Female fertility is a complex trait with age-specific changes in spontaneous dizygotic (DZ) twinning and fertility. To elucidate factors regulating female fertility and infertility, we conducted a genome-wide association study (GWAS) on mothers of spontaneous DZ twins (MoDZT) versus controls (3273 cases, 24,009 controls). This is a follow-up study to the Australia/New Zealand (ANZ) component of that previously reported (Mbarek et al., 2016), with a sample size almost twice that of the entire discovery sample meta-analysed in the previous article (and five times the ANZ contribution to that), resulting from newly available additional genotyping and representing a significant increase in power. We compare analyses with and without male controls and show unequivocally that it is better to include male controls who have been screened for recent family history, than to use only female controls. Results from the SNP based GWAS identified four genomewide significant signals, including one novel region, ZFPM1 (Zinc Finger Protein, FOG Family Member 1), on chromosome 16. Previous signals near FSHB (Follicle Stimulating Hormone beta subunit) and SMAD3 (SMAD Family Member 3) were also replicated (Mbarek et al., 2016). We also ran the GWAS with a dominance model that identified a further locus ADRB2 on chr 5. These results have been contributed to the International Twinning Genetics Consortium for inclusion in the next GWAS meta-analysis (Mbarek et al., in press).

We have adapted the Vera C. Rubin Observatory Legacy Survey of Space and Time (LSST) Science Pipelines to process data from the Gravitational-wave Optical Transient Observer (GOTO) prototype. In this paper, we describe how we used the LSST Science Pipelines to conduct forced photometry measurements on nightly GOTO data. By comparing the photometry measurements of sources taken on multiple nights, we find that the precision of our photometry is typically better than 20 mmag for sources brighter than 16 mag. We also compare our photometry measurements against colour-corrected Panoramic Survey Telescope and Rapid Response System photometry and find that the two agree to within 10 mmag (1$\sigma$) for bright (i.e., $\sim 14{\rm th} \mathrm{mag}$) sources to 200 mmag for faint (i.e., $\sim 18{\rm th} \mathrm{mag}$) sources. Additionally, we compare our results to those obtained by GOTO’s own in-house pipeline, gotophoto, and obtain similar results. Based on repeatability measurements, we measure a $5\sigma$ L-band survey depth of between 19 and 20 magnitudes, depending on observing conditions. We assess, using repeated observations of non-varying standard Sloan Digital Sky Survey stars, the accuracy of our uncertainties, which we find are typically overestimated by roughly a factor of two for bright sources (i.e., $< 15{\rm th} \mathrm{mag}$), but slightly underestimated (by roughly a factor of 1.25) for fainter sources ($> 17{\rm th} \mathrm{mag}$). Finally, we present lightcurves for a selection of variable sources and compare them to those obtained with the Zwicky Transient Factory and GAIA. Despite the LSST Software Pipelines still undergoing active development, our results show that they are already delivering robust forced photometry measurements from GOTO data.

The past few decades have seen the burgeoning of wide-field, high-cadence surveys, the most formidable of which will be the Legacy Survey of Space and Time (LSST) to be conducted by the Vera C. Rubin Observatory. So new is the field of systematic time-domain survey astronomy; however, that major scientific insights will continue to be obtained using smaller, more flexible systems than the LSST. One such example is the Gravitational-wave Optical Transient Observer (GOTO) whose primary science objective is the optical follow-up of gravitational wave events. The amount and rate of data production by GOTO and other wide-area, high-cadence surveys presents a significant challenge to data processing pipelines which need to operate in near-real time to fully exploit the time domain. In this study, we adapt the Rubin Observatory LSST Science Pipelines to process GOTO data, thereby exploring the feasibility of using this ‘off-the-shelf’ pipeline to process data from other wide-area, high-cadence surveys. In this paper, we describe how we use the LSST Science Pipelines to process raw GOTO frames to ultimately produce calibrated coadded images and photometric source catalogues. After comparing the measured astrometry and photometry to those of matched sources from PanSTARRS DR1, we find that measured source positions are typically accurate to subpixel levels, and that measured L-band photometries are accurate to $\sim50$ mmag at $m_L\sim16$ and $\sim200$ mmag at $m_L\sim18$. These values compare favourably to those obtained using GOTO’s primary, in-house pipeline, gotophoto, in spite of both pipelines having undergone further development and improvement beyond the implementations used in this study. Finally, we release a generic ‘obs package’ that others can build upon, should they wish to use the LSST Science Pipelines to process data from other facilities.

