A Data-Driven Latent Variable Approach to Validating the Research Domain Criteria Framework.

Despite the widespread use of the Research Domain Criteria (RDoC) framework in psychiatry and neuroscience, recent studies suggest that the RDoC is insufficiently specific or excessively broad relative to the underlying brain circuitry it seeks to elucidate. To address these concerns of the RDoC framework, our study employed a latent variable approach, specifically utilizing bifactor analysis. We examined a total of 84 whole-brain task-based fMRI (tfMRI) activation maps from 19 studies with a total of 6,192 participants. Within this set of 84 maps, a curated subset of 37 maps with a balanced representation of RDoC domains constituted the training set of our analysis, and the remaining held-out maps formed the internal validation set. External validation was performed with 36 peak coordinate activation maps from Neurosynth, using terms of RDoC constructs as seeds for topic meta-analysis. Our results indicate that a bifactor model with a task-general domain and splitting the cognitive systems domain into sub-domains better fits the current corpus of tfMRI data than the current RDoC framework. Our data-driven validation supports revising the RDoC framework to accurately reflect underlying brain circuitry.

A therapeutic intervention for Alzheimer's disease using ginsenoside Rg3: its role in M2 microglial activation and non-amyloidogenesis.

Previously, we have reported that ginsenoside Rg3 has typical activities for neuroprotection and Aß42 clearance by modulating microglia. In this study, we determined the pivotal role of ginsenoside Rg3 in microglia and neuronal cells. In human microglia, Rg3 and its stereoisomers significantly restored inflammatory M1 to normal M0 state and promoted M2 activation by up-regulating acute cytokines such as interleukin-10 and Arginase 1. Moreover, scavenger receptor type A (SRA) was significantly elevated in the presence of ginsenoside Rg3 and 20(S)-Rg3. This indicated that ginsenoside Rg3 could play a crucial role in Aß uptake and clearance under activated M2 state. We also observed that soluble amyloid precursor protein-alpha (sAPPα) and ADAM10 levels were increased in APP swe-transfected Nuro-2a neuronal cells, whereas sAPPß was not processed, suggesting that ginsenoside Rg3 was involved in non-amyloidogenic processing. In immunocytochemistry, SRA and a disintegrin and metalloproteinase 10 (desintegrin and metalloproteinase-containing protein 10, ADAM10) were coincidently upregulated in the presence of ginsenoside Rg3 and its stereoisomers compared to those in normal control. Taken together, these results suggested that ginsenoside Rg3 could boost acute activation of microglia, promote Aß uptake, and elevate the sAPPα processing under activated M2 state. Although in vivo studies need to be performed, it is certain that ginsenoside Rg3 is highly involved in ameliorating the pathogenesis of neurodegeneration and can be a promising candidate for treating Alzheimer's disease as a new therapeutic intervention.

Effects of excitotoxicity in the hypothalamus in transgenic mouse models of Huntington disease.

Huntington disease (HD) is a fatal neurodegenerative movement disorder caused by an expanded CAG repeat in the huntingtin gene (HTT). The mutant huntingtin protein is ubiquitously expressed, but only certain brain regions are affected. The hypothalamus has emerged as an important area of pathology with selective loss of neurons expressing the neuropeptides orexin (hypocretin), oxytocin and vasopressin in human postmortem HD tissue. Hypothalamic changes in HD may have implications for early disease manifestations affecting the regulation of sleep, emotions and metabolism. The underlying mechanisms of selective vulnerability of certain neurons in HD are not fully understood, but excitotoxicity has been proposed to play a role. Further understanding of mechanisms rendering neurons sensitive to mutant huntingtin may reveal novel targets for therapeutic interventions. In the present study, we wanted to examine whether transgenic HD mice display altered sensitivity to excitotoxicity in the hypothalamus. We first assessed effects of hypothalamic injections of the excitotoxin quinolinic acid (QA) into wild-type (WT) mice. We show that neuronal populations expressing melanin-concentrating hormone (MCH) and cocaine and amphetamine-regulated transcript (CART) display a dose-dependent sensitivity to QA. In contrast, neuronal populations expressing orexin, oxytocin, vasopressin as well as tyrosine hydroxylase in the A13 area are resistant to QA-induced toxicity. We demonstrate that the R6/2 transgenic mouse model expressing a short fragment of mutant HTT displays hypothalamic neuropathology with discrete loss of the neuronal populations expressing orexin, MCH, CART, and orexin at 12 weeks of age. The BACHD mouse model expressing full-length mutant HTT does not display any hypothalamic neuropathology at 2 months of age. There was no effect of hypothalamic injections of QA on the neuronal populations expressing orexin, MCH, CART or oxytocin in neither HD mouse model. In conclusion, we find no support for a role of excitotoxicity in the loss of hypothalamic neuronal populations in HD.

