A framework for exposure characterization and gamma dosimetry at the NMBU FIGARO irradiation facility.

PURPOSE: The FIGARO low dose 60Co gamma irradiation facility at the Norwegian University of Life Sciences, Ås, Norway, is dedicated to the study of effects on living organisms from acute or chronic ionizing radiation exposures, either alone or in combination with other stressors such as UV radiation, metals or radionuclides. Here, we present a framework of working guidelines and computer software for characterization of absorbed dose rates and accumulated doses to organisms exposed within the continuous gamma field at FIGARO. The aims of the framework are to ensure gamma exposures are well characterized, that results from exposures are correctly interpreted in terms of absorbed dose rates and accumulated doses, and that sufficient information is available so that exposures can be reproduced later or at other facilities. METHODS: The software of the framework includes a Geant4 application for Monte Carlo radiation transport simulations and tools for dose planning, recording and reporting. The working guidelines are prepared for expert users who provide simulated, calculated or estimated absorbed dose rates and for regular users who conduct exposure experiments and are responsible for record keeping. To demonstrate the developed framework, we use a case study where 14 freshwater microcosms are exposed to four levels of gamma dose rates at FIGARO. CONCLUSION: The framework guides users towards good dosimetry practices. Lessons learned could be transferable to other gamma irradiation facilities.

Effects of diet form and feeder adjustment on growth performance of nursery and finishing pigs.

Three experiments were conducted to determine the effects of feeder adjustment and diet form on growth performance of nursery (Exp. 1 and 2) and finishing (Exp. 3) pigs. Treatments were arranged as a 2 × 3 factorial with the main effects of feeder adjustment and diet form. The 2 feeder adjustments were a narrow and wide feeder adjustment (minimum gap opening of 1.27 and 2.54 cm, respectively). The 3 diet forms were meal, poor-quality pellets (70% pellets and 30% fines for Exp. 1 and 2 and 50% pellets and 50% fines for Exp. 3), and screened pellets with minimal fines (3 to 10%). In Exp. 1, 210 pigs (initially 11.9 kg BW) were used in a 21-d trial with 7 pigs per pen and 5 pens per treatment. No feeder adjustment × diet form interactions were observed. There were no differences in ADG, ADFI, or G:F due to feeder adjustment. Pigs fed the meal diet had increased ( < 0.05) ADG and ADFI compared with pigs fed the poor-quality or screened pellets. Pigs fed meal or poor-quality pellets had decreased ( < 0.05) G:F compared with pigs fed screened pellets. In Exp. 2, 1,005 nursery pigs (initially 14.1 kg BW) were used in a 28-d trial with 26 to 28 pigs per pen and 6 pens per treatment. Pigs fed from the narrow feeder adjustment had decreased ( < 0.05) ADG and ADFI compared with pigs fed from the wide adjustment with no differences in G:F. Pigs fed the meal diet had decreased ( < 0.05) ADG compared with pigs fed poor-quality or screened pellets. Pigs fed meal or poor-quality pellets had decreased ( < 0.05) G:F compared with pigs fed screened pellets. In Exp. 3, 246 pigs (initially 56.8 kg BW) were used in a 69-d trial with 5 pens per treatment and 6 or 7 pigs per pen. Overall, ADFI decreased ( < 0.05) and G:F increased ( < 0.05) for pigs fed from the narrow adjusted feeders compared with the wide adjustment with no differences in ADG. Overall, pigs fed meal diets tended to have decreased ( < 0.10) ADG and had decreased ( < 0.05) G:F compared with pigs fed screened pellets; ADG and G:F in those fed poor-quality pellets were intermediate. Feeding meal or poor-quality pellets increased ( < 0.05) ADFI compared with pigs fed screened pellets. In conclusion, feeding nursery pigs from a wide feeder gap may increase ADG and ADFI with no negative effects on G:F. For finishing pigs, reducing feeder gap reduced feed disappearance and improved G:F. In all experiments, the greatest G:F improvements from pelleting were observed when the percentage of fines was minimized.

The effects of deoxynivalenol-contaminated corn dried distillers grains with solubles in nursery pig diets and potential for mitigation by commercially available feed additives.

