Randomized controlled pilot trial with ion-exchange water softeners to prevent eczema (SOFTER trial).

BACKGROUND: Observational studies suggest an increased risk of eczema in children living in hard versus soft water areas, and there is, therefore, an interest in knowing whether softening water may prevent eczema. We evaluated the feasibility of a parallel-group assessor-blinded pilot randomized controlled trial to test whether installing a domestic ion-exchange water softener before birth in hard water areas reduces the risk of eczema in infants with a family history of atopy. METHODS: Pregnant women living in hard water areas (>250 mg/L calcium carbonate) in and around London UK, were randomized 1:1 antenatally to either have an ion-exchange water softener installed in their home or not (ie to continue to receive usual domestic hard water). Infants were assessed at birth and followed up for 6 months. The main end-points were around feasibility, the primary end-point being the proportion of eligible families screened who were willing and able to be randomized. Clinical end-points were evaluated including frequency of parent-reported doctor-diagnosed eczema and visible eczema on skin examination. Descriptive analyses were conducted, and no statistical testing was performed as this was a pilot study. RESULTS: One hundred and forty-nine families screened were eligible antenatally and 28% (41/149) could not have a water softener installed due to technical reasons or lack of landlord approval. Eighty of 149 (54%) were randomized, the primary end-point. Two participants withdrew immediately after randomization, leaving 39 participants in each arm (78 total). Attrition was 15% (12/78) by 6 months postpartum. All respondents (n = 69) to the study acceptability questionnaire reported that the study was acceptable. Fifty-six of 708 (7.9%) water samples in the water softener arm were above the hard water threshold of 20 mg/L CaCO3 . At 6 months of age 27/67 infants (40%) developed visible eczema, 12/36 (33%) vs. 15/31 (48%) in the water softener and control groups, respectively, difference -15% (95% CI -38, 8.3%), with most assessments (≥96%) remaining blinded. Similarly, a lower proportion of infants in the water softener arm had parent-reported, doctor-diagnosed eczema by 6 months compared to the control arm, 6/17 (35%) versus 9/19 (47%), difference -12% (95% CI -44, 20%). CONCLUSION: A randomized controlled trial of water softeners for the prevention of atopic eczema in high-risk infants is feasible and acceptable. TRIAL REGISTRATION: NCT03270566 (clinicaltrials.gov).

Evidence from the lamarck granodiorite for rapid late cretaceous crust formation in california.

Strontium and neodymium isotopic data for rocks from the voluminous 90-million-year-old Lamarck intrusive suite in the Sierra Nevada batholith, California, show little variation across a compositional range from gabbro to granite. Data for three different gabbro intrusions within the suite are identical within analytical error and are consistent with derivation from an enriched mantle source. Recognition of local involvement of enriched mantle during generation of the Sierran batholith modifies estimates of crustal growth rates in the United States. These data indicate that parts of the Sierra Nevada batholith may consist almost entirely of juvenile crust added during Cretaceous magmatism.

Assessment of Advanced Life Support competence when combining different test methods--reliability and validity.

UNLABELLED: Robust assessment of Advanced Life Support (ALS) competence is paramount to the credibility of ALS-provider certification and for estimating the learning outcome and retention of ALS competence following the courses. The European Resuscitation Council (ERC) provides two sets of MCQs and four Cardiac Arrest Simulation Test (CASTest) scenarios for the assessments according to guidelines 2005. AIMS: To analyse the reliability and validity of the individual sub-tests provided by ERC and to find a combination of MCQ and CASTest that provides a reliable and valid single effect measure of ALS competence. METHODS: Two groups of participants were included in this randomised, controlled experimental study: a group of newly graduated doctors, who had not taken the ALS course (N=17) and a group of students, who had passed the ALS course 9 months before the study (N=16). Reliability in terms of inter-rater agreement and generalisability across skills scenarios were estimated. Validity was studied in terms of equality of test difficulty and ability to discriminate performance between the groups. RESULTS: Inter-rater agreement on checklist scores were generally high, Intraclass Correlation Coefficients between 0.766 and 0.977. Inter-rater agreements on pass/fail decisions were not perfect. The one MCQ test was significantly more difficult than the other. There were no significant differences between CASTests. Generalisability theory was use to identify a composite of MCQ and CASTest scenarios that possessed high reliability, equality of test sets, and ability to discriminate between the two groups of supposedly different ALS competence. CONCLUSIONS: ERC sub-tests of ALS competence possess sufficient reliability and validity. A combined ALS score with equal weighting of one MCQ and one CASTest can be used as a single measurement of ALS competence.