Outcomes of Women Undergoing Excision of the Retained Cervix After Supracervical Hysterectomy.

OBJECTIVE: To characterize the indications for and complication rates of excision of the retained cervix after supracervical hysterectomy. METHODS: We performed a retrospective cohort study of women undergoing excision of the retained cervix after supracervical hysterectomy in the 2010-2014 National Inpatient Sample. International Classification of Diseases, Ninth Revision codes were used to identify indication for the procedure and surgical complications. We weighted the hospital-level data to obtain nationwide estimates of patient characteristics, surgical complications, and length of stay. RESULTS: Nationwide, 1,140 women underwent excision of the retained cervix after hysterectomy. Their mean age was 49 years, and the majority were White and privately insured. Leiomyomas were the most commonly coded indication (35%, 95% CI 29-42), followed by prolapse (14%, 95% CI 9-18). Eighteen percent (95% CI 13.0-23.1) were performed for malignancy, including 5.3% (95% CI 2.3-8.2) for cervical cancer. Only 11.5% (95% CI 7.3-15.6) of cases were performed laparoscopically. The overall complication rate was high (38%, 95% CI 32-45), particularly for bleeding complications (26%, 95% CI 20-31) and transfusion (15%, 95% CI 11-20). Gastrointestinal complication rates were second highest (8%, 95% CI 5-12); ileus was the most common gastrointestinal complication (7.0%, 95% CI 3.7-10.4). The median length of stay was 2 days (range 0-34). CONCLUSION: Women who undergo excision of the retained cervix after supracervical hysterectomy experience high rates of complications, the most common of which was bleeding. Patient counseling regarding removal of the cervix at the time of hysterectomy should include this information.

Brown Adipose Tissue: A Metabolic Regulator in a Hypothalamic Cross Talk?

Since the discovery of functionally competent, energy-consuming brown adipose tissue (BAT) in adult humans, much effort has been devoted to exploring this tissue as a means for increasing energy expenditure to counteract obesity. However, despite promising effects on metabolic rate and insulin sensitivity, no convincing evidence for weight-loss effects of cold-activated human BAT exists to date. Indeed, increasing energy expenditure would naturally induce compensatory feedback mechanisms to defend body weight. Interestingly, BAT is regulated by multiple interactions with the hypothalamus from regions overlapping with centers for feeding behavior and metabolic control. Therefore, in the further exploration of BAT as a potential source of novel drug targets, we discuss the hypothalamic orchestration of BAT activity and the relatively unexplored BAT feedback mechanisms on neuronal regulation. With a holistic view on hypothalamic-BAT interactions, we aim to raise ideas and provide a new perspective on this circuit and highlight its clinical relevance.

Association of demographic, clinical, and hospital-related factors with use of robotic hysterectomy for benign indications: A national database study.

BACKGROUND: We examined the association of patient factors, gynecologic diagnoses, and hospital characteristics with utilization of the robotic approach for benign hysterectomy. METHODS: We performed cross-sectional study of women (n = 725 050) undergoing hysterectomies in the 2012 to 2014 National Inpatient Sample. RESULTS: A total of 725 050 women underwent inpatient hysterectomy for benign indications: 70345 (10%) were performed robotically. Women were more likely to receive robotic hysterectomy at teaching hospitals (RR 1.60 [95% CI 1.54-1.66]) after adjustment for other patient factors, gynecologic diagnoses, and hospital characteristics. They were more likely to undergo robotic hysterectomy at large (RR 1.34 [95% CI 1.29-1.39]) and for-profit hospitals (RR 1.16 [95% CI 1.11-1.22]). Women were less likely to undergo robotic hysterectomy if they were rural (RR 0.68 [95% CI 0.64-0.72]), African-American (RR 0.78 [95% CI 0.74-0.82]), or publicly insured or uninsured (RR 0.55 [95% CI 0.53-0.57]) women. CONCLUSION: Significant geographic and hospital-level disparities exist in access to robotic hysterectomy in the United States.

