Ozone pollution contributes to the yield gap for beans in Uganda, East Africa, and is co-located with other agricultural stresses.

Air quality negatively impacts agriculture, reducing the yield of staple food crops. While measured data on African ground-level ozone levels are scarce, experimental studies demonstrate the damaging impact of ozone on crops. Common beans (Phaseolus vulgaris), an ozone-sensitive crop, are widely grown in Uganda. Using modelled ozone flux, agricultural surveys, and a flux-effect relationship, this study estimates yield and production losses due to ozone for Ugandan beans in 2015. Analysis at this scale allows the use of localised data, and results can be presented at a sub-regional level. Soil nutrient stress, drought, flood risk, temperature and deprivation were also mapped to investigate where stresses may coincide. Average bean yield losses due to ozone were 17% and 14% (first and second growing season respectively), equating to 184 thousand tonnes production loss. However, for some sub-regions, losses were up to 27.5% and other crop stresses also coincided in these areas. This methodology could be applied widely, allowing estimates of ozone impact for countries lacking air quality and/or experimental data. As crop productivity is below its potential in many areas of the world, changing agricultural practices to mitigate against losses due to ozone could help to reduce the crop yield gap.

Evidence-based logic chains demonstrate multiple impacts of trace metals on ecosystem services.

Trace metals can have far-reaching ecosystem impacts. In this study, we develop consistent and evidence-based logic chains to demonstrate the wider effects of trace metal contamination on a suite of ecosystem services. They demonstrate knock-on effects from an initial receptor that is sensitive to metal toxicity, along a cascade of impact, to final ecosystem services via alterations to multiple ecosystem processes. We developed logic chains to highlight two aspects of metal toxicity: for impacts of copper pollution in soil ecosystems, and for impacts of mercury in freshwaters. Each link of the chains is supported by published evidence, with an indication of the strength of the supporting science. Copper pollution to soils (134 unique chains) showed a complex network of pathways originating from direct effects on a range of invertebrate and microbial taxa and plants. In contrast, mercury pollution on freshwaters (63 unique chains) shows pathways that broadly follow the food web of this habitat, reflecting the potential for mercury bioaccumulation. Despite different pathways, there is considerable overlap in the final ecosystem services impacted by both of these metals and in both ecosystems. These included reduced human-use impacts (food, fishing), reduced human non-use impacts (amenity value) and positive or negative alterations to climate regulation (impacts on carbon sequestration). Other final ecosystem goods impacted include reduced crop production, animal production, flood regulation, drinking water quality and soil purification. Taking an ecosystem services approach demonstrates that consideration of only the direct effects of metal contamination of soils and water will considerably underestimate the total impacts of these pollutants. Construction of logic chains, evidenced by published literature, allows a robust assessment of potential impacts indicating primary, secondary and tertiary effects.

The climate benefits of high-sugar grassland may be compromised by ozone pollution.

High sugar ryegrasses (HSG) have been developed to improve the uptake, digestion and nitrogen (N)-utilisation of grazing stock, with the potential to increase production yields and benefit climate by reducing methane (CH4) and nitrous oxide (N2O) emissions from livestock farming. In this study, the effects of tropospheric ozone pollution on the seasonal growth dynamics of HSG pasture mesocosms containing Lolium perenne cv. AberMagic and Trifolium repens cv. Crusader were investigated. Species-specific ozone (O3) dose-response relationships (seasonal means: 35, 41, 47, 51, 59 & 67ppb) based on the Phytotoxic Ozone Dose (PODy) were constructed for above and below ground biomass, injury, N-fixation and forage quality. The dynamics of effects of ozone exposure on HSG pasture changed over the course of a season, with the strongest responses occurring in the first 4-8weeks. Overall, strong negative responses to ozone flux were found for root biomass, root nodule mass and N-fixation rates, and ozone adversely impacted a range of forage quality parameters including total sugar content and relative and consumable food values. These results indicate that increasing ozone pollution could decrease the N-use efficiency and reduce the sugar content of managed pasture, and thereby partially detract from some of the suggested benefits of HSG.

BVOC responses to realistic nitrogen fertilization and ozone exposure in silver birch.

