Quantitative and qualitative in vivo angiogenesis assay.
We describe the development and optimization of an in vivo angiogenesis assay utilizing gelfoam sponges impregnated with 0.4% agarose and different proangiogenic factors, such as basic fibroblast growth factor (bFGF), vascular epidermal growth factor (VEGF), tumor growth factor-alpha (TGF-alpha), and endothelial growth factor (EGF). The sponges are implanted into the subcutis of mice and harvested after different times. The gelfoam sponges are fixed, sectioned, and stained with fluorescent antibodies against CD31. The median number of CD31+ cells is determined in 10 different 0.159-mm2 fields. Proangiogenic molecules induced significant migration and proliferation of endothelial cells. To demonstrate the utility of this assay for evaluation of an antiangiogenic agent, mice were implanted with gelfoam sponges containing different proangiogenic factors and treated orally with water or PTK 787, a novel tyrosine kinase inhibitor with specific activity against the VEGF-R. PTK 787 significantly inhibited angiogenesis in sponges containing agarose + VEGF but not other proangiogenic molecules. The data show that the implanted gelfoam sponges provide a reliable quantitative assay to study in vivo angiogenesis.


Permeability testing of biomaterial membranes.
The permeability characteristics of biomaterials are critical parameters for a variety of implants. To analyse the permeability of membranes made from crosslinked ultrathin gelatin membranes and the transmigration of cells across the membranes, we combined three technical approaches: (1) a two-chamber-based permeability assay, (2) cell culturing with cytochemical analysis and (3) biochemical enzyme electrophoresis (zymography). Based on the diffusion of a coloured marker molecule in conjunction with photometric quantification, permeability data for a gelatin membrane were determined in the presence or absence of gelatin degrading fibroblasts. Cytochemical evaluation after cryosectioning of the membranes was used to ascertain whether fibroblasts had infiltrated the membrane inside. Zymography was used to investigate the potential release of proteases from fibroblasts, which are known to degrade collagen derivatives such as gelatin. Our data show that the diffusion equilibrium of a low molecular weight dye across the selected gelatin membrane is approached after about 6-8 h. Fibroblasts increase the permeability due to cavity formation in the membrane inside without penetrating the membrane for an extended time period (>21 days in vitro). Zymography indicates that cavity formation is most likely due to the secretion of matrix metalloproteinases. In summary, the combination of the depicted methods promises to facilitate a more rational development of biomaterials, because it provides a rapid means of determining permeability characteristics and bridges the gap between descriptive methodology and the mechanistic understanding of permeability alterations due to biological degradation.


[Tailored pharmacotherapy. Consultations about medication in a care programme for depression].
Despite the increasing rationalisation of mental health care, there are no specific recommendations regarding the number of contacts between a patient and a psychiatrist for the pharmacotherapy that forms part of the combined outpatient treatment (antidepressants and psychotherapy) of depression. To consider the possibility of drawing up an advisory document regarding frequency, number and duration of consultations about medication in combined treatment for depression. We reviewed the literature and had qualitative interviews with psychiatrists and trainees in psychiatric residency. The literature focuses predominantly on diagnostics and patient characteristics that determine the amount of care required. Advice on medication and pharmacotherapy is provided only by experts. According to the interviews, in psychiatric practice many factors influence the number and duration of consultations. Nevertheless, a distinctive pattern emerged. Regarding medication in the acute treatment phase, five or six visits to a psychiatrist are sufficient for most patients. Extra consultations have to be arranged for smaller groups of less stable patients and for crisis-prone patients.


Role of new anticoagulants for the prevention of venous thromboembolism after major orthopaedic surgery and in hospitalised acutely ill medical patients.
Anticoagulation therapy for the prevention of venous thromboembolic events is indicated in patients after major orthopaedic surgery and in hospitalised acutely ill medical patients, who have a high or moderate risk of venous thromboembolism (VTE), respectively. Clinical trials have clearly demonstrated that short-term anticoagulation reduces the risk of VTE in these patient groups and that longer-term anticoagulation is beneficial for some indications. Evidence-based guidelines for thromboprophylaxis have been developed based on these studies. However, despite these guidelines, thromboprophylaxis is still underused, or used suboptimally, in many patients. This is, in part, because of the limitations of traditional anticoagulants such as unfractionated heparin, low- molecular-weight heparin, synthetic pentasaccharides, and vitamin K antagonists. Newer oral anticoagulants, such as rivaroxaban, apixaban, and dabigatran etexilate, have certain advantages over traditional agents. They can be administered orally at a fixed dose without routine coagulation monitoring and have minimal food and drug interactions. These characteristics may result in better adherence to guidelines and improved patient outcomes. This review provides an overview of phase III clinical trial data for these newer anticoagulants in major orthopaedic surgery and in hospitalised acutely ill medical patients, and discusses their potential for extended use in the post-hospital discharge setting. All three newer oral anticoagulants are approved in many countries for the prevention of VTE after hip replacement or knee replacement surgery in adult patients, and it is likely that these drugs will contribute considerably towards reducing the substantial healthcare burden associated with VTE.


Human papillomavirus genotyping by a polymerase chain reaction-based genechip method in cervical carcinoma treated with neoadjuvant chemotherapy plus radical surgery.
The aim of this study was to evaluate the accuracy of human papillomavirus (HPV) genotyping by a polymerase chain reaction (PCR)-based genechip method and to determine the prognostic value of HPV genotype in bulky stage IB or IIA cervical carcinoma treated with neoadjuvant chemotherapy (NAC) and radical surgery. A total of 149 patients had adequate tissue for the study. The SPF1/GP6+ primers were used to amplify a 184 bp fragment. The amplimers were submitted for direct sequencing and hybridization with a genechip using revert-blot detection of 39 types of HPV DNA in a single reaction. Two runs of PCR with respective hybridization were performed for each tumor. The complete concordance of HPV genotyping was 80.5% (120/149) of the paired genechip results. The kappa coefficient was 0.634 (P < 0.0001). HPV DNA sequences were detected in 100% of the specimens, among which 67.8% harbored single type and 32.2% contained multiple types. HPV-16 was detected in 98.7%, HPV-18 in 22.8%, HPV-31 in 0.7%, HPV-45 in 1.3%, HPV-52 in 2.0%, HPV-58 in 6.7%, HPV-59 in 4.7%, and HPV-67 in 0.7%. In multivariate analyses, the HPV genotype [HPV-18 or HPV-16 and HPV-18 only versus all others: relative risk (RR), 2.33; 95% CI, 1.17-4.64; P = 0.016] and pre-NAC tumor size (>5 versus </=5 cm: RR, 2.25; 95% CI, 1.13-4.48; P = 0.021) were significantly related to overall survival. This PCR-based genechip method is sensitive and reproducible for HPV genotyping. The association of HPV-18 or HPV-16 and HPV-18 with poor outcome in cervical carcinoma treated with NAC plus radical surgery is confirmed.


Using Web 2.0 applications to promote health-related physical activity: findings from the WALK 2.0 randomised controlled trial.
Web 2.0 internet technology has great potential in promoting physical activity. This trial investigated the effectiveness of a Web 2.0-based intervention on physical activity behaviour, and the impact on website usage and engagement. 504 (328 women, 126 men) insufficiently active adult participants were randomly allocated to one of two web-based interventions or a paper-based Logbook group. The Web 1.0 group participated in the existing 10 000 Steps programme, while the Web 2.0 group participated in a Web 2.0-enabled physical activity intervention including user-to-user interaction through social networking capabilities. ActiGraph GT3X activity monitors were used to assess physical activity at four points across the intervention (0, 3, 12 and 18 months), and usage and engagement were assessed continuously through website usage statistics. Treatment groups differed significantly in trajectories of minutes/day of physical activity (p=0.0198), through a greater change at 3 months for Web 2.0 than Web 1.0 (7.3 min/day, 95% CI 2.4 to 12.3). In the Web 2.0 group, physical activity increased at 3 (mean change 6.8 min/day, 95% CI 3.9 to 9.6) and 12 months (3.8 min/day, 95% CI 0.5 to 7.0), but not 18 months. The Logbook group also increased physical activity at 3 (4.8 min/day, 95% CI 1.8 to 7.7) and 12 months (4.9 min/day, 95% CI 0.7 to 9.1), but not 18 months. The Web 1.0 group increased physical activity at 12 months only (4.9 min/day, 95% CI 0.5 to 9.3). The Web 2.0 group demonstrated higher levels of website engagement (p=0.3964). In comparison to a Web 1.0 intervention, a more interactive Web 2.0 intervention, as well as the paper-based Logbook intervention, improved physical activity in the short term, but that effect reduced over time, despite higher levels of engagement of the Web 2.0 group. ACTRN12611000157976.


Increased SIAH expression predicts ductal carcinoma in situ (DCIS) progression to invasive carcinoma.
Hyperactivated HER2/Neu/EGFR/RAS signaling is a major growth-promoting pathway known to drive cellular transformation and oncogenesis in breast cancers. HER2 amplification is detected in ~20% of all human breast cancer and is quite prevalent (up to 49%) in ductal carcinoma in situ (DCIS). The E3 ubiquitin ligase SIAH is considered a key downstream "gatekeeper" required for proper HER2/EGFR/RAS signal transduction. Formalin-fixed, paraffin-embedded resection specimens from 65 patients with DCIS treated with wide excision only were stained with an anti-SIAH antibody, and the percentage of tumor and normal adjacent tissue cells positive for SIAH nuclear staining were recorded. Statistical analysis was performed comparing SIAH staining in tumor cells to disease recurrence, histologic type, necrosis, hormone receptor status, and Her2/neu status, as well as nuclear grade. Correlation of SIAH expression in tumor cells with SIAH expression in normal adjacent tissue and age was also examined. Expression levels of SIAH in tumor cells was significantly higher in specimens from patients with recurrence (median = 19%) as compared to patients without recurrence (7%) (P < 0.001). There was also significantly increased SIAH expression in tumors with more aggressive features including comedo morphology (13.5% in comedo vs. 7% in other histologic types, P = 0.014). No significant association was observed between SIAH expression and estrogen receptor, progesterone receptor, and Her2/neu status. There was a significant correlation between SIAH expression in tumors and normal adjacent tissue (Spearman correlation = 0.58, P < 0.001) as well as between SIAH expression in normal adjacent tissue and patient age (Spearman correlation = -0.59, P < 0.001). No significant correlation was identified between patient age and SIAH expression in tumors (Spearman correlation = -0.23, P = 0.067). In conclusion, SIAH may represent a useful prognostic biomarker that predicts DCIS progression to invasive breast cancer.


