The Einstein-de Haas effect in an Fe15cluster.

Classical models of spin-lattice coupling are at present unable to accurately reproduce results for numerous properties of ferromagnetic materials, such as heat transport coefficients or the sudden collapse of the magnetic moment in hcp-Fe under pressure. This inability has been attributed to the absence of a proper treatment of effects that are inherently quantum mechanical in nature, notably spin-orbit coupling (SOC). This paper introduces a time-dependent, non-collinear tight binding model, complete with SOC and vector Stoner exchange terms, that is capable of simulating the Einstein-de Haas (EdH) effect in a ferromagnetic Fe15cluster. The tight binding model is used to investigate the adiabaticity timescales that determine the response of the orbital and spin angular momenta to a rotating, externally appliedBfield, and we show that the qualitative behaviors of our simulations can be extrapolated to realistic timescales by use of the adiabatic theorem. An analysis of the trends in the torque contributions with respect to the field strength demonstrates that SOC is necessary to observe a transfer of angular momentum from the electrons to the nuclei at experimentally realisticBfields. The simulations presented in this paper demonstrate the EdH effect from first principles using a Fe cluster.

Intramammary 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 treatments differentially increase serum calcium and milk cell gene expression.

Intramammary 25-hydroxyvitamin D3 (25D) and 1,25-dihydroxyvitamin D3 (1,25D) treatments stimulate immune defenses of the mammary gland. We hypothesized 25D treatment, in contrast to 1,25D, would exert activity in the mammary gland without affecting serum calcium. The objective was to determine the effect of dose and source of intramammary vitamin D treatments on milk somatic cell gene expression and serum calcium. Twenty lactating Holstein cows with somatic cell count <200,000 cells/mL of milk were used for the experiment. Cows were blocked by somatic cell count and randomly assigned to 1 of 5 intramammary treatments (n = 4 cows/treatment): placebo control (CNTRL; 0.4% Tween 20 in phosphate-buffered saline), 100 µg of 25D, 500 µg of 25D, 10 µg of 1,25D, or 50 µg of 1,25D. Treatments were administered in 2 ipsilateral quarters after milking. Blood samples were collected at 0, 12, 24, and 48 h for measurement of Ca and 1,25D. Milk samples were collected from each quarter at 0, 6, 12, 24, and 48 h relative to the start of treatments for measurement of gene expression in milk somatic cells. The 1,25D treatments increased serum concentrations of 1,25D and Ca in a dose-dependent manner with maximum 1,25D and Ca concentrations of 199 ± 6 pg/mL and 2.73 ± 0.04 mM, respectively, observed for 50 µg of 1,25D cows compared with 59 ± 6 pg/mL and 2.54 mM, respectively, for CNTRL cows. The 25D treatments did not affect serum 1,25D and Ca compared with CNTRL. The 25D and 1,25D treatments increased mRNA transcripts for vitamin D 24-hydroxylase (CYP24A1), inducible nitric oxide synthase (NOS2A), and chemokine C-C motif ligand 5 (CCL5) in a dose-dependent manner. The 50 µg of 1,25D treatment resulted in the greatest CYP24A1 expression (303-fold relative to CNTRL) at 6 h but was not different from CNTRL at 24 h. In contrast, CYP24A1 was 57-fold greater for cows that received 500 µg of 25D compared with CNTRL at 24 h. In conclusion, intramammary 25D treatment is effective at regulating gene expression in the mammary gland without systemic effects on serum 1,25D and Ca that occur with intramammary 1,25D treatment.

Effect of vitamin D source and amount on vitamin D status and response to endotoxin challenge.