Emission of BVOC (Biogenic Volatile Organic Compounds) from plant leaves in response to ozone exposure (O3) and nitrogen (N) fertilization is poorly understood. For the first time, BVOC emissions were explored in a forest tree species (silver birch, Betula pendula) exposed for two years to realistic levels of O3 (35, 48 and 69 ppb as daylight average) and N (10, 30 and 70 kg ha(-1) yr(-1), applied weekly to the soil as ammonium nitrate). The main BVOCs emitted were: α-pinene, ß-pinene, limonene, ocimene, (E)-4,8-dimethyl-1,3,7-nonatriene (DMNT) and hexanal. Ozone exposure increased BVOC emission and reduced total leaf area. The effect on emission was stronger when a short-term O3 metric (concentrations at the time of sampling) rather than a long-term one (AOT40) was used. The effect of O3 on total leaf area was not able to compensate for the stimulation of emission, so that responses to O3 at leaf and whole-plant level were similar. Nitrogen fertilization increased total leaf area, decreased α-pinene and ß-pinene emission, and increased ocimene, hexanal and DMNT emission. The increase of leaf area changed the significance of the emission response to N fertilization for most compounds. Nitrogen fertilization mitigated the effects of O3 exposure on total leaf area, while the combined effects of O3 exposure and N fertilization on BVOC emission were additive and not synergistic. In conclusion, O3 exposure and N fertilization have the potential to affect global BVOC via direct effects on plant emission rates and changes in leaf area.

N-fixation in legumes--An assessment of the potential threat posed by ozone pollution.

The growth, development and functioning of legumes are often significantly affected by exposure to tropospheric ozone (O3) pollution. However, surprisingly little is known about how leguminous Nitrogen (N) fixation responds to ozone, with a scarcity of studies addressing this question in detail. In the last decade, ozone impacts on N-fixation in soybean, cowpea, mung bean, peanut and clover have been shown for concentrations which are now commonly recorded in ambient air or are likely to occur in the near future. We provide a synthesis of the existing literature addressing this issue, and also explore the effects that may occur on an agroecosystem scale by predicting reductions in Trifolium (clovers) root nodule biomass in United Kingdom (UK) pasture based on ozone concentration data for a "high" (2006) and "average" ozone year (2008). Median 8% and 5% reductions in clover root nodule biomass in pasture across the UK were predicted for 2006 and 2008 respectively. Seasonal exposure to elevated ozone, or short-term acute concentrations >100 ppb, are sufficient to reduce N-fixation and/or impact nodulation, in a range of globally-important legumes. However, an increasing global burden of CO2, the use of artificial fertiliser, and reactive N-pollution may partially mitigate impacts of ozone on N-fixation.

Testosterone, free testosterone, and free androgen index in women: Reference intervals, biological variation, and diagnostic value in polycystic ovary syndrome.

OBJECTIVE: The objective of our study was to determine reference intervals and biologic variation for testosterone (T), free testosterone (fT), and free androgen index (FAI) in women with accurate methods and to test the discriminative value of these parameters in a polycystic ovary syndrome (PCOS)-population. METHODS: Serum was obtained daily during a normal menstrual cycle from 25 healthy women (677 data-points). A single serum sample was obtained from 44 PCOS-patients. T was measured by LC­MS/MS and by Architect® 2nd generation T Immunoassay. Sex hormone-binding globulin was measured to calculate fT and FAI. Results: Reference intervals which were established in healthy women with an ovulatory menstrual cycle were T = 0.3-1.6 nmol/L and 0.5-2.0 nmol/L, fT = 5.2-26 pmol/L and 7.2-33 pmol/L, and FAI = 0.4-2.9 and 0.6-4.4, by LC-MS/MS and immunoassay, respectively. T, fT and FAI were higher in PCOS patients than in controls (p b 0.0001). The areas under the curve of receiver operator characteristic (ROC) plots were not different for T, fT, or FAI when T was measured by LC­MS/MS versus immunoassay based on prediction of PCOS. FAI and fT were the strongest predictors of PCOS. CONCLUSIONS: When based upon the appropriate reference intervals and ROC analysis, LC-MS/MS and second generation immunoassay have equivalent clinical utility for the diagnosis of PCOS.

Highlighting the threat from current and near-future ozone pollution to clover in pasture.

Globally, the legume-rhizobia symbiosis, contained within specialised organs called root nodules, is thought to add at least 30 Tg N annually to agricultural land. The growth and functioning of a modern white clover (Trifolium repens cv. Crusader) and red clover (T. pratense cv. Merviot) cultivar were investigated in current and future ozone scenarios in solardomes. Both cultivars developed leaf injury and had significant reductions in root biomass and root nodule number in response to ozone, with Crusader also displaying a reduced size and mass of nodules. In-situ measurements of N-fixation in Crusader by acetylene reduction assay revealed reduced N-fixation rates in a future scenario with an increased background and moderate peaks of ozone. The implications for the sustainability of temperate pasture are discussed.

Plant species sensitivity distributions for ozone exposure.

