Dietary nitrate is a precursor to nitric oxide, for which plausible mechanisms exist for both beneficial and detrimental influences in multiple sclerosis (MS)(1,2). Whether dietary nitrate has any role in MS onset is unclear. We aimed to test associations between nitrate intake from food sources (plant, vegetable, animal, processed meat, and unprocessed meat) and likelihood of a first clinical diagnosis of central nervous system demyelination (FCD). We used data from the Ausimmune Study (264 cases, 474 controls). Case participants (aged 19–59 years) presenting to medical professionals in four latitudinally different regions of Australia were referred to the study with an FCD. The Australian Electoral Roll was used to recruit one to four controls per case, matched by age (± 2 years), sex and study region. Habitual dietary intake representing the 12-month period preceding the study interview was assessed to determine dietary nitrate intake. In addition to matching variables, data on education, smoking history, and history of infectious mononucleosis, weight and height were collected. A blood sample was taken for measurement of serum 25-hydroxyvitamin D concentration, which was de-seasonalised. To test associations, we used logistic regression with full propensity score matching. We used two levels of covariate matching: in model 1, cases and controls were matched on the original matching variables (age, sex, and study region); in model 2, cases and controls were additionally matched on well-established/potential risk factors for MS (education, smoking history, and history of infectious mononucleosis) and dietary factors (total energy intake and dietary misreporting). In females only (n = 573; 368 controls and 205 cases), higher nitrate intake (per 60 mg/day) from plant-based foods (fully adjusted odds ratio [aOR] = 0.50, 95% CI, 0.31, 0.81, p < 0.01) or vegetables (aOR = 0.44, 95% CI, 0.27, 0.73, p < 0.01) was statistically significantly associated with lower likelihood of FCD. No association was found between nitrate intake (any sources) and likelihood of FCD in males. To our knowledge, this is the first study to investigate dietary nitrate intake in relation to FCD. Our result that higher intake of nitrate from plant-based foods (mainly vegetables) was associated with lower likelihood of FCD in females supports our previous findings showing that following a Mediterranean diet (rich in vegetables) associates with lower likelihood of FCD(3). The lack of association in males may be due to low statistical power and/or differing food preferences and pathological processes among males and females. Our results support further research to delineate the independent effect of nitrates form other dietary factors and explore a possible beneficial role for plant-derived nitrate in people at high risk of MS.

From early on, infants show a preference for infant-directed speech (IDS) over adult-directed speech (ADS), and exposure to IDS has been correlated with language outcome measures such as vocabulary. The present multi-laboratory study explores this issue by investigating whether there is a link between early preference for IDS and later vocabulary size. Infants’ preference for IDS was tested as part of the ManyBabies 1 project, and follow-up CDI data were collected from a subsample of this dataset at 18 and 24 months. A total of 341 (18 months) and 327 (24 months) infants were tested across 21 laboratories. In neither preregistered analyses with North American and UK English, nor exploratory analyses with a larger sample did we find evidence for a relation between IDS preference and later vocabulary. We discuss implications of this finding in light of recent work suggesting that IDS preference measured in the laboratory has low test-retest reliability.

Background: Saccade and pupil responses are potential neurodegenerative disease biomarkers due to overlap between oculomotor circuitry and disease-affected areas. Instruction-based tasks have previously been examined as biomarker sources, but are arduous for patients with limited cognitive abilities; additionally, few studies have evaluated multiple neurodegenerative pathologies concurrently. Methods: The Ontario Neurodegenerative Disease Research Initiative recruited individuals with Alzheimer’s disease (AD), mild cognitive impairment (MCI), amyotrophic lateral sclerosis (ALS), frontotemporal dementia, progressive supranuclear palsy, or Parkinson’s disease (PD). Patients (n=274, age 40-86) and healthy controls (n=101, age 55-86) viewed 10 minutes of frequently changing video clips without instruction while their eyes were tracked. We evaluated differences in saccade and pupil parameters (e.g. saccade frequency and amplitude, pupil size, responses to clip changes) between groups. Results: Preliminary data indicates low-level behavioural alterations in multiple disease cohorts: increased centre bias, lower overall saccade rate and reduced saccade amplitude. After clip changes, patient groups generally demonstrated lower saccade rate but higher microsaccade rate following clip change to varying degrees. Additionally, pupil responses were blunted (AD, MCI, ALS) or exaggerated (PD). Conclusions: This task may generate behavioural biomarkers even in cognitively impaired populations. Future work should explore the possible effects of factors such as medication and disease stage.