The objectives were to test the effects of dietary vitamin D3 [cholecalciferol (CHOL)] compared with 25-hydroxyvitamin D3 [calcidiol (CAL)] on vitamin D status and response to an endotoxin challenge. Forty-five Holstein bull calves (5 ± 2 d of age) were blocked into weekly cohorts, fed a basal diet that provided 0.25 µg/kg body weight (BW) CHOL, and assigned randomly to 1 of 5 treatments: control [(CON) no additional vitamin D], 1.5 µg/kg BW CHOL (CHOL1.5), 3 µg/kg BW CHOL (CHOL3), 1.5 µg/kg BW CAL (CAL1.5), or 3 µg/kg BW CAL (CAL3). Calves were fed milk replacer until weaning at 56 d of age and had ad libitum access to water and starter grain throughout the experiment. Treatments were added daily to the diet of milk replacer until weaning and starter grain after weaning. Measures of growth, dry matter intake, and serum concentrations of vitamin D, Ca, Mg, and P were collected from 0 to 91 d of the experiment. At 91 d of the experiment, calves received an intravenous injection of 0.1 µg/kg BW lipopolysaccharide (LPS). Clinical and physiological responses were measured from 0 to 72 h relative to LPS injection. Data were analyzed with mixed models that included fixed effects of treatment and time, and random effect of block. Orthogonal contrasts evaluated the effects of (1) source (CAL vs. CHOL), (2) dose (1.5 vs. 3.0 µg/kg BW), (3) interaction between source and dose, and (4) supplementation (CON vs. all other treatments) of vitamin D. From 21 to 91 d of the experiment, mean BW of supplemented calves was less compared with CON calves, but the effect was predominantly a result of the CHOL calves, which tended to weigh less than the CAL calves. Supplementing vitamin D increased concentrations of 25-hydroxyvitamin D in serum compared with CON, but the increment from increasing the dose from 1.5 to 3.0 µg/kg BW was greater for CAL compared with CHOL (CON = 18.9, CHOL = 24.7 and 29.6, CAL = 35.6 and 65.7 ± 3.2 ng/mL, respectively). Feeding CAL also increased serum Ca and P compared with CHOL. An interaction between source and dose of treatment was observed for rectal temperature and derivatives of reactive metabolites after LPS challenge because calves receiving CHOL3 and CAL1.5 had lower rectal temperatures and plasma derivatives of reactive metabolites compared with calves receiving CHOL1.5 and CAL3. Supplementing vitamin D increased plasma P concentrations post-LPS challenge compared with CON, but plasma concentrations of Ca, Mg, fatty acids, glucose, ß-hydroxybutyrate, haptoglobin, tumor necrosis factor-α, and antioxidant potential did not differ among treatments post-LPS challenge. Last, supplementing vitamin D increased granulocytes as a percentage of blood leukocytes post-LPS challenge compared with CON. Supplementing CAL as a source of vitamin D to dairy calves was more effective at increasing serum 25-hydroxyvitamin D, Ca, and P concentrations compared with feeding CHOL. Supplemental source and dose of vitamin D also influenced responses to the LPS challenge.

The microscopic Einstein-de Haas effect.

The Einstein-de Haas (EdH) effect, where the spin angular momentum of electrons is transferred to the mechanical angular momentum of atoms, was established experimentally in 1915. While a semiclassical explanation of the effect exists, modern electronic structure methods have not yet been applied to model the phenomenon. In this paper, we investigate its microscopic origins by means of a noncollinear tight-binding model of an O2 dimer, which includes the effects of spin-orbit coupling, coupling to an external magnetic field, and vector Stoner exchange. By varying an external magnetic field in the presence of spin-orbit coupling, a torque can be generated on the dimer, validating the presence of the EdH effect. The avoided energy level crossings and the rate of change of magnetic field determine the evolution of the spin. We also find that the torque exerted on the nuclei by the electrons in a time-varying B field is not only due to the EdH effect. The other contributions arise from field-induced changes in the electronic orbital angular momentum and from the direct action of the Faraday electric field associated with the time-varying magnetic field.

Differences in soil organic carbon and soil erosion for native pasture and minimum till agricultural management systems.

There is considerable debate over how different agricultural management systems such as minimum tillage and grazing affect soil organic carbon (SOC), soil nitrogen (SN) concentrations and soil erosion over the long-term. In this study SOC, SN and erosion characteristics were compared over a ten year period for two neighbouring sites with longstanding but different land management strategies; one cropped under a minimum tillage (MT) regime and one used for grazing on largely native pasture. Both sites (Hunter Valley, New South Wales, Australia) shared the same soil type (Euchrozem) and climate. SOC and SN were both found to be ~50% higher at the grazing site while erosion was found to be significantly greater (an order of magnitude) at the cropping site despite the application of MT practices. No discernible link between erosion and either SOC, SN or C:N was evident. While both sites have temporally constant SOC, SN and C:N, the MT site offers scope for increased SOC sequestration.

