Modelling structural colour from helicoidal multi-layer thin films with natural disorder.

A coupled mode theory based on Takagi-Taupin equations describing electromagnetic scattering from distorted periodic arrays is applied to the problem of light scattering from beetles. We extend the method to include perturbations in the permittivity tensor to helicoidal arrays seen in many species of scarab beetle and optically anisotropic layered materials more generally. This extension permits analysis of typical dislocations arising from the biological assembly process and the presence of other structures in the elytra. We show that by extracting structural information from transmission electron microscopy data, including characteristic disorder parameters, good agreement with spectral specular and non-specular reflectance measurements is obtained.

A perspective on In vitro developmental neurotoxicity test assay results: An expert panel review.

For decades, there has been increasing concern about the potential developmental neurotoxicity (DNT) associated with chemicals. Regulatory agencies have historically utilized standardized in vivo testing to evaluate DNT. Owing to considerations including higher-throughput screening for DNT, reduction in animal use, and potential cost efficiencies, the development of alternative new approach methods (NAMs) occurred; specifically, the advent of the DNT in vitro test battery (DNT IVB). SciPinion convened an expert panel to address specific questions related to the interpretation of in vitro DNT test data. The consensus of the expert panel was that the DNT IVB might be used during initial screening, but it is not presently a complete or surrogate approach to determine whether a chemical is a DNT in humans. By itself, the DNT IVB does not have the ability to capture nuances and complexity of the developing nervous system and associated outcomes including behavioral ontogeny, motor activity, sensory function, and learning/memory. Presently, such developmental landmarks cannot be adequately assessed in the DNT IVB or by other NAMs. The expert panel (all who serve as co-authors of this review) recommended that additional data generation and validation is required before the DNT IVB can be considered for application within global regulatory frameworks for decision-making.

Exposure to corticosteroids in the first trimester is associated with an increased risk of urogenital congenital anomalies.

STUDY QUESTION: Does maternal exposure to first trimester corticosteroids in IVF/ICSI treatment result in an increased risk of congenital anomalies? SUMMARY ANSWER: Children born with the aid of IVF/ICSI whose mothers were treated with adjuvant corticosteroids during the first trimester had an increased risk of cryptorchidism, hypospadias and talipes. WHAT IS KNOWN ALREADY: Maternal exposure to corticosteroids may increase the risk of congenital anomalies such as cleft palate and neural tube defects. However, the existing studies have conflicting outcomes, are underpowered, and do not study a population undergoing IVF/ICSI, a group known to be at increased risk of abnormalities. STUDY DESIGN, SIZE, DURATION: This retrospective cohort analysis covering Monash IVF fertility clinics in Melbourne, Australia assessed the outcomes of 12 426 live births from both fresh and frozen embryo transfers between 2010 and 2016. PARTICIPANTS/MATERIALS, SETTING, METHODS: There were 618 live births included in our study group of mothers exposed to corticosteroids (oral prednisolone or dexamethasone) during their IVF/ICSI treatment, with the remainder of births not exposed to steroids (control, n = 11 808). The primary outcome measured was the presence of congenital anomalies and secondary outcomes were birth weight and gestation length. Multivariate binary logistic regression was used to assess the independent effects of corticosteroid exposure and the freezing of embryos, with adjustment for maternal age at oocyte retrieval, smoking status, number of cycles taken, BMI, etiology of the infertility and the use of ICSI. Results are presented as incidence rate ratios (IRRs) with 95% CIs. MAIN RESULTS AND THE ROLE OF CHANCE: Amongst 12 426 live births, and 597 birth defects, multivariate logistic regression demonstrated there was an increased incidence in talipes equinovarus (1.33% vs 0.32%, adjusted IRR = 4.30, 95% CI = 1.93, 9.58; P < 0.001), hypospadias (0.66% vs 0.18%, adjusted IRR = 5.90, 95% CI = 2.09, 16.69; P = 0.001) and cryptorchidism (0.83% vs 0.19%, adjusted IRR = 5.53, 95% CI = 1.91, 15.42; P = 0.001) in the offspring of mothers exposed to corticosteroids compared to those who were unexposed. The incidence of neither neural tube defects nor cleft palate were significantly increased in babies exposed to corticosteroids. The sex ratio of infants exposed to corticosteroids during a fresh embryo transfer cycle significantly favored males but reverted to the normal sex ratio in infants conceived in frozen embryo transfer cycles. LIMITATIONS, REASONS FOR CAUTION: This was a retrospective observational cohort study using administrative datasets with the potential for measurement error and unobserved confounding. Missing outcome data were obtained from patients using self-report leading to possible ascertainment bias. Given the rare incidence of some of the anomalies assessed, the study was underpowered to identify differences in abnormality rates for some specific anomalies. WIDER IMPLICATIONS OF THE FINDINGS: The findings of this study, the largest of its kind, suggest that caution should be heeded when prescribing corticosteroids to women undergoing IVF/ICSI, given that this study has now identified three previously unassociated serious neonatal complications (talipes, hypospadias and cryptorchidism), plus a potential alteration in sex ratio. Physicians should be careful in using corticosteroids in the critical first trimester and should counsel patients regarding the potential risks of this treatment. STUDY FUNDING/COMPETING INTEREST(S): There was no funding sought or obtained for this study. K.T., V.T., B.V. and D.Z.-F. are employees or contractors to Monash IVF and hold a minority stock position in Monash IVF. R.J.W. reports no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Lived experience of CamAPS FX closed loop system in youth with type 1 diabetes and their parents.

