TH1 and TH2 cell antigen receptors in experimental leishmaniasis.
The complexity and chronicity of parasitic infections have obscured the identification of biologically relevant antigens. Analysis of the T cell receptor repertoire used by mice infected with Leishmania major revealed the expansion of a restricted population of CD4+ cells. These cells expressed the V alpha 8-J alpha TA72, V beta 4 heterodimer in both progressive infection and protective immunity and across several major histocompatibility haplotypes. Thus, the same immunodominant parasite epitope drives the disparate outcomes of this infectious process, suggesting that candidate vaccine antigens selected by screening of immune individuals may be capable of exacerbating disease in genetically susceptible individuals.


Suppressive effects of coffee on the SOS responses induced by UV and chemical mutagens.
SOS-inducing activity of UV or chemical mutagens (AF-2, 4NQO and MNNG) was strongly suppressed by instant coffee in Salmonella typhimurium TA1535/pSK1002. As decaffeinated instant coffee showed a similarly strong suppressive effect, it would seem that caffeine, a known inhibitor of SOS responses, is not responsible for the effect observed. The suppression was also shown by freshly brewed coffee extracts. However, the suppression was absent in green coffee-bean extracts. These results suggest that coffee contains some substance(s) which, apart from caffeine, suppresses SOS-inducing activity of UV or chemical mutagens and that the suppressive substance(s) are produced by roasting coffee beans.


Herpes simplex virus triggers and then disarms a host antiviral response.
Virus infection induces an antiviral response that is predominantly associated with the synthesis and secretion of soluble interferon. Here, we report that herpes simplex virus type 1 virions induce an interferon-independent antiviral state in human embryonic lung cells that prevents plaquing of a variety of viruses. Microarray analysis of 19,000 human expressed sequence tags revealed induction of a limited set of host genes, the majority of which are also induced by interferon. Genes implicated in controlling the intracellular spread of virus and eliminating virally infected cells were among those induced. Induction of the cellular response occurred in the absence of de novo cellular protein synthesis and required viral penetration. In addition, this response was only seen when viral gene expression was inhibited, suggesting that a newly synthesized viral protein(s) may function as an inhibitor of this response.


Apraxia: a review.
Praxic functions are frequently altered following brain lesion, giving rise to apraxia - a complex pattern of impairments that is difficult to assess or interpret. In this chapter, we review the current taxonomies of apraxia and related cognitive and neuropsychological models. We also address the questions of the neuroanatomical correlates of apraxia, the relation between apraxia and aphasia and the analysis of apraxic errors. We provide a possible explanation for the difficulties encountered in investigating apraxia and also several approaches to overcome them, such as systematic investigation and modeling studies. Finally, we argue for a multidisciplinary approach. For example, apraxia should be studied in consideration with and could contribute to other fields such as normal motor control, neuroimaging and neurophysiology.


Modification of acoustic startle by microwave pulses in the rat: a preliminary report.
Single, 1.25-GHz microwave pulses of 0.8- to 1.0-microseconds duration were presented to each of four rats 100 ms before presentation of a startle-inducing acoustic stimulus. This sequential pairing of microwave pulse and acoustic stimulus was found to modify the startle response. At an energy dose to the head of 22-43 mJ/kg per pulse (peak SAR, 23-48 kW/kg), the mean latency to the startle response was longer and the mean amplitude of the response was smaller with respect to control responses that occurred to acoustic stimuli alone. However, at a higher energy dose per microwave pulse in the range of 59-107 mJ/kg (peak SAR, 63-111 kW/kg), the mean latency and amplitude of the startle response were not statistically different from the respective means of control responses.


Promoting optimal development: screening for behavioral and emotional problems.
By current estimates, at any given time, approximately 11% to 20% of children in the United States have a behavioral or emotional disorder, as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Between 37% and 39% of children will have a behavioral or emotional disorder diagnosed by 16 years of age, regardless of geographic location in the United States. Behavioral and emotional problems and concerns in children and adolescents are not being reliably identified or treated in the US health system. This clinical report focuses on the need to increase behavioral screening and offers potential changes in practice and the health system, as well as the research needed to accomplish this. This report also (1) reviews the prevalence of behavioral and emotional disorders, (2) describes factors affecting the emergence of behavioral and emotional problems, (3) articulates the current state of detection of these problems in pediatric primary care, (4) describes barriers to screening and means to overcome those barriers, and (5) discusses potential changes at a practice and systems level that are needed to facilitate successful behavioral and emotional screening. Highlighted and discussed are the many factors at the level of the pediatric practice, health system, and society contributing to these behavioral and emotional problems.


Impact of ovarian stimulation on corpus luteum function and embryonic implantation.
The luteal phase has been found to be defective in virtually all the stimulation protocols used in in-vitro fertilization (IVF), indicating that common mechanisms might be involved despite the use of different drugs. A normal luteal phase is characterised by a normal hormonal environment, normal progesterone secretion by the corpus luteum and adequate endometrial secretory transformation. Luteinizing hormone supports the corpus luteum and luteal luteinizing hormone (LH) levels have been found to be reduced in human menopausal gonadotrophin (HMG), gonadotrophin-releasing hormone (GnRH)-agonist/HMG and GnRH-antagonist/HMG protocols, probably leading to an insufficient corpus luteum function. Supraphysiological steroid serum concentrations routinely observed in stimulated cycles may adversely affect LH secretion and induce a luteal-phase defect. In turn, these high steroid serum concentrations may advance early luteal-phase endometrial development leading to embryo-endometrial asynchrony and decreased pregnancy rates in IVF cycles.


Host size-dependent anisakid infection in Baltic cod Gadus morhua associated with differential food preferences.
A significant increase in the infection level of Baltic cod Gadus morhua with the anisakid nematode larvae Contracaecum osculatum and Pseudoterranova decipiens has been recorded during recent years due to the expanding local population of grey seals Halichoerus grypus, which act as final hosts for these parasites. Here, we report from an investigation of 368 cod (total length [TL] 6-49 cm; caught in ICES Subdivision 25) that the infection level of juvenile cod (TL 6-30 cm) with larvae of C. osculatum and P. decipiens is absent or very low, whereas it increases drastically in larger cod (TL 31-48 cm). A third nematode Hysterothylacium aduncum was rarely found. The study indicates that the prey animals for large cod act as transport hosts for the parasite larvae. Analyses of stomach contents of cod caught in the same area (2007-2014) showed that small benthic organisms (including polychaetes Harmothoë sarsi) are preferred food items by small cod, the isopod Saduria entomon is taken by all size classes, and sprat Sprattus sprattus are common prey items for cod larger than 30 cm. Parasitological investigations (microscopic and molecular analyses) of H. sarsi (100 specimens) and S. entomon (40 specimens) did not reveal infection in these invertebrates, but 11.6% of sprat (265 specimens examined) was shown to be infected with 1-8 C. osculatum third stage larvae per fish. Analyses of sprat stomach contents confirmed that copepods and cladocerans are the main food items of sprat. These observations suggest that the C. osculatum life cycle in the Baltic Sea includes grey seals as final hosts, sprat as the first transport host and cod as second transport host. It may be speculated that sprat obtain infection by feeding on copepods and/or cladocerans, which could serve as the first intermediate hosts. One cannot exclude the possibility that the size-dependent C. osculatum infection of cod may contribute (indirectly or directly) to the differential mortality of larger cod (>38 cm) compared to smaller cod (<30 cm) recently recorded in the Baltic cod population.


Utilization of nurse practitioners to increase patient access to primary healthcare in Canada--thinking outside the box.
In the past decade, all Canadian provinces and territories have launched various team-based primary healthcare initiatives designed to improve access and continuity of care. Nurse practitioners (NPs) are increasingly becoming integral members of primary healthcare teams across the country. This paper draws on the results of a scoping review of the literature and qualitative key informant interviews conducted for a decision support synthesis about advanced practice nursing in Canada. We describe and analyze two novel approaches to NP integration designed to address the gap in patient access to primary healthcare: (1) the integration of NPs in traditional fee-for-service practices in British Columbia, and (2) the creation of NP-led clinics in Ontario. Although fee-for-service remuneration has been a barrier to collaborative practice, the integration of government-salaried NPs into fee-for-service practices in British Columbia has enabled the creation of inter-professional teams, and based on early evaluation findings, has increased patient access to care and patient and provider satisfaction. NP-led clinics are designed to provide inter-professional care in communities with high numbers of patients who do not have a regular primary healthcare provider. Given the shortage of physicians in communities where these clinics are being introduced, the ratio of physicians to NPs is lower than in other primary healthcare delivery models, and physicians function in more of a consulting role. Initial evaluation of the first of 26 NP-led clinics indicates increased access to care and high levels of patient and provider satisfaction. Implementing a creative mosaic of collaborative primary healthcare models that are responsive to patient needs challenges traditional assumptions about professional roles and responsibilities. To address this challenge, we endorse a recommendation that governments establish a mechanism to bring together both physician and non-physician primary healthcare providers to advise on primary healthcare policy development and implementation.


The Mountain Meadows Massacre and "poisoned springs": scientific testing of the more recent, anthrax theory.
It has been recorded that one of the possible causes that eventually escalated into the 1857 manslaughter at Mountain Meadows in Southern Utah was the poisoning of an open spring by the Fancher-Baker party as they crossed the Utah territory on their way from Arkansas to California. Historical accounts report that a number of cattle died, followed by human casualties from those that came in contact with the dead animals. Even after the Arkansas party departed, animals continued to perish and people were still afflicted by some unknown plague. Proctor Hancock Robison, a local 14-year-old boy, died shortly after skinning one of the "poisoned" cows. A careful review of the historical records, along with the more recent scientific literature, seems to exclude the likelihood of actual poisoning in favor of a more recent theory that would point to the bacterium Bacillus anthracis as the possible cause of human and animal deaths. In order to test this hypothesis, Proctor's remains were exhumed, identified through mitochondrial DNA analysis, and tested for the presence of anthrax spores. Although preliminary testing of remains and soil was negative, description of the clinical conditions that affected Proctor and other individuals does not completely rule out the hypothesis of death by anthrax.


