Magnetic resonance imaging of a randomized controlled trial investigating predictors of recovery following psychological treatment in adolescents with moderate to severe unipolar depression: study protocol for Magnetic Resonance - Improving Mood with Psychoanalytic and Cognitive Therapies (MR-IMPACT)

Background Major depressive disorders (MDD) are a debilitating and pervasive group of mental illnesses afflicting many millions of people resulting in the loss of 110 million working days and more than 2,500 suicides per annum. Adolescent MDD patients attending NHS clinics show high rates of recurrence into adult life. A meta-analysis of recent research shows that psychological treatments are not as efficacious as previously thought. Modest treatment outcomes of approximately 65% of cases responding suggest that aetiological and clinical heterogeneity may hamper the better use of existing therapies and discovery of more effective treatments. Information with respect to optimal treatment choice for individuals is lacking, with no validated biomarkers to aid therapeutic decision-making. Methods/Design Magnetic resonance-Improving Mood with Psychoanalytic and Cognitive Therapies, the MR-IMPACT study, plans to identify brain regions implicated in the pathophysiology of depressions and examine whether there are specific behavioural or neural markers predicting remission and/or subsequent relapse in a subsample of depressed adolescents recruited to the IMPACT randomised controlled trial (Registration # ISRCTN83033550). Discussion MR-IMPACT is an investigative biomarker component of the IMPACT pragmatic effectiveness trial. The aim of this investigation is to identify neural markers and regional indicators of the pathophysiology of and treatment response for MDD in adolescents. We anticipate that these data may enable more targeted treatment delivery by identifying those patients who may be optimal candidates for therapeutic response.

Electronic structure of point defects in controlled self-doping of the TiO2 (110) surface: Combined photoemission spectroscopy and density functional theory study

Point defects in metal oxides such as TiO2 are key to their applications in numerous technologies. The investigation of thermally induced nonstoichiometry in TiO2 is complicated by the difficulties in preparing and determining a desired degree of nonstoichiometry. We study controlled self-doping of TiO2 by adsorption of 1/8 and 1/16 monolayer Ti at the (110) surface using a combination of experimental and computational approaches to unravel the details of the adsorption process and the oxidation state of Ti. Upon adsorption of Ti, x-ray and ultraviolet photoemission spectroscopy (XPS and UPS) show formation of reduced Ti. Comparison of pure density functional theory (DFT) with experiment shows that pure DFT provides an inconsistent description of the electronic structure. To surmount this difficulty, we apply DFT corrected for on-site Coulomb interaction (DFT+U) to describe reduced Ti ions. The optimal value of U is 3 eV, determined from comparison of the computed Ti 3d electronic density of states with the UPS data. DFT+U and UPS show the appearance of a Ti 3d adsorbate-induced state at 1.3 eV above the valence band and 1.0 eV below the conduction band. The computations show that the adsorbed Ti atom is oxidized to Ti2+ and a fivefold coordinated surface Ti atom is reduced to Ti3+, while the remaining electron is distributed among other surface Ti atoms. The UPS data are best fitted with reduced Ti2+ and Ti3+ ions. These results demonstrate that the complexity of doped metal oxides is best understood with a combination of experiment and appropriate computations.

Shear controlled crystal size definition in a low molar mass compound using a polymeric solvent

We show that close to monodisperse crystalline fibrils of dibenzylidene sorbitol can be obtained by preparation in a polymeric solvent subjected to extended shear flow.

Rapid word learning by 15-month-olds under tightly-controlled conditions

Infants (12 to 17 months) were taught 2 novel words for 2 images of novel objects, by pairing isolated auditory labels with to-be-associated images. Comprehension was tested using a preferential looking task in which the infant was presented with both images together with an isolated auditory label. The auditory label usually, but not always, matched one of the images. Infants looked preferentially at images that matched the auditory stimulus. The experiment controlled within-subjects for both side bias and preference for previously named items. Infants showed learning after 12 presentations of the new words. Evidence is presented that, in certain circumstances, the duration of longest look at a target may be a more robust measure of target preference than overall looking time. The experiment provides support for previous demonstrations of rapid word learning by pre-vocabulary spurt children, and offers some methodological improvements to the preferential looking task.

