Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.

As the primary risk factor for cardiovascular disease (CVD), hypertension is the leading cause of preventable, premature mortality globally. Hypertension, or elevated blood pressure (BP), has a number of well-established risk factors, including genetics. A common C677T polymorphism in the gene encoding the folate metabolising enzyme methylenetetrahydrofolate reductase (MTHFR) affects 10–12% of UK and Irish populations and has been linked with 24–87% increased risk of hypertension globally. Evidence from randomised controlled trials (RCTs) conducted at this Centre has shown BP to be highly responsive (by 5–13 mmHg) to supplementation with riboflavin (MTHFR co-factor), an effect confined to homozygous individuals (TT genotype). To date, our trials have focused on peripheral BP; however, additional measures of vascular health such as central pressure are reported to be more closely correlated with CVD risk. Investigation of central BP, augmentation index (AIx) and pulse pressure amplification (PPA) may thus offer further insight into the role of this gene-nutrient interaction in blood pressure. The present study aims to investigate BP, and measures of vascular health in healthy adults stratified by MTHFR 677 genotype. Apparently healthy adults aged 18–60 years were recruited from workplaces across Northern Ireland and screened for MTHFR genotype via buccal swab. Clinic BP, anthropometry and blood sample were measured in TT individuals (n 209) and age and sex-matched CC (n 98) and CT (n 102) controls. AIx and central BP were assessed using SphygmoCor® (AtCor Medical, Australia). Preliminary results demonstrate higher BP in individuals with the MTHFR 677TT genotype compared to non-TT controls (systolic BP 134.7 ± 13.8 mmHg vs 129.7 ± 12.4 mmHg, P < 0.001; diastolic BP 81.6 ± 9.5 mmHg vs 79.7 mmHg ± 8.9 mmHg, P = 0.023, respectively). The MTHFR 677TT genotype group had significantly higher central systolic BP (119.4 ± 11.8 vs 116.7 ± 10.9 mmHg, P = 0.018), central pulse pressure (P = 0.006) and central mean pressure (P = 0.011) compared to the non-TT group. No significant differences for central diastolic BP, pulse pressure amplification, pulse pressure ratio and augmentation index were observed. This study confirms the phenotype of elevated BP in individuals with the C677T polymorphism in the gene encoding MTHFR. For the first time, this study reports that individuals with the MTHFR 677TT genotype have higher central systolic BP, central mean pressure and pulse pressure. Further investigations through RCTs investigating the effect of the MTHFR cofactor, riboflavin, on central blood pressure in these genetically at-risk adults are warranted.

Gut microbiota data obtained by DNA sequencing are not only complex because of the number of taxa that may be detected within human cohorts, but also compositional because characteristics of the microbiota are described in relative terms (e.g., “relative abundance” of particular bacterial taxa expressed as a proportion of the total abundance of taxa). Nutrition researchers often use standard principal component analysis (PCA) to derive dietary patterns from complex food data, enabling each participant's diet to be described in terms of the extent to which it fits their cohort's dietary patterns. However, compositional PCA methods are not commonly used to describe patterns of microbiota in the way that dietary patterns are used to describe diets. This approach would be useful for identifying microbiota patterns that are associated with diet and body composition. The aim of this study is to use compositional PCA to describe gut microbiota profiles in 5 year old children and explore associations between microbiota profiles, diet, body mass index (BMI) z-score, and fat mass index (FMI) z-score. This study uses a cross-sectional data for 319 children who provided a faecal sample at 5 year of age. Their primary caregiver completed a 123-item quantitative food frequency questionnaire validated for foods of relevance to the gut microbiota. Body composition was determined using dual-energy x-ray absorptiometry, and BMI and FMI z-scores calculated. Compositional PCA identified and described gut microbiota profiles at the genus level, and profiles were examined in relation to diet and body size. Three gut microbiota profiles were found. Profile 1 (positive loadings on Blautia and Bifidobacterium; negative loadings on Bacteroides) was not related to diet or body size. Profile 2 (positive loadings on Bacteroides; negative loadings on uncultured Christensenellaceae and Ruminococcaceae) was associated with a lower BMI z-score (r = -0.16, P = 0.003). Profile 3 (positive loadings on Faecalibacterium, Eubacterium and Roseburia) was associated with higher intakes of fibre (r = 0.15, P = 0.007); total (r = 0.15, P = 0.009), and insoluble (r = 0.13, P = 0.021) non-starch polysaccharides; protein (r = 0.12, P = 0.036); meat (r = 0.15, P = 0.010); and nuts, seeds and legumes (r = 0.11, P = 0.047). Further regression analyses found that profile 2 and profile 3 were independently associated with BMI z-score and diet respectively. We encourage fellow researchers to use compositional PCA as a method for identifying further links between the gut, diet and obesity, and for developing the next generation of research in which the impact on body composition of dietary interventions that modify the gut microbiota is determined.