Enhanced Recovery After Surgery (ERAS) in gynecologic oncology: System-wide implementation and audit leads to improved value and patient outcomes.

OBJECTIVE: Enhanced recovery pathways have been shown to reduce length of stay without increasing readmission or complications in numerous areas of surgery. Uptake of gynecologic oncology ERAS guidelines has been limited. We describe the effect of ERAS guideline implementation in gynecologic oncology on length of stay, patient outcomes, and economic impact for a province-wide single-payer system. METHODS: We compared pre- and post-guideline implementation outcomes in consecutive staging and debulking patients at two centers that provide the majority of surgical gynecologic oncology care in Alberta, Canada between March 2016 and April 2017. Clinical outcomes and compliance were obtained using the ERAS Interactive Audit System. Patients were followed until 30 days after discharge. Negative binomial regression was employed to adjust for patient characteristics. RESULTS: We assessed 152 pre-ERAS and 367 post-ERAS implementation patients. Mean compliance with ERAS care elements increased from 56% to 77.0% after implementation (p < 0.0001). Median length of stay for all surgeries decreased from 4.0 days to 3.0 days post-ERAS (p < 0.0001), which translated to an adjusted LOS decrease of 31.4% (95% CI = [21.7% - 39.9%], p < 0.0001). In medium/high complexity surgery median LOS was reduced by 2.0 days (p = 0.0005). Complications prior to discharge decreased from 53.3% to 36.2% post-ERAS (p = 0.0003). There was no significant difference in readmission (p = 0.6159), complications up to 30 days (p = 0.6274), or mortality (p = 0.3618) between the cohorts. The net cost savings per patient was $956 (95%CI: $162 to $1636). CONCLUSIONS: Systematic implementation of ERAS gynecologic oncology guidelines across a healthcare system improves patient outcomes and saves resources.

Long Sun-Exposures Influencing High Sub-Cutaneous Synthesis of Vitamin-D3 may be Associated with Exacerbation of Symptoms in Allergic-Asthma.

OBJECTIVES: Does excessive sun-exposure, non-use of sunscreen and/or high doses of vitamin-D3 supplements provoke exacerbation of asthma? DESIGN: Clinical examinations, retrospective records-access and questionnaire surveys were distributed to a convenience sample of allergic-asthma patient (n=183). SETTING: Patients (19-89 years) attending the outpatient respiratory clinics at Maidstone Hospital were enrolled. RESULTS: 90.3% of patients (total IgE levels ≥75 kU/L ; n=103) exposed to direct sunlight of ≥ 15 minutes per day continuously for 6-7 days presented with wheeze (χ2(1) = 7.46; p< 0.05) compared to only 9.7% patients of similar atopy-status, presenting with wheeze if exposed to sunlight of < 15 minutes per day for 6-7 days. 68.9% patients (with IgE levels ≥ 75 kU/L ; n=103), non-users of sunscreen (SPF 30 and above), exposed to direct sunlight of ≥ 15 minutes per day continuously for 6-7 days developed a wheeze, compared to fewer users of sunscreen (9.7%, n=103), exposed to the same duration of sunlight who developed asthma symptoms (p< 0.05). Vitamin-D3 supplementation in asthma-patients with clinical signs of hypovitaminosis-D (n=21), produced symptoms of morning chest-tightness (76.2%), allergic rhinitis (61.9%) and wheeze (100%), 2 weeks after initiation of treatment. CONCLUSIONS: Our results advocate direct sunlight exposure < 15 minutes per day and use of sunscreen as a novel approach to preventing atopic-asthma symptoms in allergic-asthma patients.. Activated vitamin-D3 is well-recognised to shift the immune-balance towards Th2 predominance, favouring allergic asthma. These results suggest that limiting subcutaneous synthesis of vitamin-D3 in asthma patients and re-addressing dosage of vitamin-D3 supplementation is necessary may contribute to prevent exacerbation of symptoms.

