetal outcome. The male fetus was at greater risk of a poor outcome than a female fetus in the presence of maternal asthma and an acute inflammatory event such as an asthma exacerbation. This review will examine the role of sex specific differences in placental function on fetal growth and survival.

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.

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.

Transition from paediatric surgery: how many patients do we need to plan for?

INTRODUCTION Transitional care is an NHS priority with newly published NICE guidance. Many paediatric surgical patients need quality care to continue into adulthood. We undertook an evaluation of our departmental activity to assess the magnitude of this issue. METHODS We identified all outpatients ≥ 15 years (potentially requiring imminent transition) seen over a 12 month period for all five general paediatric surgery consultants in our tertiary centre. Those patients requiring transition were highlighted and the appropriate adult team for referral recorded. RESULTS There were 2989 general paediatric surgery clinic appointments within the year; 289 (9.7%) were for young people aged 15 years or older; 62 patients (28% of those ≥ 15years) were deemed to require transition into adult care. Significantly more patients having colorectal surgery required follow-up (P = 0.0009 Chi-square test) compared with patients in other subspecialties. CONCLUSIONS More patients than expected required transition. This may be the case in other units. Current best practice includes time intensive preclinic planning, careful preparation of patient and family, followed by joint clinics. A joint clinic appointment takes 30 minutes, allowing for comprehensive handover and forging new relationships. In our department, we need at least ten transition clinics across 2 years. Coalition with adult colleagues is vital. These data enable us to plan services to provide quality care for our adolescent patients and highlights colorectal surgery as a priority.

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.

A simple tool to identify elderly patients with a surgically important acute subdural haematoma.

OBJECTIVES: ASDH in the elderly is a common and increasing problem, and differs in its pathophysiology from ASDH in younger people. Admitting doctors may have difficulty identifying those elderly patients whose lesions may benefit from surgery. The objective of this study was to determine whether simple neuroradiological measurements could identify those patients, who need urgent neurosurgical referral for consideration for surgery. DESIGN: A retrospective cohort study. PARTICIPANTS: All patients aged 65 years or greater referred to Salford Royal Foundation Trust with the diagnosis of ASDH between 01/01/2008 and 31/12/2011. METHODS: The initial presenting CT brain scans were reviewed. The linear dimensions, degree of midline shift and haematoma volume (using ABC/2 method) of all scans were measured and recorded. All presenting radiology was also assessed by a consultant neurosurgeon blind to clinical and CT scan measurement data and patients were categorised as having "surgical" lesions or not. Receiver operating characteristic (ROC) curves were generated and cut point value for 100% sensitivity and specificity were tabled to assess which combination of scan parameters best predicted a "surgical" ASDH. RESULTS: 212/483 patients were considered to have a 'surgical' lesion. All 'surgical' lesions had a volume of >35ml (range 35-435), maximum thickness of ≥10mm (range 10-49) and 99% had midline shift ≥1mm (range 0-32). The best predictor of a 'surgical' lesion was a combination of maximum haematoma thickness and midline shift which offered 100% (95% CI 98.3-100) sensitivity with 83% (95% CI 77.6-87) specificity. CONCLUSION: Surgically relevant cases of ASDH in the elderly can be reliably and objectively identified by two easily performed scan measurements, haematoma thickness and midline shift. If used in routine practice, these measurements could clarify those patients who may need urgent neurosurgical referral and might avoid unnecessary transfer to neurosurgical units in this cohort.

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.

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.

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.

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.