Quantifying the marine radiocarbon reservoir effect, offsets (ΔR), and ΔR variability over time is critical to improving dating estimates of marine samples while also providing a proxy of water mass dynamics. In the northeastern Pacific, where no high-resolution time series of ΔR has yet been established, we sampled radiocarbon (14C) from exactly dated growth increments in a multicentennial chronology of the long-lived bivalve, Pacific geoduck (Paneopea generosa) at the Tree Nob site, coastal British Columbia, Canada. Samples were taken at approximately decadal time intervals from 1725 CE to 1920 CE and indicate average ΔR values of 256 ± 22 years (1σ) consistent with existing discrete estimates. Temporal variability in ΔR is small relative to analogous Atlantic records except for an unusually old-water event, 1802–1812. The correlation between ΔR and sea surface temperature (SST) reconstructed from geoduck increment width is weakly significant (r2 = .29, p = .03), indicating warm water is generally old, when the 1802–1812 interval is excluded. This interval contains the oldest (–2.1σ) anomaly, and that is coincident with the coldest (–2.7σ) anomalies of the temperature reconstruction. An additional 32 14C values spanning 1952–1980 were detrended using a northeastern Pacific bomb pulse curve. Significant positive correlations were identified between the detrended 14C data and annual El Niño Southern Oscillation (ENSO) and summer SST such that cooler conditions are associated with older water. Thus, 14C is generally relatively stable with weak, potentially inconsistent associations to climate variables, but capable of infrequent excursions as illustrated by the unusually cold, old-water 1802–1812 interval.

Background: Eye movements reveal neurodegenerative disease processes due to overlap between oculomotor circuitry and disease-affected areas. Characterizing oculomotor behaviour in context of cognitive function may enhance disease diagnosis and monitoring. We therefore aimed to quantify cognitive impairment in neurodegenerative disease using saccade behaviour and neuropsychology. Methods: The Ontario Neurodegenerative Disease Research Initiative recruited individuals with neurodegenerative disease: one of Alzheimer’s disease, mild cognitive impairment, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson’s disease, or cerebrovascular disease. Patients (n=450, age 40-87) and healthy controls (n=149, age 42-87) completed a randomly interleaved pro- and anti-saccade task (IPAST) while their eyes were tracked. We explored the relationships of saccade parameters (e.g. task errors, reaction times) to one another and to cognitive domain-specific neuropsychological test scores (e.g. executive function, memory). Results: Task performance worsened with cognitive impairment across multiple diseases. Subsets of saccade parameters were interrelated and also differentially related to neuropsychology-based cognitive domain scores (e.g. antisaccade errors and reaction time associated with executive function). Conclusions: IPAST detects global cognitive impairment across neurodegenerative diseases. Subsets of parameters associate with one another, suggesting disparate underlying circuitry, and with different cognitive domains. This may have implications for use of IPAST as a cognitive screening tool in neurodegenerative disease.

Recent excavations by the Ancient Southwest Texas Project of Texas State University sampled a previously undocumented Younger Dryas component from Eagle Cave in the Lower Pecos Canyonlands of Texas. This stratified assemblage consists of bison (Bison antiquus) bones in association with lithic artifacts and a hearth. Bayesian modeling yields an age of 12,660–12,480 cal BP, and analyses indicate behaviors associated with the processing of a juvenile bison and the manufacture and maintenance of lithic tools. This article presents spatial, faunal, macrobotanical, chronometric, geoarchaeological, and lithic analyses relating to the Younger Dryas component within Eagle Cave. The identification of the Younger Dryas occupation in Eagle Cave should encourage archaeologists to revisit previously excavated rockshelter sites in the Lower Pecos and beyond to evaluate deposits for unrecognized, older occupations.

Grains rich in starch constitute the primary source of energy for both pigs and humans, but there is incomplete understanding of physiological mechanisms that determine the extent of digestion of grain starch in monogastric animals including pigs and humans. Slow digestion of starch to produce glucose in the small intestine (SI) leads to undigested starch escaping to the large intestine where it is fermented to produce short-chain fatty acids. Glucose generated from starch provides more energy than short-chain fatty acids for normal metabolism and growth in monogastrics. While incomplete digestion of starch leads to underutilised feed in pigs and economic losses, it is desirable in human nutrition to maintain consistent body weight in adults. Undigested nutrients reaching the ileum may trigger the ileal brake, and fermentation of undigested nutrients or fibre in the large intestine triggers the colonic brake. These intestinal brakes reduce the passage rate in an attempt to maximise nutrient utilisation, and lead to increased satiety that may reduce feed intake. The three physiological mechanisms that control grain digestion and feed intake are: (1) gastric emptying rate; (2) interplay of grain digestion and passage rate in the SI controlling the activation of the ileal brake; and (3) fermentation of undigested nutrients or fibre in the large intestine activating the colonic brake. Fibre plays an important role in influencing these mechanisms and the extent of their effects. In this review, an account of the physiological mechanisms controlling the passage rate, feed intake and enzymatic digestion of grains is presented: (1) to evaluate the merits of recently developed methods of grain/starch digestion for application purposes; and (2) to identify opportunities for future research to advance our understanding of how the combination of controlled grain digestion and fibre content can be manipulated to physiologically influence satiety and food intake.

