The interaction of relativistically intense lasers with opaque targets represents a highly non-linear, multi-dimensional parameter space. This limits the utility of sequential 1D scanning of experimental parameters for the optimization of secondary radiation, although to-date this has been the accepted methodology due to low data acquisition rates. High repetition-rate (HRR) lasers augmented by machine learning present a valuable opportunity for efficient source optimization. Here, an automated, HRR-compatible system produced high-fidelity parameter scans, revealing the influence of laser intensity on target pre-heating and proton generation. A closed-loop Bayesian optimization of maximum proton energy, through control of the laser wavefront and target position, produced proton beams with equivalent maximum energy to manually optimized laser pulses but using only 60% of the laser energy. This demonstration of automated optimization of laser-driven proton beams is a crucial step towards deeper physical insight and the construction of future radiation sources.

We present the development and characterization of a high-stability, multi-material, multi-thickness tape-drive target for laser-driven acceleration at repetition rates of up to 100 Hz. The tape surface position was measured to be stable on the sub-micrometre scale, compatible with the high-numerical aperture focusing geometries required to achieve relativistic intensity interactions with the pulse energy available in current multi-Hz and near-future higher repetition-rate lasers ($>$kHz). Long-term drift was characterized at 100 Hz demonstrating suitability for operation over extended periods. The target was continuously operated at up to 5 Hz in a recent experiment for 70,000 shots without intervention by the experimental team, with the exception of tape replacement, producing the largest data-set of relativistically intense laser–solid foil measurements to date. This tape drive provides robust targetry for the generation and study of high-repetition-rate ion beams using next-generation high-power laser systems, also enabling wider applications of laser-driven proton sources.

Prenatal diethylstilbestrol (DES) exposure is associated with increased risk of hormonally mediated cancers and other medical conditions. We evaluated the association between DES and risk of pancreatic cancer and pancreatic disorders, type 2 diabetes, and gallbladder disease, which may be involved with this malignancy. Our analyses used follow-up data from the US National Cancer Institute DES Combined Cohort Study. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for age, sex, cohort, body mass index, smoking, and alcohol for the association between prenatal DES exposure and type 2 diabetes, gallbladder disease (mainly cholelithiasis), pancreatic disorders (mainly pancreatitis), and pancreatic cancer among 5667 exposed and 3315 unexposed individuals followed from 1990 to 2017. Standardized incidence rate (SIR) ratios for pancreatic cancer were based on age-, race-, and calendar year-specific general population cancer incidence rates. In women and men combined, the hazards for total pancreatic disorders and pancreatitis were greater in the prenatally DES exposed than the unexposed (HR = 11, 95% CI 2.6–51 and HR = 7.0, 95% CI 1.5–33, respectively). DES was not associated overall with gallbladder disease (HR = 1.2, 95% CI 0.88–1.5) or diabetes (HR = 1.1, 95% CI 0.9–1.2). In women, but not in men, DES exposure was associated with increased risk of pancreatic cancer compared with the unexposed (HR: 4.1, 95% CI 0.84–20) or general population (SIR: 1.9, 95% CI 1.0–3.2). Prenatal DES exposure may increase the risk of pancreatic disorders, including pancreatitis in women and men. The data suggested elevated pancreatic cancer risk in DES-exposed women, but not in exposed men.

Quantifying tree biomass is an important research and management goal across many disciplines. For species that exhibit predictable relationships between structural metrics (e.g. diameter, height, crown breadth) and total weight, allometric calculations produce accurate estimates of above-ground biomass. However, such methods may be insufficient where inter-individual variation is large relative to individual biomass and is itself of interest (for example, variation due to herbivory). In an East African savanna bushland, we analysed photographs of small (<5 m) trees from perpendicular angles and fixed distances to estimate above-ground biomass. Pixel area of trees in photos and diameter were more strongly related to measured, above-ground biomass of destructively sampled trees than biomass estimated using a published allometric relation based on diameter alone (R2 = 0.86 versus R2 = 0.68). When tested on trees in herbivore-exclusion plots versus unfenced (open) plots, our predictive equation based on photos confirmed higher above-ground biomass in the exclusion plots than in unfenced (open) plots (P < 0.001), in contrast to no significant difference based on the allometric equation (P = 0.43). As such, our new technique based on photographs offers an accurate and cost-effective complement to existing methods for tree biomass estimation at small scales with potential application across a wide variety of settings.

Gut symbionts can augment resistance to pathogens by stimulating host-immune responses, competing for space and nutrients, or producing antimicrobial metabolites. Gut microbiota of social bees, which pollinate many crops and wildflowers, protect hosts against diverse infections and might counteract pathogen-related bee declines. Bumble bee gut microbiota, and specifically abundance of Lactobacillus ‘Firm-5’ bacteria, can enhance resistance to the trypanosomatid parasite Crithidia bombi. However, the mechanism underlying this effect remains unknown. We hypothesized that the Firm-5 bacterium Lactobacillus bombicola, which produces lactic acid, inhibits C. bombi via pH-mediated effects. Consistent with our hypothesis, L. bombicola spent medium inhibited C. bombi growth via reduction in pH that was both necessary and sufficient for inhibition. Inhibition of all parasite strains occurred within the pH range documented in honey bees, though sensitivity to acidity varied among strains. Spent medium was slightly more potent than HCl, d- and l-lactic acids for a given pH, suggesting that other metabolites also contribute to inhibition. Results implicate symbiont-mediated reduction in gut pH as a key determinant of trypanosomatid infection in bees. Future investigation into in vivo effects of gut microbiota on pH and infection intensity would test the relevance of these findings for bees threatened by trypanosomatids.