AllergoOncology: Opposite outcomes of immune tolerance in allergy and cancer.

While desired for the cure of allergy, regulatory immune cell subsets and nonclassical Th2-biased inflammatory mediators in the tumour microenvironment can contribute to immune suppression and escape of tumours from immunological detection and clearance. A key aim in the cancer field is therefore to design interventions that can break immunological tolerance and halt cancer progression, whereas on the contrary allergen immunotherapy exactly aims to induce tolerance. In this position paper, we review insights on immune tolerance derived from allergy and from cancer inflammation, focusing on what is known about the roles of key immune cells and mediators. We propose that research in the field of AllergoOncology that aims to delineate these immunological mechanisms with juxtaposed clinical consequences in allergy and cancer may point to novel avenues for therapeutic interventions that stand to benefit both disciplines.

Administration of an oxytocin receptor antagonist attenuates sexual motivation in male rats.

In male rats, oxytocin impacts both sexual arousal and certain types of consummatory sexual behaviors. However, the role of oxytocin in the motivational aspects of sexual behavior has received limited attention. Given the role that oxytocin signaling plays in consummatory sexual behaviors, it was hypothesized that pharmacological attenuation of oxytocin signaling would reduce sexual motivation in male rats. Sexually experienced Long-Evans male rats were administered either an oxytocin receptor antagonist (L368,899 hydrochloride; 1mg/kg) or vehicle control into the intraperitoneal cavity 40min prior to placement into the center chamber of a three-chambered arena designed to assess sexual motivation. During the 20-minute test, a sexually experienced stimulus male rat and a sexually receptive stimulus female rat were separately confined to smaller chambers that were attached to the larger end chambers of the arena. However, physical contact between test and stimulus rats was prevented by perforated dividers. Immediately following the sexual motivation test, test male rats were placed with a sexually receptive female to examine consummatory sexual behaviors. Although both drug and vehicle treated rats exhibited a preference for the female, treatment with an oxytocin receptor antagonist decreased the amount of time spent with the female. There were no differences between drug and vehicle treated rats in either general activity, exploratory behaviors, the amount of time spent near the stimulus male rat, or consummatory sexual behaviors. Extending previous findings, these results indicate that oxytocin receptors are involved in sexual motivation in male rats.

AllergoOncology - the impact of allergy in oncology: EAACI position paper.

Th2 immunity and allergic immune surveillance play critical roles in host responses to pathogens, parasites and allergens. Numerous studies have reported significant links between Th2 responses and cancer, including insights into the functions of IgE antibodies and associated effector cells in both antitumour immune surveillance and therapy. The interdisciplinary field of AllergoOncology was given Task Force status by the European Academy of Allergy and Clinical Immunology in 2014. Affiliated expert groups focus on the interface between allergic responses and cancer, applied to immune surveillance, immunomodulation and the functions of IgE-mediated immune responses against cancer, to derive novel insights into more effective treatments. Coincident with rapid expansion in clinical application of cancer immunotherapies, here we review the current state-of-the-art and future translational opportunities, as well as challenges in this relatively new field. Recent developments include improved understanding of Th2 antibodies, intratumoral innate allergy effector cells and mediators, IgE-mediated tumour antigen cross-presentation by dendritic cells, as well as immunotherapeutic strategies such as vaccines and recombinant antibodies, and finally, the management of allergy in daily clinical oncology. Shedding light on the crosstalk between allergic response and cancer is paving the way for new avenues of treatment.

Cancer mortality in the meat and delicatessen departments of supermarkets (1950-2006).