A Decision Aid Intervention for Family Building After Cancer: Developmental Study on the Initial Steps to Consider When Designing a Web-Based Prototype.
An important aspect of patient-centered care involves ensuring that patient-directed resources are usable, understandable, and responsive to patients' needs. A user-centered design refers to an empathy-based framework and an iterative design approach for developing a product or solution that is based on an in-depth understanding of users' needs, values, abilities, and limitations. This study presents the steps taken to develop a prototype for a patient resource for young women who have completed treatment for gonadotoxic cancer to support their decision making about follow-up fertility care and family building. User-centered design practices were used to develop Roadmap to Parenthood, a decision aid (DA) website for family building after cancer. A multidisciplinary steering group was assembled and input was provided. Guidelines from the International Patient DA Society and the Ottawa Decision Support Framework were used throughout the development process. In addition, guidelines for developing health DAs with respect to patient diversity and health literacy were also followed. The Roadmap to Parenthood DA website prototype was systematically and iteratively developed. An extensive process of designing and developing solutions from the perspective of the end user was followed. The steps taken included formative work to identify user needs; determining goals, format, and delivery; design processes (eg, personas, storyboards, information architecture, user journey mapping, and wireframing); and content development. Additional design considerations addressed the unique needs of this patient population, including the emotional experiences related to this topic and decision-making context wherein decisions could be considered iteratively while involving a multistep process. The design strategies presented in this study describe important steps in the early phases of developing a user-centered resource, which will enhance the starting point for usability testing and further design modifications. Future research will pilot test the DA and a planning tool, and evaluate improvement in the decisional conflict regarding family building after cancer. Consistent with a patient-centered approach to health care, the strategies described here may be generalized and applied to the development of other patient resources and clinical contexts to optimize usability, empathy, and user engagement.


Human genome efforts in Japan.
Some project-oriented biosciences have been promoted cooperatively by three governmental agencies in Japan: the Ministry of Education, Science and Culture, the Ministry of Health and Welfare, and the Science and Technology Agency. All three agencies have increased their budgetary requests for human genome analyses for FY 1991. The Panel on Life Sciences (chaired by Dr. W. Mori, former president of the University of Tokyo) of the Science and Technology Council of Japan which is chaired by the Prime Minister has decided to organize a working group to suggest how best to coordinate efforts in human genome analyses in Japan. The genome project was initially promoted by the Science and Technology Agency through a program for the design and construction of automated machines for DNA sequencing. Work is ongoing at the Institute of Physical and Chemical Research to integrate, by system engineering, instruments that can separate DNA fragments, perform plaque selection, carry out dideoxy reaction, and read the resulting DNA sequence. However, scientists now realize the enormity of the tasks of compiling DNA sequence data and of mapping the genes and fragments obtained, and efforts are being made to solve these problems. Academic societies have organized symposia to promote general interest in this subject. The most important way for Japan to contribute to research on human genome analyses, however, may be in the evaluation of supporting mechanisms (technical assistance and research resources) and in the recognition and preparation of the transition of biology to a big science approach.


Clinical outcome of children with suspected shunt malfunction evaluated in the emergency department.
Patients with cerebrospinal fluid shunts frequently present to the emergency department (ED) with suspected shunt malfunction. The outcome of those patients who were discharged from ED when shunt malfunction was deemed unlikely has not been previously documented. To demonstrate there is no increase in severity or likelihood of harm for patients who are discharged directly from the ED after adequate evaluation, as compared to patients who were selected for inpatient hospitalization. The report screens 3080 ED visits between 2010 and 2013 made by patients with shunted hydrocephalus. ED visits preceded by another ED visit or neurosurgical procedures within 60 days were excluded. ED visits for reasons unrelated to shunt function were excluded, and 1943 visits met the inclusion criteria. Final dispositions from the ED included home (n = 1176), admission to neurosurgery service (n = 550), and admission to other services (n = 217). Subsequent events within 30 days, including ED visits and elective and nonelective shunt-related surgery, were reviewed. The clinical characteristics of the 3 groups were similar. Of patients discharged home from the ED, 19.0% returned to ED, and 4.5% required shunt-related surgeries. Of the patients admitted for observation, 18.7% returned to ED and 14.2% required shunt-related surgery. Of the patients admitted to other hospital services, 19.6% patients returned to the ED, with 2.0% requiring surgical intervention. There were no shunt-related mortalities in any of the 3 groups. Children with cerebrospinal fluid shunts are often evaluated in the ED. Discharge from the ED, when suspicion for shunt malfunction is low, is an appropriate practice.


Outcome of COVID-19 patients with use of Tocilizumab: A single center experience.
COVID-19 pandemic has become a global concern. Cytokine release syndrome (CRS) complicates acute respiratory distress syndrome (ARDS) and causes multi-organ failure which can subsequently lead to mortality in COVID-19 patients. Tocilizumab, an interleukin-6 antagonist, has shown to salvage patients with cytokine release storm. In this study, we aim to evaluate therapeutic response of Tocilizumab in COVID-19 patients. A single-arm retrospective review of 40 patients with COVID-19, admitted to The Aga Khan University Hospital Karachi, from March 2020 to May 2020 was performed. Selection of patients for use of Tocilizumab was based on severity of disease, rapid clinical deterioration, presence of CRS and absence of any absolute contraindication to Tocilizumab. Improvement after Tocilizumab was defined as improvement in oxygen requirement and inflammatory parameters. Serum levels of inflammatory cytokines like C-reactive protein, ferritin, D-dimer and lactate dehydrogenase levels were monitored before and after administering Tocilizumab. Mean age was 62.4 years and 33 (82.5%) were male. 19 (47.5%) patients were critically sick, 18 (45%) were severely sick and 3 (7.5%) were moderately sick. 29 (77.5%) patients showed significant improvement in oxygen requirement, inflammatory parameters and chest x-rays, out of which 28 patients were discharged home. The mean duration between administration of Tocilizumab and overall improvement was 4.3 ± 3.2 days. Hence, Tocilizumab can be used as a possible treatment option in patients with COVID-19 induced CRS but needs monitoring for its adverse effects.


The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): The Perspectives of clinical immunologists from China.
The pandemic outbreak of coronavirus disease 2019 (COVID-19) is rapidly spreading all over the world. Reports from China showed that about 20% of patients developed severe disease, resulting in a fatality of 4%. In the past two months, we clinical immunologists participated in multi-rounds of MDT (multidiscipline team) discussion on the anti-inflammation management of critical COVID-19 patients, with our colleagues dispatched from Chinese leading PUMC Hospital to Wuhan to admit and treat the most severe patients. Here, from the perspective of clinical immunologists, we will discuss the clinical and immunological characteristics of severe patients, and summarize the current evidence and share our experience in anti-inflammation treatment, including glucocorticoids, IL-6 antagonist, JAK inhibitors and choloroquine/hydrocholoroquine, of patients with severe COVID-19 that may have an impaired immune system.


Catch-up saccades in head-unrestrained conditions reveal that saccade amplitude is corrected using an internal model of target movement.
This study analyzes how human participants combine saccadic and pursuit gaze movements when they track an oscillating target moving along a randomly oriented straight line with the head free to move. We found that to track the moving target appropriately, participants triggered more saccades with increasing target oscillation frequency to compensate for imperfect tracking gains. Our sinusoidal paradigm allowed us to show that saccade amplitude was better correlated with internal estimates of position and velocity error at saccade onset than with those parameters 100 ms before saccade onset as head-restrained studies have shown. An analysis of saccadic onset time revealed that most of the saccades were triggered when the target was accelerating. Finally, we found that most saccades were triggered when small position errors were combined with large velocity errors at saccade onset. This could explain why saccade amplitude was better correlated with velocity error than with position error. Therefore, our results indicate that the triggering mechanism of head-unrestrained catch-up saccades combines position and velocity error at saccade onset to program and correct saccade amplitude rather than using sensory information 100 ms before saccade onset.


ESPEN guideline: Clinical nutrition in surgery.
Early oral feeding is the preferred mode of nutrition for surgical patients. Avoidance of any nutritional therapy bears the risk of underfeeding during the postoperative course after major surgery. Considering that malnutrition and underfeeding are risk factors for postoperative complications, early enteral feeding is especially relevant for any surgical patient at nutritional risk, especially for those undergoing upper gastrointestinal surgery. The focus of this guideline is to cover nutritional aspects of the Enhanced Recovery After Surgery (ERAS) concept and the special nutritional needs of patients undergoing major surgery, e.g. for cancer, and of those developing severe complications despite best perioperative care. From a metabolic and nutritional point of view, the key aspects of perioperative care include: • integration of nutrition into the overall management of the patient • avoidance of long periods of preoperative fasting • re-establishment of oral feeding as early as possible after surgery • start of nutritional therapy early, as soon as a nutritional risk becomes apparent • metabolic control e.g. of blood glucose • reduction of factors which exacerbate stress-related catabolism or impair gastrointestinal function • minimized time on paralytic agents for ventilator management in the postoperative period • early mobilisation to facilitate protein synthesis and muscle function The guideline presents 37 recommendations for clinical practice.