The aim of this research was to look at the emergence of wearable technology and the internet of things (IoT) and their current and potential use in the health and care area. There is a wide and ever-expanding range of wearables, devices, apps, data aggregators and platforms allowing the measurement, tracking and aggregation of a multitude of health and lifestyle measures, information and behaviours. The use and application of such technology and the corresponding richness of data that it can provide bring the health and care insurance market both potential opportunities and challenges. Insurers across a range of fields are already engaging with this type of technology in their proposition designs in areas such as customer engagement, marketing and underwriting. However, it seems like we are just at the start of the journey, on a learning curve to find the optimal practical applications of such technology with many aspects as yet untried, tested or indeed backed up with quantifiable evidence. It is clear though that technology is only part of the solution, on its own it will not engage or change behaviours and insurers will need to consider this in terms of implementation and goals. In the first weeks of forming this working party, it became evident that the potential scope of this technology, the information already out there and the pace of development of it, is almost overwhelming. With many yet-unanswered questions the paper focuses on pulling together in one place relevant information for the consideration of the health and care actuary, and also to open the reader’s eyes to potential future innovations by drawing on use of the technology in other markets and spheres, and the “science fiction–like” new technology that is just around the corner. The paper explores:

• an overview of wearables and IoT and available measures,

• examples of how this technology is currently being used,

• data considerations,

• risks and challenges,

• future technology developments and

• what this may mean for the future of insurance.

We live at the dynamic interface between the solid Earth and its outer fluid envelopes. This interface, extending from the outer vegetation canopy to the base of active groundwater, was recently named the Critical Zone because it supports life and is increasingly impacted by human actions. Understanding the complex interactions between processes that operate in and shape the Critical Zone requires interdisciplinary approaches that span wide spatial and temporal scales. Tectonic processes, weathering, fluid transport, and biological processes control the function and structure of the Critical Zone. Three Critical Zone Observatories recently established by the U.S. National Science Foundation are designed to integrate studies of process interactions up to the watershed scale. A goal of the program is to build the three independently conceived observatories into a network from which broader understanding — larger spatial scales but also deeper insight — can emerge.

The miconia (Miconia calvescens) invasion of the East Maui Watershed (EMW) started from a single introduction over 40 yr ago, establishing a nascent patch network spread across 20,000 ha. In 2012, an accelerated intervention strategy was implemented utilizing the Herbicide Ballistic Technology (HBT) platform in a Hughes 500D helicopter to reduce target densities of seven nascent patches in the EMW. In a 14-mo period, a total of 48 interventions eliminated 4,029 miconia targets, with an estimated 33% increase in operations and 168% increase in recorded targets relative to the adjusted means from 2005 to 2011 data (prior to HBT adoption). This sequence of interventions covered a total net area of 1,138 ha, creating a field mosaic of overlapping search coverage (saturation) for each patch (four to eight interventions per patch). Target density reduction for each patch fit exponential decay functions (R 2 > 0.88, P < 0.05), with a majority of the target interventions spatially assigned to the highest saturation fields. The progressive decay in target density led to concomitant reductions in search efficiency (min ha−1) and herbicide use rate (grams ae ha−1) in subsequent interventions. Mean detection efficacy (± SE) between overlapping interventions (n = 41) was 0.62 ± 0.03, matching closely with the probability of detection for a random search operation and verifying imperfect (albeit precise) detection. The HBT platform increases the value of aerial surveillance operations with 98% efficacy in target elimination. Applying coverage saturation with an accelerated intervention schedule to known patch locations is an adaptive process for compensating imperfect detection and building intelligence with spatial and temporal relevance to the next operation.

Hosts strongly influence parasite fitness. However, it is challenging to disentangle host effects on genetic vs plasticity-driven traits of parasites, since parasites can evolve quickly. It remains especially difficult to determine the causes and magnitude of parasite plasticity. In successive generations, parasites may respond plastically to better infect their current type of host, or hosts may produce generally ‘good’ or ‘bad’ quality parasites. Here, we characterized parasite plasticity by taking advantage of a system in which the parasite (the yeast Metschnikowia bicuspidata, which infects Daphnia) has no detectable heritable variation, preventing rapid evolution. In experimental infection assays, we found an effect of rearing host genotype on parasite infectivity, where host genotypes produced overall high or low quality parasite spores. Additionally, these plastically induced differences were gained or lost in just a single host generation. Together, these results demonstrate phenotypic plasticity in infectivity driven by the within-host rearing environment. Such plasticity is rarely investigated in parasites, but could shape epidemiologically important traits.