AIM: To examine changes in the lived experience of type 1 diabetes after use of hybrid closed loop (CL), including the CamAPS FX CL system. MATERIALS AND METHODS: The primary study was conducted as an open-label, single-period, randomized, parallel design contrasting CL versus insulin pump (with or without continuous glucose monitoring). Participants were asked to complete patient-reported outcomes before starting CL and 3 and 6 months later. Surveys assessed diabetes distress, hypoglycaemia concerns and quality of life. Qualitative focus group data were collected at the completion of the study. RESULTS: In this sample of 98 youth (age range 6-18, mean age 12.7 ± 2.8 years) and their parents, CL use was not associated with psychosocial benefits overall. However, the subgroup (n = 12) using the CamAPS FX system showed modest improvements in quality of life and parent distress, reinforced by both survey (p < .05) and focus group responses. There were no negative effects of CL use reported by study participants. CONCLUSIONS: Closed loop use via the CamAPS FX system was associated with modest improvements in aspects of the lived experience of managing type 1 diabetes in youth and their families. Further refinements of the system may optimize the user experience.

Effect of Continuous Glucose Monitoring on Hypoglycemia in Older Adults With Type 1 Diabetes: A Randomized Clinical Trial.

Importance: Continuous glucose monitoring (CGM) provides real-time assessment of glucose levels and may be beneficial in reducing hypoglycemia in older adults with type 1 diabetes. Objective: To determine whether CGM is effective in reducing hypoglycemia compared with standard blood glucose monitoring (BGM) in older adults with type 1 diabetes. Design, Setting, and Participants: Randomized clinical trial conducted at 22 endocrinology practices in the United States among 203 adults at least 60 years of age with type 1 diabetes. Interventions: Participants were randomly assigned in a 1:1 ratio to use CGM (n = 103) or standard BGM (n = 100). Main Outcomes and Measures: The primary outcome was CGM-measured percentage of time that sensor glucose values were less than 70 mg/dL during 6 months of follow-up. There were 31 prespecified secondary outcomes, including additional CGM metrics for hypoglycemia, hyperglycemia, and glucose control; hemoglobin A1c (HbA1c); and cognition and patient-reported outcomes, with adjustment for multiple comparisons to control for false-discovery rate. Results: Of the 203 participants (median age, 68 [interquartile range {IQR}, 65-71] years; median type 1 diabetes duration, 36 [IQR, 25-48] years; 52% female; 53% insulin pump use; mean HbA1c, 7.5% [SD, 0.9%]), 83% used CGM at least 6 days per week during month 6. Median time with glucose levels less than 70 mg/dL was 5.1% (73 minutes per day) at baseline and 2.7% (39 minutes per day) during follow-up in the CGM group vs 4.7% (68 minutes per day) and 4.9% (70 minutes per day), respectively, in the standard BGM group (adjusted treatment difference, -1.9% (-27 minutes per day); 95% CI, -2.8% to -1.1% [-40 to -16 minutes per day]; P <.001). Of the 31 prespecified secondary end points, there were statistically significant differences for all 9 CGM metrics, 6 of 7 HbA1c outcomes, and none of the 15 cognitive and patient-reported outcomes. Mean HbA1c decreased in the CGM group compared with the standard BGM group (adjusted group difference, -0.3%; 95% CI, -0.4% to -0.1%; P <.001). The most commonly reported adverse events using CGM and standard BGM, respectively, were severe hypoglycemia (1 and 10), fractures (5 and 1), falls (4 and 3), and emergency department visits (6 and 8). Conclusions and Relevance: Among adults aged 60 years or older with type 1 diabetes, continuous glucose monitoring compared with standard blood glucose monitoring resulted in a small but statistically significant improvement in hypoglycemia over 6 months. Further research is needed to understand the long-term clinical benefit. Trial Registration: ClinicalTrials.gov Identifier: NCT03240432.