A randomised controlled trial of cognitive behaviour therapy for psychosis in a routine clinical service

Objective: To evaluate CBTp delivered by non-expert therapists, using CBT relevant measures. Methods: Participants (N=74) were randomised into immediate therapy or waiting list control groups. The therapy group was offered six months of therapy and followed up three months later. The waiting list group received therapy after waiting nine months (becoming the delayed therapy group). Results: Depression improved in the combined therapy group at both the end of therapy and follow-up. Other significant effects were found in only one of the two therapy groups (positive symptoms; cognitive flexibility; uncontrollability of thoughts) or one of the two timepoints (end of therapy: PANSS general symptoms, anxiety, suicidal ideation, social functioning, resistance to voices; follow-up: power beliefs about voices, negative symptoms). There was no difference in costs between the groups. Conclusions: The only robust improvement was in depression. Nevertheless, there were further encouraging but modest improvements in both emotional and cognitive variables, in addition to psychotic symptoms.

Clinical and subclinical mastitis in smallholder dairy farms in Tanzania: Risk, intervention and knowledge transfer

In a cross-sectional study of 400 randomly selected smallholder dairy farms in the Tanga and Iringa regions of Tanzania, 14.2% (95% confidence interval (CI) = 11.6-17.3) of cows had developed clinical mastitis during the previous year. The point prevalence of subclinical mastitis, defined as a quarter positive by the California Mastitis Test (CMT) or by bacteriological culture, was 46.2% (95% Cl = 43.6-48.8) and 24.3% (95% Cl = 22.2-26.6), respectively. In a longitudinal disease study in Iringa, the incidence of clinical mastitis was 31.7 cases per 100 cow-years. A randomised intervention trial indicated that intramammary antibiotics significantly reduced the proportion of bacteriologically positive quarters in the short-term (14 days post-infusion) but teat dipping had no detectable effect on bacteriological infection and CMT positive quarters. Other risk and protective factors were identified from both the cross-sectional and longitudinal included animals with Boran breeding (odds ratio (OR) = 3,40, 95% CI = 1.00-11.57, P < 0.05 for clinical mastitis, and OR = 3.51, 95% CI = 1.299.55, P < 0.01 for a CMT positive quarter), while the practice of residual calf suckling was protective for a bacteriologically positive quarter (OR = 0.63, 95% Cl = 0.48-0.81, P <= 0.001) and for a CMT positive quarter (OR = 0.69, 95% Cl = 0.63-0.75, P < 0.001). A mastitis training course for farmers and extension officers was held, and the knowledge gained and use of different methods of dissemination were assessed over time. In a subsequent randomised controlled trial, there were strong associations between knowledge gained and both the individual question asked and the combination of dissemination methods (village meeting, video and handout) used. This study demonstrated that both clinical and subclinical mastitis is common in smallholder dairying in Tanzania, and that some of the risk and protective factors for mastitis can be addressed by practical management of dairy cows following effective knowledge transfer. (c) 2006 Elsevier B.V. All rights reserved.

Clinical and subclinical mastitis in smallholder dairy farms in Tanzania: Risk, intervention and knowledge transfer

In a cross-sectional study of 400 randomly selected smallholder dairy farms in the Tanga and Iringa regions of Tanzania, 14.2% (95% confidence interval (CI) = 11.6-17.3) of cows had developed clinical mastitis during the previous year. The point prevalence of subclinical mastitis, defined as a quarter positive by the California Mastitis Test (CMT) or by bacteriological culture, was 46.2% (95% Cl = 43.6-48.8) and 24.3% (95% Cl = 22.2-26.6), respectively. In a longitudinal disease study in Iringa, the incidence of clinical mastitis was 31.7 cases per 100 cow-years. A randomised intervention trial indicated that intramammary antibiotics significantly reduced the proportion of bacteriologically positive quarters in the short-term (14 days post-infusion) but teat dipping had no detectable effect on bacteriological infection and CMT positive quarters. Other risk and protective factors were identified from both the cross-sectional and longitudinal included animals with Boran breeding (odds ratio (OR) = 3,40, 95% CI = 1.00-11.57, P < 0.05 for clinical mastitis, and OR = 3.51, 95% CI = 1.299.55, P < 0.01 for a CMT positive quarter), while the practice of residual calf suckling was protective for a bacteriologically positive quarter (OR = 0.63, 95% Cl = 0.48-0.81, P <= 0.001) and for a CMT positive quarter (OR = 0.69, 95% Cl = 0.63-0.75, P < 0.001). A mastitis training course for farmers and extension officers was held, and the knowledge gained and use of different methods of dissemination were assessed over time. In a subsequent randomised controlled trial, there were strong associations between knowledge gained and both the individual question asked and the combination of dissemination methods (village meeting, video and handout) used. This study demonstrated that both clinical and subclinical mastitis is common in smallholder dairying in Tanzania, and that some of the risk and protective factors for mastitis can be addressed by practical management of dairy cows following effective knowledge transfer. (c) 2006 Elsevier B.V. All rights reserved.