Pantoprazole in Patients at Risk for Gastrointestinal Bleeding in the ICU.

BACKGROUND: Prophylaxis for gastrointestinal stress ulceration is frequently given to patients in the intensive care unit (ICU), but its risks and benefits are unclear. METHODS: In this European, multicenter, parallel-group, blinded trial, we randomly assigned adults who had been admitted to the ICU for an acute condition (i.e., an unplanned admission) and who were at risk for gastrointestinal bleeding to receive 40 mg of intravenous pantoprazole (a proton-pump inhibitor) or placebo daily during the ICU stay. The primary outcome was death by 90 days after randomization. RESULTS: A total of 3298 patients were enrolled; 1645 were randomly assigned to the pantoprazole group and 1653 to the placebo group. Data on the primary outcome were available for 3282 patients (99.5%). At 90 days, 510 patients (31.1%) in the pantoprazole group and 499 (30.4%) in the placebo group had died (relative risk, 1.02; 95% confidence interval [CI], 0.91 to 1.13; P=0.76). During the ICU stay, at least one clinically important event (a composite of clinically important gastrointestinal bleeding, pneumonia, Clostridium difficile infection, or myocardial ischemia) had occurred in 21.9% of patients assigned to pantoprazole and 22.6% of those assigned to placebo (relative risk, 0.96; 95% CI, 0.83 to 1.11). In the pantoprazole group, 2.5% of patients had clinically important gastrointestinal bleeding, as compared with 4.2% in the placebo group. The number of patients with infections or serious adverse reactions and the percentage of days alive without life support within 90 days were similar in the two groups. CONCLUSIONS: Among adult patients in the ICU who were at risk for gastrointestinal bleeding, mortality at 90 days and the number of clinically important events were similar in those assigned to pantoprazole and those assigned to placebo. (Funded by Innovation Fund Denmark and others; SUP-ICU ClinicalTrials.gov number, NCT02467621 .).

Perceptions on use of home telemonitoring in patients with long term conditions - concordance with the Health Information Technology Acceptance Model: a qualitative collective case study.

BACKGROUND: Health information technology (HIT) may be used to improve care for increasing numbers of older people with long term conditions (LTCs) who make high demands on health and social care services. Despite its potential benefits for reducing disease exacerbations and hospitalisations, HIT home monitoring is not always accepted by patients. Using the Health Information Technology Acceptance Model (HITAM) this qualitative study examined the usefulness of the model for understanding acceptance of HIT in older people (≥60 years) participating in a RCT for older people with Chronic Obstructive Pulmonary Disease (COPD) and associated heart diseases (CHROMED). METHODS: An instrumental, collective case study design was used with qualitative interviews of patients in the intervention arm of CHROMED. These were conducted at two time points, one shortly after installation of equipment and again at the end of (or withdrawal from) the study. We used Framework Analysis to examine how well the HITAM accounted for the data. RESULTS: Participants included 21 patients aged between 60-99 years and their partners or relatives where applicable. Additional concepts for the HITAM for older people included: concerns regarding health professional access and attachment; heightened illness anxiety and desire to avoid continuation of the 'sick-role'. In the technology zone, HIT self-efficacy was associated with good organisational processes and informal support; while ease of use was connected to equipment design being suitable for older people. HIT perceived usefulness was related to establishing trends in health status, detecting early signs of infection and potential to self-manage. Due to limited feedback to users opportunities to self-manage were reduced. CONCLUSIONS: HITAM helped understand the likelihood that older people with LTCs would use HIT, but did not explain how this might result in improved self-management. In order to increase HIT acceptance among older people, equipment design and organisational factors need to be considered. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01960907 October 9 2013 (retrospectively registered) Clinical tRials fOr elderly patients with MultiplE Disease (CHROMED). Start date October 2012, end date March 2016. Date of enrolment of the first participant was February 2013.

Occupational exposure and idiopathic pulmonary fibrosis: a multicentre case-control study in Korea.

