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Health disciplines have increasingly required competency-based evaluations as a licensure prerequisite. In keeping with this trend, the Association of State and Provincial Psychology Boards (ASPPB) has begun to develop a second part to the Examination for Professional Practice in Psychology (EPPP). The resulting 2-part examination is collectively referred to as the Enhanced EPPP. Part 1 of the Enhanced EPPP, which consists of the current exam, is designed to be an assessment of knowledge. Part 2 of the Enhanced EPPP is newly developed and intended to address the need for a competency-based evaluation. To date, ASPPB has addressed some standard facets of validity for the EPPP Part 2, but not others. In addition, the EPPP Part 2 has yet to be subjected to a broader validation process, in which the suitability of the test for its intended purpose is evaluated. Implementation of the EPPP Part 2 before validation could have negative consequences for those seeking to enter the profession and for the general public (e.g., potential restriction of diversity in the psychology workforce). For jurisdictions implementing the EPPP Part 2, failure to gather and report the evidence required for use of a test in a forensic context may also open the door for legal challenges. We end with suggestions for feasible research that could significantly enhance the validation process for the EPPP Part 2 and offer jurisdictions concrete suggestions of features to look for in determining whether and when to implement the Enhanced EPPP. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Trichomonas gallinae is a protozoan pathogen that causes avian trichomonosis typically associated with columbids (canker) and birds of prey (frounce) that predate on them, and has recently emerged as an important cause of passerine disease. An archived panel of DNA from North American (USA) birds used initially to establish the ITS ribotypes was reanalysed using Iron hydrogenase (FeHyd) gene sequences to provide an alphanumeric subtyping scheme with improved resolution for strain discrimination. Thirteen novel subtypes of T. gallinae using FeHyd gene as the subtyping locus are described. Although the phylogenetic topologies derived from each single marker are complementary, they are not entirely congruent. This may reflect the complex genetic histories of the isolates analysed which appear to contain two major lineages and several that are hybrid. This new analysis consolidates much of the phylogenetic signal generated from the ITS ribotype and provides additional resolution for discrimination of T. gallinae strains. The single copy FeHyd gene provides higher resolution genotyping than ITS ribotype alone. It should be used where possible as an additional, single-marker subtyping tool for cultured isolates., (Copyright © 2019. Published by Elsevier B.V.)

A 35-year-old man presented to his optician with sudden onset diplopia and a 1-week history of headaches. He was noted to have sixth nerve palsy. The following day he was admitted to hospital with confusion and expressive dysphasia. He had been due to travel to Ghana on business and had received yellow fever (YF) vaccination 18 days prior to onset of headaches. His initial cerebrospinal fluid (CSF) revealed elevated protein, increased white cell count but was PCR negative for standard viral pathogens. Herpes simplex virus (HSV)-1 was detected by PCR in CSF at a very low level from a second lumbar puncture performed 6 days later, and the patient was treated for HSV meningoencephalitis. However, retrospective investigation for yellow fever vaccine-associated neurological disease revealed increasing titres of YF IgG in three serial CSF samples, and no evidence of HSV antibodies in CSF or plasma, ruling out HSV encephalitis., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Colonoscopy is the gold-standard investigation for direct luminal visualization of the large bowel. Studies have shown the efficacy of computed tomography colonography (CTC) is equivalent to colonoscopy in both cancer and polyp detection., Methods: A retrospective review of patients undergoing CTC from January 2013 to October 2014 was performed. Patient demographics, indication for investigation, computed tomography findings, optical colonoscopy findings and histology results were recorded., Results: Seven hundred and fifty-eight CTC were performed. Three hundred and seventeen patients were male (42%) and 441 (58%) were female. Endoscopy was advised in 209 cases. One hundred and twenty (16%) were deemed suspicious for cancer of whom 96 (80%) had optical colonoscopy. A total of 12 colorectal cancers were detected. Potential polyps were noted in 58 cases (8%). Forty-four patients underwent endoscopy (75%) and 17 polyps confirmed (38%). Two patients had foci of invasive cancer histologically. Significant extracolonic findings were identified in 60%, including five cases of gastric carcinomas. The most common other findings were gallstones and hernias., Conclusion: The rate of colorectal cancer detection in this study was 2%. The rate of biopsy proven cancer was 10% following a suspicious colonogram. Endoscopic correlation was not obtained in 20% of cases of radiological suspicion. CTC is as efficacious as optical colonoscopy for colorectal cancer and polyp detection., (© 2019 Royal Australasian College of Surgeons.)

G protein-coupled receptor (GPCR) signaling is the primary method eukaryotes use to respond to specific cues in their environment. However, the relationship between stimulus and response for each GPCR is difficult to predict due to diversity in natural signal transduction architecture and expression. Using genome engineering in yeast, we constructed an insulated, modular GPCR signal transduction system to study how the response to stimuli can be predictably tuned using synthetic tools. We delineated the contributions of a minimal set of key components via computational and experimental refactoring, identifying simple design principles for rationally tuning the dose response. Using five different GPCRs, we demonstrate how this enables cells and consortia to be engineered to respond to desired concentrations of peptides, metabolites, and hormones relevant to human health. This work enables rational tuning of cell sensing while providing a framework to guide reprogramming of GPCR-based signaling in other systems., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

In the 1950s the myxoma virus was released into European rabbit populations in Australia and Europe, decimating populations and resulting in the rapid evolution of resistance. We investigated the genetic basis of resistance by comparing the exomes of rabbits collected before and after the pandemic. We found a strong pattern of parallel evolution, with selection on standing genetic variation favoring the same alleles in Australia, France, and the United Kingdom. Many of these changes occurred in immunity-related genes, supporting a polygenic basis of resistance. We experimentally validated the role of several genes in viral replication and showed that selection acting on an interferon protein has increased the protein's antiviral effect., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Maroteaux-Lamy syndrome is a very rare multisystem disorder. Cardiac valve surgery is common in these patients who present a unique set of perioperative and intraoperative challenges to the surgeon and treating team. We describe successful mitral valve replacement using an inverted aortic prosthesis in a 29-year-old lady with Maroteaux-Lamy syndrome, with a good result at 10 months.

