Comparing the unified protocol for transdiagnostic treatment of emotional disorders to prolonged exposure for the treatment of PTSD: Design of a non-inferiority randomized controlled trial.

Background: Prolonged Exposure (PE), a trauma-focused therapy, is one of the most efficacious treatments available for PTSD. However, many people with PTSD do not lose their diagnosis following delivery of PE. The Unified Protocol (UP) for Transdiagnostic Treatment of Emotional Disorders is a non-trauma focused treatment that may offer an alternative treatment for PTSD. Methods: This paper describes the study protocol for IMPACT, an assessor-blinded randomized controlled trial that examines the non-inferiority of UP relative to PE for participants who meet DSM-5 criteria for current PTSD. One hundred and twenty adult participants with PTSD will be randomized to receive either 10 × 90-min sessions of UP or PE with a trained provider. The primary outcome is severity of PTSD symptoms assessed by the Clinician Administered PTSD Scale for DSM-5 (CAPS-5) at post-treatment. Discussion: While evidence-based treatments are available for PTSD, high levels of treatment dropout and non-response require new approaches to be tested. The UP is based on emotion regulation theory and is effective in treating anxiety and depressive disorders, however, there has been limited application to PTSD. This is the first rigorous study comparing UP to PE in a non-inferiority randomized controlled trial and may help improve clinical outcomes for those with PTSD. Trial registration: This trial was prospectively registered with the Australian New Zealand Clinical Trials Registry, Trial ID (ACTRN12619000543189).

Cranial Musculoskeletal Description of Black-Throated Finch (Aves: Passeriformes: Estrildidae) with DiceCT.

Synopsis Dietary requirements and acquisition strategies change throughout ontogeny across various clades of tetrapods, including birds. For example, birds hatch with combinations of various behavioral, physiological, and morphological factors that place them on an altricial-precocial spectrum. Passeriformes (=songbirds) in particular, a family constituting approximately more than half of known bird species, displays the most drastic difference between hatchling and adults in each of these aspects of their feeding biology. How the shift in dietary resource acquisition is managed during ontogeny alongside its relationship to the morphology of the feeding apparatus has been largely understudied within birds. Such efforts have been hampered partly due to the small size of many birds and the diminutive jaw musculature they employ. In this study, we used standard and diffusible iodine-based contrast-enhanced computed tomography in conjunction with digital dissection to quantify and describe the cranial musculature of the Black-throated Finch (Poephila cincta) at fledgling and adult stages. Our results reveal that in both the fledgling and the adult, cranial musculature shows clear and complex partitioning in the Musculus adductor mandibulae externus that is consistent with other families within Passeriformes. We quantified jaw-muscle sizes and found that the adult showed a decrease in muscle mass in comparison to the fledgling individual. We propose that this could be the result of low sample size or a physiological effect of parental care in Passeriformes. Our study shows that high-resolution visualization techniques are informative at revealing morphological discrepancies for studies that involve small specimens such as Passeriformes especially with careful specimen selection criteria.

ADAMTS-13 glycans and conformation-dependent activity.

Essentials The impact of N-linked glycosylation on ADAMTS-13 function has not been fully explored. The activity of glycan modified ADAMTS-13 was investigated under static and shear stress conditions. Terminal sialic acid on the metalloprotease domain glycans are important for ADAMTS-13 activity. The CUB domain glycans modulate ADAMTS-13 activity. SUMMARY: Background ADAMTS-13 activity can be regulated by its conformation, whereby interactions between the C-terminal CUB domains and the spacer domain maintain ADAMTS-13 in a closed conformation. ADAMTS-13 contains 10 N-linked glycans, with four sites present in theTSP2 through to CUB domains that may contribute to its conformation. Objectives/Methods We hypothesized that glycosylation contributes to ADAMTS-13 conformation and function. The proteolytic activity of glycan-modified ADAMTS-13 was assessed under static and shear stress conditions. Results Enzymatic removal of terminal silaic acid or entire N-linked glycan chains decreased activity against FRETS-VWF73 at pH 7.4 and against full-length von Willebrand factor (VWF) under shear stress. Using truncated ADAMTS-13, we demonstrated that this was attributable to loss of sialic acid from the glycans in the metalloprotease domain and an effect of N-linked glycosylation in the TSP2 through to CUB domains. Mutation of the N-linked glycan sites in the MDTCS domains reduced or abolished protein expression. However, the N707Q, N828Q, N1235Q and N1354Q (TSP2, TSP4, CUB1, and CUB2 domains, respectively) variants were expressed normally. Interestingly, the N707Q and N828Q variants showed reduced activity against FRETS-VWF73, but normal activity under flow conditions. In contrast, the N1235Q and N1354Q variants had enhanced activity against FRETS-VWF73 and VWF under shear stress. Immunoprecipitation experiments confirmed that loss of N-linked glycans in the CUB domains significantly reduced the interaction with the spacer domain and enhanced binding to the 6A6 anti-ADAMTS-13 antibody, which recognizes a cryptic epitope in the metalloprotease domain. Conclusions Together, these data demonstrate that the N-linked glycans of ADAMTS-13 play a crucial role in regulating ADAMTS-13 activity.