This study derived Species Sensitivity Distributions (SSD), representing a cumulative stressor-response distribution based on single-species sensitivity data, for ozone exposure on natural vegetation. SSDs were constructed for three species groups, i.e. trees, annual grassland and perennial grassland species, using species-specific exposure-response data. The SSDs were applied in two ways. First, critical levels were calculated for each species group and compared to current critical levels for ozone exposure. Second, spatially explicit estimates of the potentially affected fraction of plant species in Northwestern Europe were calculated, based on ambient ozone concentrations. We found that the SSD-based critical levels were lower than for the current critical levels for ozone exposure, with conventional critical levels for ozone relating to 8-20% affected plant species. Our study shows that the SSD concept can be successfully applied to both derive critical ozone levels and estimate the potentially affected species fraction of plant communities along specific ozone gradients.

Effects of ozone on inter- and intra-species competition and photosynthesis in mesocosms of Lolium perenne and Trifolium repens.

Trifolium repens and Lolium perenne were exposed as both monocultures and two-species mixtures to an episodic rural ozone regime in large, well-watered containers within solardomes for 12 weeks. There were reductions in biomass for T. repens, but not L. perenne, and the proportion of T. repens decreased in ozone-exposed mixtures compared to the control. In addition, leaf biomass of T. repens was maintained at the expense of biomass partitioning to the stolons. The decreased growth corresponded with decreased photosynthetic capacity for T. repens, however, by the end of the exposure there was also decreased photosynthetic capacity of L. perenne, a species previously considered insensitive to ozone. The observed decreases in photosynthetic efficiency and capacity in elevated ozone indicate that the ability of such ubiquitous vegetation to act as a sink for atmospheric carbon may be reduced in future climates.

Meta-analysis of the relative sensitivity of semi-natural vegetation species to ozone.

This study identified 83 species from existing publications suitable for inclusion in a database of sensitivity of species to ozone (OZOVEG database). An index, the relative sensitivity to ozone, was calculated for each species based on changes in biomass in order to test for species traits associated with ozone sensitivity. Meta-analysis of the ozone sensitivity data showed a wide inter-specific range in response to ozone. Some relationships in comparison to plant physiological and ecological characteristics were identified. Plants of the therophyte lifeform were particularly sensitive to ozone. Species with higher mature leaf N concentration were more sensitive to ozone than those with lower leaf N concentration. Some relationships between relative sensitivity to ozone and Ellenberg habitat requirements were also identified. In contrast, no relationships between relative sensitivity to ozone and mature leaf P concentration, Grime's CSR strategy, leaf longevity, flowering season, stomatal density and maximum altitude were found. The relative sensitivity of species and relationships with plant characteristics identified in this study could be used to predict sensitivity to ozone of untested species and communities.

Identifying ozone-sensitive communities of (semi-)natural vegetation suitable for mapping exceedance of critical levels.

Using published data on the responses of individual species to ozone, 54 EUNIS (European Nature Information System) level 4 communities with six or more ozone-sensitive species (%OS) and c. 20% or more species tested for ozone sensitivity, were identified as potentially ozone-sensitive. The largest number of these communities (23) was associated with Grasslands, with Heathland, scrub and tundra, and Mires, bogs and fens having the next highest representation at 11 and 8 level 4 communities each respectively. Within the grasslands classification, E4 (Alpine and sub-alpine grasslands), E5 (Woodland fringes and clearings) and E1 (Dry grasslands) were the most sensitive with 68.1, 51.6 and 48.6%OS respectively. It is feasible to map the land-cover for these and other communities at level 2, but it may not be currently possible to map the land-cover for all communities identified to be ozone-sensitive at levels 3 and 4.

A phase 3 study of three induction regimens and of priming with GM-CSF in older adults with acute myeloid leukemia: a trial by the Eastern Cooperative Oncology Group.

The optimal induction for older adults with acute myeloid leukemia (AML) is unknown. Several anthracyclines have been proposed, but the data remain equivocal. Additionally, few prospective trials of priming with hematopoietic growth factors to cycle leukemia cells prior to induction chemotherapy have been conducted. Three hundred and sixty-two older adults with previously untreated AML were randomized to either daunorubicin, idarubicin or mitoxantrone with a standard dose of cytarabine as induction therapy. In addition, 245 patients were also randomized to receive granulocyte-macrophage colony-stimulating factor (GM-CSF) or placebo beginning 2 days prior to induction chemotherapy and continuing until marrow aplasia. No difference was observed in the disease-free overall survival or in toxicity among patients receiving any of the 3 induction regimens or among those receiving growth factor or placebo for priming. However, the complete remission rate for the first 113 analyzable patients, who did not participate in the priming study and started induction therapy 3 to 5 days earlier than those who did, was significantly higher (50% versus 38%; P =.03). None of the anthracyclines is associated with improved outcome in older adults. Priming with hematopoietic growth factor did not improve response when compared with placebo. Furthermore, delaying induction therapy in older adults may lead to a lower complete remission rate.