Straight-run vs. sex separate rearing for two broiler genetic lines Part 2: Economic analysis and processing advantages.

The objective of this analysis was to evaluate the effects of raising broilers under sex separate and straight-run conditions for 2 broiler genetic lines. One-day-old Ross 308 and Ross 708 chicks (n = 1,344) were sex separated and placed in 48 pens according to rearing type: sex separate (28 males or 28 females) or straight-run (14 males + 14 females). There were 3 dietary phases: starter (zero to 17 d), grower (17 to 32 d), and finisher (32 to 48 d). Bird individual BW and group feed intakes were measured at 12, 17, 25, 32, 42, and 48 d to evaluate performance. At 33, 43, and 49 d 4 birds per pen (straight-run pens 2 males + 2 females) were sampled for carcass yield evaluation. Data were analyzed using linear and non-linear regression in order to estimate feed intake and cut-up weights at 3 separate market weights (1,700, 2,700, and 3,700 g). Returns over feed cost were estimated for a 1.8 million broiler complex for each rearing system and under 9 feed/meat price scenarios. Overall, rearing birds that were sex separated resulted in extra income that ranged from ${\$}$48,824 to ${\$}$330,300 per week, depending on the market targeted and feed and meat price scenarios. Sex separation was shown to be especially important in disadvantageous scenarios in which feed prices were high. Gains from sex separation were markedly higher for the Ross 708 than for the Ross 308 broilers. Bird variability also was evaluated at the 3 separate market ages under narrow ranges of BW that were targeted. Straight-run birds decreased the number of birds present in the desired range. Depending on market weight, straight-run rearing resulted in 9.1 to 16.6% fewer birds than sex separate rearing to meet marketing goals. It was concluded that sex separation can result in increased company profitability and have possible beneficial effects at the processing plant due to increased bird uniformity.

Straight-run vs. sex separate rearing for 2 broiler genetic lines Part 1: Live production parameters, carcass yield, and feeding behavior.

The objective of this experiment was to evaluate the effects of raising broilers under sex separate and straight-run conditions for 2 broiler strains. Day-old Ross 308 and Ross 708 chicks (n = 1,344) were separated by sex and placed in 48 pens according to the rearing type: sex separate (28 males or 28 females) or straight-run (14 males + 14 females). There were 3 dietary phases: starter (zero to 17 d), grower (17 to 32 d), and finisher (32 to 48 d). Birds' individual BW and feed intakes were measured at 12, 17, 25, 32, 42, and 48 d to evaluate performance. At 33, 43, and 49 d, 4 birds per pen were sampled for carcass yield evaluation. Additionally, from 06:00 to 06:30, 13:00 to 13:30, and 22:00 to 22:30, video records were taken to assess behavior at 45 days. Data were analyzed as CRD with a 2 × 3 factorial arrangement of treatments over time. Throughout the experiment Ross 308 were heavier than the 708, and after 17 d, male pens had the heavier birds, followed by straight-run and then females. Straight-run pens had higher BW CV in comparison with sex separate pens. Sex separate male BW was negatively impacted from 17 to 32 days. On the other hand, females raised sex separate were heavier than females raised straight-run with lower CV from 25 to 41 days. Post 25 d, FCR was the lowest in male pens whereas feed intake was the highest for these pens after 17 days. Overall, males had total carcass cut-up weights higher than straight-run and females at the 3 processing times. The Ross 708 had higher white meat yields, whereas 308 had higher yields for dark meat. Feeding behavior results were not consistent over time. However, from 13:00 to 13:30, birds in female pens spent more time eating, followed by straight-run and then males. In conclusion, raising females in a straight-run system negatively impacted performance and CV, whereas males benefited from straight-run rearing, with the differences being possibly related to feeder space competition.

Evaluation of starter dietary digestible lysine level on broilers raised under a sex-separated or straight-run housing regime, part 2: Economics of sex separation and digestible lysine level for maximum returns.