SETTING: Multicentred hospital-based cases and control subjects in Korea. OBJECTIVE: To evaluate the association between idiopathic pulmonary fibrosis (IPF) and hazardous materials to which people are occupationally exposed. DESIGN: A multicentre, hospital-based, matched case-control study was performed. The ratio of IPF cases to controls was 1:1 (n = 78 in each group). IPF cases and controls were matched in terms of age group, sex and place of residence. Conditional logistic regression analysis was performed. RESULTS: In simple logistic regression analysis, exposure to metal dust and any exposure for >1 year in an occupational setting were significantly associated with IPF (metal dust OR 4.00, 95%CI 1.34-11.97; any exposure OR 3.67, 95%CI 1.02-13.14). After adjustment for environmental and military exposures and smoking history, the OR for metal dust exposure was 4.97 (95%CI 1.36-18.17) in multiple logistic regression analysis. CONCLUSIONS: Metal dust was associated with incident IPF in Seoul and Gyeonggi Provinces in Korea. This information will be used to support a tailored preventive strategy in specific industries or occupations.

Roles of RFRP-3 in the Daily and Seasonal Regulation of Reproductive Activity in Female Syrian Hamsters.

In females, reproductive activity relies on proper integration of daily and environmental changes as well as cyclic sex-steroid feedback. This study sought to investigate the role of the hypothalamic Arg-Phe amide-related peptide (RFRP)-3 in the daily and seasonal control of reproductive activity in female Syrian hamsters by analyzing the RFRP system and investigating the effects of central administration of RFRP-3 at different reproductive stages. In long day-adapted sexually active female hamsters, the number of c-Fos-activated RFRP immunoreactive neurons was reduced in the afternoon of diestrus and proestrus; the latter was correlated with increased kisspeptin activity and the luteinizing hormone (LH) surge. Moreover, acute RFRP-3 administration decreased LH secretion when given midafternoon, before the LH surge, and had no effect at other time points of proestrus or diestrus. These data indicate that RFRP-3 exerts a tonic inhibition on LH secretion, which is lifted at the time of the preovulatory surge on the afternoon of proestrus. In short day-adapted sexually inactive female hamsters, Rfrp expression is strongly inhibited in a sex steroid-independent manner, and prolonged central infusion of RFRP-3 completely reactivated the reproductive axis through increased kisspeptin expression, gonadotropin and estradiol secretion, and gonadal weight. These findings reveal a critical role of RFRP-3 in the control of reproductive activity in female rodents and suggest that RFRP neurons, acting alongside kisspeptin neurons, are essential for proper synchronization of reproductive activity with the time of the day, the stage of the estrous cycle, and the seasonal changes in photoperiod.

RFRP Neurons - The Doorway to Understanding Seasonal Reproduction in Mammals.

Seasonal control of reproduction is critical for the perpetuation of species living in temperate zones that display major changes in climatic environment and availability of food resources. In mammals, seasonal cues are mainly provided by the annual change in the 24-h light/dark ratio (i.e., photoperiod), which is translated into the nocturnal production of the pineal hormone melatonin. The annual rhythm in this melatonin signal acts as a synchronizer ensuring that breeding occurs when environmental conditions favor survival of the offspring. Although specific mechanisms might vary among seasonal species, the hypothalamic RF (Arg-Phe) amide-related peptides (RFRP-1 and -3) are believed to play a critical role in the central control of seasonal reproduction and in all seasonal species investigated, the RFRP system is persistently inhibited in short photoperiod. Central chronic administration of RFRP-3 in short day-adapted male Syrian hamsters fully reactivates the reproductive axis despite photoinhibitory conditions, which highlights the importance of the seasonal changes in RFRP expression for proper regulation of the reproductive axis. The acute effects of RFRP peptides, however, depend on species and photoperiod, and recent studies point toward a different role of RFRP in regulating female reproductive activity. In this review, we summarize the recent advances made to understand the role and underlying mechanisms of RFRP in the seasonal control of reproduction, primarily focusing on mammalian species.

Sex differences in the photoperiodic regulation of RF-Amide related peptide (RFRP) and its receptor GPR147 in the syrian hamster.