Native cell-free transcription-translation systems offer a rapid route to characterize the regulatory elements (promoters, transcription factors) for gene expression from nonmodel microbial hosts, which can be difficult to assess through traditional in vivo approaches. One such host, Bacillus megaterium , is a giant Gram-positive bacterium with potential biotechnology applications, although many of its regulatory elements remain uncharacterized. Here, we have developed a rapid automated platform for measuring and modeling in vitro cell-free reactions and have applied this to B. megaterium to quantify a range of ribosome binding site variants and previously uncharacterized endogenous constitutive and inducible promoters. To provide quantitative models for cell-free systems, we have also applied a Bayesian approach to infer ordinary differential equation model parameters by simultaneously using time-course data from multiple experimental conditions. Using this modeling framework, we were able to infer previously unknown transcription factor binding affinities and quantify the sharing of cell-free transcription-translation resources (energy, ribosomes, RNA polymerases, nucleotides, and amino acids) using a promoter competition experiment. This allows insights into resource limiting-factors in batch cell-free synthesis mode. Our combined automated and modeling platform allows for the rapid acquisition and model-based analysis of cell-free transcription-translation data from uncharacterized microbial cell hosts, as well as resource competition within cell-free systems, which potentially can be applied to a range of cell-free synthetic biology and biotechnology applications., Competing Interests: The authors declare no conflict of interest., (Copyright © 2018 the Author(s). Published by PNAS.)

Sulfadoxine-pyrimethamine with amodiaquine is recommended by the World Health Organization as seasonal malaria chemoprevention for children aged 3 to 59 months in the sub-Sahel regions of Africa. Suboptimal dosing in children may lead to treatment failure and increased resistance. Pooled individual patient data from four previously published trials on the pharmacokinetics of sulfadoxine and pyrimethamine in 415 pediatric and 386 adult patients were analyzed using nonlinear mixed-effects modeling to evaluate the current dosing regimen and, if needed, to propose an optimized dosing regimen for children under 5 years of age. The population pharmacokinetics of sulfadoxine and pyrimethamine were both best described by a one-compartment disposition model with first-order absorption and elimination. Body weight, age, and nutritional status (measured as the weight-for-age Z-score) were found to be significant covariates. Allometric scaling with total body weight and the maturation of clearance in children by postgestational age improved the model fit. Underweight-for-age children were found to have 15.3% and 26.7% lower bioavailabilities of sulfadoxine and pyrimethamine, respectively, for each Z-score unit below -2. Under current dosing recommendations, simulation predicted that the median day 7 concentration was below the 25th percentile for a typical adult patient (50 kg) for sulfadoxine for patients in the weight bands of 8 to 9, 19 to 24, 46 to 49, and 74 to 79 kg and for pyrimethamine for patients in the weight bands of 8 to 9, 14 to 24, and 42 to 49 kg. An evidence-based dosing regimen was constructed that would achieve sulfadoxine and pyrimethamine exposures in young children and underweight-for-age young children that were similar to those currently seen in a typical adult., (Copyright © 2018 de Kock et al.)

Synthetic biology designed cell-free biosensors are a promising new tool for the detection of clinically relevant biomarkers in infectious diseases. Here, we report that a modular DNA-encoded biosensor in cell-free protein expression systems can be used to measure a bacterial biomarker of Pseudomonas aeruginosa infection from human sputum samples. By optimizing the cell-free system and sample extraction, we demonstrate that the quorum sensing molecule 3-oxo-C12-HSL in sputum samples from cystic fibrosis lungs can be quantitatively measured at nanomolar levels using our cell-free biosensor system, and is comparable to LC-MS measurements of the same samples. This study further illustrates the potential of modular cell-free biosensors as rapid, low-cost detection assays that can inform clinical practice.

High-throughput screening (HTS) is a widespread method in early drug discovery for identifying promising chemical matter that modulates a target or phenotype of interest. Because HTS campaigns involve screening millions of compounds, it is often desirable to initiate screening with a subset of the full collection. Subsequently, virtual screening methods prioritize likely active compounds in the remaining collection in an iterative process. With this approach, orthogonal virtual screening methods are often applied, necessitating the prioritization of hits from different approaches. Here, we introduce a novel method of fusing these prioritizations and benchmark it prospectively on 17 screening campaigns using virtual screening methods in three descriptor spaces. We found that the fusion approach retrieves 15% to 65% more active chemical series than any single machine-learning method and that appropriately weighting contributions of similarity and machine-learning scoring techniques can increase enrichment by 1% to 19%. We also use fusion scoring to evaluate the tradeoff between screening more chemical matter initially in lieu of replicate samples to prevent false-positives and find that the former option leads to the retrieval of more active chemical series. These results represent guidelines that can increase the rate of identification of promising active compounds in future iterative screens.

Setting: Glasgow, Scotland, UK., Background: Paradoxical reactions in tuberculosis (TB) are a notable example of our incomplete understanding of host-pathogen interactions during anti-tuberculosis treatment., Objectives: To determine risk factors for a TB paradoxical reaction, and specifically to assess for an independent association with vitamin D use., Design: Consecutive human immunodeficiency virus (HIV) negative adult patients treated for extra-pulmonary TB were identified from an Extended Surveillance of Mycobacterial Infections database. In our setting, vitamin D was variably prescribed for newly diagnosed TB patients. A previously published definition of paradoxical TB reaction was retrospectively applied to, and data on all previously described risk factors were extracted from, centralised electronic patient records. The association with vitamin D use was assessed using multivariate logistic regression., Results: Of the 249 patients included, most had TB adenopathy; 222/249 had microbiologically and/or histologically confirmed TB. Vitamin D was prescribed for 57/249 (23%) patients; 37/249 (15%) were classified as having paradoxical reactions. Younger age, acid-fast bacilli-positive invasive samples, multiple disease sites, lower lymphocyte count and vitamin D use were found to be independent risk factors., Conclusion: We speculate that vitamin D-mediated signalling of pro-inflammatory innate immune cells, along with high antigenic load, may mediate paradoxical reactions in anti-tuberculosis treatment.