Four experiments were conducted to investigate the effects of deoxynivalenol (DON) from naturally contaminated dried distillers grains with solubles (DDGS) and the efficacy of feed additives in nursery pig diets. In Exp. 1, 180 pigs (10.3 ± 0.2 kg BW) were fed 1 of 5 diets for 21 d. Diets were 1) Positive Control (PC; < 0.5 mg/kg DON), 2) Negative Control (NC; 4 mg/kg DON), 3) NC + 0.10% Biofix (Biomin Inc., Herzogenburg, Austria), 4) NC + 0.15% Cel-can (VAST Inc., Mason City, IA) and 0.50% bentonite clay, and 5) NC + 0.25% Defusion Plus (Cargill Animal Nutrition, Minneapolis, MN). Pigs fed the NC diet had poorer ( < 0.01) ADG than those fed the PC. Pigs fed Defusion Plus had improved ( < 0.03) ADG over those fed NC, whereas pigs fed Biofix or Cel-can with bentonite clay had reduced ADG ( < 0.01) compared with those fed PC. In Exp. 2, 340 pigs (11.7 ± 0.1 kg BW) were fed 1 of 8 diets for 21 d. Diets were 1) PC (< 0.5 mg/kg DON), 2) Low NC (1.5 mg/kg DON), 3) Low NC + 0.15% Biofix, 4) Low NC + 0.30% Biofix, 5) High NC (3.0 mg/kg DON), 6) High NC + 0.30% Biofix, 7) High NC + 0.45% Biofix, and 8) Diet 7 with 5% added water. Increasing the DON level reduced (linear; < 0.05) ADG, ADFI, and pig BW, and Biofix did not improve performance. In Exp. 3, 1,008 pigs (12.5 ± 0.3 kg BW) were fed 6 treatments for 24 d. Diets were 1) PC ( < 0.5 mg/kg DON), 2) NC (3 mg/kg DON), 3) NC + 0.25% Defusion, 4) NC + 0.50% Defusion, 5) Diet 3 with supplemental nutrients, and 6) Diet 5, pelleted. Pigs fed the NC had decreased ( < 0.01) ADG and ADFI, but adding Defusion improved (linear; < 0.04) ADG and ADFI over pigs fed NC. Pelleting improved ( < 0.01) both ADG and G:F, resulting in ADG above PC pigs. In Exp. 4, 980 pigs (12.0 ± 0.3 kg BW) were fed 1 of 7 diets in a 28-d trial in a 2 × 3 + 1 factorial arrangement. The 7 treatments were based on 3 diets fed in meal or pellet form: 1) PC (< 0.5 mg/kg DON), 2) NC (3 mg/kg DON), and 3) NC + 0.25% Defusion. Treatment 7 was Diet 3 with supplemental nutrients in pellet form. No interactions were observed between pelleting and Defusion. Pigs fed the NC had decreased ( < 0.01) ADG and ADFI, and pelleting improved ( < 0.01) ADG to PC levels, driven by improved ( < 0.01) G:F. Adding nutrients or Defusion had no effect. Overall, these studies show that Defusion and pelleting can help overcome some of the negative effects of DON, whereas other feed additives and additional nutrients do not.

Effects of supplemental vitamin D3 on serum 25-hydroxycholecalciferol and growth of preweaning and nursery pigs.