There is evidence that tamoxifen treatment of BRCA1 and BRCA2 carriers for prior breast cancer increases risk of endometrioid subtype endometrial cancer (EC), and suggestive evidence that BRCA1 and BRCA2 mutation carriers may be predisposed to EC in the absence of tamoxifen exposure. We assessed the association of EC with BRCA1 or BRCA2 mutation status in Australasian breast-ovarian families. Report of at least one case of EC was significantly greater in BRCA1-positive families (35/218 (16%); p = .03) and non-significantly greater in BRCA2-positive families (23/189 (12%); p = .6), compared to high-risk breast cancer families without a BRCA1/2 mutation (86/796 (11%)). EC was the first/concurrent cancer for 41% of EC cases with multiple cancer diagnoses from BRCA1/2 families, and early onset for most of these diagnoses. Mutation status was imputed for ungeno-typed individuals from 57 BRCA1/2 pedigrees reporting EC using BRCAPRO. Effects of genotype on EC diagnosis age, and interaction with tamoxifen therapy, were assessed using Cox proportional hazards regression analysis. EC risk was non-significantly marginally greater for BRCA1 carriers (hazard ratio = 1.25, 95%CI = 0.65–2.41), and BRCA2 carriers (HR = 1.12, 95%CI = 0.51–2.45), compared to non-carrier family members. Tamoxifen therapy was highly significantly associated with EC (HR = 6.68, 95%CI = 3.12–15.15; p = 1.7 x 10-6) in BRCA1/2 families, with no evidence for interaction between tamoxifen therapy and BRCA1/2 genotype. Our family-based study supports a 7-fold increase in EC risk with tamoxifen exposure for female family members from BRCA1/2 families. Early onset EC in carriers without tamoxifen use suggests that further study is required to assess association of modest EC risk with BRCA1/2 mutation status alone.

Cutaneous malignant melanoma (CMM) is a major health issue in Queensland, Australia, which has the world's highest incidence. Recent molecular and epidemiologic studies suggest that CMM arises through multiple etiological pathways involving gene–environment interactions. Understanding the potential mechanisms leading to CMM requires larger studies than those previously conducted. This article describes the design and baseline characteristics of Q-MEGA, the Queensland Study of Melanoma: Environmental and Genetic Associations, which followed up 4 population-based samples of CMM patients in Queensland, including children, adolescents, men aged over 50, and a large sample of adult cases and their families, including twins. Q-MEGA aims to investigate the roles of genetic and environmental factors, and their interaction, in the etiology of melanoma. Three thousand, four hundred and seventy-one participants took part in the follow-up study and were administered a computer-assisted telephone interview in 2002–2005. Updated data on environmental and phenotypic risk factors, and 2777 blood samples were collected from interviewed participants as well as a subset of relatives. This study provides a large and well-described population-based sample of CMM cases with follow-up data. Characteristics of the cases and repeatability of sun exposure and phenotype measures between the baseline and the follow-up surveys, from 6 to 17 years later, are also described.

Genetic diversity of Trypanosoma cruzi may play a role in pathogenesis of Chagas disease forms. Natural populations are classified into 6 Discrete Typing Units (DTUs) Tc I-VI with taxonomical status. This study aimed to identify T. cruzi DTUs in bloodstream and tissue samples of Argentinean patients with Chagas disease. PCR-based strategies allowed DTU identification in 256 clinical samples from 239 Argentinean patients. Tc V prevailed in blood from both asymptomatic and symptomatic cases and Tc I was more frequent in bloodstream, cardiac tissues and chagoma samples from immunosuppressed patients. Tc II and VI were identified in a minority of cases, while Tc III and Tc IV were not detected in the studied population. Interestingly, Tc I and Tc II/VI sequences were amplified from the same skin biopsy slice from a kidney transplant patient suffering Chagas disease reactivation. Further data also revealed the occurrence of mixed DTU populations in the human chronic infection. In conclusion, our findings provide evidence of the complexity of the dynamics of T. cruzi diversity in the natural history of human Chagas disease and allege the pathogenic role of DTUs I, II, V and VI in the studied population.

This study compared performance on the Functional Independence Measure for Children (WeeFIMTM), the Battelle Developmental Inventory Screening Test (BDIST), and the Vineland Adaptive Behavior Scales (VABS) in children with developmental disabilities. The three instruments were administered to 205 children with identified disabilities. All 205 children were tested using the WeeFIM instrument. The BDIST was administered to 101 children and the VABS to the remaining 104 children. Administration was counterbalanced and randomized across all three instruments. A proportional sampling plan was used to select the 205 children, who ranged in age from 11 to 87 months. A variety of medical diagnoses and levels of severity of motor, cognitive, and communication impairments were systematically included in the sample. Correlations (r) among subscales for all three instruments ranged from 0.42 to 0.92. Correlations for total scores ranged from 0.72 to 0.94. Analyses of potential moderator variables found no significant relation between age and severity of disability (r=0.05) or between socioeconomic status (SES) and severity of disability (r=0.21). Correlations with age were strongest for those subscale scores involving gross and fine motor skills. Correlations with SES and subscale scores ranged from 0.03 to 0.18. The three instruments provide important information regarding childhood performance in motor, self-care, communicative, cognitive, and social skills. The WeeFIM instrument requires less administration time and provides information directly relevant to evaluating functional outcomes for children with disabilities and their families.