Active efflux of bile salts by Escherichia coli.
Enteric bacteria such as Escherichia coli must tolerate high levels of bile salts, powerful detergents that disrupt biological membranes. The outer membrane barrier of gram-negative bacteria plays an important role in this resistance, but ultimately it can only retard the influx of bile salts. We therefore examined whether E. coli possessed an energy-dependent efflux mechanism for these compounds. Intact cells of E. coli K-12 appeared to pump out chenodeoxycholate, since its intracellular accumulation increased more than twofold upon deenergization of the cytoplasmic membrane by a proton conductor. Growth inhibition by bile salts and accumulation levels of chenodeoxycholate increased when mutations inactivating the acrAB and emrAB gene clusters were introduced. The AcrAB system especially appeared to play a significant role in bile acid efflux. However, another efflux system(s) also plays an important role, since the accumulation level of chenodeoxycholate increased strongly upon deenergization of acrA emrB double mutant cells. Everted membrane vesicles accumulated taurocholate in an energy-dependent manner, apparently consuming delta pH without affecting delta psi. The efflux thus appears to be catalyzed by a proton antiporter. Accumulation by the everted membrane vesicles was not decreased by mutations in acr and emrB genes and presumably reflects activity of the unknown system seen in intact cells. It followed saturation kinetics with Vmax and Km values in the neighborhood of 0.3 nmol min(-1) mg of protein(-1) and 50 microM, respectively.


ICOStomizing immunotherapies with T(H)17.
New insights on the role of costimulatory molecules in T helper cell function have yielded exciting alternatives to the development of therapeutic strategies that target T cell costimulatory pathways. Inducible costimulatory molecule (ICOS) signaling is now shown by Paulos and colleagues to support expansion of human T helper 17 (T(H)17) cells that could exert antitumor activity. Here we discuss (i) how these findings aid in our understanding of mechanisms that govern T(H)17 cell functions and (ii) the potential application of these new insights to the development of immunotherapies.


Larazotide acetate in patients with coeliac disease undergoing a gluten challenge: a randomised placebo-controlled study.
Coeliac disease, an autoimmune disorder triggered by gluten ingestion, is managed by a gluten-free diet (GFD), which is difficult for many patients. Larazotide acetate is a first-in-class oral peptide that prevents tight junction opening, and may reduce gluten uptake and associated sequelae. To evaluate the efficacy and tolerability of larazotide acetate during gluten challenge. This exploratory, double-blind, randomised, placebo-controlled study included 184 patients maintaining a GFD before and during the study. After a GFD run-in, patients were randomised to larazotide acetate (1, 4, or 8 mg three times daily) or placebo and received 2.7 grams of gluten daily for 6 weeks. Outcomes included an experimental biomarker of intestinal permeability, the lactulose-to-mannitol (LAMA) ratio and clinical symptoms assessed by Gastrointestinal Symptom Rating Scale (GSRS) and anti-transglutaminase antibody levels. No significant differences in LAMA ratios were observed between larazotide acetate and placebo groups. Larazotide acetate 1-mg limited gluten-induced symptoms measured by GSRS (P = 0.002 vs. placebo). Mean ratio of anti-tissue transglutaminase IgA levels over baseline was 19.0 in the placebo group compared with 5.78 (P = 0.010), 3.88 (P = 0.005) and 7.72 (P = 0.025) in the larazotide acetate 1-, 4-, and 8-mg groups, respectively. Adverse event rates were similar between larazotide acetate and placebo groups. Larazotide acetate reduced gluten-induced immune reactivity and symptoms in patients with coeliac disease undergoing gluten challenge and was generally well tolerated; however, no significant difference in LAMA ratios between larazotide acetate and placebo was observed. Results and design of this exploratory study can inform the design of future studies of pharmacological interventions in patients with coeliac disease.


Is television traumatic? Dreams, stress, and media exposure in the aftermath of September 11, 2001.
The terrorist attacks of September 11, 2001, were traumatic for people living throughout the United States. It has been suggested that people living far from the attacks experienced increased stress because of their exposure to the terrorist events via the media, particularly via television. Following a traumatic or stressful event, individuals may have dreams that reflect that experience. As part of a course on dreaming, individuals recorded their dreams both prior to and following the terrorist attacks of September 11, 2001. On September 12, these same individuals reported their activities and media exposure the previous day. Results revealed (a) changes in dream features following the attacks and (b) a strong relation between exposure to the events on television and changes in dream features after the attacks. Because of the study's within-subjects design, the results provide evidence for a direct association between television viewing and subsequent increases in stress and trauma.


Population and development in the Amazon: A longitudinal study of migrant settlers in the Northern Ecuadorian Amazon.
This paper examines changes over time for a full generation of migrant settlers in the Northern Ecuadorian Amazon (NEA). Data were collected from a 2014 household survey covering a subsample of households surveyed previously in 1990 and 1999. We observed changes in demographic behavior, land use, forest cover, and living conditions. As the frontier develops, human fertility is continuing to decline with contraceptive prevalence rising. Meanwhile, out-migration from colonist households, largely to destinations within the region, persists. More households have secure land tenure than in 1999, and are better off as measured by possession of assets. There is continued growth in pasture, largely at the expense of forest. Farms still serve as an important livelihood source for families, though growing cities in the NEA are creating more non-agricultural economic opportunities. Our findings provide a snapshot of demographic, economic, land use, and livelihoods changes occurring in the NEA during the past quarter century, providing useful information for policymakers seeking to balance economic and environmental goals in order to promote sustainable development as well as protect biodiversity.


English literacy as a barrier to health care information for deaf people who use Auslan.
This study sought to gain insight into how Deaf Australians who use Auslan as their primary language perceive their English literacy and if they feel that they can sufficiently access preventative and ongoing health care information, and to explore their views in regards to accessing information in Auslan. A phenomenological, inductive study, with data collected through 72 semi-structured interviews with Deaf Auslan users identified through non-probabilistic, purposeful and network sampling. Data was thematically analysed for identification of issues related to healthcare information access through English. Deaf people experience barriers in accessing healthcare information because of limited English literacy and a lack of information being available in Auslan, apart from when Auslan interpreters are present in health care appointments. Many Deaf people in Australia lack consistent access to preventative and ongoing health care information. It is important to be aware of the English literacy levels of patients. More funding is needed for the provision of interpreting services in other healthcare contexts and the translation of materials into Auslan.


Does Obesity Correlate With Worse Patient-Reported Outcomes Following Elective Anterior Cervical Discectomy and Fusion?
Studies have investigated the impact of obesity in thoracolumbar surgery; however, the effect of obesity on patient-reported outcomes (PROs) following anterior cervical discectomy and fusion (ACDF) is unknown. To examine the relationship between obesity and PROs following elective ACDF. Consecutive patients undergoing ACDF for degenerative conditions were evaluated. Patients were divided into groups with a body mass index ≥35. The EuroQol-5D, Short-Form 12 (SF-12), modified Japanese Orthopaedic Association score, and Neck Disability Index were used. Correlations between PROs and obesity were calculated at baseline and 1 year. A total of 299 patients were included, with 80 obese (27%) and 219 nonobese (73%). patients At baseline, obesity was associated with worse myelopathy (modified Japanese Orthopaedic Association score: 10.7 vs 12.2, P = .01), general physical health (SF-12 physical component scale score: 28.7 vs 31.8, P = .02), and general mental health (SF-12 mental component scale score: 38.9 vs 42.3, P = .04). All PROs improved significantly following surgery in both groups. There was no difference in absolute scores and change scores for any PRO at 12 months following surgery. Furthermore, there was no difference in the percentage of patients achieving a minimal clinically important difference for the Neck Disability Index (52% vs 56%, P = .51) and no difference in patient satisfaction (85% vs 85%, P = .85) between groups. Obesity was not associated with less improvement in PROs following ACDF. There was no difference in the proportion of patients satisfied with surgery and those achieving a minimal clinically important difference across all PROs. Obese patients may therefore achieve meaningful improvement following elective ACDF. ACDF, anterior cervical discectomy and fusionBMI, body mass indexEQ-5D, EuroQol-5DMCID, minimal clinically important differenceMCS, mental component scalemJOA, modified Japanese Orthopaedic AssociationNDI, Neck Disability IndexNRS, Numerical Rating ScalePCS, physical component scalePROs, patient-reported outcomesSF-12, Short Form 12.


Targeting the fetal acetylcholine receptor in rhabdomyosarcoma.
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood and adolescence. Recent efforts to enhance overall survival of patients with clinically advanced RMS have failed and there is a demand for conceptually novel treatments. Immune therapeutic options targeting the fetal nicotinic acetylcholine receptor (fnAChR), which is broadly expressed on RMS, are novel approaches to overcome the therapeutic resistance of RMS. Expression of the fnAChR is restricted to developing fetal muscles, some apparently dispensable ocular muscle fibers and thymic myoid cells. Therefore, after-birth fnAChR is a tumor-associated and almost tumor-specific antigen on RMS cells. This review gives an overview on nAChR function and expression pattern in RMS tumor cells, and deals with the immunological significance of fnAChR-expressing cells, including the risk of anti-nAChR autoimmunity as a potential side effect of fnAChR-directed immunotherapies. The article also addresses the advantages and disadvantages of vaccination strategies, immunotoxins and chimeric T cells targeting the fnAChR. Finally, we suggest technical and biological strategies to improve the available immunotherapeutic tools including increasing the in vivo expression of the target fnAChR on RMS cells.


Hospitalisation in the last month of life and in-hospital death of nursing home residents: a cross-sectional analysis of six European countries.
To examine the rate and characteristics of hospitalisation in the last month of life and place of death among nursing home residents and to identify related care processes, facility factors and residents' characteristics. A cross-sectional study (2015) of deceased residents in 322 nursing homes in six European countries. The nursing home manager (N=1634), physician (N=1132) and primary nurse (N=1384) completed questionnaires. Hospitalisation and place of death were analysed using generalised linear and logistic mixed models. Multivariate analyses were conducted to determine associated factors. Twelve to 26% of residents were hospitalised in the last month of life, up to 19% died in-hospital (p<0.001). Belgian residents were more likely to be hospitalised than those in Italy, the Netherlands and Poland. For those dying in-hospital, the main reason for admission was acute change in health status. Residents with a better functional status were more likely to be hospitalised or to die in-hospital. The likelihood of hospitalisation and in-hospital death increased if no conversation on preferred care with a relative was held. Not having an advance directive regarding hospitalisations increased the likelihood of hospitalisation. Although participating countries vary in hospitalisation and in-hospital death rates, between 12% (Italy) and 26% (Belgium) of nursing home residents were hospitalised in the last month of life. Close monitoring of acute changes in health status and adequate equipment seem critical to avoiding unnecessary hospitalisations. Strategies to increase discussion of preferences need to be developed. Our findings can be used by policy-makers at governmental and nursing home level.