Urine levels of HMGB1 in Systemic Lupus Erythematosus patients with and without renal manifestations.
Lupus nephritis (LN) is a severe and frequent manifestation of systemic lupus erythematosus (SLE). Its pathogenesis has not been fully elucidated but immune complexes are considered to contribute to the inflammatory pathology in LN. High Mobility Group Box 1 (HMGB1) is a nuclear non-histone protein which is secreted from different types of cells during activation and/or cell death and may act as a pro-inflammatory mediator, alone or as part of DNA-containing immune complexes in SLE. Urinary excretion of HMGB1 might reflect renal inflammatory injury. To assess whether urinary HMGB1 reflects renal inflammation we determined serum levels of HMGB1 simultaneously with its urinary levels in SLE patients with and without LN in comparison to healthy controls (HC). We also analyzed urinary HMGB1 levels in relation with clinical and serological disease activity. The study population consisted of 69 SLE patients and 17 HC. Twenty-one patients had biopsy proven active LN, 15 patients had a history of LN without current activity, and 33 patients had non-renal SLE. Serum and urine levels of HMGB1 were both measured by western blotting. Clinical and serological parameters were assessed according to routine procedures. In 17 patients with active LN a parallel analysis was performed on the expression of HMGB1 in renal biopsies. Serum and urinary levels of HMGB1 were significantly increased in patients with active LN compared to patients without active LN and HC. Similarly, renal tissue of active LN patients showed strong expression of HMGB1 at cytoplasmic and extracellular sites suggesting active release of HMGB1. Serum and urinary levels in patients without active LN were also significantly higher compared to HC. Urinary HMGB1 levels correlated with SLEDAI, and showed a negative correlation with complement C3 and C4. Levels of HMGB1 in urine of SLE patients, in particular in those with active LN, are increased and correlate with SLEDAI scores. Renal tissue of LN patients shows increased release of nuclear HMGB1 compared to control renal tissue. HMGB1, although at lower levels, is, however, also present in the urine of patients without active LN. These data suggest that urinary HMGB1 might reflect both local renal inflammation as well as systemic inflammation.


Influence of the biotope on the tick infestation of cattle and on the tick-borne pathogen repertoire of cattle ticks in Ethiopia.
The majority of vector-borne infections occur in the tropics, including Africa, but molecular eco-epidemiological studies are seldom reported from these regions. In particular, most previously published data on ticks in Ethiopia focus on species distribution, and only a few molecular studies on the occurrence of tick-borne pathogens or on ecological factors influencing these. The present study was undertaken to evaluate, if ticks collected from cattle in different Ethiopian biotopes harbour (had access to) different pathogens. In South-Western Ethiopia 1032 hard ticks were removed from cattle grazing in three kinds of tick biotopes. DNA was individually extracted from one specimen of both sexes of each tick species per cattle. These samples were molecularly analysed for the presence of tick-borne pathogens. Amblyomma variegatum was significantly more abundant on mid highland, than on moist highland. Rhipicephalus decoloratus was absent from savannah lowland, where virtually only A. cohaerens was found. In the ticks Coxiella burnetii had the highest prevalence on savannah lowland. PCR positivity to Theileria spp. did not appear to depend on the biotope, but some genotypes were unique to certain tick species. Significantly more A. variegatum specimens were rickettsia-positive, than those of other tick species. The presence of rickettsiae (R. africae) appeared to be associated with mid highland in case of A. variegatum and A. cohaerens. The low level of haemoplasma positivity seemed to be equally distributed among the tick species, but was restricted to one biotope type. The tick biotope, in which cattle are grazed, will influence not only the tick burden of these hosts, but also the spectrum of pathogens in their ticks. Thus, the presence of pathogens with alternative (non-tick-borne) transmission routes, with transstadial or with transovarial transmission by ticks appeared to be associated with the biotope type, with the tick species, or both, respectively.


First Report in Burkina Faso of Xanthomonas citri pv. mangiferaeindicae Causing Bacterial Canker on Mangifera indica.
Bacterial canker of mango (or bacterial black spot) caused by Xanthomonas citri pv. mangiferaeindicae, is an economically important disease in tropical and subtropical areas (1). X. citri pv. mangiferaeindicae can cause severe infection on a wide range of mango cultivars and induces raised, angular, black leaf lesions, sometimes with a chlorotic halo. Fruit symptoms are black, star shaped, erumpent, and exude an infectious gum. A survey was conducted in Burkina Faso in May 2010 because budwood putatively associated with an outbreak of bacterial canker in Ghana had originated from Burkina Faso (3). Leaves and twigs with suspected bacterial canker lesions were collected from mango trees of the cvs. Amélie, Brooks, and Kent and from seedlings at five localities in Comoe and Houet provinces. Severe infections were observed on the sampled trees in Burkina Faso and leaf symptoms were typical of bacterial canker. Leaves were surface sterilized for 15 to 30 s with 70% ethanol, and nonpigmented, Xanthomonas-like bacterial colonies were isolated on KC semiselective agar medium (1). On the basis of an IS1595-ligation mediated PCR assay, 18 strains from Burkina Faso produced identical fingerprints and were identified as X. citri pv. mangiferaeindicae (4). The haplotype for strains from Burkina Faso was identical to that reported from Ghana (3). Three strains from Burkina Faso (LH127-2, LH130-1, and LH131-1) were compared by multilocus sequence analysis (MLSA) with the type strain of X. citri and the pathotype strain of several X. citri pathovars, including pvs. anacardii and mangiferaeindicae, targeting the atpD, dnaK, efp, and gyrB genes (2). Nucleotide sequences were 100% identical to those of the pathotype strain of X. citri pv. mangiferaeindicae, regardless of the gene assayed, but differed from any other X. citri pathovar assayed. Leaves of mango cv. Maison Rouge, taken from the youngest vegetative flush, were infiltrated (10 inoculation sites per leaf for three replicate leaves on different plants per bacterial strain) with the same three strains from Burkina Faso. Bacterial suspensions (approximately 1 × 105 CFU/ml) were prepared in 10 mM Tris buffer (pH 7.2) from 16-h-old solid cultures on YPG agar (7 g of yeast, 7 g of peptone, 7 g of glucose, and 18 g of agar per liter, pH 7.2). The negative control treatment consisted of three leaves infiltrated with sterile Tris buffer (10 sites per leaf). Plants were incubated in a growth chamber at 30 ± 1°C by day and 26 ± 1°C by night (12-h/12-h day/night cycle) at 80 ± 5% relative humidity. Typical symptoms of bacterial canker were observed for all assayed strains 1 week after inoculation; no symptoms were observed from negative control leaves. One month after inoculation, mean X. citri pv. mangiferaeindicae populations ranging from 2 × 107 to 8 × 107 CFU/leaf lesion were recovered, which was typical of a compatible interaction (1). The origin of inoculum associated with the bacterial canker outbreak in Burkina Faso is unknown. This report documents severe infections in Burkina Faso (including premature fruit drop due to severe fruit infections) and confirms the presence of bacterial canker in western Africa. A more extensive survey for the disease should be conducted in this region. References: (1) N. Ah-You et al. Phytopathology 97:1568, 2007. (2) L. Bui Thi Ngoc et al. Int. J. Syst. Evol. Microbiol. 60:515, 2010. (3) O. Pruvost et al. Plant Dis. 95:774, 2011. (4) O. Pruvost et al. Phytopathology 101:887, 2011.


Linking inter-individual differences in the conflict adaptation effect to spontaneous brain activity.
Conflict adaptation has been widely researched in normal and clinical populations. There are large individual differences in conflict adaptation, and it has been linked to the schizotypal trait. However, no study to date has examined how individual differences in spontaneous brain activity are related to behavioral conflict adaptation (performance). Resting-state functional magnetic resonance imaging (RS-fMRI) is a promising tool to investigate this issue. The present study evaluated the regional homogeneity (ReHo) of RS-fMRI signals in order to explore the neural basis of individual differences in conflict adaptation across two independent samples comprising a total of 67 normal subjects. A partial correlation analysis was carried out to examine the relationship between ReHo and behavioral conflict adaptation, while controlling for reaction time, standard deviation and flanker interference effects. This analysis was conducted on 39 subjects' data (sample 1); the results showed significant positive correlations in the left dorsolateral prefrontal cortex (DLPFC) and left ventrolateral prefrontal cortex. We then conducted a test-validation procedure on the remaining 28 subjects' data (sample 2) to examine the reliability of the results. Regions of interest were defined based on the correlation results. Regression analysis showed that variability in ReHo values in the DLPFC accounted for 48% of the individual differences in the conflict adaptation effect in sample 2. The present findings provide further support for the importance of the DLPFC in the conflict adaptation process. More importantly, we demonstrated that ReHo of RS-fMRI signals in the DLPFC can predict behavioral performance in conflict adaptation, which provides potential biomarkers for the early detection of cognitive control deterioration.


Direct RNA nanopore sequencing of full-length coronavirus genomes provides novel insights into structural variants and enables modification analysis.
Sequence analyses of RNA virus genomes remain challenging owing to the exceptional genetic plasticity of these viruses. Because of high mutation and recombination rates, genome replication by viral RNA-dependent RNA polymerases leads to populations of closely related viruses, so-called "quasispecies." Standard (short-read) sequencing technologies are ill-suited to reconstruct large numbers of full-length haplotypes of (1) RNA virus genomes and (2) subgenome-length (sg) RNAs composed of noncontiguous genome regions. Here, we used a full-length, direct RNA sequencing (DRS) approach based on nanopores to characterize viral RNAs produced in cells infected with a human coronavirus. By using DRS, we were able to map the longest (∼26-kb) contiguous read to the viral reference genome. By combining Illumina and Oxford Nanopore sequencing, we reconstructed a highly accurate consensus sequence of the human coronavirus (HCoV)-229E genome (27.3 kb). Furthermore, by using long reads that did not require an assembly step, we were able to identify, in infected cells, diverse and novel HCoV-229E sg RNAs that remain to be characterized. Also, the DRS approach, which circumvents reverse transcription and amplification of RNA, allowed us to detect methylation sites in viral RNAs. Our work paves the way for haplotype-based analyses of viral quasispecies by showing the feasibility of intra-sample haplotype separation. Even though several technical challenges remain to be addressed to exploit the potential of the nanopore technology fully, our work illustrates that DRS may significantly advance genomic studies of complex virus populations, including predictions on long-range interactions in individual full-length viral RNA haplotypes.