Objectives: Despite changes to brain integrity with aging, some functions like basic language processes remain remarkably preserved. One theory for the maintenance of function in light of age-related brain atrophy is the engagement of compensatory brain networks. This study examined age-related changes in the neural networks recruited for simple language comprehension. Methods: Sixty-five adults (native English-speaking, right-handed, and cognitively normal) aged 17–85 years underwent a functional magnetic resonance imaging (fMRI) reading paradigm and structural scanning. The fMRI data were analyzed using independent component analysis to derive brain networks associated with reading comprehension. Results: Two typical frontotemporal language networks were identified, and these networks remained relatively stable across the wide age range. In contrast, three attention-related networks showed increased activation with increasing age. Furthermore, the increased recruitment of a dorsal attention network was negatively correlated to gray matter thickness in temporal regions, whereas an anterior frontoparietal network was positively correlated to gray matter thickness in insular regions. Conclusions: We found evidence that older adults can exert increased effort and recruit additional attentional resources to maintain their reading abilities in light of increased cortical atrophy.

Psychotropic medication use and psychiatric symptoms during pregnancy each are associated with adverse neurodevelopmental outcomes in offspring. Commonly, studies considering medication effects do not adequately assess symptoms, nor evaluate children when the effects are believed to occur, the fetal period. This study examined maternal serotonin reuptake inhibitor and polypharmacy use in relation to serial assessments of five indices of fetal neurobehavior and Bayley Scales of Infant Development at 12 months in N = 161 socioeconomically advantaged, non-Hispanic White women with a shared risk phenotype, diagnosed major depressive disorder. On average fetuses showed the expected development over gestation. In contrast, infant average Bayley psychomotor and mental development scores were low (M = 84.10 and M = 89.92, range of normal limits 85–114) with rates of delay more than 2–3 times what would be expected based on this measure's normative data. Controlling for prenatal and postnatal depressive symptoms, prenatal medication effects on neurobehavioral development were largely undetected in the fetus and infant. Mental health care directed primarily at symptoms may not address the additional psychosocial needs of women parenting infants. Speculatively, prenatal serotonin reuptake inhibitor exposure may act as a plasticity rather than risk factor, potentially enhancing receptivity to a nonoptimal postnatal environment in some mother–infant dyads.

Introduction: The optimal diagnostic strategy for children presenting to the Emergency Department (ED) with suspected appendicitis (SA), the most common non-traumatic surgical emergency in children, remains unclear. This study aims to identify which investigations and management priorities are preferred by Canadian surgeons prior to consultation from the ED. Methods: An internet survey was extended to practicing surgeons who are members of the Canadian Association of Pediatric Surgeons and Canadian Association of General Surgeons. Three case-based scenarios evaluated surgeons expected ED investigations and management for SA with varying severity of disease (simple - SA vs perforated - PA) and sex (male vs female). Differences across scenarios were determined by ANOVA and direct comparisons were reported using proportions and odds ratios with 95% confidence intervals. Results: Surveys were completed by 82 surgeons. Across the 3 cases, CBC (227/246, 92.3%) and urinalysis (188/246, 76.4%) were the sole investigations expected in >75% of responses. Expectations differed across cases for use of blood cultures (p<0.001), electrolytes (p<0.001), sexually transmitted infection testing (0.015) and ultrasound (US) (p<0.001). Blood cultures (26/82, 31.7% vs 4/82, 4.9%; OR 9.05 95%CI 2.88-37.33) and electrolytes (58/82, 70.7% vs 33/82, 40.2%; OR 3.59 95%CI 1.79-7.24) were expected more often in severe disease. US was expected more often in females (58/82,70.7% vs 25/82, 30.5%; OR 5.51, 95% CI 2.68-11.38). Expected management differed across cases for fluid boluses (p=0.01), intravenous (IV) analgesia (p<0.001) and antibiotics (p<0.001), with all differences attributed to severity of illness (fluids 73/82, 89.0% vs 59/82, 72.0% OR 3.16 95%CI 1.28-8.33; IV analgesia 66/82, 80.5% vs 42/82, 51.2% OR 3.93 95%CI 1.86-8.45; antibiotics 44/82, 53.7% vs 10/82, 12.2% OR 8.34 95%CI 3.59-20.44). Conclusion: Severity of illness and sex of the child impact the ED investigations and management expected by surgeons consulted for suspected appendicitis. Further research focusing on how these expectations influence patient outcomes should be conducted. Collaborative ED-surgery protocols for the diagnosis and management of acute appendicitis in children should be established.