RF-(Arg-Phe) related peptides (RFRP-1 and -3) are considered to play a role in the seasonal regulation of reproduction; however, the effect of the peptides depends on species and gender. This study aimed at comparing the RFRP system in male and female Syrian hamsters over long and short photoperiods to investigate the neuroanatomical basis of these differential effects. The neuroanatomical distribution of RFRP neurons and fibers, revealed using an antiserum recognizing RFRP-1 and -3, as well as GPR147 mRNA, are similar in male and female Syrian hamsters. RFRP neurons are mainly found in the medial hypothalamus, whereas RFRP projections and GPR147 mRNA are observed in the preoptic area, anteroventral-periventricular nucleus, suprachiasmatic nucleus, paraventricular nucleus, bed nucleus of the stria terminalis, ventromedial hypothalamus, habenular nucleus, and arcuate nucleus. The number of RFRP neurons is higher in females than in males, and in both sexes, the number of RFRP neurons is reduced in short photoperiods. GPR147 mRNA levels are higher in females than in males and are downregulated in short photoperiods, particularly in females. Interestingly, the number of RFRP-positive fibers in the anteroventral-periventricular nucleus is higher only in females adjusted to a short photoperiod. Our results suggest that the RFRP system, which is strongly regulated by photoperiod in both male and female Syrian hamsters, is particularly important in females, with a distinct role in the anteroventral-periventricular nucleus, possibly in the regulation of the preovulatory luteinizing hormone surge via kisspeptin neurons.

Changes in thrombin generation in children after cardiac surgery and ex-vivo response to blood products and haemostatic agents.

Impaired haemostasis has been reported in children with congenital heart disease undergoing cardiopulmonary bypass. As thrombin generation encompasses all phases of the coagulation process, this analysis might provide the best assessment of global haemostasis. A prospective study was undertaken to test the hypothesis that thrombin generation reveals an impaired haemostasis after paediatric cardiac surgery and that ex-vivo addition of platelet concentrate and haemostatic agents improves thrombin generation. The study comprised 29 children with congenital heart disease, who underwent corrective surgery including cardiopulmonary bypass. Thrombin generation was analysed both in platelet-poor plasma and platelet-rich plasma. Analysis of the thrombin generation showed a significantly prolonged lag time (Pplatelet-poorandplatelet-richplasma < 0.001), decreased peak thrombin generation (Pplatelet-poorplasma = 0.013; Pplatelet-richplasma < 0.001) as well as a decreased endogenous thrombin generation potential (Pplatelet-poorandplatelet-richplasma < 0.001) after cardiopulmonary bypass compared to baseline. Ex-vivo addition of platelet concentrate, fibrinogen concentrate and recombinant factor VIIa improved thrombin generation significantly (all P < 0.001). Changes were most pronounced after addition of platelet concentrate. The present study showed that thrombin generation was significantly reduced after cardiopulmonary bypass in children, both when analysed in platelet-poor and platelet-rich plasma. The impaired haemostasis was not only restored after ex-vivo addition of platelet concentrate but also rVIIa improved the haemostatic capacity.

Measurements of surgeons' exposure to ionizing radiation dose: comparison of conventional and mini C-arm fluoroscopy.

This study was performed to measure the equivalent scattered radiation dose delivered to susceptible organs while simulating orthopaedic surgery using conventional and mini C-arm fluoroscopy. In addition, shielding effects on the thyroid, thymus, and gonad, and the direct exposure delivered to the patient's hands were also compared. A conventional and mini C-arms were installed in an operating room, and a hand and an operator phantom were used to simulate a patient's hand and a surgeon. Photoluminescence dosimeters were used to measure the equivalent dose by scattered radiation arriving at the thyroid, thymus, and gonad on a whole-body phantom in the position of the surgeon. Equivalent scattered radiation doses were measured in four groups: (1) unshielded conventional C-arm group; (2) unshielded mini C-arm group; (3) lead-shielded conventional C-arm group; and (4) lead-shielded mini C-arm group. Equivalent scattered radiation doses to the unshielded group were significantly lower in the mini C-arm group than those in the conventional C-arm group for all organs. The gonad in the lead-shielded conventional C-arm group showed the highest equivalent dose among operator-susceptible organs, and radiation dose was reduced by approximately 96% compared with that in the unshielded group. Scattered radiation was not detected in any susceptible organ in the lead-shielded mini C-arm group. The direct radiation dose to the hand phantom measured from the mini C-arm was significantly lower than that measured from the conventional C-arm. The results show that the equivalent scattered radiation dose to the surgeon's susceptible organs and the direct radiation dose to a patient's hand can be decreased significantly by using a mini C-arm rather than a conventional C-arm. However, protective lead garments, such as a thyroid shield and apron, should be applied to minimize radiation exposure to susceptible organs, even during use of mini C-arm fluoroscopy.

High peripheral blood th17 percent associated with poor lung function in cystic fibrosis.