BORIS Expression in Ovarian Cancer Precursor Cells Alters the CTCF Cistrome and Enhances Invasiveness through GALNT14.
High-grade serous carcinoma (HGSC) is the most aggressive and predominant form of epithelial ovarian cancer and the leading cause of gynecologic cancer-related death. We have previously shown that CTCFL (also known as BORIS, Brother of the Regulator of Imprinted Sites) is expressed in most ovarian cancers, and is associated with global and promoter-specific DNA hypomethylation, advanced tumor stage, and poor prognosis. To explore its role in HGSC, we expressed BORIS in human fallopian tube secretory epithelial cells (FTSEC), the presumptive cells of origin for HGSC. BORIS-expressing cells exhibited increased motility and invasion, and BORIS expression was associated with alterations in several cancer-associated gene expression networks, including fatty acid metabolism, TNF signaling, cell migration, and ECM-receptor interactions. Importantly, GALNT14, a glycosyltransferase gene implicated in cancer cell migration and invasion, was highly induced by BORIS, and GALNT14 knockdown significantly abrogated BORIS-induced cell motility and invasion. In addition, in silico analyses provided evidence for BORIS and GALNT14 coexpression in several cancers. Finally, ChIP-seq demonstrated that expression of BORIS was associated with de novo and enhanced binding of CTCF at hundreds of loci, many of which correlated with activation of transcription at target genes, including GALNT14. Taken together, our data indicate that BORIS may promote cell motility and invasion in HGSC via upregulation of GALNT14, and suggests BORIS as a potential therapeutic target in this malignancy. IMPLICATIONS: These studies provide evidence that aberrant expression of BORIS may play a role in the progression to HGSC by enhancing the migratory and invasive properties of FTSEC.


Nitrogen behavior during sludge ozonation: a long-term observation by pilot experiments.
Sludge ozonation is a promising technology for dealing with the increasing challenge of excess sludge treatment and disposal. However, nitrogen behavior during sludge ozonation and subsequent biological removal remains unclear. To clarify the feasibility and stability of oxidizing organic nitrogen (released during sludge ozonation) in the bioreactor (but not during ozonation), and the best operational conditions for sludge ozonation, nitrogen behavior was investigated by a long-term observation. The results showed that when inlet ozone concentration increased from 30 to 80 mg O3/L, and ozonation time decreased from 29 to 11 h, less soluble organic nitrogen was oxidized to ammonia (from 66.1 to 18.7% of soluble total nitrogen). This can reduce the operational costs of sludge ozonation. Furthermore, it is feasible to convert organic nitrogen to nitrate by biological processes because full nitrification was restored in three weeks after shock loading of organic nitrogen owing to the change in ozonation conditions. After combining sludge ozonation with the anaerobic/oxic process, the mass balance for nitrogen showed that nitrogen in the excess sludge decreased with increasing sludge reduction rate. The decreased nitrogen in the excess sludge was mainly transformed to nitrogen gas by denitrification, whereas nitrogen in the effluent did not increase noticeably.


Abnormal cervical cytology and health care use: a population-based register study.
This study aimed to assess the long-term use of health care services in women with abnormal cytology results compared to women with normal cytology results. We did a nationwide population-based study, using women aged 23 to 59years participating in the national organized cervical cancer screening program. We included a study population of 40,153 women with abnormal cytology (exposed) and 752,627 women with normal cytology (non-exposed). We retrieved data from the Danish Civil Registration System, the Danish Pathology Data Bank, the National Health Service, the National Patient and the National Prescription Register. We calculated the frequencies of contacts to general practitioner (GP), to private psychiatrist and/or psychologist, admissions to hospitals and use of prescription drugs. These frequencies were calculated separately in the 5-year period "before" the cytology result and for the 5-year period "after" the result. During the "before" period exposed women had more contacts to GPs, more contacts to psychologists/psychiatrist, and more hospital admissions than non-exposed women. In both exposed and non-exposed women, health care use increased from the "before" to the "after" period. This increase was significantly higher for exposed than non-exposed women regarding contacts to GP, admissions to hospitals, and drug use. Women with abnormal cytology results constitute a selected group with a higher health care use than other women even before they have the abnormal cytology. This difference is further enhanced after the abnormal cytology result.


Antiviral Efficacy of Flavonoids against Enterovirus 71 Infection in Vitro and in Newborn Mice.
Enterovirus 71 (EV71) infection is known to cause hand, foot, and mouth disease (HFMD), which is associated with neurological complications; however, there is currently no effective treatment for this infection. Flavonoids are a large group of naturally occurring compounds with multiple bioactivities, and the inhibitory effects of several flavonoids against EV71 have been studied in cell cultures; however, to date, there are no reported data on their effects in animal models. In this study, we confirmed the in vitro activities of eight flavonoids against EV71 infection, based on the inhibition of cytopathic effects. Moreover, these flavonoids were found to reduce viral genomic RNA replication and protein synthesis. We further demonstrated the protective efficacy of these flavonoids in newborn mice challenged with a lethal dose of EV71. Apigenin, luteolin, kaempferol, formononetin, and penduletin conferred survival protection of 88.89%, 91.67%, 88.89%, 75%, and 66.67%, respectively, from the lethal EV71 challenge. In addition, isorhamnetin provided the highest mice survival protection of 100% at a dose of 10 mg/kg. This study, to the best of our knowledge, is the first to evaluate the in vivo anti-EV7l activities of multiple flavonoids, and we accordingly identified flavonoids as potential leading compounds for anti-EV71 drug development.


Tobacco, alcohol, cannabis and other illegal drug use among young adults: the socioeconomic context.
Low socioeconomic position predicts risk of substance abuse, yet few studies tested the role of preexisting familial and individual characteristics. Data come from the TEMPO (Trajectoires Epidémiologiques en Population) study (community sample in France, 1991-2009, n=1103, 22-35 years in 2009) set up among offspring of participants of an epidemiological study (GAZEL). Past 12-month substance use was assessed in 2009 by self-completed mail survey: regular tobacco smoking, alcohol abuse (AUDIT), cannabis use, problematic cannabis use (CAST), other illegal drug use. Socioeconomic position was defined by educational attainment, occupational grade, employment stability and unemployment. Covariates included demographics (age, sex, relationship status, parenthood), family background (parental income, parental tobacco smoking, parental alcohol use), and juvenile characteristics (psychological problems, academic difficulties) measured longitudinally. 35.8% of study participants were regular smokers, 14.3% abused alcohol, 22.6% used cannabis (6.3% had problematic cannabis use) and 4.1% used other illegal drugs. Except for alcohol abuse, substance use rates were systematically higher in individuals with low, rather than intermediate/high, socioeconomic position (age and sex-adjusted ORs from 1.75 for cannabis use to 2.11 for tobacco smoking and 2.44 for problematic cannabis use). In multivariate analyses these socioeconomic disparities were decreased, but remained statistically significant (except for illegal drugs other than cannabis). Tobacco smoking, alcohol, cannabis and polysubstance use are common behaviors among young adults, particularly those experiencing socioeconomic disadvantage. Interventions aiming to decrease substance abuse and reduce socioeconomic inequalities in this area should be implemented early in life.


A new planar BCN lateral heterostructure with outstanding strength and defect-mediated superior semiconducting to metallic properties.
Motivated by the recent synthesis of boron-carbon-nitride (BCN) monolayers with different atomic compositions, we propose a novel planar BCN lateral heterostructure with a combination of graphene and hexagonal boron nitride (h-BN) counterparts. Density functional theory (DFT) and classical molecular dynamics (CMD) simulations are integrated to examine the effects of defects (vacancy and Stone-Wales (SW) defects) and temperature on the physical properties of the BCN heterostructure. We found that structures with SW defects possess the lowest (4.10 eV) and those with vacancy defects possess the highest (7.32 eV) defect formation energy. DFT results show that the computed mechanical properties of the pristine and defective BCN are complementary to those of graphene, and CMD results establish that the size effect on mechanical properties is insignificant. DFT calculations also reveal that the pristine and SW defect filled BCN retain the direct semiconducting electronic characteristics, while C and B mono-vacancies interestingly make it a metallic material due to the slight overlapping of the bands at the Fermi level, and the N mono-vacancy causes a small indirect bandgap (0.08 eV). Besides, the presence of defects significantly changes the work function of BCN due to the lattice rearrangement. Herein, we argue that the defect mediated design of BCN heterostructures can provide new opportunities for plausible applications including energy conversion and storage, and high speed optical and electronic devices due to their semiconducting-metallic functionality and superior mechanical properties.


Ancient DNA reveals lack of postglacial habitat tracking in the arctic fox.
How species respond to an increased availability of habitat, for example at the end of the last glaciation, has been well established. In contrast, little is known about the opposite process, when the amount of habitat decreases. The hypothesis of habitat tracking predicts that species should be able to track both increases and decreases in habitat availability. The alternative hypothesis is that populations outside refugia become extinct during periods of unsuitable climate. To test these hypotheses, we used ancient DNA techniques to examine genetic variation in the arctic fox (Alopex lagopus) through an expansion/contraction cycle. The results show that the arctic fox in midlatitude Europe became extinct at the end of the Pleistocene and did not track the habitat when it shifted to the north. Instead, a high genetic similarity between the extant populations in Scandinavia and Siberia suggests an eastern origin for the Scandinavian population at the end of the last glaciation. These results provide new insights into how species respond to climate change, since they suggest that populations are unable to track decreases in habitat avaliability. This implies that arctic species may be particularly vulnerable to increases in global temperatures.


Functional characterization and expression of a cytosolic iron-superoxide dismutase from cowpea root nodules.
An iron-superoxide dismutase (FeSOD) with an unusual subcellular localization, VuFeSOD, has been purified from cowpea (Vigna unguiculata) nodules and leaves. The enzyme has two identical subunits of 27 kD that are not covalently bound. Comparison of its N-terminal sequence (NVAGINLL) with the cDNA-derived amino acid sequence showed that VuFeSOD is synthesized as a precursor with seven additional amino acids. The mature protein was overexpressed in Escherichia coli, and the recombinant enzyme was used to generate a polyclonal monospecific antibody. Phylogenetic and immunological data demonstrate that there are at least two types of FeSODs in plants. An enzyme homologous to VuFeSOD is present in soybean (Glycine max) and common bean (Phaseolus vulgaris) nodules but not in alfalfa (Medicago sativa) and pea (Pisum sativum) nodules. The latter two species also contain FeSODs in the leaves and nodules, but the enzymes are presumably localized to the chloroplasts and plastids. In contrast, immunoblots of the soluble nodule fraction and immunoelectron microscopy of cryo-processed nodule sections demonstrate that VuFeSOD is localized to the cytosol. Immunoblot analysis showed that the content of VuFeSOD protein increases in senescent nodules with active leghemoglobin degradation, suggesting a direct or indirect (free radical-mediated) role of the released Fe in enzyme induction. Therefore, contrary to the widely held view, FeSODs in plants are not restricted to the chloroplasts and may become an important defensive mechanism against the oxidative stress associated with senescence.