Children reared in impoverished environments are at risk for enduring psychological and physical health problems. Mechanisms by which poverty affects development, however, remain unclear. To explore one potential mechanism of poverty's impact on social–emotional and cognitive development, an experimental examination of a rodent model of scarcity-adversity was conducted and compared to results from a longitudinal study of human infants and families followed from birth (N = 1,292) who faced high levels of poverty-related scarcity-adversity. Cross-species results supported the hypothesis that altered caregiving is one pathway by which poverty adversely impacts development. Rodent mothers assigned to the scarcity-adversity condition exhibited decreased sensitive parenting and increased negative parenting relative to mothers assigned to the control condition. Furthermore, scarcity-adversity reared pups exhibited decreased developmental competence as indicated by disrupted nipple attachment, distress vocalization when in physical contact with an anesthetized mother, and reduced preference for maternal odor with corresponding changes in brain activation. Human results indicated that scarcity-adversity was inversely correlated with sensitive parenting and positively correlated with negative parenting, and that parenting fully mediated the association of poverty-related risk with infant indicators of developmental competence. Findings are discussed from the perspective of the usefulness of bidirectional–translational research to inform interventions for at-risk families.

Biodiversity conservation outside protected areas requires cooperation from affected communities, hence the extensive discussions of trade-offs in conservation, and of a so-called new conservation that addresses human relations with nature more fully. Human–wildlife conflict is one aspect of those relations, and as land use intensifies around protected areas the need to understand and manage its effects will only increase. Research on human–wildlife conflict often focuses on individual species but given that protecting wildlife requires protecting habitat, assessments of human–wildlife conflict should include subsidiary impacts that are associated with ecosystem conditions. Using a case study from Laikipia, Kenya, where conservation outside protected areas is critical, we analysed human–wildlife conflict from a household perspective, exploring the full range of impacts experienced by community members on Makurian Group Ranch. We addressed questions about four themes: (1) the relationship between experienced and reported human–wildlife conflict; (2) the results of a high-resolution assessment of experienced human–wildlife conflict; (3) the relative impact of high-frequency, low-severity conflict vs high-severity, low-frequency conflict; and (4) the effect of experienced conflict on receptivity to the conservation narrative. Our results show that high-frequency, low-severity conflict, which is often absent from reports and discussion in the literature, is a significant factor in shaping a community's perception of the cost–benefit ratio of conservation. Local, ongoing, high-resolution monitoring of human–wildlife conflict may facilitate more realistic and effective incorporation of the experienced impacts of human–wildlife conflict in conservation planning and management. Such monitoring could help to define locally appropriate trade-offs in conservation and thereby improve conservation outcomes.

Objectives: Visuospatial processing deficits have been reported in Huntington’s disease (HD). To date, no study has examined associations between visuospatial cognition and posterior brain findings in HD. Methods: We compared 119 premanifest (55> and 64<10.8 years to expected disease onset) and 104 early symptomatic (59 stage-1 and 45 stage-2) gene carriers, with 110 controls on visual search and mental rotation performance at baseline and 12 months. In the disease groups, we also examined associations between task performance and disease severity, functional capacity and structural brain measures. Results: Cross-sectionally, there were strong differences between all disease groups and controls on visual search, and between diagnosed groups and controls on mental rotation accuracy. Only the premanifest participants close to onset took longer than controls to respond correctly to mental rotation. Visual search negatively correlated with disease burden and motor symptoms in diagnosed individuals, and positively correlated with functional capacity. Mental rotation (“same”) was negatively correlated with motor symptoms in stage-2 individuals, and positively correlated with functional capacity. Visual search and mental rotation were associated with parieto-occipital (pre-/cuneus, calcarine, lingual) and temporal (posterior fusiform) volume and cortical thickness. Longitudinally, visual search deteriorated over 12 months in stage-2 individuals, with no evidence of declines in mental rotation. Conclusions: Our findings provide evidence linking early visuospatial deficits to functioning and posterior cortical dysfunction in HD. The findings are important since large research efforts have focused on fronto-striatal mediated cognitive changes, with little attention given to aspects of cognition outside of these areas. (JINS, 2016, 22, 595–608)

The following prospective longitudinal study considers the ways that protracted exposure to verbal and physical aggression between parents may take a substantial toll on emotional adjustment for 1,025 children followed from 6 to 58 months of age. Exposure to chronic poverty from infancy to early childhood as well as multiple measures of household chaos were also included as predictors of children's ability to recognize and modulate negative emotions in order to disentangle the role of interparental conflict from the socioeconomic forces that sometimes accompany it. Analyses revealed that exposure to greater levels of interparental conflict, more chaos in the household, and a higher number of years in poverty can be empirically distinguished as key contributors to 58-month-olds' ability to recognize and modulate negative emotion. Implications for models of experiential canalization of emotional processes within the context of adversity are discussed.