Development and face validity of a cerebral visual impairment motor questionnaire for children with cerebral palsy.
The objectives of this study were (i) to develop two cerebral visual impairment motor questionnaires (CVI-MQ's) for children with cerebral palsy (CP): one for children with Gross Motor Function Classification System (GMFCS) levels I, II and III and one for children with GMFCS levels IV and V; (ii) to describe their face validity and usability; and (iii) to determine their sensitivity and specificity. The initial versions of the two CVI-MQ's were developed based on literature. Subsequently, the Delphi method was used in two groups of experts, one familiar with CVI and one not familiar with CVI, in order to gain consensus about face validity and usability. The sensitivity and specificity of the CVI-MQ's were subsequently assessed in 82 children with CP with (n = 39) and without CVI (n = 43). With the receiver operating curve the cut-off scores were determined to detect possible presence or absence of CVI in children with CP. Both questionnaires showed very good face validity (percentage agreement above 96%) and good usability (percentage agreement 95%) for practical use. The CVI-MQ version for GMFCS levels I, II and III had a sensitivity of 1.00 and specificity of 0.96, with a cut-off score of 12 points or higher, and the version for GMFCS levels IV and V had a sensitivity of 0.97 and a specificity of 0.98, with a cut-off score of eight points or higher. The CVI-MQ is able to identify at-risk children with CP for the probability of having CVI.


The Peyer's patch high endothelial receptor for lymphocytes, the mucosal vascular addressin, is induced on a murine endothelial cell line by tumor necrosis factor-alpha and IL-1.
The specificity of lymphocyte homing from the blood into a tissue is determined in part by complementary pairs of adhesion receptors on lymphocytes and endothelial cells termed homing receptors and vascular addressins, respectively. The mucosal vascular addressin involved in lymphocyte homing to Peyer's patches is a 66-kDa glycoprotein, MAdCAM-1. Investigation of the regulation and molecular genetics of MAdCAM-1 have been hampered by the lack of a murine cell line expressing this adhesion molecule. We show herein using indirect immunofluorescence studies that MAdCAM-1 can be induced on a murine endothelial cell line, bEnd.3, by cytokines and LPS. Western blot analysis of MAdCAM-1 purified by affinity column chromatography from TNF-alpha-treated bEnd.3 cells demonstrates a 66-kDa protein that comigrates in SDS-PAGE with the MAdCAM-1 constitutively found on high endothelial venules in murine mesenteric lymph nodes. Comparison of MAdCAM-1 expression on the bEnd.3 cells was made to the expression of adhesion molecules ICAM-1 and VCAM-1. MAdCAM-1 and VCAM-1 are not constitutively expressed on the bEND.3 surface but can be induced in a concentration-dependent manner by LPS, TNF-alpha, and IL-1. ICAM-1 is constitutively expressed on the endothelioma surface and expression is increased by TNF-alpha, IL-1, LPS, and IFN-gamma. Surface expression of MAdCAM-1 peaks 12 to 18 h after exposure to TNF-alpha and remains elevated at 48 h, whereas expression of VCAM-1 peaks at 4 h and inducible ICAM-1 peaks between 4 and 18 h. Interestingly, IFN-gamma has differential effects on expression of these three adhesion receptors. IFN-gamma alone induces VCAM-1 and enhances ICAM-1 expression, but does not induce MAdCAM-1. Furthermore, although, preincubation of bEND.3 cells with IFN-gamma modestly increases the induction of ICAM-1 and VCAM-1 in response to TNF-alpha and IL-1, it dramatically reduces the TNF-alpha, IL-1, and LPS-induced expression of MAdCAM-1. MAdCAM-1 on bEnd.3 cells is functional as the murine T lymphoma TK1, known to bind MAdCAM-1, also binds to TNF-alpha-stimulated endothelioma but not to unstimulated cells. This binding is blocked by the antibodies against MAdCAM-1 and against the alpha 4-chain of its integrin receptor, alpha 4 beta 7, on TK1 cells.(ABSTRACT TRUNCATED AT 400 WORDS)


Cilia-like beating of active microtubule bundles.
The mechanism that drives the regular beating of individual cilia and flagella, as well as dense ciliary fields, remains unclear. We describe a minimal model system, composed of microtubules and molecular motors, which self-assemble into active bundles exhibiting beating patterns reminiscent of those found in eukaryotic cilia and flagella. These observations suggest that hundreds of molecular motors, acting within an elastic microtubule bundle, spontaneously synchronize their activity to generate large-scale oscillations. Furthermore, we also demonstrate that densely packed, actively bending bundles spontaneously synchronize their beating patterns to produce collective behavior similar to metachronal waves observed in ciliary fields. The simple in vitro system described here could provide insights into beating of isolated eukaryotic cilia and flagella, as well as their synchronization in dense ciliary fields.


Iron-associated protein interaction networks reveal the key functional modules related to survival and virulence of Pasteurella multocida.
Pasteurella multocida causes respiratory infectious diseases in a multitude of birds and mammals. A number of virulence-associated genes were reported across different strains of P. multocida, including those involved in the iron transport and metabolism. Comparative iron-associated genes of P. multocida among different animal hosts towards their interaction networks have not been fully revealed. Therefore, this study aimed to identify the iron-associated genes from core- and pan-genomes of fourteen P. multocida strains and to construct iron-associated protein interaction networks using genome-scale network analysis which might be associated with the virulence. Results showed that these fourteen strains had 1587 genes in the core-genome and 3400 genes constituting their pan-genome. Out of these, 2651 genes associated with iron transport and metabolism were selected to construct the protein interaction networks and 361 genes were incorporated into the iron-associated protein interaction network (iPIN) consisting of nine different iron-associated functional modules. After comparing with the virulence factor database (VFDB), 21 virulence-associated proteins were determined and 11 of these belonged to the heme biosynthesis module. From this study, the core heme biosynthesis module and the core outer membrane hemoglobin receptor HgbA were proposed as candidate targets to design novel antibiotics and vaccines for preventing pasteurellosis across the serotypes or animal hosts for enhanced precision agriculture to ensure sustainability in food security.


Eimeria maxima: the influence of host genotype on parasite reproduction as revealed by quantitative real-time PCR.
The influence of host genotype on susceptibility to infection with Eimeria species has long been recognised, but beyond monitoring pathological severity or magnitude of oocyst excretion attempts to quantify fluctuations in parasite reproduction within the host have previously relied upon labour-intensive microscopic analysis. The development and application of a quantitative real-time PCR assay has opened this biological 'black box', permitting the sensitive and reproducible enumeration of parasite genomes throughout the course of infection. Generic and species-specific quantitative PCR methods are described, based upon the conserved 5S ribosomal RNA coding sequence of nine avian and murine Eimeria species and the Eimeria maxima MIC1 gene, respectively. These complementary assays have been applied to study the influence of host genotype on resistance to infection with E. maxima, revealing significant differences in parasite load between 'resistant' Line C and 'susceptible' Line 15I inbred chickens 5 days after infection. Parasite DNA remained detectable up to 20 days post-infection; 11 days after the last oocysts had been detected leaving the host.


Evaluation and Acceptability of a Simplified Test of Visual Function at Birth in a Limited-Resource Setting.
Neurological examination, including visual fixation and tracking of a target, is routinely performed in the Shoklo Malaria Research Unit postnatal care units on the Thailand-Myanmar border. We aimed to evaluate a simple visual newborn test developed in Italy and performed by non-specialized personnel working in neonatal care units. An intensive training of local health staff in Thailand was conducted prior to performing assessments at 24, 48 and 72 hours of life in healthy, low-risk term singletons. The 48 and 72 hours results were then compared to values obtained to those from Italy. Parents and staff administering the test reported on acceptability. One hundred and seventy nine newborns, between June 2011 and October 2012, participated in the study. The test was rapidly completed if the infant remained in an optimal behavioral stage (7 ± 2 minutes) but the test duration increased significantly (12 ± 4 minutes, p < 0.001) if its behavior changed. Infants were able to fix a target and to discriminate a colored face at 24 hours of life. Horizontal tracking of a target was achieved by 96% (152/159) of the infants at 48 hours. Circular tracking, stripe discrimination and attention to distance significantly improved between each 24-hour test period. The test was easily performed by non-specialized local staff and well accepted by the parents. Healthy term singletons in this limited-resource setting have a visual response similar to that obtained to gestational age matched newborns in Italy. It is possible to use these results as a reference set of values for the visual assessment in Karen and Burmese infants in the first 72 hours of life. The utility of the 24 hours test should be pursued.


Catastrophic sliding bifurcations and onset of oscillations in a superconducting resonator.
This paper presents a general analysis and a concrete example of the catastrophic case of a discontinuity-induced bifurcation in so-called Filippov nonsmooth dynamical systems. Such systems are characterized by discontinuous jumps in the right-hand sides of differential equations across a phase space boundary and are often used as physical models of stick-slip motion and relay control. Sliding bifurcations of periodic orbits have recently been shown to underlie the onset of complex dynamics including chaos. In contrast to previously analyzed cases, in this work a periodic orbit is assumed to graze the boundary of a repelling sliding region, resulting in its abrupt destruction without any precursive change in its stability or period. Necessary conditions for the occurrence of such catastrophic grazing-sliding bifurcations are derived. The analysis is illustrated in a piecewise-smooth model of a stripline resonator, where it can account for the abrupt onset of self-modulating current fluctuations. The resonator device is based around a ring of NbN containing a microbridge bottleneck, whose switching between normal and super conducting states can be modeled as discontinuous, and whose fast temperature versus slow current fluctuations are modeled by a slow-fast timescale separation in the dynamics. By approximating the slow component as Filippov sliding, explicit conditions are derived for catastrophic grazing-sliding bifurcations, which can be traced out as parameters vary. The results are shown to agree well with simulations of the slow-fast model and to offer a simple explanation of one of the key features of this experimental device.