People with cystic fibrosis (CF) have been reported to make lung T cell responses that are biased towards T helper (Th) 2 or Th17. We hypothesized that CF-related T cell regulatory defects could be detected by analyzing CD4+ lymphocyte subsets in peripheral blood. Peripheral blood mononuclear cells from 42 CF patients (6 months-53 years old) and 78 healthy controls (2-61 years old) were analyzed for Th1 (IFN-γ+), Th2 (IL-4+), Th17 (IL-17+), Treg (FOXP3+), IL-10+ and TGF-ß+ CD4+ cells. We observed higher proportions of Treg, IL-10+ and TGF-ß+ CD4+ cells in CF adults (≥ 18 years old), but not children/adolescents, compared with controls. Within the CF group, high TGF-ß+% was associated with chronic Pseudomonas aeruginosa lung infection (p < 0.006). We observed no significant differences between control and CF groups in the proportions of Th1, Th2 or Th17 cells, and no association within the CF group of any subset with sex, CFTR genotype, or clinical exacerbation. However, high Th17% was strongly associated with poor lung function (FEV1 % predicted) (p = 0.0008), and this association was strongest when both lung function testing and blood sampling were performed within one week. Our results are consistent with reports of CF as a Th17 disease and suggest that peripheral blood Th17 levels may be a surrogate marker of lung function in CF.

Tracking quicksilver: estimation of mercury waste from consumer products and subsequent verification by analysis of soil, water, sediment, and plant samples from the Cebu City, Philippines, landfill.

Source attribution of mercury (Hg) is critical for policy development to minimize the impact of Hg in wastes. Mercury content of consumer products and its subsequent release into the waste stream of Cebu City, Philippines, is estimated through surveys that employed validated, enumerator-administered questionnaires. Initially, a citywide survey (n = 1636) indicates that each household annually generates 1.07 ppm Hg (i.e., mg Hg/kg waste) and that linear and compact fluorescent lamps (17.2 %) and thermometers (52.1 %) are the major sources of Hg. A subsequent survey (n = 372) in the vicinity of the city's municipal solid waste landfill shows that residents in the area annually generate 0.38 ppm Hg per household, which is less than the citywide mean; surprisingly though, less affluent respondents living closer to the landfill site reported more Hg from thermometers and sphygmomanometers. Analysis of collected soil (0.238 ppm), leachate water (6.5 ppb), sediment (0.109 ppm), and three plants (0.393 to 0.695 ppm) shows no significant variation throughout five stations in and around the landfill site, although the period of collection is significant for soil (P = 0.001) and Cenchrus echinatus (P = 0.016). Detected Hg in the landfill is considerably less than the annual estimated release, indicating that there is minimal accumulation of Hg in the soil or in plants. As a result of this project, a policy brief has been provided to the Cebu City council in aid of hazardous waste legislation.

A randomized controlled trial of in-patient treatment for anorexia nervosa in medically unstable adolescents.

BACKGROUND: Anorexia nervosa (AN) is a serious disorder incurring high costs due to hospitalization. International treatments vary, with prolonged hospitalizations in Europe and shorter hospitalizations in the USA. Uncontrolled studies suggest that longer initial hospitalizations that normalize weight produce better outcomes and fewer admissions than shorter hospitalizations with lower discharge weights. This study aimed to compare the effectiveness of hospitalization for weight restoration (WR) to medical stabilization (MS) in adolescent AN. METHOD: We performed a randomized controlled trial (RCT) with 82 adolescents, aged 12-18 years, with a DSM-IV diagnosis of AN and medical instability, admitted to two pediatric units in Australia. Participants were randomized to shorter hospitalization for MS or longer hospitalization for WR to 90% expected body weight (EBW) for gender, age and height, both followed by 20 sessions of out-patient, manualized family-based treatment (FBT). RESULTS: The primary outcome was the number of hospital days, following initial admission, at the 12-month follow-up. Secondary outcomes were the total number of hospital days used up to 12 months and full remission, defined as healthy weight (>95% EBW) and a global Eating Disorder Examination (EDE) score within 1 standard deviation (s.d.) of published means. There was no significant difference between groups in hospital days following initial admission. There were significantly more total hospital days used and post-protocol FBT sessions in the WR group. There were no moderators of primary outcome but participants with higher eating psychopathology and compulsive features reported better clinical outcomes in the MS group. CONCLUSIONS: Outcomes are similar with hospitalizations for MS or WR when combined with FBT. Cost savings would result from combining shorter hospitalization with FBT.