State-of-the-art of non-hormonal methods of contraception: I. Mechanical barrier contraception.
Mechanical barriers, specifically male condoms, command renewed interest and are used today by more people. The worldwide prevalence rate of male condoms was about 6% in 2007 corresponding to 65 million cohabiting couples. The prevalence of female barrier methods, including diaphragms, cervical caps and female condoms has declined to less than 1% of women in North America and in north-west Europe. Even smaller percentages use female barriers elsewhere. First-year life table pregnancy probabilities of mechanical barrier methods range from 4 to 19 per hundred in clinical trials. The male condom is the only proved preventive tool against several sexually transmitted infections (STIs), especially HIV. The effectiveness of the diaphragm and cervical caps in this regard appears limited. Further research is needed to measure the efficacy of female condoms in disease prevention. Sponges are not known to protect against STIs. Because of their ease of use and availability, low short-term costs, relative freedom from side effects, and usefulness in combating STIs, mechanical barrier methods, especially condoms, will continue to be used on a large scale. For our literature search we used personal files, search engines such as Popline, Medline, PubMed and Google, and data bases of WHO, FHI and Cochrane Library.


Counterfeiting in performance- and image-enhancing drugs.
The current drastic escalation in obesity may be contributing to the exponential rise in drugs used for image enhancement. Drugs such as anabolic-androgenic steroids (AAS) are perceived as a viable method of achieving a perfect physique. They are also the most widely abused drugs in sport. The Internet has encouraged the abuse of expensive drugs, particularly human growth hormone (hGH), resulting in increased importation for personal use. The substantial increase in this market has opened up avenues for counterfeiting, estimated as a multi-million pound business. The acute adverse effects from contaminated vials may result in a variety of pathologies including communicable diseases. In 2007, in the UK, a series of intramuscular abscesses, requiring surgical treatment, led us to study samples obtained from the underground market. The analysis of 38 parenteral samples and 19 oral samples of tablets was performed by a World Anti-Doping Agency (WADA) accredited laboratory, in an attempt to establish the extent of available counterfeit products. Fifty-three per cent (20) of the injectable AAS esters and 21% (4) of the oral tablets were counterfeit. Culture and sensitivity revealed the presence of skin commensal organisms, which may have contributed to the development of the abscesses. Users of AAS and hGH for sport, including bodybuilding, are currently risking their health because of counterfeit and poorly controlled products.


Distribution of three congeneric shrub species along an aridity gradient is related to seed germination and seedling emergence.
Environmental tolerance of a species has been shown to correlate positively with its geographical range. On the Ordos Plateau, three Caragana species are distributed sequentially along the precipitation gradient. We hypothesized that this geographical distribution pattern is related to environmental tolerances of the three Caragana species during seed germination and seedling emergence stages. To test this hypothesis, we examined seed germination under different temperature, light and water potentials, and monitored seedling emergence for seeds buried at eight sand depths and given different amounts of water. Seeds of C. korshinskii germinated to high percentages at 5 : 15 to 25 : 35 °C in both light and darkness, while those of C. intermedia and C. microphylla did so only at 15 : 25 and 25 : 35 °C, respectively. Nearly 30 % of the C. korshinskii seeds germinated at -1.4 MPa at 20 and 25 °C, while no seeds of the other two species did so. Under the same treatments, seedling emergence percentages of C. korshinskii were higher than those of the other two species. The rank order of tolerance to drought and sand burial of the three species is C. korshinskii > C. intermedia > C. microphylla. The amount of precipitation and sand burial depth appear to be the main selective forces responsible for the geographical distribution of these species.


Modulated textures with shape structures implied by a closed flow are processed globally.
Radial frequency (RF) patterns, shapes deformed from circular by a sinusoidal modulation of radius, have been used to demonstrate global integration of shape information around a closed path by showing that the modulation depth required to detect shape deformation decreases rapidly as larger segments of the contour are modulated. In this psychophysical study we use a field of Gabor patches to examine integration of shape information in sampled RF patterns either alone or placed within an orientation-noise background and show that orientation-noise can be disregarded during the integration of modulation information. We also examine integration in modulated textures with local orientations that flow parallel or perpendicular to an underlying RF shape-structure. In using modulated textures comprising of elements with a random radial position but with orientation modulated such that it conforms to the local orientation of an RF pattern (RF texture) we demonstrate integration around texture patterns that imply shape. Texture patterns with element orientations locally orthogonal (RFO textures) to those of RF textures, however, exhibit a rate of decrease in modulation threshold, which is substantially reduced. When the textures are scrambled by permuting the polar positions of the patches the rate of decrease in threshold with increasing number of patches modulated in orientation is reduced for RF textures but not RFO textures. Detection of modulation in both scrambled textures is shown to be consistent with the detection of local cues. We conclude that implied closure in a modulated flow appears to be critical for global integration of textures.


Evolutionary history predicts high-impact invasions by herbivorous insects.
A long-standing goal of invasion biology is to identify factors driving highly variable impacts of non-native species. Although hypotheses exist that emphasize the role of evolutionary history (e.g., enemy release hypothesis & defense-free space hypothesis), predicting the impact of non-native herbivorous insects has eluded scientists for over a century.Using a census of all 58 non-native conifer-specialist insects in North America, we quantified the contribution of over 25 factors that could affect the impact they have on their novel hosts, including insect traits (fecundity, voltinism, native range, etc.), host traits (shade tolerance, growth rate, wood density, etc.), and evolutionary relationships (between native and novel hosts and insects).We discovered that divergence times between native and novel hosts, the shade and drought tolerance of the novel host, and the presence of a coevolved congener on a shared host, were more predictive of impact than the traits of the invading insect. These factors built upon each other to strengthen our ability to predict the risk of a non-native insect becoming invasive. This research is the first to empirically support historically assumed hypotheses about the importance of evolutionary history as a major driver of impact of non-native herbivorous insects.Our novel, integrated model predicts whether a non-native insect not yet present in North America will have a one in 6.5 to a one in 2,858 chance of causing widespread mortality of a conifer species if established (R 2 = 0.91) Synthesis and applications. With this advancement, the risk to other conifer host species and regions can be assessed, and regulatory and pest management efforts can be more efficiently prioritized.


Biology of cancer and aging: a complex association with cellular senescence.
Over the last 50 years, major improvements have been made in our understanding of the driving forces, both parallel and opposing, that lead to aging and cancer. Many theories on aging first proposed in the 1950s, including those associated with telomere biology, senescence, and adult stem-cell regulation, have since gained support from cumulative experimental evidence. These views suggest that the accumulation of mutations might be a common driver of both aging and cancer. Moreover, some tumor suppressor pathways lead to aging in line with the theory of antagonist pleiotropy. According to the evolutionary-selected disposable soma theory, aging should affect primarily somatic cells. At the cellular level, both intrinsic and extrinsic pathways regulate aging and senescence. However, increasing lines of evidence support the hypothesis that these driving forces might be regulated by evolutionary-conserved pathways that modulate energy balance. According to the hyperfunction theory, aging is a quasi-program favoring both age-related diseases and cancer that could be inhibited by the regulation of longevity pathways. This review summarizes these hypotheses, as well as the experimental data that have accumulated over the last 60 years linking aging and cancer.


Physiological correlates and emotional specificity of human piloerection.
Piloerection is known as an indicator of strong emotional experiences. However, little is known about the physiological and emotional specificity of this psychophysiological response. In the presented study, piloerection was elicited by audio stimuli taken from music and film episodes. The physiological response accompanying the incidence of piloerection was recorded with respect to electrodermal, cardiovascular and respiratory measures and compared to a matched control condition. The employment of an optical recording system allowed for a direct and objective assessment of visible piloerection. The occurrence of piloerection was primarily accompanied by an increase of phasic electrodermal activity and increased respiration depth as compared to a matched control condition. This physiological response pattern is discussed in the context of dominant theories of human piloerection. Consideration of all available evidence suggests that emotional piloerection represents a valuable indicator of the state of being moved or touched.


Diagnostic Utility of Pleural Fluid Cell Block versus Pleural Biopsy Collected by Flex-Rigid Pleuroscopy for Malignant Pleural Disease: A Single Center Retrospective Analysis.
Some trials recently demonstrated the benefit of targeted treatment for malignant disease; therefore, adequate tissues are needed to detect the targeted gene. Pleural biopsy using flex-rigid pleuroscopy and pleural effusion cell block analysis are both useful for diagnosis of malignancy and obtaining adequate samples. The purpose of our study was to compare the diagnostic utility between the two methods among patients with malignant pleural disease with effusion. Data from patients who underwent flex-rigid pleuroscopy for diagnosis of pleural effusion suspicious for malignancy at the National Cancer Center Hospital, Japan between April 2011 and June 2014 were retrospectively reviewed. All procedures were performed under local anesthesia. At least 150 mL of pleural fluid was collected by pleuroscopy, followed by pleural biopsies from the abnormal site. Thirty-five patients who were finally diagnosed as malignant pleural disease were included in this study. Final diagnoses of malignancy were 24 adenocarcinoma, 1 combined adeno-small cell carcinoma, and 7 malignant pleural mesothelioma (MPM), and 3 metastatic breast cancer. The diagnostic yield was significantly higher by pleural biopsy than by cell block [94.2% (33/35) vs. 71.4% (25/35); p = 0.008]. All patients with positive results on cell block also had positive results on pleural biopsy. Eight patients with negative results on cell block had positive results on pleural biopsy (lung adenocarcinoma in 4, sarcomatoid MPM in 3, and metastatic breast cancer in 1). Two patients with negative results on both cell block and pleural biopsy were diagnosed was sarcomatoid MPM by computed tomography-guided needle biopsy and epithelioid MPM by autopsy. Pleural biopsy using flex-rigid pleuroscopy was efficient in the diagnosis of malignant pleural diseases. Flex-rigid pleuroscopy with pleural biopsy and pleural effusion cell block analysis should be considered as the initial diagnostic approach for malignant pleural diseases presenting with effusion.