Differentiation in MALDI-TOF MS and FTIR spectra between two closely related species Acidovorax oryzae and Acidovorax citrulli.
Two important plant pathogenic bacteria Acidovorax oryzae and Acidovorax citrulli are closely related and often not easy to be differentiated from each other, which often resulted in a false identification between them based on traditional methods such as carbon source utilization profile, fatty acid methyl esters, and ELISA detection tests. MALDI-TOF MS and Fourier transform infrared (FTIR) spectra have recently been successfully applied in bacterial identification and classification, which provide an alternate method for differentiating the two species. Characterization and comparison of the 10 A. oryzae strains and 10 A. citrulli strains were performed based on traditional bacteriological methods, MALDI-TOF MS, and FTIR spectroscopy. Our results showed that the identity of the two closely related plant pathogenic bacteria A. oryzae and A. citrulli was able to be confirmed by both pathogenicity tests and species-specific PCR, but the two species were difficult to be differentiated based on Biolog and FAME profile as well as 16 S rRNA sequence analysis. However, there were significant differences in MALDI-TOF MS and FTIR spectra between the two species of Acidovorax. MALDI-TOF MS revealed that 22 and 18 peaks were specific to A. oryzae and A. citrulli, respectively, while FTIR spectra of the two species of Acidovorax have the specific peaks at 1738, 1311, 1128, 1078, 989 cm(-1) and at 1337, 968, 933, 916, 786 cm(-1), respectively. This study indicated that MALDI-TOF MS and FTIR spectra may give a new strategy for rapid bacterial identification and differentiation of the two closely related species of Acidovorax.


The highly virulent variola and monkeypox viruses express secreted inhibitors of type I interferon.
Variola virus (VARV) caused smallpox, one of the most devastating human diseases and the first to be eradicated, but its deliberate release represents a dangerous threat. Virulent orthopoxviruses infecting humans, such as monkeypox virus (MPXV), could fill the niche left by smallpox eradication and the cessation of vaccination. However, immunomodulatory activities and virulence determinants of VARV and MPXV remain largely unexplored. We report the molecular characterization of the VARV- and MPXV-secreted type I interferon-binding proteins, which interact with the cell surface after secretion and prevent type I interferon responses. The proteins expressed in the baculovirus system have been purified, and their interferon-binding properties characterized by surface plasmon resonance. The ability of these proteins to inhibit a broad range of interferons was investigated to identify potential adaptation to the human immune system. Furthermore, we demonstrate by Western blot and activity assays the expression of the type I interferon inhibitor during VARV and MPXV infections. These findings are relevant for the design of new vaccines and therapeutics to smallpox and emergent virulent orthopoxviruses because the type I interferon-binding protein is a major virulence factor in animal models, vaccination with this protein induces protective immunity, and its neutralization prevents disease progression.


Complementary medicine: legal status of the non-licensed provider in the USA.
European providers of complementary medicine may be surprised by the formal strictures which their US counterparts face. A major hurdle to holistic practice in the USA is the statutory prohibition against the unlicensed practice of medicine. State statutes define 'medicine' broadly, creating a legal risk for unlicensed providers of holistic health care, as well as for licensed providers whose services are deemed to exceed their legislatively authorized scope of practice and cross into 'diagnosis' and 'treatment' of disease. This paper does not address scope of practice; rather, it focuses on the legal status of non-licensed (or 'unenfranchised') providers. For these providers, seeking occupational licensure will provide some protection against medical practice acts, as well as opportunity to elevate professional competence and prestige. However, many holistic providers prefer to remain outside the regulatory scheme. Mandatory licensure, title licensure and registration offer means of upgrading professional status and achieving state sanction for professional practice.


The effect of malaria on childhood anemia in a quasi-experimental study of 7,384 twins from 23 Sub-Saharan African countries.
Young children in Sub-Saharan Africa (SSA), particularly those from resource-limited settings, are heavily burdened by anemia and malaria. While malaria infected children frequently become anemic (hemoglobin < 110 g/L), anemia is a strongly multifactorial disease with many other risk factors than malaria. Due to the complex and often overlapping contributors to anemia, it remains challenging to isolate the true impact of malaria on population level hemoglobin concentrations. We quantified the malaria-induced effect on hemoglobin levels in children under 5 years of age, leveraging data from 7,384 twins and other multiples, aged 6 to 59 months, from 57 nationally representative Demographic and Health Surveys (DHSs) from 23 SSA countries from 2006 to 2019. The quasi-experimental twin fixed-effect design let us minimize the impact of potential confounders that do not vary between twins. Our analyses of twins revealed a malaria-induced hemoglobin decrease in infected twins of 9 g/L (95% CI -10; -7, p<0.001). The relative risk of severe anemia was higher (RR = 3.01, 95% CI 1.79; 5.1, p<0.001) among malaria positive children, compared to malaria negative children. Conversely, malaria positive children are only half as likely to be non-anemic (RR = 0.51, 95% CI 0.43; 0.61, p<0.001). Even after rigorous control for confounding through a twin fixed-effects study design, malaria substantially decreased hemoglobin levels among SSA twins, rendering them much more susceptible to severe anemia. This effect reflects the population-level effect of malaria on anemia.


Axonally derived matrilin-2 induces proinflammatory responses that exacerbate autoimmune neuroinflammation.
In patients with multiple sclerosis (MS) and mice with experimental autoimmune encephalomyelitis (EAE), inflammatory axonal injury is a major determinant of disability; however, the drivers of this injury are incompletely understood. Here, we used the EAE model and determined that the extracellular matrix protein matrilin-2 (MATN2) is an endogenous neuronal molecule that is regulated in association with inflammatory axonal injury. Compared with WT mice, mice harboring a deletion of Matn2 exhibited reduced disease severity and axon damage following induction of EAE. Evaluation of neuron-macrophage cocultures revealed that exogenous MATN2 specifically signals through TLR4 and directly induces expression of proinflammatory genes in macrophages, promoting axonal damage. Moreover, the MATN2-induced proinflammatory response was attenuated greatly in macrophages from Myd88 KO mice. Examination of brain sections from patients with MS revealed that MATN2 is expressed in lesions but not in normal-appearing white matter. Together, our results indicate that MATN2 is a deleterious endogenous neuroaxonal injury response signal that activates innate immune cells and could contribute to early axonal damage in CNS inflammatory diseases like MS.


Temporal filtering by double diffraction.
We present a theoretical analysis of the temporal behavior of double-diffraction setups. It applies, in particular, to Talbot and Montgomery interferometers, whose operation is based on the self-imaging effect. The use of both types of interferometer as temporal filters for optical and terahertz applications was recently suggested. We show that double-diffraction setups can be modeled as communications channels with dispersive behavior caused by diffraction. We develop mathematical expressions for the phase delay, the group velocity, and the group-velocity dispersion for both quasi-monochromatic and polychromatic case. Based on these results, the temporal impulse response of a double-diffraction setup is derived. Finally, a general description of its practical implementation are presented.


Reminiscence through the Lens of Social Media.
Reminiscence is used to support and create new social bonds and give meaning to life. Originally perceived as a preoccupation of the aged, we now recognize that reminiscence has value throughout the lifespan. Increasingly, social media can be used to both support and prompt reminiscence, with Facebook's Lookback or Year in Review as recent examples. This work takes prompted reminiscence further, asking what forms and functions of reminiscence are supported by social media. Utilizing the online service MySocialBook, we invited participants to curate content from their personal Facebook account to then be transformed into a printed book. We used that book as a prompt for discussion of the reminiscence function of the curated material, using Westerhof and Bohlmeijer's (2014) reminiscence framework as a starting point. We conclude that this framework is valuable in understanding the role of social media in reminiscence, but note that earlier models, such as Webster's Reminiscence Functions Scale, are also relevant. We contribute to the reminiscence debate by adding a technological lens to the process of life review, whilst concurring with other researchers in this field that a robust conceptual framework is lacking, particularly when considering the forms of reminiscence that are most salient for younger people.


Myoelectric activity of the small intestine in enterotoxin-induced diarrhea of calves.
Electrodes were surgically implanted at 15-cm intervals in the jejunum and ileum of 4 healthy neonatal calves so that myoelectric activity could be recorded on 2 consecutive days. On the first day, each calf received a control treatment, and myoelectric activity was recorded for 340 minutes. Phase I was recorded for a mean of 175.8 +/- 22.8 minutes (51.5%), phase II for 124 +/- 27.4 minutes (36.5%), and phase III for 40.3 +/- 6 minutes (11.9%). On the second day, each calf was treated with approximately 200 micrograms of heat-stable enterotoxin (STa) of Escherichia coli orally. All calves developed diarrhea after the administration of STa. Phase I was recorded for a mean of 92.5 +/- 42.3 minutes (27.2%), phase II for 227.3 +/- 52.5 minutes (66.9%), and phase III for 20.3 +/- 11.4 minutes (6.0%). Increase in phase II and decrease in phases I and III after STa administration were significant (P less than 0.05). Duration of the migrating myoelectric complex was longer after STa administration (median, 64 minutes), compared with the control treatment (median, 54 minutes). Minute rhythms, recorded on the day of toxin administration, ranged from 49 to 153 minutes. There was no difference between the number of migrating action potential complexes on the control days (range, 1 to 10), compared with those on treatment days (range, 1 to 14). These findings are suggestive that enterotoxin-induced diarrhea of calves is accompanied by increased total spiking activity and minute rhythms in the distal portion of the jejunum and ileum.