The aim of the present work was to address experimentally the possible impact of exposure to air pollution during gestation on the differentiation and function of the gonads of the offspring using a rabbit model. Rabbits were exposed daily to diluted diesel exhaust gas or filtered air from the 3rd until the 27th day of gestation, during which time germ cells migrate in genital ridges and divide, and fetal sex is determined. Offspring gonads were collected shortly before birth (28th day of gestation) or after puberty (7.5 months after birth). The structure of the gonads was analyzed by histological and immunohistological methods. Serum concentrations of testosterone and anti-Müllerian hormone were determined using ELISA. The morphology and the endocrine function of the gonads collected just at the arrest of the exposure were similar in polluted and control animals in both sexes. No differences were observed as well in gonads collected after puberty. Sperm was collected at the head of the epididymis in adults. Sperm motility and DNA fragmentation were measured. Among all parameters analyzed, only the sperm DNA fragmentation rate was increased three-fold in exposed males. Mechanisms responsible for these modifications and their physiological consequences are to be further clarified.

Soil-applied herbicides alone or followed by postemergence (POST) applications of CGA-277476 were evaluated for season-long weed control in soybean. Common cocklebur, hemp sesbania, and pitted morningglory control was not consistently improved with a soil-applied herbicide followed by a POST application of 79 g ai/ha CGA-277476. However, in locations with heavy weed pressure, a tank-mix of chlorimuron + metribuzin + trifluralin or imazaquin + pendimethalin followed by CGA-277476 improved common cocklebur, hemp sesbania, and pitted morningglory over CGA-277476 alone. Sequential application of CGA-277476 following SAN 582 improved weed control over SAN 582 alone. When weed pressure was not severe, there were no differences in control from CGA-277476 alone or following soil-applied herbicides. A POST application of CGA-277476 following soil-applied herbicides did not consistently improve soybean yield over CGA-277476 alone. Yield from soybean treated with SAN 582 was improved when CGA-277476 was applied. In contrast, when chlorimuron + metribuzin + trifluralin or imazaquin + pendimethalin were applied at planting, yield was similar with or without POST application of CGA-277476.

Field experiments were conducted at three Mississippi locations to evaluate potential antagonism when postemergence graminicides were tank-mixed with CGA-277476 and to determine if the antagonism could be overcome with an increase in graminicide rate. At all locations when the 1X rate of clethodim, fluazifop-P, or quizalofop was tank-mixed with 79 g ai/ ha CGA-277476, johnsongrass, broadleaf signalgrass, and barnyardgrass control was reduced 5 to 30%. When the graminicide rates were increased to 1.5X, antagonism was still present for fluazifop-P and quizalofop. However, 156 g ai/ha clethodim overcame the antagonism when tank-mixed with 79 g/ha CGA-277476 compared to 105 g/ha clethodim. CGA-277476 alone controlled barnyardgrass and broadleaf signalgrass 38 to 63% and johnsongrass 60 to 85%. There were no differences in soybean yields with graminicides applied alone or tank-mixed with CGA-277476.

Field research was conducted at three locations in Mississippi to evaluate CGA-277476 tank mixtures with four broadleaf herbicides for possible improvement of broadleaf weed control. Tank mixtures in this research were typically additive, although some instances of antagonism were noted. Control of morningglory (Ipomoea) species and hemp sesbania (Sesbania exaltata) was not consistently improved by the addition of acifluorfen, chlorimuron, fomesafen, or imazaquin to 59 or 79 g ai/ha CGA-277476. However, when a large population of weeds was present, the addition of acifluorfen, chlorimuron, or fomesafen to 59 or 79 g/ha CGA-277476 improved control over CGA-277476 alone. Prickly sida (Sida spinosa) was not controlled more than 68% with any treatment in this study; however, horse purslane (Trianthema portulacastrum) was controlled at least 90% with either 79 g/ha CGA-277476 alone or tank-mixed with acifluorfen, fomesafen, chlorimuron, or imazaquin. The addition of CGA-277476 to acifluorfen or fomesafen did not improve control over acifluorfen or fomesafen alone on any of the weeds evaluated; however, the addition of CGA-277476 to imazaquin improved hemp sesbania control over imazaquin alone. Tank mixtures did not result in yields greater than CGA-277476 alone in areas with moderate weed pressure, whereas in areas with severe weed pressure, tank mixtures improved soybean (Glycine max) yield over CGA-277476 alone.