Effect of restricted suckling of calves on the productivity of crossbred dairy cattle

An experiment on restricted suckling of crossbred dairy cows was conducted at the Livestock Research Centre, Tanga in north-east Tanzania. The objective of the experiment was to evaluate the comparative productivity of Bos taurus x Bos indicus cows of medium and high levels of Bos taurus inheritance, whose calves were either bucket-reared or suckled residual milk. Lactation milk yield, length and persistency were 1563 L, 289 days, and 1.0, respectively, for the bucket-reared and 1592 L, 289 days and 1.4, respectively, for the suckling group. Days to observed oestrus, first insemination and conception for cows whose calves were bucket-reared were 47, 74 and 115 days, respectively, and 57, 81 and 126 days, respectively, for the suckling cows. The calf weights were similar at 1 year of age. The productivity of the cows, measured as the annual milk offtake, was not significantly higher for those that suckled their calves than for those whose calves were bucket-reared.

Productivity of crossbred dairy cows suckling their calves for 12 or 24 weeks post calving

An experiment on restricted suckling of crossbred dairy cows was conducted at the Livestock Research Centre, Tanga in northeast Tanzania. Thirty-six Bos taurus (Holstein Friesian and Jersey) x Bos indicus (East African Zebu) cows were allocated alternately as they calved to suckling their calves for either 12 or 24 weeks after calving. Cows grazed improved pastures and were offered 4 kg concentrate daily. Milking occurred twice daily by hand; calves were allowed to suck residual milk for 30 min following each milking. Calves were also allowed access to grazing and were offered a maximum of I kg concentrate daily to 24 weeks of age. Weaning age had no significant effect on lactation milk yield for human consumption, the mean (SE) yield being 1806 (102.0) L and 1705 (129. 1) L for 12- and 24-week weaning, respectively. Cows from the two treatments suffered similar losses of live weight and body condition score during lactation and neither group had returned to the original body condition score 40 weeks following calving. Post-partum anoestrous intervals were prolonged. Although not significant, cows suckling calves to 24 weeks had a mean interval to first oestrus extended by 38 days compared with cows suckling calves to 12 weeks. The mean (SE) daily live weight gains of the calves to 52 weeks were 263 (14.1) g/day and 230 (18.1) g/day for calves weaned at 12 and 24 weeks, respectively, such that 12-month weights were 119 (5.6) kg and 110 (7.3) kg, respectively. Twelve-week-weaned calves consumed more concentrate (p < 0.05) from 13 to 24 weeks than did 24-week weaned calves. Calculation of residual milk consumption removed by calves from birth to 12 weeks indicated that it accounted for 28% of total yield. No benefits in cow and calf performance and welfare were found to justify prolonging the suckling period to 24 weeks.

Donepezil for the symptomatic treatment of patients with mild to moderate Alzheimer's disease: a meta-analysis of individual patient data from randomised controlled trials

Background: The objective was to evaluate the efficacy and tolerability of donepezil (5 and 10 mg/day) compared with placebo in alleviating manifestations of mild to moderate Alzheimer's disease (AD). Method: A systematic review of individual patient data from Phase II and III double-blind, randomised, placebo-controlled studies of up to 24 weeks and completed by 20 December 1999. The main outcome measures were the ADAS-cog, the CIBIC-plus, and reports of adverse events. Results: A total of 2376 patients from ten trials were randomised to either donepezil 5 mg/day (n = 821), 10 mg/day (n = 662) or placebo (n = 893). Cognitive performance was better in patients receiving donepezil than in patients receiving placebo. At 12 weeks the differences in ADAS-cog scores were 5 mg/day-placebo: - 2.1 [95% confidence interval (CI), - 2.6 to - 1.6; p < 0.001], 10 mg/day-placebo: - 2.5 ( - 3.1 to - 2.0; p < 0.001). The corresponding results at 24 weeks were - 2.0 ( - 2.7 to - 1.3; p < 0.001) and - 3.1 ( - 3.9 to - 2.4; p < 0.001). The difference between the 5 and 10 mg/day doses was significant at 24 weeks (p = 0.005). The odds ratios (OR) of improvement on the CIBIC-plus at 12 weeks were: 5 mg/day-placebo 1.8 (1.5 to 2.1; p < 0.001), 10 mg/day-placebo 1.9 (1.5 to 2.4; p < 0.001). The corresponding values at 24 weeks were 1.9 (1.5 to 2.4; p = 0.001) and 2.1 (1.6 to 2.8; p < 0.001). Donepezil was well tolerated; adverse events were cholinergic in nature and generally of mild severity and brief in duration. Conclusion: Donepezil (5 and 10 mg/day) provides meaningful benefits in alleviating deficits in cognitive and clinician-rated global function in AD patients relative to placebo. Increased improvements in cognition were indicated for the higher dose. Copyright © 2004 John Wiley & Sons, Ltd.