Vitamin D deficiency is recognised as a public health problem globally, and a high prevalence of deficiency has previously been reported in Australia. This study details the prevalence of vitamin D deficiency in a nationally representative sample of Australian adults aged ≥25 years, using an internationally standardised method to measure serum 25-hydroxyvitamin D (25(OH)D) concentrations and identifies demographic and lifestyle factors associated with vitamin D deficiency. We used data from the 2011–2013 Australian Health Survey (n 5034 with complete information on potential predictors and serum 25(OH)D concentrations). Serum 25(OH)D concentrations were measured by a liquid chromatography-tandem MS that is certified to the reference measurement procedures developed by the National Institute of Standards and Technology, Ghent University and the US Centers for Disease Control and Prevention. Vitamin D deficiency and insufficiency were defined as serum 25(OH)D concentrations <50 nmol/l and 50 to <75 nmol/l, respectively. Overall, 20 % of participants (19 % men; 21 % women) were classified as vitamin D deficient, with a further 43 % classified as insufficient (45 % men; 42 % women). Independent predictors of vitamin D deficiency included being born in a country other than Australia or the main English-speaking countries, residing in southern (higher latitude) states of Australia, being assessed during winter or spring, being obese, smoking (women only), having low physical activity levels and not taking vitamin D or Ca supplements. Given our increasingly indoor lifestyles, there is a need to develop and promote strategies to maintain adequate vitamin D status through safe sun exposure and dietary approaches.

Toxic trace elements present an environmental hazard in the vicinity of mining and smelting activities. However, the processes of transfer of these elements to groundwater and to plants are not always clear. Tharsis mine, in the Iberian pyrite belt (SW Spain), has been exploited since 2500 BC, with extensive smelting taking place from the 1850s until the 1920s. Sixty four soil (mainly topsoils) and vegetation samples were collected in February 2001 and analysed by ICP-AES for 23 elements. Concentrations are 6—6300 mg kg-1 As and 14—24800 mg kg-1 Pb in soils, and 0.20—9 mg kg-1 As and 2—195 mg kg-1 Pb in vegetation. Trace element concentrations decrease rapidly away from the mine, with As and Pb concentrations in the range 6—1850 mg kg—1 (median 22 mg kg—1) and 14—31 mg kg—1 (median 43 mg kg—1), respectively, 1 km away from the mine. These concentrations are low when compared to other well-studied mining and smelting areas (e.g. 600 mg kg—1 As at 8 km from Yellowknife smelter, Canada; >100 mg kg—1 Pb over 270 km2 around the Pb-Zn Port Pirie smelter, South Australia; mean of 1419 mg kg—1 Pb around Aberystwyth smelter, Wales, UK). The high metal content of the vegetation and the low soil pH (mean pH 4.93) indicate the potential for trace element mobility which could explain the relatively low concentration of metals in Tharsis topsoils and cause threats to plans to redevelop the Tharsis area as an orange plantation.

The Yellow Chat Epthianura crocea is comprised of three disjunct subspecies. Subspecies E. c. macgregori (Capricorn Yellow Chat) is listed as Critically Endangered under the EPBC Act and has a distribution that also appears to be disjunct, with a limited geographic area of less than 7,000 ha. Some populations are threatened by rapid industrial development, and it is important for conservation of the subspecies to determine the extent to which the putative populations are connected. We used 14 microsatellite markers to measure genetic diversity and to determine the extent of gene flow between two disjunct populations at the northern and southern extremes of the subspecies’ range. No significant differences in genetic diversity (number of alleles and heterozygosity) were observed, but clear population structuring was apparent, with obvious differentiation between the northern and southern populations. The most likely explanation for reduced gene flow between the two populations is either the development of a geographic barrier as a consequence of shrinkage of the marine plains associated with the rise in sea levels following the last glacial maxima, or reduced connectivity across the largely unsuitable pasture and forest habitat that now separates the two populations, exacerbated by declining population size and fewer potential emigrants. Regardless of the mechanism, restricted gene flow between these two populations has important consequences for their ongoing conservation. The relative isolation of the smaller southern groups (the Fitzroy River delta and Curtis Island) from the much larger northern group (both sides of the Broad Sound) makes the southern population more vulnerable to local extinction. Conservation efforts should focus on nature refuge agreements with land owners agreeing to maintain favourable grazing management practices in perpetuity, particularly in the northern area where most chats occur. Supplemental exchanges of individuals from northern and southern populations should be explored as a way of increasing genetic diversity and reducing inbreeding.