Gender, Cultural Influences, and Coping with Musculoskeletal Pain at Work: The Experience of Malaysian Female Office Workers.
Purpose Workers with musculoskeletal pain (MSP) often continue to work despite their condition. Understanding the factors that enable them to remain at work provides insights into the development of appropriate workplace accommodations. This qualitative study aims to explore the strategies utilised by female Malaysian office workers with MSP to maintain productive employment. Methods A qualitative approach using thematic analysis was used. Individual semi-structured interviews were conducted with 13 female Malaysian office workers with MSP. Initial codes were identified and refined through iterative discussion to further develop the emerging codes and modify the coding framework. A further stage of coding was undertaken to eliminate redundant codes and establish analytic connections between distinct themes. Results Two major themes were identified: managing the demands of work and maintaining employment with persistent musculoskeletal pain. Participants reported developing strategies to assist them to remain at work, but most focused on individually initiated adaptations or peer support, rather than systemic changes to work systems or practices. A combination of the patriarchal and hierarchical cultural occupational context emerged as a critical factor in the finding of individual or peer based adaptations rather than organizational accommodations. Conclusions It is recommended that supervisors be educated in the benefits of maintaining and retaining employees with MSP, and encouraged to challenge cultural norms and develop appropriate flexible workplace accommodations through consultation and negotiation with these workers.


Physical-Biological Coupling in the Western South China Sea: The Response of Phytoplankton Community to a Mesoscale Cyclonic Eddy.
It is widely recognized that the mesoscale eddies play an important part in the biogeochemical cycle in ocean ecosystem, especially in the oligotrophic tropical zones. So here a heterogeneous cyclonic eddy in its flourishing stage was detected using remote sensing and in situ biogeochemical observation in the western South China Sea (SCS) in early September, 2007. The high-performance liquid chromatography method was used to identify the photosynthetic pigments. And the CHEMical TAXonomy (CHEMTAX) was applied to calculate the contribution of nine phytoplankton groups to the total chlorophyll a (TChl a) biomass. The deep chlorophyll a maximum layer (DCML) was raised to form a dome structure in the eddy center while there was no distinct enhancement for TChl a biomass. The integrated TChl a concentration in the upper 100 m water column was also constant from the eddy center to the surrounding water outside the eddy. However the TChl a biomass in the surface layer (at 5 m) in the eddy center was promoted 2.6-fold compared to the biomass outside the eddy (p < 0.001). Thus, the slight enhancement of TChl a biomass of euphotic zone integration within the eddy was mainly from the phytoplankton in the upper mixed zone rather than the DCML. The phytoplankton community was primarily contributed by diatoms, prasinophytes, and Synechococcus at the DCML within the eddy, while less was contributed by haptophytes_8 and Prochlorococcus. The TChl a biomass for most of the phytoplankton groups increased at the surface layer in the eddy center under the effect of nutrient pumping. The doming isopycnal within the eddy supplied nutrients gently into the upper mixing layer, and there was remarkable enhancement in phytoplankton biomass at the surface layer with 10.5% TChl a biomass of water column in eddy center and 3.7% at reference stations. So the slight increasing in the water column integrated phytoplankton biomass might be attributed to the stimulated phytoplankton biomass at the surface layer.


Dose-dependent effects of mandibular advancement on upper airway collapsibility and muscle function in obstructive sleep apnea.
Mandibular advancement splints (MAS) are the leading treatment alternative to continuous positive airway pressure (CPAP) for obstructive sleep apnea (OSA). However, not all patients experience clinical benefit and treatment prediction remains challenging. Understanding the effects of mandibular advancement on pharyngeal collapsibility and muscle function may provide valuable information on the mechanisms of MAS, and thereby help to develop novel approaches for patient selection. Thus, we aimed to determine dose-dependent effects of mandibular advancement on pharyngeal collapsibility and muscle function concurrently in OSA patients undergoing MAS therapy. Twelve (11 male) MAS-naïve patients underwent a detailed physiology sleep study (polysomnography) to quantify pharyngeal collapsibility (PCRIT), pharyngeal muscle responsiveness to negative pharyngeal pressure (via genioglossus intramuscular electromyography and an epiglottic pressure sensor) and effectiveness to restore airflow and minute ventilation (Vi) after 1-minute transient CPAP reductions (induced airflow-limitation) at three mandibular advancement positions: 0% (habitual bite), 50% and 100% of the maximum comfortable mandibular advancement. Standard clinical polysomnography after MAS therapy optimization was performed to determine treatment outcome. Overall, participants were obese with severe OSA (mean ± SD: BMI = 31 ± 4 kg/m2, apnea-hypopnea index [AHI] = 33 ± 14 events/hour). PCRIT decreased with mandibular advancement in a dose-dependent manner (1.8 ± 3.9 vs. -0.9 ± 2.9 vs. -4.0 ± 3.6 cmH2O; p < 0.001). There was no systematic change in genioglossus muscle responsiveness (p = 0.09) or effectiveness to restore peak airflow (p = 0.4) or Vi (p = 0.7) with mandibular advancement. Mandibular advancement reduces pharyngeal collapsibility in a dose-dependent manner without systematically changing genioglossus muscle function in a predominantly obese and severe OSA population. This indicates that the primary mode of action of MAS therapy is via improvement in passive pharyngeal anatomy.


A critical appraisal of propensity-score matching in the medical literature between 1996 and 2003.
Propensity-score methods are increasingly being used to reduce the impact of treatment-selection bias in the estimation of treatment effects using observational data. Commonly used propensity-score methods include covariate adjustment using the propensity score, stratification on the propensity score, and propensity-score matching. Empirical and theoretical research has demonstrated that matching on the propensity score eliminates a greater proportion of baseline differences between treated and untreated subjects than does stratification on the propensity score. However, the analysis of propensity-score-matched samples requires statistical methods appropriate for matched-pairs data. We critically evaluated 47 articles that were published between 1996 and 2003 in the medical literature and that employed propensity-score matching. We found that only two of the articles reported the balance of baseline characteristics between treated and untreated subjects in the matched sample and used correct statistical methods to assess the degree of imbalance. Thirteen (28 per cent) of the articles explicitly used statistical methods appropriate for the analysis of matched data when estimating the treatment effect and its statistical significance. Common errors included using the log-rank test to compare Kaplan-Meier survival curves in the matched sample, using Cox regression, logistic regression, chi-squared tests, t-tests, and Wilcoxon rank sum tests in the matched sample, thereby failing to account for the matched nature of the data. We provide guidelines for the analysis and reporting of studies that employ propensity-score matching.


Absolute standardless calibration of photodetectors based on quantum two-photon fields.
A new method of absolute calibration of photodetectors based on a nonclassical effect in nonlinear optics is discussed. The combined influence of a monochromatic flux of pump photons and quantum vacuum noise on a nonlinear crystal with no center of symmetry results in the appearance of rigorously correlated pairs of photons with continuous spectral distribution in the spontaneous parametric scattering of light (spontaneous parametric downconversion) process. The presence of an optical field in a broad spectral range created by the two-photon states (biphotons) makes it possible to develop a new method of measuring the spectral distribution of the absolute value of the quantum efficiency of photodetectors, both in photon counting and in analog regimes, that does not use any calibrated standard light sources (étalons). The feasibility of the method is demonstrated on different types of photomultiplier tube.


Hospital characteristics associated with increased conversion rates among organ donors in New England.
It is unknown whether hospital characteristics affect institutional performance with regard to organ donation. We sought to determine which hospital- and patient-level characteristics are associated with high organ donor conversion rates after brain death (DBD). Data were extracted from the regional Organ Procurement Organization (2011-2014) and other sources. Hospitals were stratified into high-conversion hospitals (HCH; upper-tertile) and low-conversion hospitals (LCH; lower-tertile) according to conversion rates. Hospital- and patient-characteristics were compared between groups. There were 564 potential DBD donors in 27 hospitals. Conversion rates differed between hospitals in different states (p < 0.001). HCH were more likely to be small (median bed size 194 vs. 337; p = 0.024), non-teaching hospitals (40% vs. 88%; p = 0.025), non-trauma center (30% vs. 77%; p = 0.040). Potential donors differed between HCH and LCH in race (p < 0.01) and mechanism of injury/disease process (p < 0.01). There is significant variation between hospitals in terms of organ donor conversion rates. This suggests that there is a pool of potential donors in large specialized hospitals that are not successfully converted to DBD.


Moral Distress: Identification Among Inpatient Oncology Nurses in an Academic Health System.
Moral distress occurs when clinicians know the morally correct action to take but are unable to follow through because of internal and external constraints. It is associated with negative consequences, such as burnout, decreased job satisfaction, avoidance, and turnover. The purpose of this study was to describe the frequency and level of moral distress among inpatient oncology nurses and to identify possible associations among nurses' demographic characteristics, work experience, and moral distress levels. Ninety-three inpatient oncology nurses from a large academic health system completed the Moral Distress Scale-Revised (MDS-R). Additional questions included intent to leave and requests for changes in patient assignments because of moral distress. Years as a nurse, changing or considering changing patient assignments, and changing care provided to a patient because of moral distress were statistically significantly associated with higher MDS-R scores. Participants reported using palliative care consultations, pastoral care, and social work to assist with their moral distress.