Marble, a non-porous stone composed of calcite, is subject to acid rain dissolution due to its relatively high dissolution rate. With the goal of preventing such damage, we have investigated the deposition of films of relatively insoluble hydroxyapatite (HAP) on marble. This paper investigates the factors that affect the nucleation and growth kinetics of HAP on marble. A mild, wet chemical synthesis route, in which diammonium hydrogen phosphate (DAP) salt was reacted with marble, alone and with cationic and anionic precursors under different reaction conditions, was used to produce inorganic HAP films on the mineral surface. Film nucleation, growth and metastable phase evolution were studied, using techniques such as scanning electron microscopy (SEM) and grazing incidence X-ray diffraction (GID). The onset of nucleation, and the growth rate of the film, increased with cationic (calcium) and anionic (carbonate) precursor additions. The calcium and phosphate precursors also influenced metastable phase formation, introducing a new phase.

Dispute resolution institutions facilitate agreements and preserve the peace whenever property rights are imperfect. In weak states, strengthening formal institutions can take decades, and so state and aid interventions also try to shape informal practices and norms governing disputes. Their goal is to improve bargaining and commitment, thus limiting disputes and violence. Mass education campaigns that promote alternative dispute resolution (ADR) are common examples of these interventions. We studied the short-term impacts of one such campaign in Liberia, where property disputes are endemic. Residents of 86 of 246 towns randomly received training in ADR practices and norms; this training reached 15% of adults. One year later, treated towns had higher resolution of land disputes and lower violence. Impacts spilled over to untrained residents. We also saw unintended consequences: more extrajudicial punishment and (weakly) more nonviolent disagreements. Results imply that mass education can change high-stakes behaviors, and improving informal bargaining and enforcement behavior can promote order in weak states.

Bacteriophytochromes (BphPs) are red-light photoreceptors found in photosynthetic and nonphotosynthetic bacteria that have been recently engineered as infrared fluorescent tissue markers. Light-induced, global structural changes are proposed to originate within their covalently bound biliverdin chromophore and propagate through the protein. Classical BphPs undergo reversible photoconversion between spectrally distinct light absorbing states, red (Pr) and far-red (Pfr), respectively. RpBph3 (P3), from Rhodopseudomonas palustris, photoconverts between a Pr and a unique near-red (Pnr) light-absorbing state. Due to size and photosensitivity of BphPs, structures of the intact proteins have not been resolved by nuclear magnetic resonance and/or X-ray crystallography. Therefore, structural details about the light and dark-adapted structures of the intact BphPs are not well understood at the molecular level. We have utilized fluid cell atomic force microscopy (AFM) to investigate the domain structure of intact P3 in its light-adapted state (Pnr). By varying the concentration of the protein, deposition time, and the ionic strength of the buffer, the aggregation of P3 on a mica surface can be controlled and single dimers may be observed in a biologically relevant media. Domain resolution has been achieved for several orientations of the dimer on the surface. The structural dimensions of the dimer have been compared to a modeled BphP in its intact form generated using PyMOL software. AFM experiments are currently underway to analyze the dark-adapted state (Pr) of P3 in order to observe the anticipated structural changes. Ultimately, the goal is to use AFM and other surface analytical methods such as scanning tunneling microscopy and electron microscopy to gain new insight into the unique photochemistry of P3.

We investigate the role of asymmetries in the line spread function of the 2-degree field (2dF) spectrograph and the variations in these asymmetries with the CCD, the plate, the time of observation, and the fibre. A data-reduction pipeline is developed that takes these deformations into account for the calibration and cross-correlation of the spectra. We show that, using the emission lines of calibration lamp observations, we can fit the line spread function with the sum of two Gaussian functions representing the theoretical signal and a perturbation of the system. This model is then used to calibrate the spectra and generate templates by downgrading high-resolution spectra. Thus, we can cross-correlate the observed spectra with templates degraded in the same way. Our reduction pipeline is tested on real observations and provides a significant improvement in the accuracy of the radial velocities obtained. In particular, the systematic errors that were as high as ∼20 km s−1 when applying the AAO reduction package 2DFDR are now reduced to ∼5 km s−1. Even though the 2dF spectrograph is to be decommissioned at the end of 2005, the analysis of archival data and previous studies could be improved by the reduction procedure we propose here.