Defining the limits of detection for chromosome rearrangements in the preimplantation embryo using next generation sequencing.

STUDY QUESTION: Is next generation sequencing (NGS) capable of detecting smaller sub-chromosomal rearrangements in human embryos than the manufacturer's quoted resolution suggests? SUMMARY ANSWER: NGS was able to detect unbalanced chromosome segments smaller than the manufacturer's resolution. WHAT IS KNOWN ALREADY: Array Comparative Genomic Hybridization (array-CGH) has been the gold standard platform used for PGD of chromosome rearrangements. NGS is a viable alternative to array-CGH for PGD of chromosome arrangements given that the manufacturer's guidelines quote a resolution of ≥20 Mb. However, as many patients carry a chromosome rearrangement <20 Mb, the detection limits of NGS warrant further investigation. STUDY DESIGN, SIZE, DURATION: This study involved a retrospective assessment of stored DNA samples from embryos that had previously been diagnosed as unbalanced by array-CGH as part of routine PGD in two separate IVF clinics between November 2013 and April 2017. SurePlex whole genome amplification (WGA) products derived from DNA extracted from an embryo biopsy sample known to carry an unbalanced form of a chromosome rearrangement were subjected to a specific NGS workflow (VeriSeq PGS). The results from the two technologies were compared for each sample. PARTICIPANTS/MATERIALS, SETTING, METHODS: WGA products from 200 embryos known to carry unbalanced rearrangements were sequenced and analysed. These embryos had been created by 75 patients known to carry a chromosome rearrangement (68 reciprocal translocations, 3 pericentric inversions, 1 paracentric inversion, 2 insertions and 1 dual reciprocal and inversion). Each sample was assessed for the size of the segmental gain/loss (Mb), copy number for each segment and chromosome, segregation pattern, the number of bins in the analysis software used and concordance with array-CGH results. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 294 unbalanced chromosome segments were assessed. NGS was capable of detecting 285/294 (97%) unbalanced segments previously identified using array-CGH. The final PGD diagnosis was concordant for 200/200 (100%) embryos. In total, 44/75 (59%) patients contained an unbalanced chromosome segment below the quoted 20 Mb manufacturer's stated resolution. Of these, 35/44 (80%) patients had segments that were able to be detected using NGS, whilst maintaining clinical outcome concordance. LIMITATIONS, REASONS FOR CAUTION: Our study subset did not include any rearrangements involving the Y chromosome. NGS has less available bins per chromosome compared to the array-CGH platform used, thus it remains possible that chromosome rearrangements predicted to be small but still detectable by array-CGH may not be feasible for testing using NGS. This should be considered when undertaking a theoretical feasibility assessment for detecting the chromosome rearrangement in question. Only one specific workflow for WGA and NGS was investigated in this study. WIDER IMPLICATIONS OF THE FINDINGS: This study has shown that NGS is available for the detection of unbalanced chromosome rearrangements ≥10 Mb. STUDY FUNDING/COMPETING INTEREST(S): Part sponsorship of the VeriSeq PGS kits used was provided by Illumina. The remainder of the kits were provided by two commercial IVF clinics. None of the authors has any conflicting interests to declare. TRIAL REGISTRATION NUMBER: N/A.