Meat cutters and meat wrappers in the meat department of supermarkets are exposed to oncogenic viruses present in raw meat from cattle, pigs, sheep, and poultry, and their products (unpasteurized milk and raw eggs). Up to the mid 1970s, meat wrappers were also exposed to carcinogens present in fumes emitted from the machine used to wrap meat. Because of this we studied cancer mortality in a cohort of 10,701 workers in the meat and delicatessen departments of supermarkets, and we report here the findings after the third follow-up. Standardized mortality ratios (SMR) were estimated in the cohort as a whole and in race/sex subgroups, using the US population for comparison. Study subjects were followed up from January 1950 to December 2006. Significantly increased SMRs of 1.3 (95% CI, 1.2-1.5), and 2.7 (95% CI, 1.2-5.3) were recorded for cancers of the lung, and tonsils/oropharynx, respectively, in the entire cohort, affecting nearly all race/sex subgroups. SMRs of 4.6 (95% CI, 1.0-13.6) for cancer of the floor of the mouth, and 2.8 (95% CI, 1.3-5.3) for cancer of the gall bladder and biliary tract were recorded only in White male meatcutters. Significantly decreased SMRs were observed for a few cancers. It is not known if the observed excess of cancers is a result of occupational exposures. However, substantial evidence points to fumes from the wrapping machine as a possible candidate for explaining the excess in female meat wrappers. Nested case-control studies that can examine risks from occupational exposures in greater detail, and adequately control for confounding factors are now needed, to permit specifically investigate the role of the oncogenic viruses, fumes and non-occupational risk factors in the occurrence of these cancers. The findings are important, not only occupationally but also because the general population may also experience these exposures, albeit to a lesser degree.

Preclinical assessment of a new magnetic resonance-based technique for determining bone quality by characterization of trabecular microarchitecture.

The utility of HR-CT to study longitudinal changes in bone microarchitecture is limited by subject radiation exposure. Although MR is not subject to this limitation, it is limited both by patient movement that occurs during prolonged scanning at distal sites, and by the signal-to-noise ratio that is achievable for high-resolution images in a reasonable scan time at proximal sites. Recently, a novel MR-based technique, fine structure analysis (FSA) (Chase et al. Localised one-dimensional magnetic resonance spatial frequency spectroscopy. PCT/US2012/068284 2012, James and Chase Magnetic field gradient structure characteristic assessment using one-dimensional (1D) spatial frequency distribution analysis. 7932720 B2, 2011) has been developed which provides both high-resolution and fast scan times, but which generates at a designated set of spatial positions (voxels) a one-dimensional signal of spatial frequencies. Appendix 1 provides a brief introduction to FSA. This article describes an initial exploration of FSA for the rapid, non-invasive characterization of trabecular microarchitecture in a preclinical setting. For L4 vertebrae of sham and ovariectomized (OVX) rats, we compared FSA-generated metrics with those from CT datasets and from CT-derived histomorphometry parameters, trabecular number (Tb.N), bone volume density (BV/TV), trabecular thickness (Tb.Th) and trabecular separation (Tb.Sp). OVX caused a reduction of the higher frequency structures that correspond to a denser trabecular lattice, while increasing the preponderance of lower frequency structures, which correspond to a more open lattice. As one example measure, the centroid of the FSA spectrum (which we refer to as fSAcB) showed strong correlation in the same region with CT-derived histomorphometry values: Tb.Sp: r -0.63, p < 0.001; Tb.N: r 0.71, p < 0.001; BV/TV: r 0.64, p < 0.001, Tb.Th: r 0.44, p < 0.05. Furthermore, we found a 17.5% reduction in fSAcB in OVX rats (p < 0.0001). In a longitudinal study, FSA showed that the age-related increase in higher frequency structures was abolished in OVX rats, being replaced with a 78-194% increase in lower frequency structures (2.4-2.8 objects/mm range), indicating a more sparse trabecular lattice (p < 0.05). The MR-based fine structure analysis enables high-resolution, radiation-free, rapid quantification of bone structures in one dimension (the specific point and direction being chosen by the clinician) of the spine.

Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease.

Eleven susceptibility loci for late-onset Alzheimer's disease (LOAD) were identified by previous studies; however, a large portion of the genetic risk for this disease remains unexplained. We conducted a large, two-stage meta-analysis of genome-wide association studies (GWAS) in individuals of European ancestry. In stage 1, we used genotyped and imputed data (7,055,881 SNPs) to perform meta-analysis on 4 previously published GWAS data sets consisting of 17,008 Alzheimer's disease cases and 37,154 controls. In stage 2, 11,632 SNPs were genotyped and tested for association in an independent set of 8,572 Alzheimer's disease cases and 11,312 controls. In addition to the APOE locus (encoding apolipoprotein E), 19 loci reached genome-wide significance (P < 5 × 10(-8)) in the combined stage 1 and stage 2 analysis, of which 11 are newly associated with Alzheimer's disease.