The effect of selective decontamination of the digestive tract on mortality in multiple trauma patients: a multicenter randomized controlled trial

Objective: Evaluation of selective decontamination of the digestive tract (SDD) on late mortality in ventilated trauma patients in an intensive care unit (ICU). Methods: A multicenter, randomized controlled trial was undertaken in 401 trauma patients with Hospital Trauma Index-Injury Severity Score of 16 or higher. Patients were randomized to control (n = 200) or SDD (n = 201), using polymyxin E, tobramycin, and amphotericin B in throat and gut throughout ICU treatment combined with cefotaxime for 4 days. Primary endpoint was late mortality excluding early death from hemorrhage or craniocerebral injury. Secondary endpoints were infection and organ dysfunction. Results: Mortality was 20.9% with SDD and 22.0% in controls. Overall late mortality was 15.3% (57/372) as 29 patients died from cerebral injury, 16 SDD and 13 control. The odds ratio (95% confidence intervals) of late mortality for SDD relative to control was 0.75 (0.40-1.37), corresponding to estimates of 13.4% SDD and 17.2% control. The overall infection rate was reduced in the test group (48.8% vs. 61.0%). SDD reduced lower airway infections (30.9% vs. 50.0%) and bloodstream infections due to aerobic Gram-negative bacilli (2.5% vs. 7.5%). No difference in organ dysfunction was found. Concluson: This study demonstrates that SDD significantly reduces infection in multiple trauma, although this RCT in 401 patients was underpowered to detect a mortality benefit.

The role of exotic plants in the invasion of Seychelles by the polyphagous insect Aleurodicus disperses: a phylogenetically controlled analysis

The accidental introduction of the spiralling whitefly, Aleurodicus dispersus Russell (Homoptera: Aleyrodidae) to Seychelles in late 2003 is exploited during early 2005 to study interactions between A. dispersus, native and exotic host plants and their associated arthropod fauna. The numbers of A. dispersus egg spirals and pupae, predator and herbivore taxa were recorded for eight related native/exotic pairs of host plants found on Mahe, the largest island in Seychelles. Our data revealed no significant difference in herbivore density (excluding A. dispersus) between related native and exotic plants, which suggests that the exotic plants do not benefit from 'enemy release'. There were also no differences in predator density, or combined species richness between native and exotic plants. Together these data suggest that 'biotic resistance' to invasion is also unlikely. Despite the apparent lack of differences in community structure significantly fewer A. dispersus egg spirals and pupae were found on the native plants than on the exotic plants. Additional data on A. dispersus density were collected on Cousin Island, a managed nature reserve in which exotic plants are carefully controlled. Significantly higher densities of A. dispersus were observed on Mahe, where exotic plants are abundant, than on Cousin. These data suggest that the rapid invasion of Seychelles by A. dispersus may largely be due to the high proportion of plant species that are both exotic and hosts of A. dispersus; no support was found for either the 'enemy release' or the 'biotic resistance' hypotheses.

