Crop production in the USA is frequently limited by a lack of pollinators.

Most of the world's crops depend on pollinators, so declines in both managed and wild bees raise concerns about food security. However, the degree to which insect pollination is actually limiting current crop production is poorly understood, as is the role of wild species (as opposed to managed honeybees) in pollinating crops, particularly in intensive production areas. We established a nationwide study to assess the extent of pollinator limitation in seven crops at 131 locations situated across major crop-producing areas of the USA. We found that five out of seven crops showed evidence of pollinator limitation. Wild bees and honeybees provided comparable amounts of pollination for most crops, even in agriculturally intensive regions. We estimated the nationwide annual production value of wild pollinators to the seven crops we studied at over $1.5 billion; the value of wild bee pollination of all pollinator-dependent crops would be much greater. Our findings show that pollinator declines could translate directly into decreased yields or production for most of the crops studied, and that wild species contribute substantially to pollination of most study crops in major crop-producing regions.

Ranibizumab for the treatment of choroidal neovascularisation secondary to pathological myopia: interim analysis of the REPAIR study.

AIMS: To evaluate the efficacy and safety of intravitreal ranibizumab in patients with choroidal neovascularisation secondary to pathological myopia (myopic CNV). Data are from a pre-planned, 6-month interim analysis. METHODS: Phase II, open-label, single arm, multicentre, 12-month study, recruiting patients (aged ≥18 years) with active primary or recurrent subfoveal or juxtafoveal myopic CNV, with a best-corrected visual acuity (BCVA) score of 24-78 Early Treatment Diabetic Retinopathy Study (ETDRS) letters in the study eye and a diagnosis of high myopia of at least -6 dioptres. Patients received 0.5 mg ranibizumab administered intravitreally to the study eye, followed by monthly injections given as needed (based on a predefined algorithm) for up to 11 months. RESULTS: At 6 months, mean BCVA improved from baseline by 12.2 letters, as did central macular thickness (in this interim analysis defined as a measure of either central subfield macular thickness or centre point macular thickness) from baseline by 108 µm in the 48 study eyes of 48 patients. Fewer patients had centre-involving intraretinal oedema (13.0% vs 91.5%), intraretinal cysts (10.9% vs 57.4%), or subretinal fluid (13.0% vs 66.0%) at 6 months than at baseline. Patients received a mean of 1.9 retreatments, were satisfied with ranibizumab treatment, and well being was maintained. No new safety signals were identified. CONCLUSIONS: Results from the planned interim analysis support the role of ranibizumab in the treatment of myopic CNV, with excellent efficacy achieved with a low number of injections and few serious adverse events.

Quantifying the attenuation of the ketamine pharmacological magnetic resonance imaging response in humans: a validation using antipsychotic and glutamatergic agents.

Ketamine acts as an N-methyl-D-aspartate receptor antagonist and evokes psychotomimetic symptoms resembling schizophrenia in healthy humans. Imaging markers of acute ketamine challenge have the potential to provide a powerful assay of novel therapies for psychiatric illness, although to date this assay has not been fully validated in humans. Pharmacological magnetic resonance imaging (phMRI) was conducted in a randomized, placebo-controlled crossover design in healthy volunteers. The study comprised a control and three ketamine infusion sessions, two of which included pretreatment with lamotrigine or risperidone, compounds hypothesized to reduce ketamine-induced glutamate release. The modulation of the ketamine phMRI response was investigated using univariate analysis of prespecified regions and a novel application of multivariate analysis across the whole-brain response. Lamotrigine and risperidone resulted in widespread attenuation of the ketamine-induced increases in signal, including the frontal and thalamic regions. A contrasting effect across both pretreatments was observed only in the subgenual prefrontal cortex, in which ketamine produced a reduction in signal. Multivariate techniques proved successful in both classifying ketamine from placebo (100%) and identifying the probability of scans belonging to the ketamine class (ketamine pretreated with placebo: 0.89). Following pretreatment, these predictive probabilities were reduced to 0.58 and 0.49 for lamotrigine and risperidone, respectively. We have provided clear demonstration of a ketamine phMRI response and its attenuation with both lamotrigine and risperidone. The analytical methodology used could be readily applied to investigate the mechanistic action of novel compounds relevant for psychiatric disorders such as schizophrenia and depression.

Test-retest reliability of the BOLD pharmacological MRI response to ketamine in healthy volunteers.