The objective of this experiment was to determine the maximum net returns digestible lysine (dLys) levels (MNRL) when maintaining the ideal amino acid ratio for starter diets of broilers raised sex separate or comingled (straight-run). A total of 3,240 Ross 708 chicks was separated by sex and placed in 90 pens by 2 rearing types: sex separate (36 males or 36 females) or straight-run (18 males + 18 females). Each rearing type was fed 6 starter diets (25 d) formulated to have dLys levels between 1.05 and 1.80%. A common grower diet with 1.02% of dLys was fed from 25 to 32 days. Body weight gain (BWG) and feed intake were assessed at 25 and 32 d for performance evaluation. Additionally, at 26 and 33 d, 4 birds per pen were sampled for carcass yield evaluation. Data were modeled using response surface methodology in order to estimate feed intake and whole carcass weight at 1,600 g live BW. Returns over feed cost were estimated for a 1.8-million-broiler complex of each rearing system under 9 feed/meat price scenarios. Results indicated that females needed more feed to reach market weight, followed by straight-run birds, and then males. At medium meat and feed prices, female birds had MNRL at 1.07% dLys, whereas straight-run and males had MNRL at 1.05%. As feed and meat prices increased, females had MNRL increased up to 1.15% dLys. Sex separation resulted in increased revenue under certain feed and meat prices, and before sex separation cost was deducted. When the sexing cost was subtracted from the returns, sex separation was not shown to be economically viable when targeting birds for light market BW.

Cytogenetic response to alpha-interferon is predicted in early chronic phase chronic myeloid leukemia by M-bcr breakpoint location.

Alpha-interferon (alpha-IFN) therapy is an effective agent in early chronic phase (ECP) chronic myeloid leukemia (CML), achieving hematologic control in the majority and major cytogenetic response (MCR) (reduction in Ph' +ve metaphases to < 35%) in a substantial minority. Currently no pretreatment markers exist to ascertain likelihood of meaningful response. The site of breakpoint in M-bcr and relationship to prognosis is controversial. Studies have been hampered by variation in definition of breakpoint and difference in treatment protocols. In this study of ECP CML patients, Southern analysis and reverse transcription polymerase chain reaction (RT-PCR) were used to determine breakpoint location. Patients received alpha-IFN (9 x 10(6) units/day) and dose-adjusted hydroxyurea (HU) to maintain granulocyte count between 1.0-2.0 x 10(9)/l for 6 months or more. Twelve of 31 patients entered on the study achieved a MCR. The Sokal index did not predict for cytogenetic response to alpha-IFN. Eight of 11 patients with 5' breakpoint achieved MCR compared to only four of 20 patients with 3' breakpoint (P = 0.007). These results suggest site of M-bcr rearrangement may be predictive of response to alpha-IFN therapy. If verified by further study, this may allow more appropriate use of alpha-IFN with respect to other modalities such as allogeneic transplant.

Gold catalysis: on the phenol synthesis.

[reaction--see text] For the gold-catalyzed phenol synthesis an intramolecular migration of the oxygen atom was proven. Several other late transition metals with d(8) configuration allow this conversion, providing evidence for Au(III) being a catalytically active species. On the other hand gold was still the most active catalyst and gives the cleanest conversion. With additional alkynyl substituents another ring could be closed to provide doubly annellated arenes.

Umbilical cord sclerosis as an indicator of congenital syphilis.

In two cases of congenital syphilis examination of the umbilical cord showed a distinctive picture of perivascular sclerosis and inflammation. Large numbers of spirochaetes were shown in the sclerotic zone in both cases. No organisms were demonstrable in the placental disc and there were no morphological changes suggestive of syphilis. It is concluded that the finding of sclerosing funisitis, together with the clinical circumstances, should raise the possibility of congenital syphilis.

Pharmacokinetics of oral indoramin.

A randomized crossover study was carried out in 7 healthy subjects to investigate the pharmacokinetics of indoramin from two oral formulations (film-coated and uncoated 50 mg tablets) and to determine the effect of a standard mean on the plasma concentration time curve of the film-coated form. The results indicated that peak plasma concentrations occurred in 1 to 4 hours after treatment with a single dose of 2 tablets, with an overall elimination half-life of 5 hours. No significant differences could be shown between treatments in any of the pharmacokinetic variables determined. However, administration of film-coated indoramin after a standard meal narrowed the range of peak concentrations but the time at which peak concentrations of the drug occurred did not appear to be related to whether or not indoramin was given after the meal.

Clinical evaluation of fenticonazole cream in cutaneous fungal infections: a comparison with miconazole cream.