Developing a questionnaire to assess the health effects of bioaerosols.

BACKGROUND: Bioaerosol exposure occurs in several industries including green waste recycling, poultry farming, grain, animal feed and cotton production. Whilst several studies have investigated exposure and health effects in compost workers, the best questions to ask about health are uncertain. AIMS: This study aimed to develop a questionnaire to assess health symptoms in compost workers. METHODS: A 46-item questionnaire to ascertain possible symptoms of occupational illness related to bioaerosol exposure in a cohort of UK industrial compost workers and delivery in an interviewer-led format. The reliability of the questionnaire was assessed using Cronbach's α. A principal component analysis (PCA) was conducted to condense the questionnaire for practical purposes. RESULTS: One hundred and eleven (89%) workers completed the questionnaire. All items showed very good reliability (Cronbach's α = 0.83). After removing perfectly correlated questions from the data set, the PCA was conducted on a reduced data set of 28 items to explore underlying themes. Nine components were identified that explained 77% of the total variation. Nine of the questions removed prior to PCA due to perfect correlation were reintroduced because they added clinical value. The final questionnaire therefore consisted of 37 items and retained very adequate reliability (Cronbach's α = 0.76). CONCLUSIONS: Our health questionnaire has demonstrated adequate reliability when used within this industrial composting workforce. Further applications may include health surveillance, investigating outbreaks of occupational disease or research. Future work should examine the predictive validity of the questionnaire in these settings.

Single and multiple mating reduces longevity of female dumpling squid (Euprymna tasmanica).

For many species, mating is a necessary yet costly activity. The costs involved can have an important influence on the evolution of life histories and senescence. Females of many species mate multiply, and this behaviour can inflict a longevity cost. Most studies investigating the effects of multiple mating on female survival have been conducted on insects, and the effects in other taxa are largely unknown. We investigate the effects of both a single mating and a second mating on longevity in female dumpling squid (Euprymna tasmanica), a species in which both sexes mate multiply. Through comparing the longevity of virgin, once-mated and twice-mated females, we found that a single mating reduced female life span by 15 days on average. A second mating resulted in an additional 8 day (on average) longevity cost, despite no difference in total clutch mass, number of clutches, single egg mass or number of eggs per clutch between once-mated and twice-mated females. This demonstrates a cost to multiple mating which may be independent of the cost of egg production. Furthermore, total clutch mass and female life span were positively correlated, whereas female life span decreased with increasing average water temperature. The presence of an additive effect of reproduction on longevity suggests that multiple mating in cephalopods may have benefits that outweigh these costs, or that there is a conflict in optimal mating frequency between males and females.

Comparative study of image contrast in scanning electron microscope and helium ion microscope.

Images of Ga+ -implanted amorphous silicon layers in a 110 n-type silicon substrate have been collected by a range of detectors in a scanning electron microscope and a helium ion microscope. The effects of the implantation dose and imaging parameters (beam energy, dwell time, etc.) on the image contrast were investigated. We demonstrate a similar relationship for both the helium ion microscope Everhart-Thornley and scanning electron microscope Inlens detectors between the contrast of the images and the Ga+ density and imaging parameters. These results also show that dynamic charging effects have a significant impact on the quantification of the helium ion microscope and scanning electron microscope contrast.

Comparative treatment effectiveness of direct acting antiviral regimens for hepatitis C: Data from the Veterans administration.