Correlation between polymorphisms of the reduced folate carrier gene (SLC19A1) and survival after pemetrexed-based therapy in non-small cell lung cancer: a North Central Cancer Treatment Group-based exploratory study.
To correlate polymorphisms in genes involved in the transport, activation, and inactivation of pemetrexed with the outcome of patients with advanced non-small cell lung cancer (NSCLC) treated with pemetrexed. Data from a phase II NSCLC trial evaluating the optimal schedule of gemcitabine and pemetrexed were used. All patients with available DNA were genotyped for polymorphisms in FPGS, GGH, and SLC19A1 genes. Patients with various genotypes were compared for efficacy and adverse events resulting from pemetrexed. Fifty-four patients had genotype results for all polymorphisms studied. Patients with the homozygous variant genotypes for SLC19A1 IVS4(2117) C>T, IVS5(9148) C>A, and wild-type genotype for exon6(2522) C>T had a significantly better overall survival compared with their counterparts (median overall survival in months: 8.9 [CC] versus 14.0 [CT] versus 16.7 [TT]; 9.4 [CC] versus 10.3 [CA] versus 22.7 [AA]; and 22.7 [CC] versus 10.3 [CT] versus 9.4 [TT] respectively; all log rank p = 0.03). Patients with the heterozygous TC genotype for GGH IVS5(1042) T>C had greater rates of confirmed response + stable disease compared with the TT genotype (85% versus 60%; odds ratio = 4.0; p = 0.06). A greater risk for grade 3/4 SGPT (ALT) elevation was observed in patients heterozygous (GA) for the FPGS IVS1 (28) G>A polymorphism compared with the GG genotype (43% versus 13%; odds ratio = 5.0, p = 0.07). All results were largely consistent within patients with nonsquamous (n = 40) histology. Polymorphisms in SLC1A91 seem to predict for survival differences in pemetrexed-treated NSCLC. Additionally, polymorphisms in GGH and FPGS have marginal associations with response and adverse event. These results should be validated in larger prospective studies using pemetrexed.


Rapid, Fully Automated Digital Immunoassay for p24 Protein with the Sensitivity of Nucleic Acid Amplification for Detecting Acute HIV Infection.
Nucleic acid testing (NAT) has become the standard for high sensitivity in detecting low levels of virus. However, adoption of NAT can be cost prohibitive in low-resource settings where access to extreme sensitivity could be clinically advantageous for early detection of infection. We report development and preliminary validation of a simple, low-cost, fully automated digital p24 antigen immunoassay with the sensitivity of quantitative NAT viral load (NAT-VL) methods for detection of acute HIV infection. We developed an investigational 69-min immunoassay for p24 capsid protein for use on a novel digital analyzer on the basis of single-molecule-array technology. We evaluated the assay for sensitivity by dilution of standardized preparations of p24, cultured HIV, and preseroconversion samples. We characterized analytical performance and concordance with 2 NAT-VL methods and 2 contemporary p24 Ag/Ab combination immunoassays with dilutions of viral isolates and samples from the earliest stages of HIV infection. Analytical sensitivity was 0.0025 ng/L p24, equivalent to 60 HIV RNA copies/mL. The limit of quantification was 0.0076 ng/L, and imprecision across 10 runs was <10% for samples as low as 0.09 ng/L. Clinical specificity was 95.1%. Sensitivity concordance vs NAT-VL on dilutions of preseroconversion samples and Group M viral isolates was 100%. The digital immunoassay exhibited >4000-fold greater sensitivity than contemporary immunoassays for p24 and sensitivity equivalent to that of NAT methods for early detection of HIV. The data indicate that NAT-level sensitivity for acute HIV infection is possible with a simple, low-cost digital immunoassay.


Antarctic ecosystems in transition - life between stresses and opportunities.
Important findings from the second decade of the 21st century on the impact of environmental change on biological processes in the Antarctic were synthesised by 26 international experts. Ten key messages emerged that have stakeholder-relevance and/or a high impact for the scientific community. They address (i) altered biogeochemical cycles, (ii) ocean acidification, (iii) climate change hotspots, (iv) unexpected dynamism in seabed-dwelling populations, (v) spatial range shifts, (vi) adaptation and thermal resilience, (vii) sea ice related biological fluctuations, (viii) pollution, (ix) endangered terrestrial endemism and (x) the discovery of unknown habitats. Most Antarctic biotas are exposed to multiple stresses and considered vulnerable to environmental change due to narrow tolerance ranges, rapid change, projected circumpolar impacts, low potential for timely genetic adaptation, and migration barriers. Important ecosystem functions, such as primary production and energy transfer between trophic levels, have already changed, and biodiversity patterns have shifted. A confidence assessment of the degree of 'scientific understanding' revealed an intermediate level for most of the more detailed sub-messages, indicating that process-oriented research has been successful in the past decade. Additional efforts are necessary, however, to achieve the level of robustness in scientific knowledge that is required to inform protection measures of the unique Antarctic terrestrial and marine ecosystems, and their contributions to global biodiversity and ecosystem services.


Transfemoral endovascular stented graft treatment of aorto-iliac and femoropopliteal occlusive disease for limb salvage.
Endovascular stented grafts employ a new technique that blends intravascular stent and prosthetic graft technologies. These devices may be used to treat arterial aneurysms, occlusive disease, and vascular injuries. This report describes the application of stented grafts to the treatment of limb-threatening ischemia secondary to occlusive disease of the aorta, iliac, and femoral arteries. Three patients with limb-threatening ischemia and severe comorbid medical illnesses were treated with transvascular stented grafts that were composed of 6-mm thin-walled polytetrafluoroethylene grafts and Palmaz balloon expandable stents. The grafts were inserted through a cutdown in an artery remote from the site of occlusion and introduced into the vascular system within 14-Fr introducer sheaths. Technical success was documented in all three patients with restoration of arterial continuity following stent graft deployment. Patency and limb salvage has been achieved to 1 year. One patient required further dilatation of the proximal stent at 6 weeks. Complications were limited to an iliofemoral deep vein thrombosis in one patient. Endovascular stented grafts can be inserted to treat limb-threatening ischemia. Although these initial results are encouraging, greater experience in more patients observed for longer periods of time is necessary before this technique can be advocated for widespread use.


Amorphous Calcium Carbonate Based-Microparticles for Peptide Pulmonary Delivery.
Amorphous calcium carbonate (ACC) is known to interact with proteins, for example, in biogenic ACC, to form stable amorphous phases. The control of amorphous/crystalline and inorganic/organic ratios in inhalable calcium carbonate microparticles may enable particle properties to be adapted to suit the requirements of dry powders for pulmonary delivery by oral inhalation. For example, an amorphous phase can immobilize and stabilize polypeptides in their native structure and amorphous and crystalline phases have different mechanical properties. Therefore, inhalable composite microparticles made of inorganic (i.e., calcium carbonate and calcium formate) and organic (i.e., hyaluronan (HA)) amorphous and crystalline phases were investigated for peptide and protein pulmonary aerosol delivery. The crystalline/amorphous ratio and polymorphic form of the inorganic component was altered by changing the microparticle drying rate and by changing the ammonium carbonate and HA initial concentration. The bioactivity of the model peptide, salmon calcitonin (sCT), coprocessed with alpha-1-antitrypsin (AAT), a model protein with peptidase inhibitor activity, was maintained during processing and the microparticles had excellent aerodynamic properties, making them suitable for pulmonary aerosol delivery. The bioavailability of sCT after aerosol delivery as sCT and AAT-loaded composite microparticles to rats was 4-times higher than that of sCT solution.


Pepper arginine decarboxylase is required for polyamine and γ-aminobutyric acid signaling in cell death and defense response.
The Xanthomonas campestris pv vesicatoria (Xcv) effector AvrBsT induces a hypersensitive cell death in pepper (Capsicum annuum). However, the molecular mechanisms underlying AvrBsT-triggered cell death are not fully understood. Here, we identified pepper arginine decarboxylase (CaADC1) as an AvrBsT-interacting protein, which is early and strongly induced in incompatible pepper-Xcv interactions. Bimolecular fluorescence complementation and coimmunoprecipitation assays showed that the CaADC1-AvrBsT complex was localized to the cytoplasm. Transient coexpression of CaADC1 with avrBsT in Nicotiana benthamiana leaves specifically enhanced AvrBsT-triggered cell death, accompanied by an accumulation of polyamines, nitric oxide (NO), and hydrogen peroxide (H₂O₂) bursts. Among the polyamines, spermine application strongly induced NO and H₂O₂ bursts, ultimately leading to cell death. CaADC1 silencing in pepper leaves significantly compromised NO and H₂O₂ accumulation and cell death induction, leading to the enhanced avirulent Xcv growth during infection. The levels of salicylic acid, polyamines, and γ-aminobutyric acid (GABA), and the expression of defense response genes during avirulent Xcv infection, were distinctly lower in CaADC1-silenced plants than those in the empty vector control plants. GABA application significantly inhibited avirulent Xcv growth in CaADC1-silenced leaves and the empty vector control plants. Together, these results suggest that CaADC1 may act as a key defense and cell death regulator via mediation of polyamine and GABA metabolism.


Occurrence of Anthracnose Caused by Colletotrichum malvarum on Althaea officinalis in Italy.
The cultivation of medicinal plants is increasing in some areas of central Italy where the climate is suitable for organic farming and the production of high-quality plant products. During April and May 2003, plants of Althaea officinalis L. at the seedling stage (two-to-four true leaves) maintained in unheated greenhouses before their transplantation to open fields showed an unusual foliar disease. Necrotic leaf spots of variable shape and size were followed by a rapid wilting of leaves that frequently resulted in a blight of the young plants. Small leaf pieces showing symptoms were sampled, surface treated in 0.1% HgCl2 for 30 s, rinsed twice in sterile water, placed on potato dextrose agar (PDA) (pH 5.5) in petri dishes, and incubated for 7 days at 25 ± 2°C. Colletotrichum malvarum (Braun & Casp.) Southworth (1,2) was consistently recovered from affected tissues. The fungus produced dark colonies with whitish aerial mycelium and acervuli containing hyaline, cylindrical conidia (14 to 25 × 3 to 6 μm) on PDA. The pathogenicity of four fungal isolates was tested by inoculating two, true leaves of 10 plants (A. officinalis) with a conidial suspension (5 × 105 conidia ml-1) from a 10-day-old culture. Plants sprayed with water served as controls. All seedlings were placed in a greenhouse at 24± 2°C under natural light conditions and covered with plastic bags for the first 24 h. Each pathogenicity test was repeated one time. After 5 to 7 days, the inoculated seedlings showed small necrotic leaf spots identical to those observed under natural conditions. Affected leaf areas rapidly enlarged and within a few days, the young plants wilted. No symptoms appeared on the noninoculated controls. C. malvarum was consistently reisolated from the symptomatic test seedlings, whereas the fungus was never isolated from control plants. Standard seed health methods (agar plate and blotter) carried out on samples from the same seed lots used for the unheated greenhouse trials were negative for the presence of the pathogen. The occurrence of anthracnose may be attributed to windborne conidia of C. malvarum coming from infected wild malvaceae species and cultivated hosts grown in open fields in the neighborhood of seedling greenhouses. To our knowledge, this is the first report of C. malvarum on A. officinalis in Italy. References: (1) W. Brandenburger. Page 386 in: Parasitische pilze an gefäbpflanzen in Europa. Fisher Verlag, Stuttgart, Germany, 1985. (2) B. C. Sutton. The genus Glomerella and its anamoroph Colletotrichum. Pages 1-26 in: Colletotrichum, Biology, Pathology and Control. J. A. Bailey and M. J. Jeger eds. CAB International, Wallingford, U.K., 1992.