Space magnetometer based on an anisotropic magnetoresistive hybrid sensor.

We report on the design and development of a low resource, dual sensor vector magnetometer for space science applications on very small spacecraft. It is based on a hybrid device combining an orthogonal triad of commercial anisotropic magnetoresistive (AMR) sensors with a totem pole H-Bridge drive on a ceramic substrate. The drive enables AMR operation in the more sensitive flipped mode and this is achieved without the need for current spike transmission down a sensor harness. The magnetometer has sensitivity of better than 3 nT in a 0-10 Hz band and a total mass of 104 g. Three instruments have been launched as part of the TRIO-CINEMA space weather mission, inter-calibration against the International Geomagnetic Reference Field model makes it possible to extract physical signals such as field-aligned current deflections of 20-60 nT within an approximately 45,000 nT ambient field.

Maternal iron deficiency and its effect on essential fatty acid and eicosanoid metabolism and spatial memory in the guinea pig offspring.

Iron deficiency is prevalent among infants and pregnant women in industrialized country. The goal of this study was to evaluate the impact of moderate maternal iron deficiency on the offspring's fatty acid and eicosanoid metabolism and spatial memory in guinea pigs. An iron-sufficient (IS) or iron-deficient (ID) diet was fed 14 days before mating and throughout pregnancy and lactation. The pups were tested for spatial memory on post-natal days 4-7. On post-natal day 9, the biochemical analysis included the pup's brain fatty acid profiles, prostaglandin (PGE(2) and PGF(2alpha)) concentrations and cyclooxygenase II protein levels. Spatial memory and indices of eicosanoid metabolism were comparable in both dietary groups. However, n-3 fatty acids were significantly higher (p<0.05) in brain of pups from the ID group. The data suggest that maternal iron deficiency results in a modification of the fatty acid profile of the offspring's brain that is not associated with any spatial memory deficits during early development.

Validation of an FFQ to assess dietary protein intake in type 2 diabetic subjects attending primary health-care services in Mali.

OBJECTIVE: To validate a 53-item quantitative FFQ (QFFQ) for the assessment of dietary protein intake in type 2 diabetic outpatients in Bamako, Mali. DESIGN: Consumption of protein-containing foods over the week preceding the interview was measured with a 7d QFFQ and compared with intakes measured with 48-h recalls. SETTING: Centre National de Lutte contre le Diabète. SUBJECTS: Seventeen male and forty female adults with type 2 diabetes. RESULTS: Correlation between protein intakes estimated using the QFFQ and 48h recalls was 0.63 (P < 0.0001). There was no significant difference between the two methods concerning the total protein daily intakes and intakes per kilogram of body weight. The QFFQ indicated that foods of animal origin were a lesser source of protein. Animal protein intake did not differ between men and women but sources did. In men, the main sources were beef (54 % of total animal protein), fish (15 %) and milk powder (8 %). In women, the principal sources were fish (28 %), beef (20 %) and birds (13 %). In contrast, plant protein intake was significantly higher in men than in women (P = 0.01), but the same plant foods contributed in similar proportions for both genders, rice being by far the greatest source (47 % of plant protein in men, 53 % in women). CONCLUSION: The QFFQ developed in this study is a valid tool to evaluate dietary protein intakes in Malian diabetic subjects. While the total protein intakes were low in both men and women, differences in choices and amounts of protein food sources were shown.