BACKGROUND AND AIMS: Data addressing real world effectiveness of direct acting antiviral agents in hepatitis C infected patients are now emerging. This study compared the sustained virologic response rates achieved 12 weeks post-treatment in patients treated with three such agents by the Veterans Health Administration. METHODS: A retrospective cohort study was conducted using patients who terminated treatment by July 1, 2015. Data were retrieved from the Veterans Health Administration electronic medical records system. Patients were included if sufficient viral load laboratory data were available to determine sustained virologic response. Applying an intention to treat approach and logistic regression analysis, the sustained virologic response rates achieved were compared across drug regimens. RESULTS: A total of 11 464 patients met study selection criteria. Without controlling for other risk factors, sustained virologic response at least 12 weeks post treatment was achieved in 92% of ledipasvir/ sofosbuvir, 86% of ombitasvir/paritaprevir/ritonavir/dasabuvir, and 83% of simeprevir/sofosbuvir patients. After adjusting for patient characteristics, simeprevir/sofosbuvir (93.3%) and ledipasvir/sofosbuvir (96.2%) patients were statistically more likely than ombitasvir/paritaprevir/ritonavir/dasabuvir (91.8%) patients to demonstrate sustained virologic response. Human immunodeficiency virus, hepatitis B infection, diabetes, obesity, previous treatment history and augmentation therapy using ribavirin did not impact sustained virologic response rates. Sustained virologic response rates were lower for patients under age 65, with cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, indications of fibrosis, or a non-genotype 1 infection. Women and Caucasian patients were more likely to achieve a sustained virologic response. CONCLUSIONS: All three direct acting antiviral regimens appear highly effective in achieving sustained virologic response.

Birth of a relativistic outflow in the unusual γ-ray transient Swift J164449.3+573451.

Active galactic nuclei, which are powered by long-term accretion onto central supermassive black holes, produce relativistic jets with lifetimes of at least one million years, and the observation of the birth of such a jet is therefore unlikely. Transient accretion onto a supermassive black hole, for example through the tidal disruption of a stray star, thus offers a rare opportunity to study the birth of a relativistic jet. On 25 March 2011, an unusual transient source (Swift J164449.3+573451) was found, potentially representing such an accretion event. Here we report observations spanning centimetre to millimetre wavelengths and covering the first month of evolution of a luminous radio transient associated with Swift J164449.3+573451. The radio transient coincides with the nucleus of an inactive galaxy. We conclude that we are seeing a newly formed relativistic outflow, launched by transient accretion onto a million-solar-mass black hole. A relativistic outflow is not predicted in this situation, but we show that the tidal disruption of a star naturally explains the observed high-energy properties and radio luminosity and the inferred rate of such events. The weaker beaming in the radio-frequency spectrum relative to γ-rays or X-rays suggests that radio searches may uncover similar events out to redshifts of z ≈ 6.

Geographic variation in hybridization and ecological differentiation between three syntopic, morphologically similar species of montane lizards.

To understand factors shaping species boundaries in closely related taxa, a powerful approach is to compare levels of genetic admixture at multiple points of contact and determine how this relates to intrinsic and extrinsic factors, such as genetic, morphological and ecological differentiation. In the Australian Alps, the threatened alpine bog skink Pseudemoia cryodroma co-occurs with two morphologically and ecologically similar congeners, P. entrecasteauxii and P. pagenstecheri, and all three species are suspected to hybridize. We predicted that the frequency of hybridization should be negatively correlated with genetic divergence, morphological differentiation and microhabitat separation. We tested this hypothesis using a mitochondrial locus, 13 microsatellite loci, morphological and microhabitat data and compared results across three geographically isolated sites. Despite strong genetic structure between species, we detected hybridization between all species pairs, including evidence of backcrossed individuals at the two sites where all three species are syntopic. Hybridization frequencies were not consistently associated with genetic, morphological or ecological differentiation. Furthermore, P. entrecasteauxii and P. pagenstecheri only hybridized at the two sites where they are syntopic with P. cryodroma, but not at the largest site where P. cryodroma was not recorded, suggesting that P. cryodroma may serve as a bridging species. This study reveals the complex dynamics within a three species hybrid zone and provides a baseline for assessing the impact of climate change and anthropogenic habitat modification on future hybridization frequencies.