The pharmacological MRI (phMRI) technique is being increasingly used in both pre-clinical and clinical models to investigate pharmacological effects on task-free brain function. Ketamine, an N-methyl-d-aspartate receptor (NMDAR) antagonist, induces a strong phMRI response and represents a promising pharmacological model to investigate the role of glutamatergic abnormalities in psychiatric symptomatology. The aim of this study was to assess whether the brain response to ketamine is reliable in order to validate ketamine phMRI as a mechanistic marker of glutamatergic dysfunction and to determine its utility in repeated measures designs to detect the modulatory effect of other drugs. Thus we assessed the test-retest reliability of the brain response to ketamine in healthy volunteers and identified an optimal modelling approach with reliability as our selection criterion. PhMRI data were collected from 10 healthy male participants, at rest, on two separate occasions. Subanaesthetic doses of I.V. ketamine infusion (target plasma levels 50 ng/mL and 75 ng/mL) were administered in both sessions. Test-retest reliability of the ketamine phMRI response was assessed voxel-wise and on pre-defined ROIs for a range of temporal design matrices including different combinations of nuisance regressors designed to model shape variance, linear drift and head motion. Effect sizes are also reported. All models showed a significant and widespread response to low-dose ketamine in predicted cerebral networks and as expected, increasing the number of model parameters improved model fit. Reliability of the predefined ROIs differed between the different models assessed. Using reliability as the selection criterion, a model capturing subject motion and linear drift performed the best across two sessions. The anatomical distribution of effects for all models was consistent with results of previous imaging studies in humans with BOLD signal increases in regions including midline cingulate and supracingulate cortex, thalamus, insula, anterior temporal lobe and ventrolateral prefrontal structures, and BOLD signal decreases in the subgenual cingulate cortex. This study represents the first investigation of the test-retest reliability of the BOLD phMRI response to acute ketamine challenge. All models tested were effective at describing the ketamine response although the design matrix associated with the highest reliability may represent a robust and well-characterised ketamine phMRI assay more suitable for repeated-measures designs. This ketamine assay is applicable as a model of neurotransmitter dysfunction suitable as a pharmacodynamic imaging tool to test and validate modulatory interventions, as a model of NMDA hypofunction in psychiatric disorders, and may be adapted to understand potential antidepressant and analgesic effects of NMDAR antagonists.

Effect of prior metabolic rate on the kinetics of oxygen uptake during moderate-intensity exercise.

Pulmonary oxygen uptake (VO2) dynamics during moderate-intensity exercise are often assumed to be dynamically linear (i.e. neither the gain nor the time constant (tau) of the response varies as a function of work rate). However, faster, slower and unchanged VO2 kinetics have been reported during work-to-work transitions compared to rest-to-work transitions, all within the moderate-intensity domain. In an attempt to resolve these discrepancies and to improve the confidence of the parameter estimation, we determined the VO2 response dynamics using the averaged response to repeated exercise bouts in seven healthy male volunteers. Each subject initially performed a ramp-incremental exercise test for the estimation of the lactate threshold (thetaL). They then performed an average of four repetitions of each of three constant-work-rate (WR) tests: (1) between 20 W and a work rate of 50% (WR50) between 20 W and 90% thetaL (step 1-->2), (2) between WR50 and 90% thetaL (step 2-->3), and (3) between 20 W and 90% thetaL (step 1-->3); 6 min was spent at each work rate increment and decrement. Parameters of the kinetic response of phase II VO2 were established by non-linear least-squares fitting techniques. The kinetics of VO2 were significantly slower at the upper reaches of the moderate-intensity domain (step 2-->3) compared to steps 1-->2 and 1-->3 [group mean (SD) phase II tau: step 1-->2 25.3 (4.9) s, step 2-->3 40.0 (7.4) s and step 1-->3 32.2 (6.9) s]. The off-transient values of tau were not significantly different from each other: 36.8 (16.3) s, 38.9 (11.6) s and 30.8 (5.7) s for steps 1-->2, 2-->3 and 1-->3, respectively. Surprisingly, the on-transient gain (G, deltaVO2/deltaWR) was also found to vary among the three steps [G = 10.56 (0.42) ml x min(-1) W(-1) 11.85 (0.64) ml x min(-1) W(-1) and 11.23 (0.52) ml x min(-1) W(-1) for steps 1-->2, 2-->3 and 1-->3, respectively]; the off-transient G did not vary significantly and was close to that for the on-transient step 1-->3 in all cases. Our results do not support a dynamically linear system model of VO2 during cycle ergometer exercise even in the moderate-intensity domain. The greater oxygen deficit per unit power increment in the higher reaches of the moderate-intensity domain necessitates a greater transient lactate contribution to the energy transfer, or a greater phosphocreatine breakdown, or possibly both.

Soluble beta-galactoside specific lectin is developmentally regulated in lungs of neonatal black mice and beige mice.