Four experiments were conducted to investigate the effects of varying concentrations of supplemental vitamin D3 on pig growth, feed preference, serum 25-hydroxycholecalciferol [25(OH)D3] , and bone mineralization of nursing and weanling pigs. In Exp. 1, 270 pigs (1.71 ± 0.01 kg BW) were administered 1 of 3 oral vitamin D3 dosages (none, 40,000, or 80,000 IU vitamin D3) on d 1 or 2 of age. Increasing oral vitamin D3 increased serum 25(OH)D3 on d 10 and 20 (quadratic, P < 0.01) and d 30 (linear, P < 0.01). No differences were observed in ADG before weaning or for nursery ADG, ADFI, or G:F. Vitamin D3 concentration had no effect on bone ash concentration or bone histological traits evaluated on d 19 or 35. In Exp. 2, 398 barrows (initially 7 d of age) were used in a 2 × 2 split plot design to determine the influence of vitamin D3 before (none or 40,000 IU vitamin D3 in an oral dose) or after weaning (1,378 or 13,780 IU vitamin D3/kg in nursery diets from d 21 to 31 of age) in a 45-d trial. Before weaning (7 to 21 d of age), oral vitamin D3 dose did not influence growth but increased (P < 0.01) serum 25(OH)D3 at weaning (d 21) and tended (P = 0.08) to increase 25(OH)D3 on d 31. Increasing dietary vitamin D3 concentration from d 21 to 31 increased (P < 0.01) serum 25(OH)D3 on d 31. Neither the oral vitamin D3 dose nor nursery vitamin D3 supplements influenced nursery ADG, ADFI, or G:F. In Exp. 3, 864 pigs (initially 21 d of age) were allotted to 1 of 2 water solubilized vitamin D3 treatments (none or 16,516 IU/L vitamin D3 provided in the drinking water from d 0 to 10) in a 30-d study. Providing vitamin D3 increased serum 25(OH)D3 concentrations on d 10, 20, and 30; however, vitamin D3 supplementation did not affect overall (d 0 to 30) ADG, ADFI, or G:F. In Exp. 4, 72 pigs were used in a feed preference study consisting of 2 feed preference comparisons. Pigs did not differentiate diets containing either 1,378 or 13,780 IU vitamin D3/kg but consumed less (P < 0.01) of a diet containing 44,100 IU vitamin D3/kg compared with the diet containing 1,378 IU vitamin D3/kg. Overall, these studies demonstrate that supplementing vitamin D3 above basal concentrations used in these studies is effective at increasing circulating 25(OH)D3, but the supplement did not influence growth or bone mineralization. Also, concentrations of vitamin D3 of 44,100 IU/kg of the diet may negatively affect feed preference of nursery pigs.

The psychological impact of split-thickness skin grafts.

OBJECTIVE: To measure the psychological distress associated with a split-thickness skin graft (STSG). METHOD: A retrospective postal questionnaire survey of 102 patients who had undergone a STSG procedure within the last 3.5 years. Outcomes measures included the Hospital Anxiety and Depression Scale (HADS), Derriford Appearance Scale (DAS-59) and subjective rating scales (SRS) of noticeability and worry about the grafted and donor area. RESUTLS: Scores on the SRS correlated positively with HADS and DAS-59 scores. Rates of anxiety were higher than depression (19% vs 13%, respectively). Greater than 10% of the sample experienced significant appearance-related distress when compared to standardised test norms. Concerns about the grafted area were higher than for the donor site, but those concerned about the graft were also likely to be concerned about the donor area. Aged (< 60 years) and reason for surgery (trauma as opposed to cancer) were associated with significantly higher scores on appearance measures. CONCLUSION: STSG is not associated with high levels of psychological distress, However, there is a small but significant monitory who experience appearance-related distress, low mood and anxiety who would benefit from targeted psychological intervention, Demographic factors, such as age or gender, and length of time since surgery, are not useful discriminators in identifying vulnerable individuals. Simple SRS of visibility and worry correlate significantly with standardised psychological measures. These can be used as a short and effective screening tool to identify individuals who would benefit from postoperative psychological input. DECLARATION OF INTERNET: There were no external sources sources of funding for this study. The authors have no conflicts of interest to declare.

Swelling transition of a clay induced by heating.

Clays are of paramount importance for soil stability, but also in applications ranging from oil recovery to composites and hydrogels. Generically, clays are divided into two subclasses: macroscopically swelling, 'active' clays that have the capacity for taking up large amounts of water to form stable gels, and 'passive' or non-swelling clays; the former stabilize soils whereas the latter are known to lead to landslides. However, it has been unclear so far what mechanisms underlie clay swelling. Here, we report the first observation of a temperature-induced transition from a passive to an active, swelling clay. We propose a simple description of the swelling transition; while net attractive interactions are dominant at low temperatures so that the clay particles remain attached to each other in stacks, at higher temperatures it is energetically favourable for the clay to swell due to the entropy that is gained by counterions which are liberated during swelling.

Low priority? A cross sectional study of appearance anxiety in 500 consecutive referrals for cosmetic surgery.