Measuring Care Continuity: A Comparison of Claims-based Methods.

BACKGROUND: Assessing care continuity is important in evaluating the impact of health care reform and changes to health care delivery. Multiple measures of care continuity have been developed for use with claims data. OBJECTIVE: This study examined whether alternative continuity measures provide distinct assessments of coordination within predefined episodes of care. RESEARCH DESIGN AND SUBJECTS: This was a retrospective cohort study using 2008-2009 claims files for a national 5% sample of beneficiaries with congestive heart failure, chronic obstructive pulmonary disease, and diabetes mellitus. MEASURES: Correlations among 4 measures of care continuity-the Bice-Boxerman Continuity of Care Index, Herfindahl Index, usual provider of care, and Sequential Continuity of Care Index-were derived at the provider- and practice-levels. RESULTS: Across the 3 conditions, results on 4 claims-based care coordination measures were highly correlated at the provider-level (Pearson correlation coefficient r=0.87-0.98) and practice-level (r=0.75-0.98). Correlation of the results was also high for the same measures between the provider- and practice-levels (r=0.65-0.92). CONCLUSIONS: Claims-based care continuity measures are all highly correlated with one another within episodes of care.

Ornament size and colour as alternative strategies for effective communication in gliding lizards.

Sexual ornamentation needs to be conspicuous to be effective in attracting potential mates and defending territories and indeed, a multitude of ways exists to achieve this. Two principal mechanisms for increasing conspicuousness are to increase the ornament's colour or brightness contrast against the background and to increase the size of the ornament. We assessed the relationship between the colour and size of the dewlap, a large extendible throat-fan, across a range of species of gliding lizards (Agamidae; genus Draco) from Malaysia and the Philippines. We found a negative relationship across species between colour contrast against the background and dewlap size in males, but not in females, suggesting that males of different species use increasing colour contrast and dewlap size as alternative strategies for effective communication. Male dewlap size also increases with increasing sexual size dimorphism, and dewlap colour and brightness contrast increase with increasing sexual dichromatism in colour and brightness, respectively, suggesting that sexual selection may act on both dewlap size and colour. We further found evidence that relative predation intensity, as measured from predator attacks on models placed in the field, may play a role in the choice of strategy (high chromatic contrast or large dewlap area) a species employs. More broadly, these results highlight that each component in a signal (such as colour or size) may be influenced by different selection pressures and that by assessing components individually, we can gain a greater understanding of the evolution of signal diversity.

A faint type of supernova from a white dwarf with a helium-rich companion.

Supernovae are thought to arise from two different physical processes. The cores of massive, short-lived stars undergo gravitational core collapse and typically eject a few solar masses during their explosion. These are thought to appear as type Ib/c and type II supernovae, and are associated with young stellar populations. In contrast, the thermonuclear detonation of a carbon-oxygen white dwarf, whose mass approaches the Chandrasekhar limit, is thought to produce type Ia supernovae. Such supernovae are observed in both young and old stellar environments. Here we report a faint type Ib supernova, SN 2005E, in the halo of the nearby isolated galaxy, NGC 1032. The 'old' environment near the supernova location, and the very low derived ejected mass ( approximately 0.3 solar masses), argue strongly against a core-collapse origin. Spectroscopic observations and analysis reveal high ejecta velocities, dominated by helium-burning products, probably excluding this as a subluminous or a regular type Ia supernova. We conclude that it arises from a low-mass, old progenitor, likely to have been a helium-accreting white dwarf in a binary. The ejecta contain more calcium than observed in other types of supernovae and probably large amounts of radioactive (44)Ti.

Health surveillance for occupational asthma in the UK.