Leaf mass per area (MA) is a central ecological trait that is intercorrelated with leaf life span, photosynthetic rate, nutrient concentration, and palatability to herbivores. These coordinated variables form a globally convergent leaf economics spectrum, which represents a general continuum running from rapid resource acquisition to maximized resource retention. Leaf economics are little studied in ancient ecosystems because they cannot be directly measured from leaf fossils. Here we use a large extant data set (65 sites; 667 species-site pairs) to develop a new, easily measured scaling relationship between petiole width and leaf mass, normalized for leaf area; this enables MA estimation for fossil leaves from petiole width and leaf area, two variables that are commonly measurable in leaf compression floras. The calibration data are restricted to woody angiosperms exclusive of monocots, but a preliminary data set (25 species) suggests that broad-leaved gymnosperms exhibit a similar scaling. Application to two well-studied, classic Eocene floras demonstrates that MA can be quantified in fossil assemblages. First, our results are consistent with predictions from paleobotanical and paleoclimatic studies of these floras. We found exclusively low-MA species from Republic (Washington, U.S.A., 49 Ma), a humid, warm-temperate flora with a strong deciduous component among the angiosperms, and a wide MA range in a seasonally dry, warm-temperate flora from the Green River Formation at Bonanza (Utah, U.S.A., 47 Ma), presumed to comprise a mix of short and long leaf life spans. Second, reconstructed MA in the fossil species is negatively correlated with levels of insect herbivory, whether measured as the proportion of leaves with insect damage, the proportion of leaf area removed by herbivores, or the diversity of insect-damage morphotypes. These correlations are consistent with herbivory observations in extant floras and they reflect fundamental trade-offs in plant-herbivore associations. Our results indicate that several key aspects of plant and plant-animal ecology can now be quantified in the fossil record and demonstrate that herbivory has helped shape the evolution of leaf structure for millions of years.

There are now significant data to support the hypothesis that early life nutrition in the fetus, infant and young child can have profound effects on long-term health. This review considers some of this evidence with specific reference to the current burden of disease in Australia and New Zealand. As the findings of further research become available, recommendations on optimizing early life nutrition should be formulated and made widely available as part of the preventative health policy agenda in both Australia and New Zealand.

Purification of amyloid plaque core proteins (APCP) from Alzheimer's disease brains to complete homogeneity and in high yield permitted its chemical fractionation and characterization of its components. APCP is mainly made of β-amyloid (βA) and an assortment of glycoproteins (accounting for 20%) rich in carbohydrates compatible with N-and O-linked saccharides. When added to tissue culture of sympathetic and sensory neurons APCP and βA inhibited neuritic sprouting, a reversible phenomenon at low doses. Higher concentrations of both substances kill the neurons in culture. APCP is significantly more toxic than βA, suggesting the minor components may play an important role in increasing the toxicity of βA. If the observed toxic effects of APCP in situ are occurring in vivo during the course of AD, then the accumulation of these extracellular proteins could be largely responsible for some of the neuronal death observed in this neuropathology.

Diethylstilbestrol (DES) is a non-steroidal estrogen that was commonly prescribed during pregnancy from the late 1940s to 1971. A potent endocrine disruptor, prenatal DES exposure has been linked with reproductive tract malformations, adverse pregnancy outcomes, cancer, infertility and earlier menopause. DES was used for years as a growth promoter in animal production. Some animal studies suggest that prenatal DES exposure is associated with obesity and metabolic disturbances. Using data from the National Cancer Institute DES Follow-Up Study, we evaluated the association between DES and adult obesity, weight gain from age 20 to mid-life, central adiposity and height among 2871 prenatally exposed and 1352 unexposed women between 23 and 52 years of age (median 41.5) at baseline in 1994. DES exposure status was confirmed by prenatal medical record review. We used multivariable log-binomial models to calculate risk ratios (RRs) for obesity in 2006, and linear regression to calculate mean differences in body mass index, weight gain, waist circumference and height. The adjusted RR for DES and obesity was 1.09 [95% confidence interval (CI): 0.97, 1.22], and RRs were 1.23 (CI: 1.07, 1.42) and 1.05 (CI: 0.91, 1.20) for low and high estimated total DES dose, respectively, compared with no exposure. DES-exposed women gained slightly more weight than unexposed women [mean difference, 0.70 kg (CI: −0.27, 1.66)]. This study suggests that prenatal DES exposure may be associated with a small increase in adult obesity.

The concept of Developmental Origins of Health and Disease initially stemmed from the developmental programming of metabolic diseases. Reproductive functions and fertility in adulthood may also be programmed during foetal development. We studied the impact of dietary-induced maternal hyperlipidaemia and hypercholesterolaemia (HH), administered at 10 weeks of age and throughout the gestation and lactation, on male reproductive functions of rabbit offspring. Male rabbits born to HH dams and fed a control diet had significantly lighter testes and epididymes compared with rabbits born to control dams at adulthood. No significant changes in sperm concentration, sperm DNA integrity and sperm membrane composition were observed, but serum-free testosterone concentrations were decreased in HH males. This study confirms the importance of maternal metabolic status for the development of male reproductive organs.