Philanthropy's new agenda: creating value.
During the past two decades, the number of charitable foundations in the United States has doubled while the value of their assets has increased more than 1,100%. As new wealth continues to pour into foundations, the authors take a timely look at the field and conclude that radical change is needed. First, they explain why. Compared with direct giving, foundations are strongly favored through tax preferences whose value increases in rising stock markets. As a nation, then, we make a substantial investment in foundation philanthropy that goes well beyond the original gifts of private donors. We should therefore expect foundations to achieve a social impact disproportionate to their spending. If foundations serve merely as passive conduits for giving, then they not only fall far short of their potential but also fail to meet an important societal obligation. Drawing on Porter's work on competition and strategy, the authors then present a framework for thinking systematically about how foundations create value and how the various approaches to value creation can be deployed within the context of an overarching strategy. Although many foundations talk about "strategic" giving, much current practice is at odds with strategy. Among the common problems, foundations scatter their funding too broadly, they overlook the value-creating potential of longer and closer working relationships with grantees, and they pay insufficient attention to the ultimate results of the work they fund. This article lays out a blueprint for change, challenging foundation leaders to spearhead the evolution of philanthropy from private acts of conscience into a professional field.


Metabolite Spectral Accuracy on Orbitraps.
Orbitraps are high-resolution ion-trap mass spectrometers that are widely used in metabolomics. While the mass accuracy and resolving power of orbitraps have been extensively documented, their spectral accuracy, i.e., accuracy in measuring the abundances of isotopic peaks, remains less studied. In analyzing spectra of unlabeled metabolites, we discovered a systematic under representation of heavier natural isotopic species, especially for high molecular weight metabolites (∼20% under-measurement of [M + 1]/[M + 0] ratio at m/z 600). We hypothesize that these discrepancies arise for metabolites far from the lower limit of the mass scan range, due to the weaker containment in the C-trap that results in suboptimal trajectories inside the Orbitrap analyzer. Consistent with this, spectral fidelity was restored by dividing the mass scan range (initially 75 m/z to 1000 m/z) into two scan events, one for lower molecular weight and the other for higher molecular weight metabolites. Having thus obtained accurate mass spectra at high resolution, we found that natural isotope correction for high-resolution labeling data requires more sophisticated algorithms than typically employed: the correction algorithm must take into account whether isotopologues with the same nominal mass are resolved. We present an algorithm and associated open-source code, named AccuCor, for this purpose. Together, these improvements in instrument parameters and natural isotope correction enable more accurate measurement of metabolite labeling and thus metabolic flux.


Nonsuicidal self-harm in youth: a population-based survey.
Nonsuicidal self-harm includes cutting, scratching, burning and minor overdosing. There have been few studies that have examined the rate of self-harm and mental-health correlates among community-based youth. We performed a population-based study to determine the prevalence of nonsuicidal self-harm, its mental-health correlates and help-seeking behaviour. We used data from the Victoria Healthy Youth Survey, a population-based longitudinal survey of youth aged 14-21 in Victoria, British Columbia. The survey included questions about the history, method, frequency, age of onset and help-seeking for nonsuicidal self-harm. Youth were interviewed between February and June 2005. Univariable group differences were analyzed using students t test for continuous data and chi2 for binary or categorical data. Multivariate analyses were conducted by use of multivariate analysis of variance and logistic regression. Ninety-six of 568 (16.9%) youth indicated that they had ever harmed themselves. Self-injuries such as cutting, scratching and self-hitting were the most common forms of nonsuicidal self-harm (83.2%). The mean age of onset was 15.2 years. Of those who reported nonsuicidal self-harm, 56% had sought help for this behaviour. Participants who reported 5 or more symptoms (out of 6) in a given symptom category were more likely than those who reported less than 5 symptoms to report nonsuicidal self-harm for the following categories: depressive mood (odds ratio [OR] 2.18, confidence interval [CI] 1.28-3.7) and problems with regulation of attention, impulsivity and activity (OR 2.24, CI 1.33-3.76). We found a high lifetime prevalence of nonsuicidal self-harm. Many mental-health symptoms were associated with this behaviour, particularly those with depressive mood and attention-related problems. Just over half of youth reported seeking help for nonsuicidal self-harm. Clinicians who encounter youth should be vigilant to assess for this behaviour in youth who present with mental health issues.


Antioxidant properties of mesalamine in colitis inhibit phosphoinositide 3-kinase signaling in progenitor cells.
Mesalamine, 5-aminosalicylic acid (5-ASA), is a potent antioxidant and is known to enhance peroxisome proliferator-activated receptor γ activity in the intestine. Our previous studies suggested reduced Phosphoinositide 3-Kinase (PI3K)/β-catenin signaling as a mechanism for 5-ASA chemoprevention in chronic ulcerative colitis (CUC). We now hypothesize that 5-ASA mediates changes in intestinal epithelial cell (IEC) reactive oxygen species during colitis to affect phosphatase and tensin homolog (PTEN), PI3K, and β-catenin signaling. Here, we examined effects of 5-ASA on oxidant-induced cell signaling pathways in HT-29 cells, IECs from mice, and biopsy tissue from control and CUC patients. Samples were selected to control for inflammation between untreated and 5-ASA-treated CUC patients. Direct evaluation of IEC in H2O2-stimulated whole colonic crypts indicated that 5-ASA reduces reactive oxygen species levels in lower crypt IECs where long-lived progenitor cells reside. Analysis of biopsies from patient samples revealed that 5-ASA increases expression of the antioxidant catalase in CUC patients. Also, 5-ASA increased nuclear peroxisome proliferator-activated receptor γ protein and target gene expression. Data showed 5-ASA-induced peroxisome proliferator-activated receptor γ DNA binding to the PTEN promoter (chromatin immunoprecipitation) and reduced both phosphorylated and oxidized (inactive) PTEN protein levels. Analysis of patient samples revealed 5-ASA that also reduced levels of active phosphorylated Akt in inflamed colitis tissue. Reduced PI3K/Akt signaling and expression of β-catenin target genes in 5-ASA-treated CUC patients additionally suggests enhanced PTEN activity as well. Therefore, 5-ASA reduces CUC-induced reactive oxygen species in colonic progenitor cells and enhances PTEN activity, thus attenuating PI3K/Akt signaling. These data suggest that the antioxidant properties of 5-ASA may be the predominant mechanism for 5-ASA chemoprevention.


Medical validity in Eastern and Western traditions.
When comparing biomedical treatments and traditional treatments from China and India, validity is established by a randomized placebo-controlled trial (RPCT). While the advantages of RPCT are uncontestable, its requirements handicap validation of treatments from Eastern traditions, which are integrated within a worldview that encompasses natural philosophy, theology, empirically based clinical experience, and spiritual and moral tenets. RPCT evolved during a time when comparatively little was known about Eastern medical traditions; about the effects of emotional, cognitive, and cultural factors on healing; or about the evolutionary biology and psychology of innate mind/body mechanisms, such as those producing placebo responses, which may constitute evolved adaptations naturally selected during human evolution. A fair way of both securing the advantages provided by RPCT and balancing them with a methodology that ensures safe and efficacious treatments from other traditions can be facilitated by examining medical validity in light of generalizations from evolutionary psychology and the cultural study of medicine.


Nonreciprocal complementation of KNOX gene function in land plants.
Class I KNOTTED-LIKE HOMEOBOX (KNOX) proteins regulate development of the multicellular diploid sporophyte in both mosses and flowering plants; however, the morphological context in which they function differs. In order to determine how Class I KNOX function was modified as land plants evolved, phylogenetic analyses and cross-species complementation assays were performed. Our data reveal that a duplication within the charophyte sister group to land plants led to distinct Class I and Class II KNOX gene families. Subsequently, Class I sequences diverged substantially in the nonvascular bryophyte groups (liverworts, mosses and hornworts), with moss sequences being most similar to those in vascular plants. Despite this similarity, moss mutants were not complemented by vascular plant KNOX genes. Conversely, the Arabidopsis brevipedicellus (bp-9) mutant was complemented by the PpMKN2 gene from the moss Physcomitrella patens. Lycophyte KNOX genes also complemented bp-9 whereas fern genes only partially complemented the mutant. This lycophyte/fern distinction is mirrored in the phylogeny of KNOX-interacting BELL proteins, in that a gene duplication occurred after divergence of the two groups. Together, our results imply that the moss MKN2 protein can function in a broader developmental context than vascular plant KNOX proteins, the narrower scope having evolved progressively as lycophytes, ferns and flowering plants diverged.


Abilities of berberine and chemically modified berberines to inhibit proliferation of pancreatic cancer cells.
Berberine (BBR) is a common nutraceutical consumed by millions worldwide. BBR has many different effects on human health, e.g., diabetes, diarrhea, inflammation and now more recently it has been proposed to have potent anti-cancer effects. BBR has been shown to suppress the growth of cancer cells more than normal cells. BBR has been proposed to exert its growth-inhibitory effects by many different biochemical mechanisms including: suppression of cell cycle progression, induction of reactive oxygen species, induction of apoptosis and autophagy and interactions with DNA potentially leading to DNA damage, and altered gene expression. Pancreatic cancer is a leading cancer worldwide associated with a poor prognosis. As our population ages, pancreatic cancer has an increasing incidence and will likely become the second leading cause of death from cancer. There are few truly-effective therapeutic options for pancreatic cancer. Surgery and certain chemotherapeutic drugs are used to treat pancreatic cancer patients. Novel approaches to treat pancreatic cancer patients are direly needed as they usually survive for less than a year after being diagnosed. In the following manuscript, we discuss the abilities of BBR and certain chemically-modified BBRs (NAX compounds) to suppress growth of pancreatic cancer cells.