BACKGROUND: Periodic health surveillance (HS) of workers can identify early cases of occupational asthma. Information about its uptake and its content in the UK is lacking. AIMS: To identify the overall levels of uptake and quality of HS for occupational asthma within three high-risk industry sectors in the UK. METHODS: A telephone survey of employers, and their occupational health (OH) professionals, carried out in three sectors with exposures potentially capable of causing occupational asthma (bakeries, wood working and motor vehicle repair). RESULTS: A total of 457 organizations participated (31% response rate). About 77% employed <10 people, 17% between 10 and 50 and 6% >50. Risk assessments were common (67%) and 14% carried out some form of HS for occupational asthma, rising to 19% if only organizations reporting asthma hazards and risks were considered. HS was carried out both by in-house (31%) and external providers (69%). Organizational policies were often used to define HS approaches (80%), but infrequently shared with the OH provider. OH providers described considerable variation in practice. Record keeping was universal, but worker-held records were not reported. HS tools were generally developed in-house. Lung function was commonly measured, but only limited interpretation evident. Referral of workers to local specialist respiratory services was variable. CONCLUSIONS: This study provided new insights into the real world of HS for occupational asthma. We consider that future work could and should define simpler, more practical and evidence-based approaches to HS to ensure maximal consistency and use of high-quality approaches.

When two obese parents are worse than one! Impacts on embryo and fetal development.

The prevalence of overweight and obesity in reproductive-age adults is increasing worldwide. While the effects of either paternal or maternal obesity on gamete health and subsequent fertility and pregnancy have been reported independently, the combination of having both parents overweight/obese on fecundity and offspring health has received minimal attention. Using a 2 × 2 study design in rodents we established the relative contributions of paternal and maternal obesity on fetal and embryo development and whether combined paternal and maternal obesity had an additive effect. Here, we show that parental obesity reduces fetal and placental weights without altering pregnancy establishment and is not dependent on an in utero exposure to a high-fat diet. Interestingly combined parental obesity seemed to accumulate both the negative influences of paternal and maternal obesity had alone on embryo and fetal health rather than an amplification, manifested as reduced embryo developmental competency, reduced blastocyst cell numbers, impaired mitochondrial function, and alterations to active and repressive embryonic chromatin marks, resulting in aberrant placental gene expression and reduced fetal liver mtDNA copy numbers. Further understanding both the maternal cytoplasmic and paternal genetic interactions during this early developmental time frame will be vital for understanding how developmental programming is regulated and for the proposition of interventions to mitigate their effects.

A gamma-ray burst at a redshift of z approximately 8.2.

Long-duration gamma-ray bursts (GRBs) are thought to result from the explosions of certain massive stars, and some are bright enough that they should be observable out to redshifts of z > 20 using current technology. Hitherto, the highest redshift measured for any object was z = 6.96, for a Lyman-alpha emitting galaxy. Here we report that GRB 090423 lies at a redshift of z approximately 8.2, implying that massive stars were being produced and dying as GRBs approximately 630 Myr after the Big Bang. The burst also pinpoints the location of its host galaxy.

Interleukin (IL)-17A, F and AF in inflammation: a study in collagen-induced arthritis and rheumatoid arthritis.

Interleukin (IL)-17 plays a critical role in inflammation. Most studies to date have elucidated the inflammatory role of IL-17A, often referred to as IL-17. IL-17F is a member of the IL-17 family bearing 50% homology to IL-17A and can also be present as heterodimer IL-17AF. This study elucidates the distribution and contribution of IL-17A, F and AF in inflammatory arthritis. Neutralizing antibody to IL-17A alone or IL-17F alone or in combination was utilized in the mouse collagen-induced arthritis (CIA) model to elucidate the contribution of each subtype in mediating inflammation. IL-17A, F and AF were all increased during inflammatory arthritis. Neutralization of IL-17A reduced the severity of arthritis, neutralization of IL-17A+IL-17F had the same effect as neutralizing IL-17A, while neutralization of IL-17F had no effect. Moreover, significantly higher levels of IL-17A and IL-17F were detected in peripheral blood mononuclear cells (PBMC) from patients with rheumatoid arthritis (RA) in comparison to patients with osteoarthritis (OA). IL-17A and AF were detected in synovial fluid mononuclear cells (SFMC) in RA and OA, with IL-17A being significantly higher in RA patients. Enriched CD3(+) T cells from RA PBMCs produced singnificantly high levels of IL-17A and IL-17AF in comparison to OA peripheral blood CD3(+) T cells. IL-17A, F and AF were undetectable in T cells from SFMCs from RA and OA. While IL-17A, F, and AF were all induced during CIA, IL-17A played a dominant role. Furthermore, production of IL-17A, and not IL-17F or IL-17AF, was elevated in PBMCs, SFMCs and enriched peripheral blood CD3(+) T in RA.