Fungi are a valuable source of enzymatic diversity and therapeutic natural products including antibiotics. Here we engineer the baker's yeast Saccharomyces cerevisiae to produce and secrete the antibiotic penicillin, a beta-lactam nonribosomal peptide, by taking genes from a filamentous fungus and directing their efficient expression and subcellular localization. Using synthetic biology tools combined with long-read DNA sequencing, we optimize productivity by 50-fold to produce bioactive yields that allow spent S. cerevisiae growth media to have antibacterial action against Streptococcus bacteria. This work demonstrates that S. cerevisiae can be engineered to perform the complex biosynthesis of multicellular fungi, opening up the possibility of using yeast to accelerate rational engineering of nonribosomal peptide antibiotics.

Golden Gate cloning is a prominent DNA assembly tool in synthetic biology for the assembly of plasmid constructs often used in combinatorial pathway optimization, with a number of assembly kits developed specifically for yeast and plant-based expression. However, its use for synthetic biology in commonly used bacterial systems such as Escherichia coli has surprisingly been overlooked. Here, we introduce EcoFlex a simplified modular package of DNA parts for a variety of applications in E. coli, cell-free protein synthesis, protein purification and hierarchical assembly of transcription units based on the MoClo assembly standard. The kit features a library of constitutive promoters, T7 expression, RBS strength variants, synthetic terminators, protein purification tags and fluorescence proteins. We validate EcoFlex by assembling a 68-part containing (20 genes) plasmid (31 kb), characterize in vivo and in vitro library parts, and perform combinatorial pathway assembly, using pooled libraries of either fluorescent proteins or the biosynthetic genes for the antimicrobial pigment violacein as a proof-of-concept. To minimize pathway screening, we also introduce a secondary module design site to simplify MoClo pathway optimization. In summary, EcoFlex provides a standardized and multifunctional kit for a variety of applications in E. coli synthetic biology.

The current study tested if proximal transmission of positive and negative affect occurs bidirectionally between mothers and their adolescent children in valence-specific patterns (e.g., maternal positive affect to adolescent positive, but not negative, affect) across a period of 7 minutes and between minutes. Whether adolescent gender moderated transmission effects was also explored. One hundred thirty-5 mothers (29-60 years old) and their children (12-16 years old, 49% female) independently completed questionnaires and then jointly engaged in a naturalistic 7-min problem-solving discussion. Transmission was examined by testing how 1 person's expressed affect (assessed observationally) changed the other person's self-reported state affect across the task. In path analyses, support for bidirectional transmission of negative affect emerged. Transmission was valence-specific, however, evidence for transmission of positive affect was not found. Results also supported cross-valence transmission of negative affect specifically from adolescents to their mothers, such that adolescent expressed negative affect predicted reduced maternal self-reported positive affect. Utilizing cross-lagged path analyses to further examine these findings between minutes revealed that transmission did not occur between specific minutes. Results largely support previous theoretical work on the orthogonal structure of affect and the bidirectionality of parent-adolescent affective interactions. Given this evidence for reciprocal transmission of affect across (not between) minutes in a microsocial context, implications for successful emotion coregulation in parent-adolescent interactions and how these mechanisms may predict long-term outcomes are discussed. (PsycINFO Database Record, ((c) 2016 APA, all rights reserved).)

Background: There are thousands of survivors of the 2014 Ebola outbreak in west Africa. Ebola virus can persist in survivors for months in immune-privileged sites; however, viral relapse causing life-threatening and potentially transmissible disease has not been described. We report a case of late relapse in a patient who had been treated for severe Ebola virus disease with high viral load (peak cycle threshold value 13.2)., Methods: A 39-year-old female nurse from Scotland, who had assisted the humanitarian effort in Sierra Leone, had received intensive supportive treatment and experimental antiviral therapies, and had been discharged with undetectable Ebola virus RNA in peripheral blood. The patient was readmitted to hospital 9 months after discharge with symptoms of acute meningitis, and was found to have Ebola virus in cerebrospinal fluid (CSF). She was treated with supportive therapy and experimental antiviral drug GS-5734 (Gilead Sciences, San Francisco, Foster City, CA, USA). We monitored Ebola virus RNA in CSF and plasma, and sequenced the viral genome using an unbiased metagenomic approach., Findings: On admission, reverse transcriptase PCR identified Ebola virus RNA at a higher level in CSF (cycle threshold value 23.7) than plasma (31.3); infectious virus was only recovered from CSF. The patient developed progressive meningoencephalitis with cranial neuropathies and radiculopathy. Clinical recovery was associated with addition of high-dose corticosteroids during GS-5734 treatment. CSF Ebola virus RNA slowly declined and was undetectable following 14 days of treatment with GS-5734. Sequencing of plasma and CSF viral genome revealed only two non-coding changes compared with the original infecting virus., Interpretation: Our report shows that previously unanticipated, late, severe relapses of Ebola virus can occur, in this case in the CNS. This finding fundamentally redefines what is known about the natural history of Ebola virus infection. Vigilance should be maintained in the thousands of Ebola survivors for cases of relapsed infection. The potential for these cases to initiate new transmission chains is a serious public health concern., Funding: Royal Free London NHS Foundation Trust., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