The Xenopus LIM-homeodomain protein Xlim5 regulates the differential adhesion properties of early ectoderm cells.
One of the earliest lineage restriction events in embryogenesis is the specification of the primary germ layers: ectoderm, mesoderm and endoderm. In Xenopus, germ layer specification occurs prior to gastrulation and requires the transcription factor VegT both for the cell-autonomous specification of endoderm and the generation of mesoderm-inducing signals. In the absence of VegT, ectoderm is formed in all regions of the embryo. In this work, we show that VegT-depleted vegetal cells (prospective endoderm) behave like animal cells in sorting assays and ectopically express early markers of ectoderm. To gain insight into how ectoderm is specified, we looked for candidate ectoderm-specific genes that are ectopically expressed in VegT-depleted embryos, and examined the role of one of these, the LIM homeobox gene Xlim5, in ectoderm development. We show that overexpression of Xlim5 in prospective endoderm cells is sufficient to impair sorting of animal cells from vegetal cells but is not sufficient (at similar doses) to induce ectoderm-specific genes. In whole embryos, Xlim5 causes vegetal cells to segregate inappropriately to other germ layers and express late differentiation markers of that germ layer. Inhibition of Xlim5 function using an Engrailed repressor construct or a morpholino oligonucleotide causes loss of animal cell adhesion or delay in neural fold morphogenesis, respectively, without significantly affecting early ectoderm gene expression. Taken together, our results provide evidence that a primary role for Xlim5 is to specifically regulate differential cell adhesion behaviour of the ectoderm.


What is new in perceptual learning?
What is new in perceptual learning? In the early days of research, specificity was the hallmark of perceptual learning; that is, improvements following training were limited to the trained stimulus features. For example, training with a stimulus improves performance for this stimulus but not for the same stimulus when rotated by 90° (Ball & Sekuler, 1987; Spang, Grimsen, Herzog, & Fahle, 2010). Because of this specificity, learning was thought to be mediated by neural changes at the early stages of vision. In the last decade, many procedures were discovered in which transfer occurs from trained to untrained conditions under certain conditions. The location of learning is now often thought to occur in higher stage of vision and decision-making. This special issue shows how the field has progressed along these lines.


Population ageing and healthcare expenditure projections: new evidence from a time to death approach.
Health care expenditure (HCE) is not distributed evenly over a person's life course. How much is spent on the elderly is important as they are a population group that is increasing in size. However other factors, such as death-related costs that are known to be high, need be considered as well in any expenditure projections and budget planning decisions. This article analyses, for the first time in Scotland, how expenditure projections for acute inpatient care are influenced when applying two different analytical approaches: (1) accounting for healthcare (HC) spending at the end of life and (2) accounting for demographic changes only. The association between socioeconomic status and HC utilisation and costs at the end of life is also estimated. A representative, longitudinal data set is used. Survival analysis is employed to allow inclusion of surviving sample members. Cost estimates are derived from a two-part regression model. Future population estimates were obtained for both methods and multiplied separately by cost estimates. Time to death (TTD), age at death and the interaction between these two have a significant effect on HC costs. As individuals approach death, those living in more deprived areas are less likely to be hospitalised than those individuals living in the more affluent areas, although this does not translate into incurring statistically significant higher costs. Projected HCE for acute inpatient care for the year 2028 was approximately 7% higher under the demographic approach as compared to a TTD approach. The analysis showed that if death is postponed into older ages, HCE (and HC budgets) would not increase to the same extent if these factors were ignored. Such factors would be ignored if the population that is in their last year(s) of life were not taken into consideration when obtaining cost estimates.


Assessing the Reliability of Ultrasound Imaging to Examine Radial Nerve Excursion.
Ultrasound imaging allows cost effective in vivo analysis for quantifying peripheral nerve excursion. This study used ultrasound imaging to quantify longitudinal radial nerve excursion during various active and passive wrist movements in healthy participants. Frame-by-frame cross-correlation software allowed calculation of nerve excursion from video sequences. The reliability of ultrasound measurement of longitudinal radial nerve excursion was moderate to high (intraclass correlation coefficient range = 0.63-0.86, standard error of measurement 0.19-0.48). Radial nerve excursion ranged from 0.41 to 4.03 mm induced by wrist flexion and 0.28 to 2.91 mm induced by wrist ulnar deviation. No significant difference was seen in radial nerve excursion during either wrist movement (p > 0.05). Wrist movements performed in forearm supination produced larger overall nerve excursion (1.41 ± 0.32 mm) compared with those performed in forearm pronation (1.06 ± 0.31 mm) (p < 0.01). Real-time ultrasound is a reliable, cost-effective, in vivo method for analysis of radial nerve excursion.


Pineal cysts - a benign consequence of mild hypoxia in a near-term brain?
Pineal cysts are benign glial uniloculated or multiloculated fluid-filled sacs located in the pineal gland region. Small pineal cysts are often found incidentally in healthy adults in 1.5-10.8%. Large cysts may cause neurological problems due to pressure exertion on adjacent structures. We have used prospective, observational study of an inception cohort of 16 adolescents of mean age 21.69 years (SD=±0.87) with mild (68.7%) to moderate (31.3%) HIE: 7 girls (43.8%) and 9 (56.3%) boys, born with mean gestational age of 35.75 weeks (SD=±3.80) and mean birthweight of 2 644 g (SD=±815). HIE was confirmed by presence of abnormal CTG and/or meconium and/or Apgar scores less than 7 at 5 minutes and/or need for resuscitation and/or cord pH less than 7.2 and /or BE more than -15. The clinical assessment of HIE was done according to the Sarnat-Sarnat scoring. Neonatal data, including EEG and imaging data, were collected. Adolescents were scanned with 3T Magnetom Trio Tim, Siemens, head coil 12 channels, regular sequences and sagittal 3D magnetization-prepared rapid acquisition gradient echo (MPRAGE) sequence with voxel size 1 mm3. Neurological outcome was determined. In 1 patient we found cortical dysplasia and 1 had a panic attack hence their data were omitted. In the group of 14 we have incidentally found in 5 patients a larger, asymptomatic pineal cysts with the overall incidence of 36%. Other MR findings in the group were in 50% white matter injury, in 50% thinner corpus callosum. No statistically significant difference between neonatal cUS and late follow-up MRI (p=0.881) was found. Correlation was not significant with Spearman correlation coefficient 0.201. Presence of pineal cysts was linked to thinner corpus callosum (p=0.005). We propose that larger pineal cyst, in the absence of other imaging findings except for thinner corpus callosum, is a benign consequence of mild hypoxia in a near-term brain. Our findings warrant a larger study.


Pediatric migraine: abortive management in the emergency department.
Studies suggest that headache accounts for approximately 1% of pediatric emergency department (ED) visits. ED physicians must distinguish between primary headaches, such as a tension or migraine, and secondary headaches caused by systemic disease including neoplasm, infection, or intracranial hemorrhage. A recent study found that 40% of children presenting to the ED with headache were diagnosed with a primary headache, and 75% of these were migraine. Once the diagnosis of migraine has been made, the ED physician is faced with the challenge of determining appropriate abortive treatment. This review summarizes the most recent literature on pediatric migraine with an emphasis on diagnosis and abortive treatment in the ED.


Complement receptor 1 variants confer protection from severe malaria in Odisha, India.
In Plasmodium falciparum infection, complement receptor-1 (CR1) on erythrocyte's surface and ABO blood group play important roles in formation of rosettes which are presumed to be contributory in the pathogenesis of severe malaria. Although several studies have attempted to determine the association of CR1 polymorphisms with severe malaria, observations remain inconsistent. Therefore, a case control study and meta-analysis was performed to address this issue. Common CR1 polymorphisms (intron 27 and exon 22) and blood group were typed in 353 cases of severe malaria (SM) [97 cerebral malaria (CM), 129 multi-organ dysfunction (MOD), 127 non-cerebral severe malaria (NCSM)], 141 un-complicated malaria and 100 healthy controls from an endemic region of Odisha, India. Relevant publications for meta-analysis were searched from the database. The homozygous polymorphisms of CR1 intron 27 and exon 22 (TT and GG) and alleles (T and G) that are associated with low expression of CR1 on red blood cells, conferred significant protection against CM, MOD and malaria deaths. Combined analysis showed significant association of blood group B/intron 27-AA/exon 22-AA with susceptibility to SM (CM and MOD). Meta-analysis revealed that the CR1 exon 22 low expression polymorphism is significantly associated with protection against severe malaria. The results of the present study demonstrate that common CR1 variants significantly protect against severe malaria in an endemic area.


Dose requirements for UVC disinfection of catheter biofilms.
Bacterial biofilms on permanent catheters are the major sources of infection. Exposure to ultraviolet-C (UVC) light has been proposed as a method for disinfecting the inner surface of catheters. Specification of a UVC-based device for in vivo disinfection is based on the knowledge of the required doses to kill catheter biofilm. Given these doses and the power of available UVC light sources, calculation of the necessary treatment times is then possible. To determine the required doses, contaminated urinary catheters were used as test samples and UVC treated in vitro. Patient catheters (n = 67) were collected and cut into segments of equal size and treated with various UVC doses. After treatment, the biofilm was removed by scraping and quantified by counting colony forming units. Percentage killing rates were determined by calculating ratios between UVC-treated samples and controls (no UVC treatment). Mean killing rates were 89.6% (0.5 min), 98% (2 min), and 99% (60 min). Approximately 99% killing was obtained with a UVC dose of 15 kJ m(-2). This dose, which is about 100 to 1000 times greater than the lethal dose for planktonic cells, is expected to be the maximum dose required to maintain newly inserted catheters free of contamination. The combination of high doses required to kill mature biofilm and the limited effect of current UVC light sources result in a relative long treatment time ( approximately 60 min). If a UVC-based method is to be of practical use for disinfection of catheters in the clinic, repeated preventive treatments should be carried out on newly inserted catheters.