[Dietary iron and iron deficiency anemia among adolescent girls from Benin]. / Apports alimentaires en fer et anémie ferriprive chez des adolescentes au Bénin.

BACKGROUND: Iron deficiency anemia affects a large number of women in developing countries, especially during childbearing years. Few studies determined the association between estimated absorbable iron intakes and iron deficiency. METHODS: The association between dietary iron intake and iron status was studied in 100 adolescent girls aged 14-16 years from Benin. Fifty adolescents were boarding at the school, while 50 lived at home. Biochemical indices of iron status included: hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin concentration, serum iron, total iron-binding capacity and % transferrin saturation. Dietary intakes were obtained by two 24-hour recalls and absorbable iron intakes were estimated using Monsen's model. The probability approach was used to estimate inadequacy in iron intake. RESULTS: While 73% of adolescents met the recommendations for dietary iron intake, only 27% had estimated absorbable iron intake above the average requirement for absorbed iron. Non-heme iron represented 97.2% of the total iron intake. Forty three percent of subjects were anemic (hemoglobin<120 g/l). Iron deficiency defined by a four-model index based on > or =2 abnormal values in the four independent indicators of iron status used (serum iron, total iron-binding capacity, mean corpuscular volume, mean corpuscular hemoglobin concentration) was present in 14% of the subjects, while 13% had iron deficiency anaemia (hemoglobin<120 g/l+four-model index). Using a multiple regression analysis, total absorbable iron intakes (including iron supplements) were highly and positively associated with hemoglobin and hematocrit concentrations (P=0.000001 and P=0.00007 respectively). CONCLUSION: In this group of adolescents, total absorbable iron intakes were related to iron deficiency. Efforts should be made to increase the heme iron content of the diet and the bioavailability of non-heme iron by promoting affordable local foods rich in iron and promoters of iron absorption (Vitamin C and meat, poultry and fish factor).

The introduction of halothane into clinical practice: the Oxford experience.

This paper reviews the clinical situation in anaesthesia before the introduction of halothane into clinical practice in 1956, emphasising the limitations of agents available at the time. The background to the development of halogenated hydrocarbon compounds as anaesthesia agents is presented, including the involvement of Imperial Chemical Industries in England. The Nuffield Department of Anaesthetics was involved in the clinical trials and the designing and execution of these. The results of their work and the problems encountered are presented.

Vivian Richard Ebsary, A.M. biomedical engineer, inventor, philanthropist.

Vivian Ebsary was an inventor, designer and manufacturer of varied pieces of medical equipment, particularly those involving pumps. These included hypothermia machines and the heart-lung cardiopulmonary bypass machines used in Australian and New Zealand hospitals from the mid 1950s until well into the 1970s. Ebsary also designed and manufactured anaesthetic machines, a hyperbaric unit, scoliosis implant equipment, a chairlift and many other devices for use in the general community. This paper presents an overview of his life's involvement with medicine and medical technology in Australia.

Visual mechanisms of spatial disorientation in Alzheimer's disease.

Impaired optic flow perception may contribute to the visuospatial disorientation of Alzheimer's disease (AD). We find that 36% of AD patients have elevated perceptual thresholds for left/right outward radial optic flow discrimination. This impairment is related to independent visual motion processing deficits affecting the perception of left/right motion-defined boundaries and in/out radial motion. Elevated optic flow thresholds in AD are correlated with greater difficulty in the Road Map test of visuospatial function (r = -0.5) and in on-the-road driving tests (r = -0.83). When local motion cues are removed from optic flow, subjects must rely on the global pattern of motion. This reveals global pattern perceptual deficits that affect most AD patients (85%) and some normal elderly subjects (21%). This deficit might combine with impaired local motion processing to undermine the alternative perceptual strategies for visuospatial orientation. The greater prevalence of global pattern deficits suggests that it might precede local motion processing impairments, possibly relating to the sequence of early hippocampal and later posterior cortical damage that is typical of AD.