Effect of hyaluronidase on ocular motility and eyelid function in sub-Tenon's anaesthesia: randomised controlled trial

Purpose: To assess the effect of hyaluronidase on eye and eyelid movements when used as an adjunct in sub-Tenon's anaesthesia. Methods: A total of 60 patients who had sub-Tenon's anaesthesia prior to phacoemulsification surgery were divided into two equal groups in a double-masked randomised controlled fashion. Of these, Group A had 4 ml lignocaine 2%, while Group B had 4ml lignocaine 2% with the addition of sodium hyaluronidase 75 IU/ml. Ocular motility, levator, and orbicularis oculi function were measured in all patients at 5 and 8 min. Levator function was scored from 0 (no function) to 3 (complete function) while orbicularis function was scored from 0 to 2. The score for ocular motility was the sum in four positions of gaze, each position scoring from 0 to 2. Results were compared using a nonparametric test. Results Group B achieved significantly better ocular and lid akinesia than Group A both at 5 and 8 min with P < 0.01. The median scores for levator function at 5 and 8 min were 2 for Group A and 0 for Group B. For orbicularis function, the median scores at both time intervals were 2 for Group A and 1 for Group B. For ocular motility, the median score for Group A at 5 min was 3 and at 8 min was 2.5; for Group B at 5 min was 0.5 and at 8 min was 0. Conclusions: The addition of hyaluronidase in sub-Tenon's anaesthesia has a significant effect in improving ocular and lid (levator and orbicularis) akinesia.

Hypotensive effects of hawthorn for patients with diabetes taking prescription drugs: a randomised controlled trial

Background Hawthorn (Crataegus laevigata) leaves, flowers and berries are used by herbal practitioners in the UK to treat hypertension in conjunction with prescribed drugs. Small-scale human studies support this approach. Aim To investigate the effects of hawthorn for hypertension in patients with type 2 diabetes taking prescribed drugs. Design of study Randomised controlled trial. Setting General practices in Reading, UK. Method Patients with type 2 diabetes (n = 79) were randomised to daily 1200 mg hawthorn extract (n = 39) or placebo (n = 40) for 16 weeks. At baseline and outcome a wellbeing questionnaire was completed and blood pressure and fasting blood samples taken. A food frequency questionnaire estimated nutrient intake. Results Hypotensive drugs were used by 71% of the study population with a mean intake of 4.4 hypoglycaemic and/or hypotensive drugs. Fat intake was lower and sugar intake higher than recommendations, and low micronutrient intake was prevalent. There was a significant group difference in mean diastolic blood pressure reductions (P = 0.035): the hawthorn group showed greater reductions (baseline: 85.6 mmHg, 95% confidence interval [Cl] = 83.3 to 87.8; outcome: 83.0 mmHg, 95% Cl = 80.5 to 85.7) than the placebo group (baseline: 84.5 mmHg, 95% Cl = 82 to 87; outcome: 85.0 mmHg, 95% Cl = 82.2 to 87.8). There was no group difference in systolic blood pressure reduction from baseline (3.6 and 0.8 mmHg for hawthorn and placebo groups, respectively; P = 0.329). Although mean fat intake met current recommendations, mean sugar intake was higher and there were indications of potential multiple micronutrient deficiencies. No herb-drug interaction was found and minor health complaints were reduced from baseline in both groups. Conclusions This is the first randomised controlled trial to demonstrate a hypotensive effect of hawthorn in patients with diabetes taking medication.

Development of the mammalian urethra is controlled by Fgfr2-IIIb

Development of external genitalia in mammalian embryos requires tight coordination of a complex series of morphogenetic events involving outgrowth, proximodistal and dorsoventral patterning, and epithelial tubulogenesis. Hypospadias is a congenital defect of the external genitalia that results from failure of urethral tube closure. Although this is the second most common birth defect in humans, affecting one in every 250 children, the molecular mechanisms that regulate morphogenesis of the mammalian urethra are poorly understood. We report that mice lacking the IIIb isoform of fibroblast growth factor receptor 2 (Fgfr2) exhibit severe hypospadias. Urethral signaling regions, as indicated by Shh and Fgf8 expression, are established in Fgfr2-IIIb null mice; however, cell proliferation arrests prematurely and maturation of the urethral epithelium is disrupted. Fgfr2-IIIb(-/-) mutants fail to maintain the progenitor cell population required for uroepithelial renewal during tubular morphogenesis. In addition, we show that antagonism of the androgen receptor (AR) leads to loss of Fgfr2-IIIb and Fgf10 expression in the urethra, and an associated hypospadias phenotype, suggesting that these genes are downstream targets of AR during external genital development. Genitourinary defects resulting from disruption of AR activity, by either genetic or environmental factors, may therefore involve negative regulation of the Fgfr2 pathway. This represents the first example of how the developing genitourinary system integrates cues from systemically circulating steroid hormones with a locally expressed growth factor pathway.