The beige mouse, a mutant of the C57 black mouse, is best known as a model of the Chediak-Higashi syndrome. Recently, it was found that alveolar maturation in neonatal beige mice is impaired, resulting in abnormally large alveoli. In guinea pigs, hamsters, and rats there is an elevated activity of a soluble, beta-galactoside-binding lectin in lungs at the age when alveolar maturation is in progress. Our present studies were done to find out if the temporal relationship between elevated lectin activity and alveolar maturation also occurs in mice and, further, if the impaired alveolar maturation in beige mice might be linked to the lectin. We found that the temporal relationship between lectin activity and alveolar maturation is also present in black and beige mice, with a peak in specific lectin activity occurring at about 8 days after birth. We also found that the major lectin purified from black or beige mice has essentially the same subunit molecular weight, isoelectric point, and amino acid composition. In conclusion, we found nothing abnormal about the lectin or its developmental regulation that can explain the impaired alveolar maturation in neonatal beige mice. The results do not rule out the possibility of an important role for the lectin in normal lung development or the possibility that some aspect of function or localization of the lectin or its ligands, not related to total lung lectin hemagglutinating activity, may be altered in the beige mouse.

A case report of massive vulvar edema during tocolysis of preterm labor.

Bilateral vulvar edema that is not associated with preeclampsia has been reported only rarely during pregnancy or the puerperium. A primiparous patient in premature labor at 34 weeks' gestation with no history of lymphatic or venous obstruction underwent combination tocolysis with intravenous ritodrine and magnesium sulfate. On the fifth day of tocolysis, edema developed in the right labium majus pudendi and gradually spread to the left labia during the ensuing 24 hours. The patient remained afebrile, normotensive, and without signs of localized infection or anasarca. A trial of triple intravenous antibiotics and local skin care proved ineffective. By the ninth hospital day, the edema and discomfort had progressed, thereby precluding vaginal examination without sedation. In spite of progressive cervical dilatation with tocolysis, cesarean delivery was performed. With no further treatment, the vulvar edema gradually resolved during the next week.

Ethanol-induced changes in neuronal membrane order. An NMR study.

The effects of ethanol-d6 on the lipid matrix of rat brain neuronal membranes were investigated by delayed Fourier transform 1H-NMR techniques. At 24 degrees C, neither 0.1 nor 0.2% (v/v) ethanol-d6 measurably affected the methylene resonance intensity. However, 0.4 and 1.0% ethanol-d6 increased resonance intensity, 35 and 51%, respectively. With increasing temperature, a decrease in resonance intensity for 0.1% ethanol-d6 was observed reaching a maximum of 20% at 42 degrees C. Furthermore, increasing temperature attenuated the increases in resonance intensity seen with 0.4 and 1.0% ethanol-d6. At 24 degrees C, no concentration of ethanol-d6 had a significant effect on the choline methyl resonance. However, with increasing temperature both 0.1 and 0.2% ethanol-d6 decreased this resonance's intensity. The intensity of the terminal methyl resonance was increased in a dose related fashion by ethanol-d6, reaching a maximum of +41% at 1.0% (24 degrees C). Increasing temperature attenuated this effect, but no concentration of ethanol-d6 significantly decreased resonance intensity. The increases and decreases in resonance intensity induced by ethanol-d6 are interpreted in terms of a decrease and an increase in membrane order, respectively. It is proposed that ethanol-d6 exerts two effects on neuronal membranes, an ordering effect on the membrane surface and a disordering effect in the membrane interior. A higher enthalpy of ethanol binding to the surface as compared to the interior of the membrane leads to an attenuation of the ethanol disordering effect with increasing temperature.

Determination of ethanol partition coefficients to the interior and the surface of dipalmityl-phosphatidylcholine liposomes using deuterium nuclear magnetic resonance spectroscopy.

The binding of ethanol-d6 to dipalmityl-phosphatidylcholine liposomes (DPPC) can be separated into two processes, namely, ethanol in the bilayer and on the surface of the bilayer. For the deuterons of the methylene group, the T2 of both bound states is shorter than the respective preexchange lifetime (tau beta) and therefore the amount of ethanol bound to both sites can be determined from the decrease in the methylene intensity resonance in the presence of DPPC. For the methyl resonance, however, only the T2 of deuterons on ethanol bound to the surface is less than its tau beta and the amount of surface bound ethanol-d6 can be determined. Subtraction yields the amount of ethanol bound within the bilayer. The partition coefficient for internally bound ethanol remains constant from 0 to 3.5 m ethanol. Surface binding is, however, highly cooperative.