5-HTTLPR and BDNF Val66Met polymorphisms moderate effects of stress on rumination.

This study examined whether polymorphisms in the serotonin transporter (SLC6A4, 5-HTTLPR) and brain-derived neurotropic factor (BDNF Val66Met, rs6265) genes moderate the relationship between life stress and rumination. Participants were a large homogenous group of healthy, unmedicated, never depressed individuals with few current symptoms of depression (N = 273). Results indicate that individuals with two short (S) alleles of the 5-HTTLPR polymorphism or two Met alleles of the BDNF Val66Met polymorphism ruminate more under conditions of life stress, compared to the other genotypes. Moreover, the accumulation of risk alleles (i.e. S and Met alleles) across genes is associated with significantly greater rumination in the context of life stress. These results suggest that both 5-HTTLPR and BDNF Val66Met moderate the relationship between life stress and rumination. These findings support the notion that variation in these genes is associated with biological sensitivity to the negative effects of stress.

Enhanced angular current intensity from Schottky emitters.

Even though the Schottky emitter is a high-brightness source of choice for electron beam systems, its angular current intensity is substantially lower than that of thermionic cathodes, rendering the emitter impractical for applications that require high beam current. In this study, two strategies were attempted to enhance its angular intensity, and their experimental results are reported. The first scheme is to employ a higher extraction field for increasing the brightness. However, the tip shape transformation was found to induce undesirably elevated emission from the facet edges at high fields. The second scheme exploits the fact that the angular intensity is proportional to the square of the electron gun focal length [Fujita, S. & Shimoyama, H. (2005) Theory of cathode trajectory characterization by canonical mapping transformation. J. Electron Microsc. 54, 331-343], which can be increased by scaling-up the emitter tip radius. A high angular current intensity (J(Omega) approximately 1.5 mA sr(-1)) was obtained from a scaled-up emitter. Preliminary performance tests were conducted on an electron probe-forming column by substituting the new emitter for the original tungsten filament gun. The beam current up to a few microamperes was achieved with submicron spatial resolution.

The global portfolio of new antimalarial medicines under development.

With the elimination of malaria now considered a realistic goal, it would be useful for scientists and policy makers to have an inventory of the arsenal of antimalarials, current and prospective, that could help make this goal a reality. In order to provide an overview of antimalarial projects in recent clinical development, we review here the global portfolio of antimalarial drugs in clinical phases of development complemented by projects in the preclinical and early discovery phases. The portfolio is discussed in terms of the novelty of the new molecules and their potential health impact in terms of addressing the requirements for the control and eventual eradication of malaria.

Does adiposity status influence femoral cortical strength in rodent models of growth hormone deficiency?

Growth hormone (GH)-deficiency is usually associated with elevated adiposity, hyperleptinemia, and increased fracture risk. Since leptin is thought to enhance cortical bone formation, we have investigated the contribution of elevated adiposity and hyperleptinemia on femoral strength in rodent models of GH deficiency. Quantification of the transpubertal development of femoral strength in the moderately GH-deficient/hyperleptinemic Tgr rat and the profoundly GH-deficient/hypoleptinemic dw/dw rat revealed that the mechanical properties of cortical bone in these two models were similarly compromised, a 25-30% reduction in failure load being entirely due to impairment of geometric variables. In contrast, murine models of partial (GH antagonist transgenic) and complete (GH receptor-null) loss of GH signaling and elevated adiposity showed an impairment of femoral cortical strength proportionate to the reduction of GH signaling. To determine whether impaired femoral strength is exacerbated by obesity/hyperleptinemia, femoral strength was assessed in dw/dw rats following two developmental manipulations that elevate abdominal adiposity and circulating leptin, neonatal monosodium glutamate (MSG) treatment, and maintenance on an elevated fat diet. The additional impairment of femoral strength following MSG treatment is likely to have resulted from a reduction in residual activity of the hypothalamo-pituitary-GH-IGF-I axis, but consumption of elevated dietary fat, which did not reduce circulating IGF-I, failed to exacerbate the compromised femoral strength in dw/dw rats. Taken together, our data indicate that the obesity and hyperleptinemia usually associated with GH deficiency do not exert a significant influence over the strength of cortical bone.