[Evaluation of nutrition instruction in a group of Senegalese students at the secondary level]. / Evaluation d'un enseignement sur la nutrition auprès d'élèves Sénégalais de niveau secondaire.

BACKGROUND: In Senegal, nutrition instruction was implanted in 1981 in the national curriculum of biology and has never been evaluated since. METHODS: The purpose of this study, was to evaluate the effect of a six weeks nutrition instruction program on improving nutrition knowledge and nutrition attitudes in an experimental group including 81 subjects aged 16.7+/-1.2 years and a control group including 80 subjects aged 15.7+/-1.3 years. These subjects came respectively from third and fourth grade. A questionnaire on knowledge and one on attitudes were administered to the experimental group, before and after the nutrition instruction, while the control group, who did not received any nutrition instruction, also answered the questionnaires. RESULTS: Results indicate that the adjusted mean knowledge posttest scores did not significantly increase in the experimental group compared to the control group. In addition, the adjusted mean attitude postscores of the boys and girls of the experimental group on the attitude scale "Nutrition affects health" were significantly higher from that of the control group. CONCLUSION: An evaluation of the nutrition curriculum and the teaching methods is suggested in order to improve the effectiveness of this nutrition program.

A comparison of molecular and enzyme-based assays for the detection of thiopurine methyltransferase mutations.

S-Methylation by thiopurine methyltransferase (TPMT) is an important route of metabolism for the thiopurine drugs. About one in 300 individuals are homozygous for a TPMT mutation associated with very low enzyme activity and severe myelosuppression if treated with standard doses of drug. To validate the use of molecular genetic techniques for the detection of TPMT deficiency, we have determined red blood cell TPMT activity in 240 adult blood donors and 55 normal children. Genotype was determined by restriction fragment length analysis of polymerase chain reaction products in a cohort of 79 of the blood donors and five cases of azathioprine-induced myelosupression, and this confirmed a close relationship between genotype and phenotype. In 17 of the 24 cases in which mutations were found, DNA was also available from remission bone marrow. In one of these cases, DNA from the remission marrow sample indicated the presence of a non-mutated allele that had not been seen in the blast DNA sample obtained at presentation. These results indicate that polymerase chain reaction-based assays give reliable and robust results for the detection of TPMT deficiency, but that caution should be exercised in relying exclusively on DNA obtained from lymphoblasts in childhood leukaemia.

K-ras mutations, rectal crypt cells proliferation, and meat consumption in patients with left-sided colorectal carcinoma.

It has been suggested that N-nitroso compounds derived from meat may increase the risk of K-ras mutations in the human colon. We sought evidence of associations between red meat consumption, frequency and type of K-ras mutations in resected tumours, and the rate of crypt cell proliferation (CCP) in the normal mucosa of patients with left-sided colorectal carcinoma. Meat consumption was assessed by food frequency questionnaire, and CCP was determined in rectal biopsies obtained prior to surgery. K-ras mutations in the resected tumours were determined using a PCR-based oligonucleotide hybridization assay. Fifteen K-ras mutations were detected in tumours from 43 patients; 13/15 in codon 12, 3/15 in codon 13, and 1/15 in both codons 12 and 13. All mutations were G-->A or G-->T transitions. There was no statistically significant difference between intakes of red meat in patients with a K-ras mutation (92.4 +/- 9.7 g/day) and those without (82.3 +/- 7.7 g/day). Rectal CCP was significantly higher in patients than in healthy controls, but there was no correlation with meat consumption or K-ras mutation. These data do not support the hypothesis that meat consumption is a risk factor for acquisition of K-ras mutations during colorectal carcinogenesis.

Energy, macro- and micronutrient intake of 5-year-old urban black South African children in 1984 and 1995.