Low priority treatment guidance is used in the National Health Service to manage requests for cosmetic surgery where there is no associated functional impairment. Provision is made in this guidance to provide surgery on exceptional grounds, and this may include significant psychological distress. However, without a good understanding of the common factors that underpin requests for surgery, ideally in the local population, it is very difficult to define an exception in a clear and consistent way. A prospective study of consecutive referrals for cosmetic surgery in an NHS plastic surgery unit was therefore completed over a five-year period. Five hundred and one men and women aged between 16 and 79 (mean 34.5 years) were assessed using standardised questionnaires and clinical interview carried out by two clinical psychologists specialising in the field. Results indicated very marked impact of appearance-related anxiety with significant withdrawal from social activities particularly intimate behaviour. Coping behaviours ranged from use of concealing clothing and complete social avoidance to ominous high risk strategies such as repeated pregnancy with late termination to maintain breast size. Treatment goals were predominantly psychosocial. High levels of psychological morbidity can be characterised as typical of people requesting cosmetic procedures in the NHS rather than exceptional, making the achievement of equitable access to limited resources impossible. Rather than define this population as 'low-priority', a constructive approach is to examine the utility of psychological interventions in a design which evaluates the comparative benefits of surgical and psychological approaches to management of appearance anxiety.

Nematic textures in colloidal dispersions of Na-fluorohectorite synthetic clay.

We have studied stable strata of gravity-induced phase separation in suspensions of synthetic Na-fluorohectorite clay in saline solutions. We have observed how the strata depend on clay concentration as well as on salt content. The mass distribution and density variation at the isotropic-nematic interface indicate that existing models and assumptions in existing simulations are able to relatively well account for the observed behavior. We suggest that discrepancies could be due to the high polydispersity and the irregular shape of our Na-fluorohectorite particles, as well as diffusive double-layer effects, which could result in a competition between nematic ordering and gelation. The dependence on ionic strength displays three main regimes irrespective of clay concentration. At low ionic strength (approximately 0.1-5 mM NaCl), the Debye screening length is longer than the van der Waals force range. In this regime, the particles repel each other electrostatically and entropy-driven Onsager-type nematic ordering may occur, although gelation effects could also play a role. For ionic strengths above about 5 mM, we believe that the van der Waals force comes into play and that particles attract each other locally according to the classical Derjaguin, Landau, Verwey, and Overbeek (DLVO) model of colloid interactions, resulting in a small-domain regime of attractive nematiclike ordering. In the third regime, for ionic strengths above approximately 10 mM, the clay particles aggregate into larger assemblies, due to the dominant van der Waals force, and the observed birefringency is reduced. We have studied the nematic phase in detail between crossed polarizers and have found textures showing nematic Schlieren patterns. By rotating the polarizers as well as the samples, we have observed examples of disclinations of strengths -1, -1/2, and +1.

CYP2D6 gene test in psychiatric patients and healthy volunteers.

BACKGROUND: Antipsychotic drug therapy meets difficulties in predicting response in psychiatric patients. The medical treatment of these patients may be improved significantly by systematic phamacogenetic diagnosis identifying the drug metabolic capacities of each patient. Genetic polymorphisms in the coding sequence for the drug metabolizing cytochrome P450 enzyme CYP2D6 represent a pharmacogenetic target. METHODS: A cohort (n = 225) representing psychiatric patients seen during an 18-month trial period was included in the project after the subjects accepted a blood sample being taken to analyse their CYP2D6 allelic composition. To investigate any putative difference in allele frequencies among the psychiatric patients compared to earlier publications on allele frequencies in Caucasian populations, another cohort (n = 122) of local healthy volunteers was likewise included. RESULTS: Allelic frequencies in the psychiatric patients and healthy volunteers were indistinguishable. Alleles *1 and *2 encoding for normal enzyme activity and alleles *3, *4, *5, *6, *13/*16 representing non-active forms were found as well as alleles *9, *10, *41 encoding for enzymes with decreased activity. Furthermore, examples of the previously described duplications of *1 and *2, which result in enhanced enzyme activity, were also identified. CONCLUSION: A systematic CYP2D6 gene test of hospitalized psychiatric patients revealed the identification of pharmacogenetically relevant alleles affecting capacity to metabolize antipsychotics. The frequencies of phenotypes in affected patients were 8.4 % intermediate metabolizers (IMs), 8.4 % poor metabolizers (PMs) and 3.1 % ultrafast metabolizers (UMs), whereas 52.4 % were extensive metabolizers (EMs) and 27.6 % heterozygous EMs.