1.Malaria is the tropical disease most commonly imported into the UK, with 1300-1800 cases reported each year, and 2-11 deaths. 2. Approximately three quarters of reported malaria cases in the UK are caused by Plasmodium falciparum, which is capable of invading a high proportion of red blood cells and rapidly leading to severe or life-threatening multi-organ disease. 3. Most non-falciparum malaria cases are caused by Plasmodium vivax; a few cases are caused by the other species of plasmodium: Plasmodium ovale, Plasmodium malariae or Plasmodium knowlesi. 4. Mixed infections with more than one species of parasite can occur; they commonly involve P. falciparum with the attendant risks of severe malaria. 5. There are no typical clinical features of malaria; even fever is not invariably present. Malaria in children (and sometimes in adults) may present with misleading symptoms such as gastrointestinal features, sore throat or lower respiratory complaints. 6. A diagnosis of malaria must always be sought in a feverish or sick child or adult who has visited malaria-endemic areas. Specific country information on malaria can be found at http://travelhealthpro.org.uk/. P. falciparum infection rarely presents more than six months after exposure but presentation of other species can occur more than a year after exposure. 7. Management of malaria depends on awareness of the diagnosis and on performing the correct diagnostic tests: the diagnosis cannot be excluded until more than one blood specimen has been examined. Other travel related infections, especially viral haemorrhagic fevers, should also be considered. 8. The optimum diagnostic procedure is examination of thick and thin blood films by an expert to detect and speciate the malarial parasites. P. falciparum and P. vivax (depending upon the product) malaria can be diagnosed almost as accurately using rapid diagnostic tests (RDTs) which detect plasmodial antigens. RDTs for other Plasmodium species are not as reliable. 9. Most patients treated for P. falciparum malaria should be admitted to hospital for at least 24 h as patients can deteriorate suddenly, especially early in the course of treatment. In specialised units seeing large numbers of patients, outpatient treatment may be considered if specific protocols for patient selection and follow up are in place. 10. Uncomplicated P. falciparum malaria should be treated with an artemisinin combination therapy (Grade 1A). Artemether-lumefantrine (Riamet(®)) is the drug of choice (Grade 2C) and dihydroartemisinin-piperaquine (Eurartesim(®)) is an alternative. Quinine or atovaquone-proguanil (Malarone(®)) can be used if an ACT is not available. Quinine is highly effective but poorly-tolerated in prolonged treatment and should be used in combination with an additional drug, usually oral doxycycline. 11. Severe falciparum malaria, or infections complicated by a relatively high parasite count (more than 2% of red blood cells parasitized) should be treated with intravenous therapy until the patient is well enough to continue with oral treatment. Severe malaria is a rare complication of P. vivax or P. knowlesi infection and also requires parenteral therapy. 12. The treatment of choice for severe or complicated malaria in adults and children is intravenous artesunate (Grade 1A). Intravenous artesunate is unlicensed in the EU but is available in many centres. The alternative is intravenous quinine, which should be started immediately if artesunate is not available (Grade 1A). Patients treated with intravenous quinine require careful monitoring for hypoglycemia. 13. Patients with severe or complicated malaria should be managed in a high-dependency or intensive care environment. They may require haemodynamic support and management of: acute respiratory distress syndrome, disseminated intravascular coagulation, acute kidney injury, seizures, and severe intercurrent infections including Gram-negative bacteraemia/septicaemia. 14. Children with severe malaria should also be treated with empirical broad spectrum antibiotics until bacterial infection can be excluded (Grade 1B). 15. Haemolysis occurs in approximately 10-15% patients following intravenous artesunate treatment. Haemoglobin concentrations should be checked approximately 14 days following treatment in those treated with IV artemisinins (Grade 2C). 16. Falciparum malaria in pregnancy is more likely to be complicated: the placenta contains high levels of parasites, stillbirth or early delivery may occur and diagnosis can be difficult if parasites are concentrated in the placenta and scanty in the blood. 17. Uncomplicated falciparum malaria in the second and third trimester of pregnancy should be treated with artemether-lumefantrine (Grade 2B). Uncomplicated falciparum malaria in the first trimester of pregnancy should usually be treated with quinine and clindamycin but specialist advice should be sought. Severe malaria in any trimester of pregnancy should be treated as for any other patient with artesunate preferred over quinine (Grade 1C). 18. Children with uncomplicated malaria should be treated with an ACT (artemether-lumefantrine or dihydroartemisinin-piperaquine) as first line treatment (Grade 1A). Quinine with doxycycline or clindamycin, or atovaquone-proguanil at appropriate doses for weight can also be used. Doxycycline should not be given to children under 12 years. 19. Either an oral ACT or chloroquine can be used for the treatment of non-falciparum malaria. An oral ACT is preferred for a mixed infection, if there is uncertainty about the infecting species, or for P. vivax infection from areas where chloroquine resistance is common (Grade 1B). 20. Dormant parasites (hypnozoites) persist in the liver after treatment of P. vivax or P. ovale infection: the only currently effective drug for eradication of hypnozoites is primaquine (1A). Primaquine is more effective at preventing relapse if taken at the same time as chloroquine (Grade 1C). 21. Primaquine should be avoided or given with caution under expert supervision in patients with Glucose-6-phosphate dehydrogenase deficiency (G6PD), in whom it may cause severe haemolysis. 22. Primaquine (for eradication of P. vivax or P. ovale hypnozoites) is contraindicated in pregnancy and when breastfeeding (until the G6PD status of child is known); after initial treatment for these infections a pregnant woman should take weekly chloroquine prophylaxis until after delivery or cessation of breastfeeding when hypnozoite eradication can be considered. 23. An acute attack of malaria does not confer protection from future attacks: individuals who have had malaria should take effective anti-mosquito precautions and chemoprophylaxis during future visits to endemic areas., (Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Objective: To assess, within communities experiencing Ebola virus outbreaks, the risks associated with the disposal of human waste and to generate recommendations for mitigating such risks., Methods: A team with expertise in the Hazard Analysis of Critical Control Points framework identified waste products from the care of individuals with Ebola virus disease and constructed, tested and confirmed flow diagrams showing the creation of such products. After listing potential hazards associated with each step in each flow diagram, the team conducted a hazard analysis, determined critical control points and made recommendations to mitigate the transmission risks at each control point., Findings: The collection, transportation, cleaning and shared use of blood-soiled fomites and the shared use of latrines contaminated with blood or bloodied faeces appeared to be associated with particularly high levels of risk of Ebola virus transmission. More moderate levels of risk were associated with the collection and transportation of material contaminated with bodily fluids other than blood, shared use of latrines soiled with such fluids, the cleaning and shared use of fomites soiled with such fluids, and the contamination of the environment during the collection and transportation of blood-contaminated waste., Conclusion: The risk of the waste-related transmission of Ebola virus could be reduced by the use of full personal protective equipment, appropriate hand hygiene and an appropriate disinfectant after careful cleaning. Use of the Hazard Analysis of Critical Control Points framework could facilitate rapid responses to outbreaks of emerging infectious disease.