Introducing genetic testing for cardiovascular disease in primary care: a qualitative study.

BACKGROUND: While primary care systematically offers conventional cardiovascular risk assessment, genetic tests for coronary heart disease (CHD) are increasingly commercially available to patients. It is unclear how individuals may respond to these new sources of risk information. AIM: To explore how patients who have had a recent conventional cardiovascular risk assessment, perceive additional information from genetic testing for CHD. DESIGN AND SETTING: Qualitative interview study in 12 practices in Nottinghamshire from both urban and rural settings. METHOD: Interviews were conducted with 29 adults, who consented to genetic testing after having had a conventional cardiovascular risk assessment. RESULTS: Individuals' principal motivation for genetic testing was their family history of CHD and a desire to convey the results to their children. After testing, however, there was limited recall of genetic test results and scepticism about the value of informing their children. Participants dealt with conflicting findings from the genetic test, family history, and conventional assessment by either focusing on genetic risk or environmental lifestyle factors. In some participants, genetic test results appeared to reinforce healthy behaviour but others were falsely reassured, despite having an 'above-average' conventional cardiovascular risk score. CONCLUSION: Although genetic testing was acceptable, participants were unclear how to interpret genetic risk results. To facilitate healthy behaviour, health professionals should explore patients' understanding of genetic test results in light of their family history and conventional risk assessment.

Ex-vivo response to blood products and haemostatic agents after paediatric cardiac surgery.

Bleeding complications after cardiac surgery are of particular importance in children because they are more prone to volume overload. To optimize haemostatic intervention, the coagulopathy has to be characterized, and knowledge about the effect of blood products and haemostatic agents is needed. The aims of the present study were to investigate changes in coagulation profiles after paediatric cardiac surgery and the effect after ex-vivo addition of blood products and haemostatic agents. Coagulation profiles were evaluated by thromboelastometry (ROTEM) in 54 children before and immediately after cardiac surgery. The haemostatic potential of various factor concentrates (fibrinogen concentrate, recombinant factor VIIa and factor XIII), fresh frozen plasma (FFP), pooled platelets and tranexamic acid was investigated. After surgery, the coagulation profiles revealed significantly prolonged clotting time (P=0.008), and reduced clot propagation (P<0.001) as well as reduced whole blood clot stability (P<0.001). Ex-vivo addition of pooled platelets fully reversed the postoperative coagulopathy; this was also seen after addition of recombinant factor VIIa although less pronounced. Finally, addition of fibrinogen concentrate, FFP or tranexamic acid improved clot stability significantly. Whole blood coagulation was significantly impaired after cardiac surgery in children. Ex-vivo studies showed a total reversal of the coagulopathy after addition of pooled platelets and significantly improved clot stability after addition of fibrinogen concentrate, FFP and tranexamic acid, respectively.

Combining geometric morphometrics, molecular phylogeny, and micropaleontology to assess evolutionary patterns in Mallomonas (Synurophyceae: Heterokontophyta).

Synurophytes, also known as scaled chrysophytes, are ecologically important algae that produce an array of siliceous structures upon which their taxonomy is based. Despite occupying a key position within the photosynthetic heterokonts, the evolutionary history of synurophytes remains poorly constrained. Here, modern and Middle Eocene siliceous scales of the morphotaxon Mallomonas insignis are used as a model to investigate synurophyte evolutionary patterns. Structural details of scale morphology were examined comparatively with scanning electron microscopy and scored for geometric morphometric analyses to assess the stability of shape characters. Although consistent size differences exist (modern scales are larger than Eocene counterparts), the populations cannot be differentiated on the basis of shape or microstructural detail, implying considerable evolutionary stasis in scale morphology. A time-calibrated relaxed molecular clock analysis using a three-gene concatenated data set (27 strains) suggests that the M. insignis lineage predates the available fossil record, having diverged from closest congeneric taxa in the Cretaceous (≥94 Ma). However, the molecular analysis also implies that considerable genetic variability is present within several morphotaxa of Mallomonas, implying that substantial genetic variability has arisen despite the retention of uniform scale morphologies, and resulting in the widespread occurrence of cryptic taxa. Results from the synurophyte lineage are consistent with the notion of protracted ghost ranges (>10 Ma) implied by the molecular phylogenies of other algal groups, together pointing to the paucity of the fossil record of these organisms on these timescales.