Implications of Optic Disc Tilt in the Progression of Primary Open-Angle Glaucoma.
To evaluate the effect of optic disc tilt on the progression of glaucoma in myopic glaucomatous eyes. The disc tilt ratio was estimated on disc photographs. Glaucomatous progression was determined either by stereoscopic optic disc/retinal nerve fiber layer photographs or serial visual field data. All participants were categorized into two groups according to tilt ratio (nontilted [<1.3] or tilted [≥1.3]). Kaplan-Meier life-table analysis was used to compare the survival experiences (time to confirmed glaucomatous progression) between groups. The hazard ratios (HRs) for the associations between potential risk factors and progression were determined by using Cox proportional hazards modeling. A total of 85 eyes in 85 myopic glaucoma patients (axial length > 24 mm; mean follow-up, 4.1 years) were included. Among them, 42 eyes (49.4%) demonstrated progression and 43 eyes (50.6%) were stable on follow-up. The mean disc tilt ratio was significantly smaller, and the prevalence of disc hemorrhage higher, in the progression than the stable group (P = 0.032, P = < 0.001, respectively). The cumulative probability of progression was 24.7% in the tilted group and 68.7% in the nontilted group (P = 0.005). Disc hemorrhage (HR = 3.317; P = 0.001) and the tilt ratio (HR = 0.110; P = 0.046) were predictive of progression. Myopic eyes with tilted disc demonstrated a smaller probability of glaucomatous progression. Optic disc tilt may be protective against glaucoma progression, or tilted myopic glaucomatous eyes may have less progressive characteristic by nature.


Gas exchange after pulmonary thromboemoblization in dogs.
Gas exchange following experimental pulmonary thromboembolization was studied with an inert gas elimination technique in 17 dogs. Pulmonary arterial, systemic arterial, and expired gas concentrations of six gases infused intravenously were measured before embolization and 5, 10, 15, 30, 60, and 120 minutes after embolization. Distributions of ventilation-perfusion (VA/Q) ratios were derived from the measured concentrations. In all dogs, embolization caused an increase in blood flow and ventilation to VA/Q ratios less than 1. There were no lung units with VA/Q ratios between 10 and 100 before embolization, but, in two-thirds of the dogs, such regions developed after embolization. Ventilation to unperfused lung showed a transient increase of 2-6%. Radioisotope studies of lobes removed post-mortem indicated that thromboemboli rarely caused complete abolition of lobar blood flow. Pulmonary embolization did not cause arteriovenous shunts to appear. The hypoxemia caused by embolization could be accounted for by the changes in VA/Q distributions. Over the 2-hour period after embolization, lung function improved as the distributions partially returned toward the preembolization patterns.


Infections in children with down syndrome and acute myeloid leukemia: a report from the Canadian infections in AML research group.
Children with Down syndrome (DS) are at high risk of infectious toxicity when treated with acute lymphoblastic leukemia chemotherapy protocols optimized in children without DS. Our objective was to determine if children with DS and acute myeloid leukemia (AML) have a different risk of infection when treated with chemotherapy protocols developed for children with DS compared to AML treatment protocols developed for children without DS. We conducted a retrospective, population-based cohort study that included DS children ≤ 18 years of age with de novo, non-M3 AML diagnosed between January 1995 and December 2004, and treated at 15 Canadian centers. Patients were monitored for infection from initiation of AML treatment until recovery from the last cycle of chemotherapy, conditioning for hematopoietic stem cell transplantation, relapse, persistent disease or death (whichever occurred first). Trained research associates abstracted all information from each site. There were 31 children with DS included; median age was 1.7 (range 0.1-11.1) years. Eleven were treated according to a DS-specific protocol while 20 were treated with non-DS specific protocols. A total of 157 courses of chemotherapy were delivered. Microbiologically documented sterile site infection occurred in 11.9% and 14.3% of DS-specific and non-DS specific AML treatment courses respectively. Sepsis was rare and there were no infection-related deaths. In multiple regression, treatment with a DS-specific protocol was independently associated with a reduction in microbiologically documented sterile site infection (adjusted odds ratio (OR) 0.65, 95% confidence interval (CI) 0.42-0.99; P = 0.044), and clinically documented infection (adjusted OR 0.36, 95% CI 0.14-0.91; P = 0.031) but not bacteremia (adjusted OR 0.73, 95% CI 0.44-1.22; P = 0.231). Our study suggests that children with DS do not experience excessive infectious toxicity during treatment for AML compared to children without DS. Incorporation of DS-specific AML treatment protocols is associated with a more favorable infection profile for children with DS-AML.


Process design and economic analysis of a citrus waste biorefinery with biofuels and limonene as products.
Process design and economic analysis of a biorefinery for the treatment of citrus wastes (CW) at different capacities was carried out. The CW is hydrolyzed using dilute sulfuric acid and then further processed to produce limonene, ethanol and biogas. The total cost of ethanol for base case process with 100,000 tons/year CW capacity was calculated as 0.91 USD/L, assuming 10 USD/ton handling and transportation cost of CW to the plant. However, this price is sensitive to the plant capacity. With constant price of methane and limonene, changing the plant capacity from 25,000 to 400,000 tons CW per year results in reducing ethanol costs from 2.55 to 0.46 USD/L in an economically feasible process. In addition, the ethanol production cost is sensitive to the transportation cost of CW. Increasing this cost from 10 to 30 USD/ton for the base case results in increasing the ethanol costs from 0.91 to 1.42 USD/L.


Internal construct validity of the Warwick-Edinburgh Mental Well-being Scale (WEMWBS): a Rasch analysis using data from the Scottish Health Education Population Survey.
The Warwick-Edinburgh Mental Well-Being Scale (WEMWBS) was developed to meet demand for instruments to measure mental well-being. It comprises 14 positively phrased Likert-style items and fulfils classic criteria for scale development. We report here the internal construct validity of WEMWBS from the perspective of the Rasch measurement model. The model was applied to data collected from 779 respondents in Wave 12 (Autumn 2006) of the Scottish Health Education Population Survey. Respondents were aged 16-74 (average 41.9) yrs. Initial fit to model expectations was poor. The items 'I've been feeling good about myself', 'I've been interested in new things' and 'I've been feeling cheerful' all showed significant misfit to model expectations, and were deleted. This led to a marginal improvement in fit to the model. After further analysis, more items were deleted and a strict unidimensional seven item scale (the Short Warwick Edinburgh Mental Well-Being Scale (SWEMWBS)) was resolved. Many items deleted because of misfit with model expectations showed considerable bias for gender. Two retained items also demonstrated bias for gender but, at the scale level, cancelled out. One further retained item 'I've been feeling optimistic about the future' showed bias for age. The correlation between the 14 item and 7 item versions was 0.954.Given fit to the Rasch model, and strict unidimensionality, SWEMWBS provides an interval scale estimate of mental well-being. A short 7 item version of WEMWBS was found to satisfy the strict unidimensionality expectations of the Rasch model, and be largely free of bias. This scale, SWEMWBS, provides a raw score-interval scale transformation for use in parametric procedures. In terms of face validity, SWEMWBS presents a more restricted view of mental well-being than the 14 item WEMWBS, with most items representing aspects of psychological and eudemonic well-being, and few covering hedonic well-being or affect. However, robust measurement properties combined with brevity make SWEMWBS preferable to WEMWBS at present for monitoring mental well-being in populations. Where face validity is an issue there remain arguments for continuing to collect data on the full 14 item WEMWBS.


Classical conditioning and retention in normal and mutant Drosophila melanogaster.
By changing the conditioned discrimination paradigm of Quinn et al. (1974) from an instrumental procedure to a classical (Pavlovian) one, we have demonstrated strong learning in wildtype flies. About 150 flies were sequestered in a closed chamber and trained by exposing them sequentially to two odors in air currents. Flies received twelve electric shock pulses in the presence of the first odor (CS+) but not in the presence of the second odor (CS-). To test for conditioned avoidance responses, flies were transported to a T-maze choice point, between converging currents of the two odors. Typically, 95% of trained flies avoided the shock-associated odor (CS+). Acquisition of learning was a function of the number of shock pulses received during CS+ presentation and was asymptotic within one training cycle. Conditioned avoidance increased with increasing shock intensity or odor concentration and was very resistant to extinction. Learning was best when CS+ presentations overlap shock (delay conditioning) and then decreased with increasing CS-US interstimulus intervals. Shocking flies immediately before CS+ presentation (backward conditioning) produced no learning. Nonassociative control procedures (CS Alone, US Alone and Explicitly Unpaired) produced slight decreases in avoidance responses, but these affected both odors equally and did not alter our associative learning index (A). Memory in wild-type flies decayed gradually over the first seven hours after training and still was present 24 h later. The mutants amnesiac, rutabaga and dunce showed appreciable learning acquisition, but their memories decayed very rapidly during the first 30 min. After this, the rates of decay slowed sharply; conditioned avoidance still was measureable at least three hours after training.


Condom use and sexuality communication with adults: a study among high school students in South Africa and Tanzania.
Fostering adolescents' communication on sexuality issues with their parents and other significant adults is often assumed to be an important component of intervention programmes aimed at promoting healthy adolescent sexual practices. However, there are few studies describing the relationship between such communication and sexual practices, particularly in sub-Saharan Africa. This study examined the relationships between adolescents' communication with significant adults and their condom use in three sites in this region. Data stem from a multi-site randomized controlled trial of a school-based HIV prevention intervention implemented in Cape Town and Mankweng, South Africa and Dar es Salaam, Tanzania. Only data from comparison schools were used. The design is therefore a prospective panel study with three waves of data collections. Data were collected in 2004 from 6,251 participants in 40 schools. Associations between adolescents' communication with adults about sexuality issues and their use of condoms were analysed cross-sectionally using analysis of variance, as well as prospectively using multiple ordinal logistic regression analysis. Cross-sectional analyses showed that consistent condom users had significantly higher mean scores on communication (across topics and communication partners) than both occasional users and never-users, who had the lowest scores. After controlling for condom use at the first data collection occasion in each model as well as for possible confounders, communication scores significantly predicted consistent condom use prospectively in all three ordinal logistic regression models (Model R(2) = .23 to .31). The findings are consistent with the assertion that communication on sexuality issues between adolescents and significant adults results in safer sexual practices, as reflected by condom use, among in-school adolescents. The associations between communication variables and condom use might have been stronger if we had measured additional aspects of communication such as whether or not it was initiated by the adolescents themselves, the quality of advice provided by adults, and if it took place in a context of positive adult-adolescent interaction. Studies with experimental designs are needed in order to provide stronger evidence of causality.