Depression is frequently considered a disorder of impaired affect regulation with deficits across both positive and negative affective systems. However, where deficits in emotion regulation occur in youth, specifically regarding regulation of positive emotions, is relatively unknown. The current study tested whether deficits in broad (felt and expressed) and specific (up-regulation and maintenance) positive emotion processes are associated with youth depressive symptoms. Adolescents (n = 134; 65 girls) in grades 7 to 9 completed a self-report measure of depressive symptoms prior to participating in two parent-child interactions tasks, a rewarding trivia task and a problem-solving conflict task. During the interaction tasks, adolescent's overall self-reported experience and observed expression of positive affect (PA) was examined. Following the reward task, youth's ability to up-regulate PA (PA response) and maintain PA while buffering against NA (PA persistence) was explored observationally. Results suggested that reduced experience and expression of PA was associated with depression symptoms, but only in a context that elicited negative emotions. No association was found between PA response and depression symptoms; however, shorter PA persistence was associated with elevated depressive symptoms. Youth higher in depressive symptoms appear able to respond similarly to rewarding events, but fail to maintain PA and ward off NA when transitioning from a positive to negative task.

Cancer complicates approximately 0.1% of all pregnancies, and the incidence is expected to increase, as more women elect to defer child-bearing to a later age. For these women and the clinicians treating them, there is little rigorous evidence with which to guide their management, but thought must be given to the effects of chemotherapeutic agents on the developing fetus and the effects of physiological changes within the pregnant women. We examine the evidence available for the effects of cytotoxic chemotherapy on the development of the fetus and for the health of the child in the longer term, and the effects of transplacental transfer and physiological changes of pregnancy on the pharmacokinetics of these drugs. These factors may have significant influence on the appropriate dosing of chemotherapeutic agents in pregnant women, compared to their nonpregnant counterparts, and further research is required into the implications of these findings for the successful treatment of cancer in pregnancy.

A socioaffective specificity model was tested in which positive and negative affect differentially mediated relations of family emotional climate to youth internalizing symptoms. Participants were 134 7(th)-9(th) grade adolescents (65 girls; 86 % Caucasian) and mothers who completed measures of emotion-related family processes, experienced affect, anxiety, and depression. Results suggested that a family environment characterized by maternal psychological control and family negative emotion expressiveness predicted greater anxiety and depression, and was mediated by experienced negative affect. Conversely, a family emotional environment characterized by low maternal warmth and low positive emotion expressiveness predicted only depression, and was mediated through lowered experienced positive affect. This study synthesizes a theoretical model of typical family emotion socialization with an extant affect-based model of shared and unique aspects of anxiety and depression symptom expression.

Background: Enterotoxigenic Escherichia coli (ETEC) is a major cause of travellers' diarrhoea. We investigated the efficacy and safety of a skin-patch vaccine containing the pathogen's heat-labile toxin (LT) in a population of travellers to Mexico and Guatemala., Methods: In this phase 3, randomised, double-blind, placebo-controlled field trial, healthy adults (aged 18-64 years) travelling from Germany or the UK to Mexico or Guatemala were assigned in a 1:1 ratio by a dynamic electronic randomisation system to receive transcutaneous immunisation with a patch containing 37.5 μg of ETEC LT or a placebo patch. Participants, site staff, and the investigators who did the analyses were masked to group assignment. Participants were vaccinated before travel, with two patches given 14 days apart. In the destination country, participants tracked stool output in a diary and provided stool samples for pathogen identification if diarrhoea occurred. The primary endpoint was the proportion of participants with at least one episode of moderate-to-severe diarrhoea (defined as four or more unformed stools in a 24 h period) in which either or both ETEC enterotoxins (LT and heat-stable toxin [ST]) were detected. The study is registered at ClinicalTrials.gov, number NCT00993681., Findings: 2036 participants were recruited and randomly assigned between Oct 14, 2009, and Aug 13, 2010, with 1016 allocated to receive the LT patch and 1020 the placebo patch. 821 participants in the LT-patch group and 823 in the placebo group received both vaccinations and were analysed in the per-protocol population. 30 (3.7%, 95% CI 2.5-5.2) participants in the LT-patch group and 46 (5.6%, 4.1-7.4) in the placebo group had moderate or severe ETEC diarrhoea (vaccine efficacy 34.6%, -2.2 to 58.9; p=0.0621). 9333 local (ie, patch-site) adverse events (including erythema, rash, pruritus, hyperpigmentation, pain, hypopigmentation, and oedema) occurred in 943 (93%) of 1015 participants in the LT-patch group, compared with 1444 local adverse events in 574 (56%) of 1019 participants in the placebo group (p<0.0001). Serious adverse events occurred in 25 participants (14 in the LT-patch group and 11 in the placebo group), with all regarded as either unrelated or possibly related to treatment. Vaccine-induced hyperpigmentation persisted for at least 180 days after vaccination in 150 (18%) of the 849 participants who received both vaccinations and returned for final assessment in the LT-patch group, compared with none of the 842 participants in the placebo group. The vaccine was immunogenic, with a post-vaccination geometric mean titre of LT-specific serum immunoglobulin G of 3400.29, compared with 315.41 in the placebo group., Interpretation: Although the LT antigen was delivered effectively by the skin patch, the vaccine did not protect travellers against diarrhoea caused by ETEC or other organisms. Future vaccines against travellers' diarrhoea might need to include several antigens against various diarrhoeal pathogens, and might need to be able to generate mucosal and higher systemic immunity., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Depressive symptomatology is associated with impaired recognition of emotion. Previous investigations have predominantly focused on emotion recognition of static facial expressions neglecting the influence of social interaction and critical contextual factors. In the current study, we investigated how youth and maternal symptoms of depression may be associated with emotion recognition biases during familial interactions across distinct contextual settings. Further, we explored if an individual's current emotional state may account for youth and maternal emotion recognition biases. Mother-adolescent dyads (N = 128) completed measures of depressive symptomatology and participated in three family interactions, each designed to elicit distinct emotions. Mothers and youth completed state affect ratings pertaining to self and other at the conclusion of each interaction task. Using multiple regression, depressive symptoms in both mothers and adolescents were associated with biased recognition of both positive affect (i.e., happy, excited) and negative affect (i.e., sadness, anger, frustration); however, this bias emerged primarily in contexts with a less strong emotional signal. Using actor-partner interdependence models, results suggested that youth's own state affect accounted for depression-related biases in their recognition of maternal affect. State affect did not function similarly in explaining depression-related biases for maternal recognition of adolescent emotion. Together these findings suggest a similar negative bias in emotion recognition associated with depressive symptoms in both adolescents and mothers in real-life situations, albeit potentially driven by different mechanisms.