Phased Array Feed (PAF) technology is the next major advancement in radio astronomy in terms of combining high sensitivity and large field of view. The Focal L-band Array for the Green Bank Telescope (FLAG) is one of the most sensitive PAFs developed so far. It consists of 19 dual-polarization elements mounted on a prime focus dewar resulting in seven beams on the sky. Its unprecedented system temperature of ~17 K will lead to a 3 fold increase in pulsar survey speeds as compared to contemporary single pixel feeds. Early science observations were conducted in a recently concluded commissioning phase of the FLAG where we clearly demonstrated its science capabilities. We observed a selection of normal and millisecond pulsars and detected giant pulses from PSR B1937+21.

This paper presents latest thinking from the Institute and Faculty of Actuaries’ Model Risk Working Party and follows on from their Phase I work, Model Risk: Daring to Open the Black Box. This is a more practical paper and presents the contributors’ experiences of model risk gained from a wide range of financial and non-financial organisations with suggestions for good practice and proven methods to reduce model risk. After a recap of the Phase I work, examples of model risk communication are given covering communication: to the Board; to the regulator; and to external stakeholders. We present a practical framework for model risk management and quantification with examples of the key actors, processes and cultural challenge. Lessons learned are then presented from other industries that make extensive use of models and include the weather forecasting, software and aerospace industries. Finally, a series of case studies in practical model risk management and mitigation are presented from the contributors’ own experiences covering primarily financial services.

Preplant incorporation of alachlor [2-chloro-N-(2,6-diethylphenyl)-N-(methoxymethyl)acetamide] at 3.6 kg ai/ha, metolachlor [2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-1-methylethyl)acetamide] at 2.2 kg ai/ha, and tank mixtures of imazaquin {2-[4,5-dihydro-4-methyl-4-(1-methylethyl)-5-oxo-1H-imidazol-2-yl]-3-quinolinecarboxylic acid} with either alachlor at 0.14 + 2.2 kg ai/ha or metolachlor at 0.14 + 1.1 kg ai/ha controlled >90% red rice (Oryza sativa L. # ORYSA) in soybeans [Glycine max (L.) Merr.]. Also, FMC-57020 [2-(2-chlorophenyl)methyl-4,4-dimethyl-3-isoxazolidinone] at 1.7 kg ai/ha applied preplant incorporated controlled > 80% of the red rice. DPX-Y6202 {2-[4-[(6-chloro-2-quinoxalinyl)oxy]-phenoxy]-propionic acid, ethyl ester} was the best and most consistent postemergence herbicide treatment for red rice control when applied once at 0.28 kg ai/ha or sequentially at 0.14 kg ai/ha each time. Haloxyfop {2-[4-[[3-chloro-5-(trifluoromethyl)-2-pyridinyl]oxy] phenoxy] propanoic acid} applied at 0.16 kg ai/ha followed by another application at 0.14 kg ai/ha gave excellent red rice control in 2 of 3 years. Soybeans were uninjured by the herbicide treatments and yield was higher from treated than untreated soybeans.

Low birth weight is associated with increased risk of cardiovascular disease in adulthood. Intrauterine growth restriction (IUGR) hearts have fewer CMs in early postnatal life, which may impair postnatal cardiovascular function and hence, explain increased disease risk, but whether the cardiomyocyte deficit persists to adult life is unknown. We therefore studied the effects of experimentally induced placental restriction (PR) on cardiac outcomes in young adult sheep. Heart size, cardiomyocyte number, nuclearity and size were measured in control (n=5) and PR (n=5) male sheep at 1 year of age. PR lambs were 36% lighter at birth (P=0.007), had 38% faster neonatal relative growth rates (P=0.001) and had 21% lighter heart weights relative to body weight as adults (P=0.024) than control lambs. Cardiomyocyte number, nuclearity and size in the left ventricle did not differ between control and PR adults; hearts of both groups contained cardiomyocytes (CM) with between one and four nuclei. Overall, cardiomyocyte number in the adult left ventricle correlated positively with birth weight but not with adult weight. This study is the first to demonstrate that intrauterine growth directly influences the complement of CM in the adult heart. Cardiomyocyte size was not correlated with cardiomyocyte number or birth weight. Our results suggest that body weight at birth affects lifelong cardiac functional reserve. We hypothesise that decreased cardiomyocyte number of low birth weight individuals may impair their capacity to adapt to additional challenges such as obesity and ageing.