Food habits change over time. This paper reports results of nutritional studies among 5-year-old urban black children in 1984 and 1995 in the Johannesburg/Soweto area. The objective was to compare energy, macro- and micronutrient intake of 5-year-old urban black South African children. Dietary intake was assessed by detailed dietary histories in 1984 and food frequency questionnaires in 1995, conducted by trained interviewers. The intake of energy, macro- and most micronutrients was higher in 1995 than in 1984, except for vitamin A, ascorbic acid, copper and iron. Fat intake increased from 52 g/day in 1984 to 95 g/day in 1995. Only biotin and vitamin D fell below 67% of the recommended dietary allowances (RDA) for 4- to 6-year-olds, but mean intakes concealed the high percentage of children that had intakes below the RDA in 1984 and 1995. Urban black 5-year-old South African children consumed a low-fat (30% of total energy), high-carbohydrate (61% of total energy) diet in 1984, but a typical westernised diet by 1995 (fat 41% and carbohydrate 52% of total energy). With these changes, current reliable nutrition information is needed to assess the existing and future health needs of all South Africans.

An open clinical trial of venlafaxine treatment of fibromyalgia.

Of 15 patients with fibromyalgia who were first evaluated for the presence of Axis I psychiatric diagnoses by use of the Structured Clinical Interview for DSM-IV, 11 completed an open 8-week trial with the novel antidepressant venlafaxine. Six (55%) of 11 completers experienced a > or = 50% reduction of fibromyalgia symptoms. The presence of lifetime psychiatric disorders, particularly depressive and anxiety disorders, predicted a positive response to venlafaxine. These findings suggest that it is important to assess for comorbid psychiatric disorders in patients with fibromyalgia and that venlafaxine may be helpful to some of these patients.

Ecological constraints drive social evolution in the African mole-rats.

The African mole-rats (family Bathyergidae) are subterranean hystricomorph rodents occurring in a variety of habitats and displaying levels of sociality which range from solitary to eusocial, making them a unique mammalian taxonomic group to test ecological influences on sociality. Here, we use an extensive DNA-based phylogeny and comparative analysis to investigate the relationship between ecology, sociality and evolution within the family. Mitochondrial cytochrome-b and 12s rRNA trees reveal that the solitary species are monophyletic when compared to the social species. The naked mole-rat (Heterocephalus glaber) is ancestral and divergent from the Damaraland mole-rat (Cryptomys damarensis), supporting previous findings that have suggested the multiple evolution of eusociality within the family. The Cryptomys genus is species-rich and contains taxa exhibiting different levels of sociality, which can be divided into two distinct clades. A total of seven independent comparisons were generated within the phylogeny, and three ecological variables were significantly correlated with social group size: geophyte density (p < 0.05), mean months per year of rainfall greater than 25 mm (p < 0.001), and the coefficient of rainfall variation (p = 0.001). These results support the food-aridity hypothesis for the evolution of highly social cooperative behaviour in the Bathyergidae, and are consistent with the current theoretical framework for skew theory.

Micro- and macrogeographical genetic structure of colonies of naked mole-rats Heterocephalus glaber.

Patterns of genetic structure in eusocial naked mole-rat populations were quantified within and among geographically distant populations using multilocus DNA fingerprinting and mitochondrial DNA (mtDNA) sequence analysis. Individuals within colonies were genetically almost monomorphic, sharing the same mtDNA control region haplotype and having coefficients of band sharing estimated from DNA fingerprints ranging from 0.93 to 0.99. Family analysis of a hybrid captive colony of naked mole-rats with increased levels of genetic variability using multilocus DNA fingerprinting gave results consistent with Mendelian inheritance, and has revealed for the first time that multiple paternity can occur. In a survey of wild colonies from Ethiopia, Somalia and locations in northern and southern Kenya, we have examined mtDNA control region sequence variation in 42 individuals from 15 colonies, and together with multilocus DNA fingerprinting and mtDNA cytochrome-b sequence analysis in selected individuals have shown that these populations show considerable genetic divergence. Most of the variance in sequence divergence was found to be between geographical locations (phi ct = 0.68) and there was a significant correlation between sequence divergence and geographical separation of haplotypes. Six colonies from Mtito Andei in southern Kenya shared the same control region haplotype, suggesting a recent common maternal ancestor. In contrast, out of four colonies at Lerata in north Kenya, three haplotypes were identified, and phylogenetic analysis suggests that this area may be a zone where two distinct lineages are in close proximity. Genetic distances were maximal between Ethiopian and southern Kenyan populations at 5.8% for cytochrome-b, and are approaching interspecific values seen between other Bathyergids.