Clinical effectiveness of a brief educational intervention in Type 1 diabetes: results from the BITES (Brief Intervention in Type 1 diabetes, Education for Self-efficacy) trial.

AIMS: Intensive 5-day educational interventions for people with Type 1 diabetes have shown improved outcomes in a number of European studies. The aim was to assess the effectiveness of a brief (2.5 days) psycho-educational intervention. METHODS: Our randomized trial in a secondary-care setting had 54 and 60 participants allocated to intervention and control groups, respectively. Primary outcomes were HbA1c and severe hypoglycaemia. Secondary outcomes were blood pressure, weight, height, lipids and psychometric profile. RESULTS: HbA1c showed no statistically significant change at 3 months [difference = 0.01, 95% confidence interval (CI) -0.23, 0.26, P = 0.92], 6 months (difference = -0.06, 95% CI -0.32, 0.20, P = 0.67) and 12 months (difference = 0.01, 95% CI -0.30, 0.32, P = 0.94). Incidence of severe hypoglycaemia (per patient per year) in the intervention group (0.41) and control group (0.48) was not statistically different. Treatment satisfaction improved at 3 months (difference = 9.4, 95% CI 5.2, 13.6, P = 0.0005), 6 months (difference = 10.4, 95% CI 6.0, 14.8, P = 0.0005) and 12 months (difference = 7.1, 95% CI 2.1, 12.1, P = 0.006). The 'Managing psychological aspects' and 'Setting and achieving goals' dimensions of the Diabetes Empowerment Scale also showed significant improvement at 3, 6 and 12 months. Diabetes Knowledge Test, Illness Perception Questionnaire, Hypoglycaemia Fear Scale and Short Form 36 showed no significant change. CONCLUSIONS: This brief intervention had no significant impact on HbA(1c) or severe hypoglycaemia, but improved diabetes treatment satisfaction and patient empowerment. Current Controlled Trials ISRCTN75807800.

The pregnancy-induced increase in baseline circulating growth hormone in rats is not induced by ghrelin.

The elevation in baseline circulating growth hormone (GH) that occurs in pregnant rats is thought to arise from increased pituitary GH secretion, but the underlying mechanism remains unclear. Distribution, Fourier and algorithmic analyses confirmed that the pregnancy-induced increase in circulating GH in 3-week pregnant rats was due to a 13-fold increase in baseline circulating GH (P < 0.01), without any significant alteration in the parameters of episodic secretion. Electron microscopy revealed that pregnancy resulted in a reduction in the proportion of mammosomatotrophs (P < 0.01) and an increase in type II lactotrophs (P < 0.05), without any significant change in the somatotroph population. However, the density of the secretory granules in somatotrophs from 3-week pregnant rats was reduced (P < 0.05), and their distribution markedly polarised; the granules being grouped nearest the vasculature. Pituitary GH content was not increased, but steady-state GH mRNA levels declined progressively during pregnancy (P < 0.05). In situ hybridisation revealed that pregnancy was accompanied by a suppression of GH-releasing hormone mRNA expression in the arcuate nuclei (P < 0.05) and enhanced somatostatin mRNA expression in the periventricular nuclei (P < 0.05), an expression pattern normally associated with increased GH feedback. Although gastric ghrelin mRNA expression was elevated by 50% in 3-week pregnant rats (P < 0.01), circulating ghrelin, GH-secretagogue receptor mRNA expression and the GH response to a bolus i.v. injection of exogenous ghrelin were all largely unaffected during pregnancy. Although trace amounts of 'pituitary' GH could be detected in the placenta with radioimmunoassay, significant GH-immunoreactivity could not be observed by immunohistochemistry, indicating that rat placenta itself does not produce 'pituitary' GH. Although not excluding the possibility that the pregnancy-associated elevation in baseline circulating GH could arise from alternative extra-pituitary sources (e.g. the ovary), our data indicate that this phenomenon is most likely to result from a direct alteration of somatotroph function.