Scoring Cercospora Leaf Spot on Sugar Beet: Comparison of UGV and UAV Phenotyping Systems.
Selection of sugar beet (Beta vulgaris L.) cultivars that are resistant to Cercospora Leaf Spot (CLS) disease is critical to increase yield. Such selection requires an automatic, fast, and objective method to assess CLS severity on thousands of cultivars in the field. For this purpose, we compare the use of submillimeter scale RGB imagery acquired from an Unmanned Ground Vehicle (UGV) under active illumination and centimeter scale multispectral imagery acquired from an Unmanned Aerial Vehicle (UAV) under passive illumination. Several variables are extracted from the images (spot density and spot size for UGV, green fraction for UGV and UAV) and related to visual scores assessed by an expert. Results show that spot density and green fraction are critical variables to assess low and high CLS severities, respectively, which emphasizes the importance of having submillimeter images to early detect CLS in field conditions. Genotype sensitivity to CLS can then be accurately retrieved based on time integrals of UGV- and UAV-derived scores. While UGV shows the best estimation performance, UAV can show accurate estimates of cultivar sensitivity if the data are properly acquired. Advantages and limitations of UGV, UAV, and visual scoring methods are finally discussed in the perspective of high-throughput phenotyping.


Anatomy of the lamprey ear: morphological evidence for occurrence of horizontal semicircular ducts in the labyrinth of Petromyzon marinus.
In jawed (gnathostome) vertebrates, the inner ears have three semicircular canals arranged orthogonally in the three Cartesian planes: one horizontal (lateral) and two vertical canals. They function as detectors for angular acceleration in their respective planes. Living jawless craniates, cyclostomes (hagfish and lamprey) and their fossil records seemingly lack a lateral horizontal canal. The jawless vertebrate hagfish inner ear is described as a torus or doughnut, having one vertical canal, and the jawless vertebrate lamprey having two. These observations on the anatomy of the cyclostome (jawless vertebrate) inner ear have been unchallenged for over a century, and the question of how these jawless vertebrates perceive angular acceleration in the yaw (horizontal) planes has remained open. To provide an answer to this open question we reevaluated the anatomy of the inner ear in the lamprey, using stereoscopic dissection and scanning electron microscopy. The present study reveals a novel observation: the lamprey has two horizontal semicircular ducts in each labyrinth. Furthermore, the horizontal ducts in the lamprey, in contrast to those of jawed vertebrates, are located on the medial surface in the labyrinth rather than on the lateral surface. Our data on the lamprey horizontal duct suggest that the appearance of the horizontal canal characteristic of gnathostomes (lateral) and lampreys (medial) are mutually exclusive and indicate a parallel evolution of both systems, one in cyclostomes and one in gnathostome ancestors.


Factors associated with potential medication-herb/natural product interactions in a rural community.
Use of both conventional medicines and herbs/natural products are increasing in the United States. Consequently, individuals are more likely to be exposed to potentially harmful interactions between these products. To examine the use of both herbs/natural products and conventional medications in a rural community, examine the prevalence of potential interactions between herbs/natural products and conventional medications, and identify factors associated with exposure to such interactions. Population-based epidemiological study. Data for this paper were collected between 1999 and 2004 as part of the Johnston County Osteoarthritis Project. Limited to civilian, noninstitutionalized, white or African American residents, aged 45 years or older, of Johnston County, North Carolina. Data used in this paper are from 2523 individuals who completed face-to-face interviews. Prevalence of herb/natural product use and exposure to potential interactions between these products and conventional medications. Nineteen percent (n=488) of participants used at least 1 herb/natural product. Among those who used both conventional medications and herbs/natural products, more than 1 in 5 (97 [21.9%]) were using a combination of products associated with a potential interaction. Odds of exposure to a potential interaction were lower among people who had health insurance and increased with the number of products used. Many people are exposed to potential interactions between herbs/natural products and conventional medications. Research is needed to better understand the effect such interactions may have on patient care.


Seroprevalence of Toxoplasma gondii and direct genotyping using minisequencing in free-range pigs in Burkina Faso.
Swine are a major source of meat for humans. As such, they can play an important role in the epidemiology of human toxoplasmosis. Therefore, we performed an epidemiological study to determine the prevalence and genotypes of Toxoplasma gondii in Burkina Fasan swine. The prevalence of T. gondii infection was evaluated in a 3-month prospective study at the slaughterhouse of Bobo-Dioulasso, Burkina Faso. Anti-Toxoplasma IgG titers were determined on meat juices from pig diaphragms using a commercially available ELISA assay. The DNA was extracted from 25mg of heart biopsies of seropositive animals (IgG ≥50% of the control) and the presence of T. gondii DNA was detected using a quantitative PCR assay. Genotyping was performed directly on DNA from PCR-positive biopsies using high-resolution melting and minisequencing analyses of the repeated B1 gene. The prevalence of carcasses positive for anti-Toxoplasma IgG was 29% (87/300) with no difference according to sex and age in contrast to the village of origin (p=0.018). Of the 87 seropositive animals, two were PCR positive (parasitic load at 64 and 128 parasites/mg of heart biopsy). Two new genotypes belonging to Type II and Type III and different from the genotypes previously described using minisequencing were identified. Our study provides the first T. gondii seroprevalence data in Burkina Fasan swine. In addition, this direct typing method suggests diversity of the T. gondii genotypes circulating in domestic animals in Burkina Faso. This needs to be confirmed on a wider sampling of subjects.


Support Needs Approach for Patients (SNAP) tool: a validation study.
Patient-identified need is key to delivering holistic, supportive, person-centred care, but we lack tools enabling patients to express what they need to manage life with a long-term condition. The Support Needs Approach for Patients (SNAP) tool was developed to enable patients with advanced chronic obstructive pulmonary disease (COPD) identify and express their unmet support needs to healthcare professionals (HCPs), but its validity is unknown. This study aimed to establish face, content and criterion validity of the SNAP tool. Two-stage mixed-methods study involving patients with advanced COPD and their carers. Stage 1: Face and content validity assessed though focus groups involving patients and carers considering appropriateness, relevance and completeness of the SNAP tool. Data were analysed using conventional content analysis. Stage 2: Content and criterion validity assessed in a postal survey through patient self-completion of the SNAP tool and disease impact measures (Chronic Respiratory Questionnaire, COPD Assessment Test, and Hospital Anxiety and Depression Scale). Content validity assessed using summary statistics; criterion validity via correlations between tool items and impact measures. Two hundred and forty patients and carers participated. Stage 1 patient and informal carer participants were recruited from two primary care practices and Stage 2 patients from 28 practices. Participating practices located in the East of England were recruited via the NIHR Clinical Research Network: Eastern. Patients and carers found the tool patient-friendly and comprehensive, with potential clinical utility. No tool items were redundant. Clear correlations were found between tool items and the majority of items in the impact measures. The SNAP tool has good face, content and criterion validity. It has potential to support the delivery of holistic, supportive, person-centred care by enabling patients to identify and express their unmet support needs to HCPs.


Identification of a novel circovirus in Australian ravens (Corvus coronoides) with feather disease.
The complete genome of a novel Circovirus isolated from an Australian raven (Corvus coronoides) with feather lesions similar to those that occur in psittacine beak and feather disease is reported. Degenerate polymerase chain reaction primers were designed to amplify and sequence novel Circovirus DNA from affected feathers. Sequence analysis indicated that the tentatively named raven circovirus (RaCV) was 1898 nucleotides in size with two major open reading frames synonymous with other avian circoviruses, ORF C1 and ORF V1, likely to encode a putative capsid protein (Cap) and replicase-associated protein (Rep), respectively. In common with other circoviruses was the conservation of several nucleotide structures and amino acid motifs implicated in virus replication. Comparison with other members of the Circoviridae demonstrated that RaCV shares the greatest sequence homology with canary circovirus (CaCV) and pigeon circovirus (PiCV) and was more distantly related to the beak and feather disease virus, goose circovirus, duck circovirus and the two porcine circoviruses, PCV1 and PCV2. Phylogenetic analysis of the genome and the putative Cap and Rep proteins provided further evidence of the close relationship of RaCV with CaCV and PiCV.


Redo surgery in ascending aorta and aortic arch.
Reinterventions following previous ascending aorta and aortic arch repair are uncommon, but technically challenging and often burdened with high morbidity and mortality. The aim of this article is to present a single-center experience in the treatment of this complex pathology, using different surgical approaches. Between 1999 and 2014, 17 patients (14 males, mean age 73±16 years) underwent ascending aorta and aortic arch redo surgery at our Department. A prospectively maintained database including thoracic aortic procedures was reviewed retrospectively to collect data on redo patients. In 13 cases the index procedure was an endovascular or hybrid procedure on the aortic arch performed at our Department, for an in-house reintervention rate of 6.9% (13/188). In 10 cases the cause of reintervention was stent-graft distal migration, treated by means of endovascular relining in all cases, associated with adjunctive supra-aortic trunks debranching via sternotomy in 6 cases. In 5 cases the cause of reintervention was retrograde ascending aortic dissection, in 1 case ascending aortic anastomotic pseudoaneurysm following supra-aortic trunk debranching, and in 1 case mediastinitis following implantation of an endovascular plug previously used to treat an ascending aortic pseudoaneurysm. In these last 7 cases, all patients were treated by means of ascending and arch surgical replacement under deep hypothermic circulatory arrest (DHCA) and antegrade cerebral perfusion (ACP). No 30-day mortality was observed. Major perioperative morbidity included 1 paraplegia, 1 minor stroke, 1 bleeding requiring reintervention, and 3 cases of respiratory failure requiring prolonged intubation (2) or tracheostomy (1). In our experience, incidence of serious complications requiring reinterventions following ascending aorta or aortic arch repair is not negligible. Redo surgery in ascending aorta and aortic arch is feasible in high-volume and experienced centers, as it often requires hybrid repair via midline sternotomy, or surgical replacement under DHCA and ACP.


A 57-Year-Old Man With Subacute Progressive Hemoptysis and Fevers.
A 57-year-old man was admitted for 1 month of accelerating hemoptysis and hematemesis. Two weeks earlier, he first presented with fevers and hemoptysis of 2 weeks' duration and was diagnosed with community-acquired pneumonia treated with 5 days of ceftriaxone and azithromycin. He improved and was discharged, but his hemoptysis recurred 1 day after discharge and progressed over 9 days, leading to the present admission. He endorsed an 5-kg weight loss, daily fevers up to 39.4°C, and night sweats since discharge. His medical history was significant for peptic ulcer disease complicated by a perforated gastric ulcer 30 years ago, type 2 diabetes, and Barrett esophagus with recent normal upper endoscopy. The patient had coarctation of the aorta repaired 35 years ago. The patient takes aspirin, atorvastatin, and pantoprazole. He emigrated from Mexico 10 years before presentation and lives in Texas with his family. He returns to Mexico several times per year, most recently 2 days before admission. He works at a supermarket. He does not smoke, drink, or use illicit drugs. He denied sick contacts, pets, or incarceration.