Lamotrigine plasma levels reduced by oral contraceptives.

Although it is known that the use of oral contraceptives (OC's) can induce glucuronide conjugating enzymes, currently no data exists as to the potential that the elimination of the glucuronidated drug lamotrigine (LTG) is increased by OC's. We present seven cases in whom the plasma levels of LTG were significantly decreased by OC's (mean 49%, range 41-64%). The interaction was of clinical relevance in most of the patients who either experienced increased seizure frequency/recurrence of seizures after OC's had been added, or adverse effects following withdrawal of OC's.

Enantioconvergent synthesis by sequential asymmetric Horner-Wadsworth-Emmons and palladium-catalyzed allylic substitution reactions.

A new method for enantioconvergent synthesis has been developed. The strategy relies on the combination of an asymmetric Horner-Wadsworth-Emmons (HWE) reaction and a palladium-catalyzed allylic substitution. Different alpha-oxygen-substituted, racemic aldehydes were initially transformed by asymmetric HWE reactions into mixtures of two major alpha,beta-unsaturated esters, possessing opposite configurations at their allylic stereocenters as well as opposite alkene geometry. Subsequently, these isomeric mixtures of alkenes could be subjected to palladium-catalyzed allylic substitution reactions with carbon, nitrogen, and oxygen nucleophiles. In this latter step, the respective (E) and (Z) alkene substrate isomers were observed to react with opposite stereospecificity: the (E) alkene reacted with retention and the (Z) alkene with inversion of stereochemistry with respect to both the allylic stereocenter and the alkene geometry. Thus, a single gamma-substituted ester was obtained as the overall product, in high isomeric purity. The method was applied to a synthesis of a subunit of the iejimalides, a group of cytotoxic macrolides.

Prospectively measured red cell folate levels in methotrexate treated patients with rheumatoid arthritis: relation to withdrawal and side effects.

OBJECTIVE: To investigate whether red cell folate (RCF) levels relate to side effects, withdrawals, or disease activity during treatment with the folic acid antagonist methotrexate (MTX) for rheumatoid arthritis (RA). METHODS: Side effects were recorded monthly, RCF levels were measured by lactoglobulin binding radioassays, and 8 variables for disease activity were measured in a placebo controlled double blind trial of 28 weeks' duration comparing efficacy of MTX (n = 23) and D-penicillamine (n = 23). RESULTS: From Week 20 RCF levels decreased only in the MTX group (p < 0.02), and 5 MTX treated patients withdrew due to side effects. Withdrawals had lower RCF values at Weeks 0 and 9 compared to the remaining patients (p < 0.05). Folate deficiency evolved in 5 patients; 2 of these developed cytopenia. Aberrations in the scheduled dosage increase were related to lower pretreatment values of RCF (p = 0.007). Side effect scores were inversely correlated to RCF values at Weeks 0, 9, and 28 (p < 0.05). RCF levels measured concomitantly with liver enzyme elevation were lower than the remaining values (p < 0.001). When side effects were reported, 96% of concomitantly measured RCF values were below 800 nmol/l. RCF values at entry did not correlate to improvement in any variable for disease activity, or a graded overall improvement. CONCLUSION: RCF levels decrease during MTX treatment and relate to side effects, withdrawals, liver enzyme elevations and aberrant MTX dosage increase, but not to the therapeutic effect. RCF above 800 nmol/l protects against side effects.

Nutritional status of Danish rheumatoid arthritis patients and effects of a diet adjusted in energy intake, fish-meal, and antioxidants.