Volumetric computerized tomography as a measurement of periprosthetic acetabular osteolysis and its correlation with wear.

Osteolysis, which is considered to be a major source of morbidity following total hip joint replacement, has been notoriously difficult to measure accurately, particularly in the acetabular area. In order to study periacetabular osteolysis, specialized software for computerized tomography (CT) scan image analysis has been developed. This software (3D-CT) eliminates metal artifacts, allows three-dimensional segmentation of the CT image, and reconstructs the segmented image to provide an accurate representation and measurement of volume for osteolytic lesions. In the present study, 20 patients underwent periacetabular osteolytic volume determination using 3D-CT, functional assessment (using the Harris Hip Scale, the Western Ontario and McMaster University Osteoarthritis Index, and the short form 36 questionnaire), and two-dimensional analysis of volumetic polyethylene wear using digitalized plain films. Periacetabular osteolysis correlated directly with the polyethylene wear rate (relative risk [RR] = 0.494, P = 0.027). If one patient with an acetabular revision, one patient with recurrent dislocation, and one patient with a Biomet prosthesis are excluded, then the correlation between wear and osteolysis is improved (RR = 0.685, P = 0.002). In summary, the current study demonstrates both the feasibility of CT imaging of periacetabular osteolysis and the correlation between polyethylene wear and osteolytic volume, providing a potential outcome measure for clinical trials that are designed to examine interventions in this complex disease process.

Importance of inhibin B in the regulation of FSH secretion in the human male.

Regulation of FSH secretion in the male involves a complex balance between stimulation by GnRH from the hypothalamus, inhibitory feedback by sex steroids (T and E2) and inhibin B (Inh B) from the gonads, and autocrine/paracrine modulation by activin and follistatin within the pituitary. The aim of the present study was to delineate the feedback control of FSH in the human male with specific reference to the relative roles of sex steroids vs. Inh B. Two experimental human models were used: 1) normal (NL) men subjected to acute sex steroid withdrawal (-T, -E2, + Inh B), and 2) functional castrate males (-T, -E2, -Inh B). Nine NL men (age range, 25-45 yr) and three castrate males (age range, 23-47 yr) were studied. The NL men underwent acute sex steroid suppression using high dose ketoconazole (1-g loading dose, followed by 400 mg, orally, four times daily for 150 h). Gonadotropin secretion was characterized by frequent blood sampling every 10 min for 12 h at baseline and on d 3 and 6 of sex steroid ablation. In the three castrate subjects, blood sampling was performed every 5 min for 24 h 8 wk after discontinuing androgen replacement therapy. In the NL men, treatment with ketoconazole resulted in a decline to castrate levels in T (451 +/- 20 to 38 +/- 7 ng/dl; P < 0.0005) and E2 (39 +/- 4 to 15 +/- 2 pg/ml; P < 0.005) and a modest, but significant, decline in Inh B levels, which remained within the normal range (183 +/- 19 to 136 +/- 13 pg/ml; P < 0.005). This suppression of sex steroids was associated with a more marked increase in mean LH (9.5 +/- 0.9 to 24.9 +/- 2.0 IU/liter; P < 0.0001) than FSH levels (5.1 +/- 0.7 to 10.0 +/- 1.5 IU/liter; P < 0.005), with the latter not exceeding the normal adult male range. The castrate subjects had a mean T level of 66 +/- 8 ng/dl, an E2 level of 20 +/- 1 pg/ml, and undetectable Inh B levels. Despite a similar sex steroid milieu, the mean FSH levels observed in NL men after acute sex steroid ablation were approximately 6-fold lower than those seen in the castrate subjects (10.0 +/- 1.5 vs. 59.5 +/- 17.7 IU/liter; P < 0.0005). In contrast, mean LH levels in the NL men were less than 3-fold lower than those in castrate subjects (24.9 +/- 2.0 vs. 66.8 +/- 20.1 IU/liter; P < 0.005). From this human model of acute sex steroid withdrawal, we conclude that Inh B is likely to be the major feedback regulator of FSH secretion in the human male.

Vaccinia virus-free recovery of vesicular stomatitis virus.