Avian trichomonosis, caused by the flagellated protozoan Trichomonas gallinae, is a recently emerged infectious disease of British passerines. The aetiological agent, a clonal epidemic strain of the parasite, has caused unprecedented finch mortality and population-level declines in Britain and has since spread to continental Europe. To better understand the potential origin of this epidemic and to further investigate its host range, T. gallinae DNA extracts were collected from parasite culture and tissue samples from a range of avian species in Britain. Sequence typing at the ITS1/5.8S rRNA/ITS2 region resolved three distinct ITS region types circulating in free-ranging British birds. Subtyping by sequence analyses at the Fe-hydrogenase gene demonstrated further strain variation within these ITS region types. The UK finch epidemic strain was preponderant amongst columbids sampled, however, wide strain diversity was encountered in isolates from a relatively small number of pigeons, suggesting further strains present in columbid populations across the UK are yet to be identified. Fe-hydrogenase gene sequence data in isolates from birds of prey with disease were predominantly identical to the UK finch epidemic strain, demonstrating its presence as a virulent strain in UK birds of prey since at least 2009.

Highly pathogenic avian influenza virus (HPAI) strain H5N1 has had direct and indirect economic impacts arising from direct mortality and control programmes in over 50 countries reporting poultry outbreaks. HPAI H5N1 is now reported as the most widespread and expensive zoonotic disease recorded and continues to pose a global health threat. The aim of this research was to assess the potential of utilising Hazard Analysis of Critical Control Points (HACCP) assessments in providing a framework for a rapid response to emerging infectious disease outbreaks. This novel approach applies a scientific process, widely used in food production systems, to assess risks related to a specific emerging health threat within a known zoonotic disease hotspot. We conducted a HACCP assessment for HPAI viruses within Vietnam's domestic poultry trade and relate our findings to the existing literature. Our HACCP assessment identified poultry flock isolation, transportation, slaughter, preparation and consumption as critical control points for Vietnam's domestic poultry trade. Introduction of the preventative measures highlighted through this HACCP evaluation would reduce the risks posed by HPAI viruses and pressure on the national economy. We conclude that this HACCP assessment provides compelling evidence for the future potential that HACCP analyses could play in initiating a rapid response to emerging infectious diseases.