This study deals with the nutritional status of Danish RA patients and address the question of whether or not RA can be directly influenced by dietary manipulation. In a prospective, single-blinded study of 6 months duration, 109 patients with active RA were randomly assigned to either treatment with or without a specialized diet. The energy consumption was adjusted to normal standards of body weights and the intake of fish meals and antioxidants were increased. A daily food diary was completed by the patients, and the total intake of 47 different food-elements was calculated. Nutritional status together with disease activity parameters were recorded. At baseline, the Danish RA-patients had neglected food habits with a significant reduction in intake of total energy, of D-vitamin and of E-vitamin. A very low intake of n-3 fatty acids was also found. During the study, 28 of the 109 patients dropped out, introducing a confounding effect on the overall result. In the remaining 81, those following the diet demonstrated a significant improvement in the duration of morning stiffness, number of swollen joints, pain status, and reduced cost of medicine, while doctors global assessment, laboratory data, X-ray, and daily activities were unaltered. In conclusion, dietary analysis and appropriate, corrective advice should be offered to Danish RA patients.

Simultaneous determination of lofepramine and desipramine by a high-performance liquid chromatographic method used for therapeutic drug monitoring.

A simple reversed-phase HPLC method with ultraviolet detection for the simultaneous measurement of lofepramine and desipramine is described. Only a single alkaline extraction was used, with clomipramine as internal standard. The column used was a Supelco PCN column, and the mobile phase was acetonitrile-methanol-0.015 M phosphate buffer (120:35:100, v/v). The average recoveries were 78.8% for desipramine and 103.8% for lofepramine, and limits of quantitation were 25 and 5 nmol/l, respectively. The inter-assay C.V.s for lofepramine and desipramine were 6.0 and 7.6%, respectively. The method is specific and has excellent accuracy, and has been used for therapeutic drug monitoring of patients with depressions treated with lofepramine. Mean steady-state plasma concentrations found for lofepramine and desipramine were 8.5 +/- 6.1 and 123.6 +/- 120.6 nmol/l, respectively. It is concluded that lofepramine in itself has an antidepressive effect.

Gas chromatographic determination with flash methylation of palmitic acid in amniotic fluid in prediction of fetal lung maturity.

A new method for determination of palmitic acid in amniotic fluid was developed. The dipalmitoyl lecithin was hydrolysed, and after extraction the palmitic acid was flash methylated in the injector of the gas chromatograph. The between batch coefficient of variation was 6.0% at 40 and 70 mumol/l of palmitic acid concentrations in 500 microliters amniotic fluid. The accuracy of the method was demonstrated by linearity, recovery and correlation studies. The correlation coefficient was 0.98 between the new and bortrifluoride methylating method. The concentrations of lecithin and palmitic acid in amniotic fluid showed a correlation coefficient of 0.97. If the concentration of palmitic acid falls below 80 mumol/l respiration distress syndrome is likely. The new method was simple and easy to carry out and could be adjusted for haemoglobin contamination of the amniotic fluid. It was concluded that the determination of palmitic acid in amniotic fluid was a reliable method for the assessment of fetal lung maturity that could replace the determination of lecithin concentration.

Artificial hyperventilation during 21 years in three cases of complete respiratory paralysis.

Three patients with paralytic poliomyelitis have been ventilated via tracheostomy with uncuffed silver cannula for 21 years, with high tidal volumes of atmospheric air (8.3, 7.2, and 5.4 ml/kg b.wt.), at a frequency of 20, passive expiration, and without periodic hyperinflation. No pulmonary complications were seen during the whole of this period. The total compliance was significantly decreased. The pulmonary physiological shunt relative to the total pulmonary blood flow (Qs/Qt) was slightly increased. PaO2 was nevertheless normal, probably due to a high alveolar PO2 caused by the hyperventilation. The physiological dead space realtive to the tidal volume (VD/VT) was within the noraml range, but VD was high in one case. Two of the patients disclosed an extremely low CO2 production and a PaCO2 averaging 12 mmHg, with small fluctuations during a 24-hour study. This profound respiratory alkalosis was only partly compensated in the arterial blood (pH: 7.54 and 7.50), suggesting a new state of acid-base equilibrium. The cerebrospinal fluid lactate was significantly increased to about 4 mmol/l, but the patients revealed no signs of impaired cerebral function. A reduction of the degree of hypocapnia by the use of a mechanical dead space is recommended.