A randomized, double-blind, parallel-group, multi-centre clinical trial was undertaken in 60 patients with dermatophytosis or pityriasis versicolor to compare topical 2% fenticonazole cream with topical 2% miconazole cream. Treatment, by twice-daily application, was for 4 weeks or until earlier complete resolution of disease. Assessment was by laboratory mycological investigation and regular clinical/symptomatic evaluation, both during and for 2 to 6 weeks after therapy. Fifty-three patients satisfactorily completed the trial, 28 of whom received fenticonazole and 25 miconazole. The groups were adequately well-matched. All assessment criteria showed fenticonazole to be at least as efficacious as miconazole, with no statistically significant differences between the two treatments. A number of assessment criteria, however, did show trends in favour of fenticonazole. Fenticonazole resulted in mycological findings becoming negative in 92%, i.e. all but 2 of 25 patients, by the end of treatment and a similar proportion (91%, 21 of 23 patients) remained mycologically negative 2 to 4 weeks after the end of therapy. With miconazole, only 79% (19 of 24 patients) became mycologically negative during treatment and this figure decreased further to 74% (14 of 19 patients) after therapy. Essentially similar results were seen for clinical assessments of erythema, itching and desquamation, these features being significantly and progressively eliminated or improved by both treatments in high proportions of patients during therapy, followed by little tendency to return after the cessation of therapy. Overall clinical assessments demonstrated statistically significant improvement during the second, third and fourth weeks of treatment with both drugs. Only 4 patients (two with each treatment) were reported as showing clinical deterioration at any stage during the trial, in all cases after the end of therapy. There were no reports of local or systemic adverse reactions to either drug, and laboratory screening investigations failed to reveal any signs of toxicity. These results indicate that a 4-week course of twice daily topical 2% fenticonazole cream is extremely well tolerated and is at least as efficacious as an equivalent regimen of 2% miconazole for the treatment of cutaneous dermatophytosis or pityriasis versicolor. Trends in the results suggest that fenticonazole may prove to be more efficacious than miconazole, particularly in relation to elimination of laboratory evidence of persistent fungal infection, which could be reflected in a lower incidence of subsequent relapse of the disease.

Thermal preference behavior following clonidine, norepinephrine, isoproterenol, and ephedrine.

A thermal gradient (temperature range 7-45 degrees C) was used to assess ambient temperature (Ta) preferences of rats following treatment with clonidine (25 microg/kg), norepinephrine (NE, 250 microg/kg), isoproterenol (ISO, 50 microg/kg), and ephedrine (EPH, 10 mg/kg). Clonidine produced a preference for a temperature (31.5 degrees C) slightly warmer than that preferred after saline (28.3 degrees C), but this resulted in no significant change in posttest colonic temperature (Tc). NE, ISO and EPH produced a preference for a colder region of the gradient (20-22 degrees C) compared to saline (24.5-28.9 degrees C). Posttest Tc was reduced significantly from 37.7-37.9 degrees C after saline to 37.2 degrees C (NE), 37.3 degrees C (ISO), and 36.8 degrees C (EPH). Thus, given the opportunity to select an environmental temperature, the animals selected a Ta that resulted in significantly lower body temperatures after NE, ISO, and EPH. This suggests that paradoxical thermoregulatory effects of these thermogenic adrenergic agonists are due, at least in part, to a preference for a lower body temperature.

The Australasian Reference Thromboplastin: I. A study in bleeding patients.

The prothrombin time, activated partial thromboplastin time, thrombin time, and skin bleeding time, with assays of factors II, VII, IX, and X, platelet count, and liver function tests were performed on a group of patients receiving long term warfarin therapy. There were 17 bleeding patients and 13 non-bleeding patients. A study was made, using the Australasian Reference Thromboplastin and 2 other thromboplastic reagents in common use. The Australasian Reference Thromboplastin was shown to be more sensitive to the coumarin induced coagulation defect than rabbit brain thromboplastin, and hence of more value in preventing haemorrhagic complications. The level of factor II assayed by the one stage method was a useful independent indicator of the intensity of oral anticoagulation, and correlated well with the development of bleeding.

The Australasian Reference Thromboplastin: II. Are corrected prothrombin ratios valid?

A comparative study was made of 2 thromboplastins, the Australasian Reference Thromboplastin, and Simplastin, in a large group of patients on long-term Warfarin therapy. 373 individual samples were obtained. Calibration constants were obtained for those patients with prothrombin ratios within the therapeutic range, and for those well outside the therapeutic range, and found to be different. Study of the relationship between the 2 thromboplastins indicates that comparability is linear only within a specified limited range of prothrombin ratios. At the two extreme ends the relationship is curved, suggesting a logarithmic relationship. Attention is drawn to the need of caution in interpretation of corrected ratios calculated on a linear relationship especially when the ratio is above 4.0 as this may have clinical implications.