Objective: Understanding magnitudes of variability when measuring tumor size may be valuable in improving detection of tumor change and thus evaluating tumor response to therapy in clinical trials and care. Our study explored intra- and inter-reader variability of tumor uni-dimensional (1D), bi-dimensional (2D), and volumetric (VOL) measurements using manual and computer-aided methods (CAM) on CT scans reconstructed at different slice intervals., Materials and Methods: Raw CT data from 30 patients enrolled in oncology clinical trials was reconstructed at 5, 2.5, and 1.25 mm slice intervals. 118 lesions in the lungs, liver, and lymph nodes were analyzed. For each lesion, two independent radiologists manually and, separately, using computer software, measured the maximum diameter (1D), maximum perpendicular diameter, and volume (CAM only). One of them blindly repeated the measurements. Intra- and inter-reader variability for the manual method and CAM were analyzed using linear mixed-effects models and Bland-Altman method., Results: For the three slice intervals, the maximum coefficients of variation for manual intra-/inter-reader variability were 6.9%/9.0% (1D) and 12.3%/18.0% (2D), and for CAM were 5.4%/9.3% (1D), 11.3%/18.8% (2D) and 9.3%/18.0% (VOL). Maximal 95% reference ranges for the percentage difference in intra-reader measurements for manual 1D and 2D, and CAM VOL were (-15.5%, 25.8%), (-27.1%, 51.6%), and (-22.3%, 33.6%), respectively., Conclusions: Variability in measuring the diameter and volume of solid tumors, manually and by CAM, is affected by CT slice interval. The 2.5mm slice interval provides the least measurement variability. Among the three techniques, 2D has the greatest measurement variability compared to 1D and 3D., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Up to one-third of dairy calves are born after dystocia and this is a major cause of calf mortality. This study investigated the neonatal physiology, survival, health and subsequent growth of dairy calves following dystocia and is the first longitudinal study to analyse multiple effects and to look beyond the perinatal period. A total of 455 live born Holstein calves (N: No assistance, n=360; FN: Farmer assistance but normally presented calf, n=82; FM: Farmer assistance of malpresented calf, n=13) were followed from birth to first service (heifers) or until leaving the farm (bulls). Compared to N calves, FN and FM animals had higher salivary cortisol concentrations at day 1 (P<0.001) and FN calves had lower passive immune transfer (P=0.03). Dystocia had no biologically significant impact on rectal temperature throughout the first 4 days (P>0.05). During the first 60 days, FM calves had a higher proportion of days with non-routine health treatments (P<0.05) and, by the time of weaning, mortality in FN and FM heifers was higher than in N calves (2.8×; P<0.01). However, in surviving calves, growth to first service was not affected by dystocia category (P>0.05). Calves which survive dystocia experience lower passive immunity transfer, higher mortality and higher indicators of physiological stress. Such calves have poorer welfare in the neonatal period and possibly beyond. Strategies need to be implemented to improve the subsequent health and welfare of such calves and to lower the incidence of dystocia., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objective: The objective of this study was to determine if dexamethasone intravitreal implant 0.7 mg (Ozurdex; Allergan, Inc) with bevacizumab (Avastin; Genentech, Inc) therapy can be synergistic, providing further improvements in visual acuity, sustainability, and macular thickness when compared with dexamethasone intravitreal implant 0.7 mg alone., Methods: This is a prospective, interventional case series intended to monitor changes in visual acuity and macular thickness in patients diagnosed with retinal vein occlusion (RVO), after injection of bevacizumab followed by a scheduled dexamethasone intravitreal implant. This study was designed to emulate patient care as received in the typical ophthalmology practice. Patients diagnosed with RVO, who were seen between September 2009 and July 2010, were included in this study if they had received previous anti-vascular endothelial growth factor therapy. Patients were included in analysis if the previous anti-vascular endothelial growth factor therapy was at least 6 weeks before and optical coherence tomography (OCT) was >300 μm on spectral-domain OCT. Exclusion criteria included history of vitrectomy, and/or rubeotic or advanced glaucoma. All patients were evaluated with Snellen visual acuity and measured for macular thickness (calculated by spectral-domain OCT) and intraocular pressure. At baseline, all patients were injected with bevacizumab, followed by dexamethasone intravitreal implant injection 2 weeks later. These patients were reexamined on a monthly basis and retreated when edema occurred., Results: The primary outcome measure was the time to reinjection based on OCT and vision criteria. The secondary outcomes were increases in visual acuity and the reduction of OCT thickness during that period. Thirty-four eyes of 33 patients, with a mean age of 72.8 years, were identified. Thirty-five percent were diagnosed with central RVO, while the other 65% were with branch RVO. Of these patients, 97% gained vision during the study. Mean visual acuity improved from initially 11 letters to a maximum of 25 letters during the study period. In addition, vision improved by at least 15 letters in 29% of patients initially up to 64% during the study period. Macular thickness decreased with the combination treatment by OCT, and the effect continued an average of 126 days from the initial bevacizumab treatment. Retreatment was unnecessary in 18% of the population during the 6-month study period., Conclusion: This study demonstrates efficacy and the duration of effect using a combination of bevacizumab and dexamethasone versus dexamethasone alone. The combination is synergistic, increasing visual acuity and prolonging the time between injections, compared with either of these medications alone. Therefore, the combination of a vascular endothelial growth factor inhibitor and a dexamethasone implant may be a valuable option for RVO treatment.

This work describes a novel surface-scattering technique which combines resonance enhanced multiphoton ionization (REMPI) with velocity-map imaging (VMI) to yield quantum-state and 2D velocity component resolved distributions in the scattered molecular flux. As an initial test system, we explore hyperthermal scattering (E(inc) = 21(5) kcal mol(-1)) of jet cooled HCl from Au(111) on atomically flat mica surfaces at 500 K. The resulting images reveal 2D (v(in-plane) and v(out-of-plane)) velocity distributions dominated by two primary features: trapping/thermal-desorption (TD) and a hyperthermal, impulsively scattering (IS) distribution. In particular, the IS component is strongly forward scattered and largely resolved in the velocity map images, which allows us to probe correlations between rotational and translational degrees of freedom in the IS flux without any model dependent deconvolution from the TD fraction. These correlations reveal that HCl molecules which have undergone a large decrease in velocity parallel to scattering plane have actually gained the most rotational energy, reminiscent of a dynamical energy constraint between these two degrees of freedom. The data are reduced to a rotational energy map that correlates with velocity along and normal to the scattering plane, revealing that exchange occurs primarily between rotation and the in-plane kinetic energy component, with v(out-of-plane) playing a relatively minor role.