Pannexin 3 regulates proliferation and differentiation of odontoblasts via its hemichannel activities.
Highly coordinated regulation of cell proliferation and differentiation contributes to the formation of functionally shaped and sized teeth; however, the mechanism underlying the switch from cell cycle exit to cell differentiation during odontogenesis is poorly understood. Recently, we identified pannexin 3 (Panx3) as a member of the pannexin gap junction protein family from tooth germs. The expression of Panx3 was predominately localized in preodontoblasts that arise from dental papilla cells and can differentiate into dentin-secreting odontoblasts. Panx3 also co-localized with p21, a cyclin-dependent kinase inhibitor protein, in preodontoblasts. Panx3 was expressed in primary dental mesenchymal cells and in the mDP dental mesenchymal cell line. Both Panx3 and p21 were induced during the differentiation of mDP cells. Overexpression of Panx3 in mDP cells reduced cell proliferation via up-regulation of p21, but not of p27, and promoted the Bone morphogenetic protein 2 (BMP2)-induced phosphorylation of Smad1/5/8 and the expression of dentin sialophosphoprotein (Dspp), a marker of differentiated odontoblasts. Furthermore, Panx3 released intracellular ATP into the extracellular space through its hemichannel and induced the phosphorylation of AMP-activated protein kinase (AMPK). 5-Aminoimidazole-4-carboxamide-ribonucleoside (AICAR), an activator of AMPK, reduced mDP cell proliferation and induced p21 expression. Conversely, knockdown of endogenous Panx3 by siRNA inhibited AMPK phosphorylation, p21 expression, and the phosphorylation of Smad1/5/8 even in the presence of BMP2. Taken together, our results suggest that Panx3 modulates intracellular ATP levels, resulting in the inhibition of odontoblast proliferation through the AMPK/p21 signaling pathway and promotion of cell differentiation by the BMP/Smad signaling pathway.


A descriptive survey of cancer helplines in the United Kingdom: Who they are, the services offered, and the accessibility of those services.
There are more than 1500 UK health helplines in operation, yet we have scant knowledge about the resources in place to support the seeking and delivering of cancer-related telephone help and support. This research aimed to identify and describe cancer and cancer-related helpline service provision: the number of helplines available, the variety of services provided, and the accessibility of those services. This study used online national questionnaire survey sent to 95 cancer and cancer-related helplines in the United Kingdom. A total of 69 (73%) of 95 surveyed cancer and cancer-related helplines completed the survey. Most helplines/organizations were registered charities, supported by donations; 73.5% of helplines had national coverage. Most helplines served all age-groups, ethnic groups, and men and women. Only 13.4% had a number that was free from landlines and most mobile networks, and 56.6% could only be contacted during working hours. More than 50% of helplines reported no provisions for callers with additional needs, and 55% had no clinical staff available to callers. Ongoing support and training for helpline staff was available but variable. Although cancer helplines in the United Kingdom offer reasonably broad coverage across the country, there are still potential barriers to accessibility. There are also opportunities to optimize the training of staff/volunteers across the sector. There are further prospects for helplines to enhance services and sustain appropriate and realistic quality standards.


Miliary mesothelioma: a new clinical and radiological presentation in mesothelioma patients with prolonged survival after trimodality therapy.
Malignant pleural mesothelioma is usually a fatal disease and is considered a locally aggressive tumor. Consequently, distant metastases are very rare and a diffuse involvement of the lung is seldom reported. However, due to more efficient chemotherapy protocols and aggressive management strategies including induction chemotherapy followed by extrapleural pneumonectomy and adjuvant high-dose hemithoracic radiation therapy, so called trimodality therapy, survival is prolonged in selected patients. Therefore, new presentations of the disease are appearing with new diagnostic and therapeutic challenges. Herein, we report two cases of treated mesothelioma patients who developed a miliary mesothelioma in the remaining lung 36 and 41 months after undergoing multimodal therapy. Diagnostic assessment and therapeutic strategy are discussed taking into account the different evolutions of each patient.


Too sick to work, too healthy to qualify: a cross-country analysis of the effect of changes to disability benefits.
Denmark and Sweden have implemented reforms that narrowed disability benefit eligibility criteria. Such reforms in combination with increasing work demands create a pincer movement where in particular those with moderate health problems might be unable to comply with work demands, but still not qualify for permanent disability benefits, ending up with temporary means-tested or no benefits. This paper examines whether this actually happened before and after the reforms. The Survey of Health, Ageing and Retirement in Europe (SHARE) study waves 1-2 and 4-6 in Denmark and Sweden for the age group 50-59 years (N=5384) was used to analyse changes in employment rates and benefits among people with different levels of health before, during and after disability benefit reforms. Interaction between time and health in relation to employment versus permanent or temporary benefits was used as a criterion for whether our hypotheses was confirmed. Overall, employment rates have increased in the age group, but only among the healthy. The OR for receiving temporary or no benefits increased from 1.25 (95% CI: 0.81 to 1.90) before to 1.73 (95% CI: 1.14 to 2.61) after policy reforms for the 29% with moderate health problems and from 2.89 (95% CI: 1.66 to 5.03) to 6.71 (95% CI: 3.94 to 11.42) among the 11% with severe health problems. The interaction between time and health was statistically significant (p<0.001). People with impaired health and workability are forced into a life with temporary means-tested or no benefits when pressed by rising work demands and stricter disability benefit eligibility criteria.


White cells facilitate opposite- and same-sex mating of opaque cells in Candida albicans.
Modes of sexual reproduction in eukaryotic organisms are extremely diverse. The human fungal pathogen Candida albicans undergoes a phenotypic switch from the white to the opaque phase in order to become mating-competent. In this study, we report that functionally- and morphologically-differentiated white and opaque cells show a coordinated behavior during mating. Although white cells are mating-incompetent, they can produce sexual pheromones when treated with pheromones of the opposite mating type or by physically interacting with opaque cells of the opposite mating type. In a co-culture system, pheromones released by white cells induce opaque cells to form mating projections, and facilitate both opposite- and same-sex mating of opaque cells. Deletion of genes encoding the pheromone precursor proteins and inactivation of the pheromone response signaling pathway (Ste2-MAPK-Cph1) impair the promoting role of white cells (MTLa) in the sexual mating of opaque cells. White and opaque cells communicate via a paracrine pheromone signaling system, creating an environment conducive to sexual mating. This coordination between the two different cell types may be a trade-off strategy between sexual and asexual lifestyles in C. albicans.


Semantic categorization precedes affective evaluation of visual scenes.
We compared the primacy of affective versus semantic categorization by using forced-choice saccadic and manual response tasks. Participants viewed paired emotional and neutral scenes involving humans or animals flashed rapidly in extrafoveal vision. Participants were instructed to categorize the targets by saccading toward the location occupied by a predefined target scene. The affective task involved saccading toward an unpleasant or pleasant scene, and the semantic task involved saccading toward a scene containing an animal. Both affective and semantic target scenes could be reliably categorized in less than 220 ms, but semantic categorization was always faster than affective categorization. This finding was replicated with singly, foveally presented scenes and manual responses. In comparison with foveal presentation, extrafoveal presentation slowed down the categorization of affective targets more than that of semantic targets. Exposure threshold for accurate categorization was lower for semantic information than for affective information. Superordinate-, basic-, and subordinate-level semantic categorizations were faster than affective evaluation. We conclude that affective analysis of scenes cannot bypass object recognition. Rather, semantic categorization precedes and is required for affective evaluation.


Association of antral mucosal levels of interleukin 8 and reactive oxygen radicals in patients infected with Helicobacter pylori.
1. Helicobacter pylori infection is characterized by an infiltration of neutrophils in the gastric mucosa. Neutrophil activation is an important source of reactive oxygen radicals, which cause tissue damage. Studies have shown that in Helicobacter pylori-infected patients there is increased mucosal production of interleukin 8. However, the role of interleukin 8 in the Helicobacter pylori-related inflammatory process and its relationship with reactive oxygen radicals remains to be clarified. The aims of this study were to investigate if there is any association between antral mucosal levels of interleukin 8 and reactive oxygen radicals and their relationship to gastric antral inflammation. 2. Fifty-two patients referred for endoscopy were recruited into the study. Gastric antral biopsies were taken for histology, culture and measurement of interleukin 8 and chemiluminescence (measuring reactive oxygen radicals). Interleukin 8 was measured by ELISA and the result expressed as pg/mg biopsy. Luminol-enhanced chemiluminescence was measured as mV min-1 mg-1 biopsy. Antral inflammation was assessed by a pathologist in a blinded fashion. 3. Antral mucosal levels of interleukin 8 and reactive oxygen radicals were significantly higher in Helicobacter pylori-colonized mucosa than in Helicobacter pylori-negative mucosa. After the eradication of Helicobacter pylori in patients with duodenal ulcer the median values (ranges) of interleukin 8 and reactive oxygen radicals fell from 1.21 (0.10-2.40) to 0.65 (0.00-1.60) and from 110.0 (10.0-959.0) to 14.5 (0.0-85.0) respectively. There was a positive correlation between interleukin 8 concentration and chemiluminescence response in the antral mucosa (r = 0.72). A higher interleukin 8 concentration was associated with greater neutrophil infiltration (r = 0.72) and mononuclear cell infiltration (r = 0.55); the magnitude of the chemiluminescence response was also positively associated with neutrophil (r = 0.77) and mononuclear cell infiltration (r = 0.59). 4. Interleukin 8 concentration is associated with an infiltration of neutrophils and mononuclear cells and is correlated with the production of reactive oxygen radicals in antral gastric mucosa infected with Helicobacter pylori. These findings suggest that interleukin 8 may be important in attracting and activating phagocytes to release reactive oxygen radicals, thereby causing mucosal damage.