Mitochondrial SIRT3 and its target glutamate dehydrogenase are altered in follicular cells of women with reduced ovarian reserve or advanced maternal age.

STUDY QUESTION: Is the activity of sirtuin 3 (SIRT3) altered in granulosa and cumulus cells from young women with reduced ovarian reserve or women of advanced maternal age? SUMMARY ANSWER: SIRT3 mRNA and active protein in granulosa and cumulus cells were decreased in women with reduced ovarian reserve and advanced maternal age. WHAT IS KNOWN ALREADY: Young women with reduced ovarian reserve or women of advanced maternal age have reduced oocyte viability, possibly due to altered granulosa and cumulus cell metabolism. The mitochondrial SIRT3 protein may be implicated in these processes as it is able to sense the metabolic state of the cell and alter mitochondrial protein function post-translationally. STUDY DESIGN, SIZE, DURATION: This is a prospective cohort study, in which women (n = 72) undergoing routine IVF/ICSI were recruited and allocated to one of three cohorts based on age and ovarian reserve (as assessed by serum anti-Mullerian hormone level). Women were classified as young (≤35 years) or of advanced maternal age (≥40 years). PARTICIPANTS/MATERIALS, SETTING, METHODS: Granulosa and cumulus cells were collected. SIRT3 mRNA and protein levels and protein activity was analysed in granulosa and cumulus cells via quantitative PCR, immunohistochemistry and western blotting, and deacetylation activity, respectively. Activity of the glutamate dehydrogenase (GDH) enzyme, a known target of SIRT3, was assessed, and acetylated proteins in mitochondria isolated from granulosa and cumulus cells were separated by immunoprecipitation and acetylation of GDH assessed by western blotting. Data for women with good prognosis (young women with normal ovarian reserve) were compared with those from young women with reduced ovarian reserve and those of advanced maternal age. MAIN RESULTS AND THE ROLE OF CHANCE: SIRT3 mRNA and active protein were present in granulosa and cumulus cells and co-localized to the mitochondria. SIRT3 mRNA in granulosa cells was decreased in young women with reduced ovarian reserve and advanced maternal age versus young women with normal ovarian reserve (P < 0.05). SIRT3 mRNA in cumulus cells was decreased in women of advanced maternal age versus young women with normal ovarian reserve only (P < 0.05). Granulosa cell GDH activity was decreased in young women with reduced ovarian reserve and in women of advanced maternal age (P < 0.05), whereas cumulus cell GDH activity was reduced in the advanced maternal age group only (P < 0.05). The acetylation profile of GDH in mitochondria revealed increased acetylation of GDH in granulosa and cumulus cells from women of advanced maternal age (P < 0.05) while young women with reduced ovarian reserve had increased GDH acetylation in granulosa cells only (P < 0.05). LIMITATIONS, REASONS FOR CAUTION: Although patients were allocated to groups based on maternal age and ovarian reserve and matched for BMI, other maternal factors may also alter the 'molecular health' of ovarian cells. WIDER IMPLICATIONS OF THE FINDINGS: Our data suggest that SIRT3 post-translational modification of mitochondrial enzymes in human granulosa and cumulus cells may regulate GDH activity, thus altering the metabolic milieu surrounding the developing oocyte. Owing to the association between the decline in oocyte quality and pregnancy rates in women of advanced maternal age and the possible association with reduced ovarian reserve, knowledge of perturbed SIRT3 function in granulosa and cumulus cells may lead to novel therapies to improve mitochondrial metabolism in the oocyte and follicular cells in women undergoing IVF treatment. STUDY FUNDING/COMPETING INTEREST(S): No conflicts of interest to declare. Research was funded by an NHMRC project grant.