Trichomonas gallinae is a protozoan parasite that is well characterised as a cause of trichomonosis in columbid and raptor species world-wide. The parasite emerged as a novel infection of British passerines in 2005, leading to epidemic mortality associated with significant declines of breeding populations of greenfinches (Carduelis chloris) and chaffinches (Fringilla coelebs). We characterised the extent of T. gallinae genotypic heterogeneity within the affected wild British avifauna by analysing individual isolates from 17 of the species affected. To do so, we employed improved platform-based multilocus typing tools as well as the hydrogenosomal Fe-hydrogenase gene as a single marker locus for fine-typing. We found no evidence of heterogeneity amongst the parasites infecting British passerines, indicating that a clonal strain of T. gallinae is the causative agent of this emerging infectious disease., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Harvest of the central one-third of the patella tendon (PT) is routinely performed for anterior cruciate ligament reconstruction (ACLR). Patella infera may ensue. In this study we unilaterally resected the central one-third of the PT in 20 sheep, without reconstructing or defunctionalizing the native ACL, and examined the effects at 3, 6, 12, and 24 weeks postoperatively on PT length, histological appearance of the donor defect and in vitro stifle joint kinematics. Mean length increases (p > 0.263) in the operated tendons of 0.3%, 2.8%, 0.5%, and 2.4% were observed at 3, 6, 12, and 24 weeks. A significant proximal shift of the patella correlated well with a mean 2.35° retardation of patellar flexion (r = 0.440, p = 0.001). A mean net 4.9° decrease in medial patellar tilt was also observed (p < 0.001), but was not coupled with changes in tibial rotation. Donor defect tissue showed a distinct progression of healing with time, remodeling from dense scar tissue at 3 weeks to bundles of well-organized collagen enveloped by vascularized loose connective tissue at 24 weeks but was not associated with the restoration of kinematics. These results suggest that resection of the central one-third of the PT and leaving the defect open in the ovine stifle joint may be associated with increased PT length and changes in patellar kinematics which do not recover 6 months postoperatively. The lack of patella infera may render this animal model unsuitable for the interpretation of joint kinematics following PT resection for human ACLR., (Copyright © 2010 Orthopaedic Research Society.)

Global wildlife trade is financially lucrative, frequently illegal and increases the risk for zoonotic disease transmission. This paper presents the first interdisciplinary study of Vietnam's illegal wild bird trade focussing on those aspects which may contribute to the transmission of diseases such as Highly Pathogenic Avian Influenza (HPAI) H5N1. Comparing January 2009 data with that of May 2007, we found a five-fold increase to 9,117 birds on sale in Hanoi. Ninety-five percent of Hanoian bird vendors appear unaware of trade regulations and across Vietnam vendors buy birds sourced outside of their province. Approximately 25% of the species common to Vietnam's bird trade are known to be HPAI H5N1 susceptible. The anthropogenic movement of birds within the trade chain and the range of HPAI-susceptible species, often traded alongside poultry, increase the risk Vietnam's bird trade presents for the transmission of pathogens such as HPAI H5N1. These results will assist in the control and monitoring of emerging zoonotic diseases and conservation of Southeast Asia's avifauna.

Patients with gynecologic malignancies are evaluated with a combination of imaging modalities including ultrasonography (US), computed tomography (CT), and magnetic resonance (MR) imaging. US has a primary role in detecting and characterizing endometrial and adnexal pathology. CT is one of the primary modalities in staging malignancy and detecting recurrence. MR imaging is characterized by superior contrast resolution and specificity. This article reviews the role of radiologic imaging for the characterization of gynecologic masses and for staging, planning, and monitoring treatment, as well as for the assessment of tumor recurrence of the most common gynecologic malignancies., (Copyright © 2011 Elsevier Inc. All rights reserved.)

In addition to parasite resistance, inadequate levels of exposure to antimalarial drugs may contribute to treatment failure. We developed population pharmacokinetic (PK) models to describe the distribution of sulfadoxine (SDX) and pyrimethamine (PYM) in children with uncomplicated malaria in Malawi. The concentration levels of antimalarial drugs in whole blood were determined using high-performance liquid chromatography. We found no evidence of underdosing in children as compared with adults; the children had drug exposure levels similar to those described in adults. Treatment failure was more likely in children with lower PYM concentrations on day 14 (P = 0.024), and there was a trend for lower SDX concentrations on day 14 (P = 0.061). SDX and PYM concentrations at levels predictive of treatment failure have been identified at day 14. Less than one-third of the children displayed drug concentration levels above these thresholds after receiving the recommended SDX-pyrimethamine (SP) dose. Our findings suggest that PK factors contributed to the observed high rate of treatment failure, and we therefore recommend a higher SP dose for children under the age of 5 years.

Objectives: The bone-patellar tendon-bone complex is routinely harvested for anterior cruciate ligament reconstruction in humans. Patella infera may ensue. However, the contribution from resection of the central one-third of the patellar tendon (PT) to potentially altered patellofemoral kinematics, in addition to those induced by a positional shift of the patella, are yet to be distinguished. Objectives of this study were to characterize changes in intraoperative patellar kinematics and PT length in nine sheep immediately following unilateral resection of the central one-third PT, and again at six, 12 and 24 weeks postoperatively., Methods: Following implantation of bone-screws into the patella and tibia, electromagnetic receivers were anchored to these, and then passively-induced, unloaded patellar kinematics were captured. Patellar kinematics were referenced to the tibial coordinate frame and analysed using non-parametric tests (Wilcoxon Signed Rank Test)., Results: Resection alone did cause significant alteration in kinematics at the time of surgery (p <0.05). Postoperatively, a mean increase in PT length of 2.6 mm was detected in the operated stifles, reflected partly as a net 2.8 mm proximal patellar shift (p <0.001). This was accompanied by a mean net six degree medial shift in the patellar tilt pattern (p <0.001). Significant changes to patellar spin in the latter parts of flexion were also observed (p <0.005). Kinematic and length changes did not recover up to 24 weeks postoperatively., Clinical Significance: The data obtained in this study suggests that both the patellar height and integrity of the PT are important determinants of patellar kinematics in the ovine stifle joint.

This study elaborated on associations between youth's trauma-related emotional numbing across multiple affective domains (e.g., fear, sadness, happiness, anger) and delinquent behaviors. The study also examined whether the effects of posttrauma emotional numbing varied by the occurrence of posttrauma arousal symptoms. Participants were 123 middle school boys and girls from working-class, urban communities. Emotional numbing, particularly diminished fear, was related to both home and community violence exposure. Numbing of fearful emotions was associated with all types of delinquent behaviors examined. In addition, numbing of sadness was associated with aggression. Interactions between numbing of fear and hyperarousal suggested a complex pattern of emotional processing following exposure to traumatic events in which numbing related to delinquent behavior only in the context of high posttrauma arousal. These patterns may coalesce to place youth at risk for early involvement in delinquent behaviors.