Bone histomorphometry in 1,25(OH)2D3- and vitamin D3-treated aged laying hens.

Aged laying hens at oviposition were given four levels of dietary vitamin D3 and three levels of 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) to determine the effects of the additives on the medullary and endosteal bone. Oxytetracycline hydrochloride labeling and histomorphometry of undecalcified sections were used in the determination of changes in medullary bone and endosteal surface of mid-diaphyseal tibiotarsal bones. Treatment with 1,25(OH)2D3 increased mineralized medullary bone area, endosteal surface length, amount of tetracycline labeling in medullary and endosteal bone, total number of osteoclasts on endosteal and medullary bone, and appositional rate of mineralizing bone. Vitamin D3 increased mineralized medullary bone area and total tetracycline labeling in endosteal bone but decreased endosteal mineral apposition rate. Medullary bone matrix with no mineral was observed only in the group receiving neither supplement. These areas were much larger than typical osteoid seams usually seen in trabecular bone. Both 1,25(OH)2D3 and vitamin D3 were effective in stimulating bone formation and retention of mineral within medullary bone matrix at oviposition.

Complex biological responses to the experimental acidification of Little Rock Lake, Wisconsin, USA.

Acidification can affect aquatic organisms directly through hydrogen ion toxicity, and indirectly through disrupted food web dynamics and altered abiotic conditions. Field populations from selected taxa were studied during the Little Rock Lake whole-basin acidification experiment to illustrate patterns whose timing suggests direct (i.e. immediate) or indirect (i.e. delayed or non-uniform) responses to pH change. As the treatment basin was acidified to pH 5.6, 5.2 and 4.7, immediate changes consistent with a direct pH response were observed for species representing several trophic levels. For other taxa (e.g. littoral invertebrates associated with filamentous algal mats, several species of pelagic zooplankton), indirect mechanisms induced by food web changes were more likely explanations for abundance patterns. The results presented here suggest that the responses of aquatic ecosystems to acidification involve a complex interplay between direct pH effects and subsequent indirect interactions.

Immediate versus delayed repair of skin defects following resection of carcinoma.

Facial defects resulting from excision of skin malignancies may be reconstructed with flaps or grafts immediately or in delayed fashion, or the wound may be allowed to heal by secondary intention. The merits of each option are discussed along with a brief review of the pertinent details of wound healing. A small delay in reconstruction of up to 3 to 4 days can be tolerated safely with no compromise of results. When healing by secondary intention is chosen, fenestration speeds coverage of the wound, and moist dressings with antibiotic ointment effectively prevent infection and expedite epithelialization.

A technique for the laboratory determination of recirculation in single needle dialysis.

Recirculation is an important factor in single needle dialysis and, if high, can compromise treatment efficiency. To provide information regarding recirculation characteristics of access devices used in single needle dialysis, we have developed a new technique to characterise recirculation and have used this to measure the recirculation of a Terumo 15G fistula needle and a VasCath SC2300 single lumen catheter. The experimentally obtained results agreed well with those established clinically (8.5 +/- 2.4% and 18.4 +/- 3.4%). The experimental results have also demonstrated a dependence on access type, pump speeds and fistula flow rate. A comparison of experimental data with theoretical predictions showed that the latter exceeded those measured with the largest contribution being due to the experimental fistula.

Research note: current methods used in determination and evaluation of tibia strength: a correlation study involving birds fed various levels of cholecalciferol.

Tibiae were removed from 300 75-wk-old laying hens for tibia strength analysis using two methods, direct photon absorptiometry and tibia breaking strength. Left tibiae with flesh intact were used for bone density determination with direct photon absorptiometry. Right tibiae were cleaned and dried for determination of tibia weight and tibia breaking strength. Partial correlation coefficients were estimated among bone density, tibia breaking strength, tibia weight, and body weight. A significant correlation was observed between tibia breaking strength and bone density measurements (r = .66, P less than or equal to .0001). Tibia weight and tibia breaking strength were also significantly correlated (r = .62, P less than or equal to .0001), as well as bone weight and bone density (r = .71, P less than or equal to .0001). Tibia weight and BW were also significantly correlated (r = .66, P less than or equal to .0001), necessitating covariance adjustment for BW. Bone densitometry measurements are less variable than tibia breaking strength measurements, and bone densitometry does not require cleaning bones of flesh before measurement.