The advent of reverse-genetics represents a powerful new approach to elucidate aspects of negative-sense RNA virus replication. The reverse-genetics system established previously for vesicular stomatitis virus (VSV) required four plasmids encoding the nucleoprotein (N), phosphoprotein (P), polymerase (L), and the full-length, anti-genomic RNA. Transcription to yield the antigenomic RNA as well as the N, P, and L, mRNAs was initiated by bacteriophage T7 polymerase expressed from a recombinant Vaccinia virus. In this report, we describe the successful recovery of infectious VSV in the absence of Vaccinia virus. The N, P, and L genes of VSV were inserted downstream of both the T7 promoter and an internal ribosomal entry site (IRES element). T7 polymerase was expressed constitutively from BSR-T7/5 cells. RTPCR was used to confirm that the recovered VSV was derived from transfected DNA. Virion protein profile, CPE in tissue culture, and virus titer of the recombinant VSV were indistinguishable from those of parental VSV. Thus, the need for Vaccinia virus is eliminated with this system, making it an attractive, alternative approach for the recovery of infectious VSV from DNA.

Treatment of aggressive non-Hodgkin's lymphoma in elderly patients with thiotepa, Novantrone (mitoxantrone), vincristine, prednisone (TNOP).

The aging of the population and the increased incidence of non-Hodgkin's lymphoma will result in a large number of elderly patients with this disorder. Newer therapies will be required for this group of patients. This article reports a new therapy for elderly patients with diffuse aggressive non-Hodgkin's lymphoma. Patients were treated with TNOP (thiotepa 20 mg/m(2), mitoxantrone (Novantrone) 10 mg/m(2), vincristine (Oncovin) 1 mg/m(2) all on day 1 and prednisone 60 mg/m(2) on days 1 through 5 of a 21-day course. Twenty-six patients were enrolled on study. The patients' ages ranged from 66 years to 87 years, with a mean age of 75.5 years. Eleven patients had a partial response (42%) and 4 patients had a complete response (15%) for a total response of 57%. Eighty-one percent of patients survived 1 year and 54% survived for 2 years. The median survival was 26 months. Hematologic and nonhematologic toxicity was tolerable. We believe that TNOP is an excellent therapeutic option in this group of elderly patients, particularly in the palliative setting.

Optimization of scanning transmission X-ray microscopy for the identification and quantitation of reinforcing particles in polyurethanes.

The morphology, size distributions, spatial distributions, and quantitative chemical compositions of co-polymer polyol-reinforcing particles in a polyurethane have been investigated with scanning transmission X-ray microscopy (STXM). A detailed discussion of microscope operating procedures is presented and ways to avoid potential artifacts are discussed. Images at selected photon energies in the C 1s, N 1s and O 1s regions allow unambiguous identification of styrene-acrylonitrile-based (SAN) copolymer and polyisocyanate polyaddition product-based (PIPA) reinforcing particles down to particle sizes at the limit of the spatial resolution (50 nm). Quantitative analysis of the chemical composition of individual reinforcing particles is achieved by fitting C 1s spectra to linear combinations of reference spectra. Regression analyses of sequences of images recorded through the chemically sensitive ranges of the C 1s, N 1s and O 1s spectra are used to generate quantitative compositional maps, which provide a fast and effective means of investigating compositional distributions over a large number of reinforcing particles. The size distribution of all particles determined by STXM is shown to be similar to that determined by TEM. The size distributions of each type of reinforcing particle, which differ considerably, were obtained by analysis of STXM images at chemically selective energies.

The fertile eunuch variant of idiopathic hypogonadotropic hypogonadism: spontaneous reversal associated with a homozygous mutation in the gonadotropin-releasing hormone receptor.

Mutations in the GnRH receptor (GnRH-R) gene have been reported to cause idiopathic hypogonadotropic hypogonadism (IHH). Herein, we describe a 26-yr-old male with a mild phenotypic form of IHH, the fertile eunuch syndrome (IHH in the presence of normal testicular size and some degree of spermatogenesis), associated with a homozygous mutation (Gln106Arg) in the GnRH-R. This mutation, located in the first extracellular loop of the GnRH-R, has been previously shown to decrease but not eliminate GnRH binding. The proband had hypogonadal testosterone levels, detectable but apulsatile gonadotropin secretion, and a normal adult male testicular size of 17 mL at baseline. After only 4 months of treatment with hCG alone, he developed sperm in his ejaculate and his wife conceived. Following cessation of hCG therapy, the patient demonstrated reversal of his hypogonadotropism as evidenced by normal adult male testosterone levels and the appearance of pulsatile luteinizing hormone secretion. This case thus expands the emerging clinical spectrum of GnRH-R mutations, provides the first genetic basis for the fertile eunuch variant of IHH and documents the occurrence of reversible IHH in a patient with a GnRH-R mutation.