Environmental drivers of distribution and reef development of the Mediterranean coral Cladocora caespitosa

Cladocora caespitosa is the only Mediterranean scleractinian similar to tropical reef-building corals. While this species is part of the recent fossil history of the Mediterranean Sea, it is currently considered endangered due to its decline during the last decades. Environmental factors affecting the distribution and persistence of extensive bank reefs of this endemic species across its whole geographic range are poorly understood. In this study, we examined the environmental response of C. caespitosa and its main types of assemblages using ecological niche modeling and ordination analysis. We also predicted other suitable areas for the occurrence of the species and assessed the conservation effectiveness of Mediterranean marine protected areas (MPAs) for this coral. We found that phosphate concentration and wave height were factors affecting both the occurrence of this versatile species and the distribution of its extensive bioconstructions in the Mediterranean Sea. A set of factors (diffuse attenuation coefficient, calcite and nitrate concentrations, mean wave height, sea surface temperature, and shape of the coast) likely act as environmental barriers preventing the species from expansion to the Atlantic Ocean and the Black Sea. Uncertainties in our large-scale statistical results and departures from previous physiological and ecological studies are also discussed under an integrative perspective. This study reveals that Mediterranean MPAs encompass eight of the ten banks and 16 of the 21 beds of C. caespitosa. Preservation of water clarity by avoiding phosphate discharges may improve the protection of this emblematic species.Spanish Ministry of Economy and Competitiveness [CTM2014-57949-R]info:eu-repo/semantics/publishedVersio

High expression of Lewis(y/b )antigens is associated with decreased survival in lymph node negative breast carcinomas

INTRODUCTION: There is sufficient evidence that blood group related Lewis antigens are tumour-associated molecules. The Lewis(y )and Lewis(b )antigens are complex carbohydrates that are over-expressed by breast, lung, colon and ovarian cancers. The SC101 mAb is a unique Lewis(y/b )binding antibody that binds to native and extended Lewis(y )and Lewis(b )haptens, displaying no cross reactivity with H type 1, H type 2, Lewis(x )or normal blood group antigens. METHODS: Immunohistochemical detection of Lewis(y/b )was performed on 660 formalin-fixed, paraffin embedded breast tumour specimens using a streptavidin-biotin peroxidase technique. Tissue from these patients had previously been included in tissue microarrays. This cohort comprises a well characterized series of patients with primary operable breast cancer diagnosed between 1987 and 1992, obtained from the Nottingham Tenovus Primary Breast Carcinoma Series. This includes patients 70 years of age or less, with a mean follow up of 7 years. RESULTS: Of the breast carcinomas, 370 of 660 (56%) were negative for Lewis(y/b )expression, 110 (17%) cases showed a low level of expression (<25% of positive cells) and only 54 cases (8%) showed extensive expression of Lewis(y/b )(>75% of positive cells). We found significant positive associations between histological grade (p < 0.001), Nottingham Prognostic Index (p = 0.016), tumour type (p = 0.007) and the level of Lewis (y/b )expression. There was a significant correlation between the proportion of Lewis(y/b )positive tumour cells and survival in lymph-node negative patients (p = 0.006). CONCLUSION: The unique epitope recognised by SC101 mAb on Lewis(y/b )hapten is over-expressed on breast tumour tissue compared with normal breast. In this large series of invasive breast cancers, higher expression of Lewis(y/b )was more often found in high grade and poor prognosis tumours compared to good prognosis cancers. Moreover, in lymph node negative breast carcinomas, over-expression of Lewis(y/b )hapten was associated with significantly decreased patient survival

<i>Toxoplasma gondii</i> peptide ligands open the gate of the HLA class I binding groove

HLA class I presentation of pathogen-derived peptide ligands is essential for CD8+ T-cell recognition of Toxoplasma gondii infected cells. Currently, little data exist pertaining to peptides that are presented after T. gondii infection. Herein we purify HLA-A*02:01 complexes from T. gondii infected cells and characterize the peptide ligands using LCMS. We identify 195 T. gondii encoded ligands originating from both secreted and cytoplasmic proteins. Surprisingly, T. gondii ligands are significantly longer than uninfected host ligands, and these longer pathogen-derived peptides maintain a canonical N-terminal binding core yet exhibit a C-terminal extension of 1-30 amino acids. Structural analysis demonstrates that binding of extended peptides opens the HLA class I F' pocket, allowing the C-terminal extension to protrude through one end of the binding groove. In summary, we demonstrate that unrealized structural flexibility makes MHC class I receptive to parasite-derived ligands that exhibit unique C-terminal peptide extensions.Fil: McMurtrey, Curtis. University of Oklahoma; Estados UnidosFil: Trolle, Thomas. Technical University of Denmark; Dinamarca. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Sansom, Tiffany. University at Buffalo; Estados UnidosFil: Remesh, Soumya G.. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Kaever, Thomas. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Bardet, Wilfried. University of Oklahoma; Estados UnidosFil: Jackson, Kenneth. University of Oklahoma; Estados UnidosFil: McLeod, Rima. University of Chicago; Estados UnidosFil: Sette, Alessandro. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Nielsen, Morten. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina. Technical University of Denmark; DinamarcaFil: Zajonc, Dirk M.. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Blader, Ira J. University at Buffalo; Estados UnidosFil: Peters, Bjoern. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Hildebrand, William. University of Oklahoma; Estados Unido

Predictors for nurses and midwives' readiness towards self-directed learning: An integrated review

Aim. To systematically review the existing evidence on predictors for nurses and midwives' readiness towards Self-directed Learning (SDL). Background. Increased complexities in healthcare settings demand that nurses and midwives become involved in lifelong learning by means of self-directed learning (SDL) for delivering quality healthcare. More evidence is available for the self-directed learning readiness (SDLR) of nursing and midwifery students, less is systematically derived on predictors for nurses and midwives' readiness to SDL. Design. An integrative systematic review. Methods. Systematic searches were carried out using the following five electronic databases: PubMed, Science Direct, Google Scholar, Ovid Medline and Embase. Studies published in English language from 2000 to 2017 were included. The integrative systematic review framework developed by Whittemore and Knafl (2005) was used to analyse and summarise the key themes. Results. Of 804 initial screening papers, in total of eight eligible studies (six quantitative and two qualitative) were found. Integrative analysis resulted in four themes as predictors for nurses and midwives' readiness towards SDL: 1) personal characteristics, 2) working environment, 3) online learning and SDLR, and 4) process of SDL. Review found that, although demographic characteristics of nurses and midwives do not influence their SDLR, work environment often influences their SDLR. Furthermore, nurses and midwives have a positive interest in online learning that is often used to improve their knowledge acquisition. Conclusion. The review concludes that qualified nurses and midwives have a unique SDL predictors and process; hence, a personalized SDL programme should be prescribed based on personality traits so as to achieve better SDL outcomes. Future research should address the facilitating factors for SDLR, barriers to SDLR and strategies to improve SDLR among nurses and more importantly midwives, as limited evidence is available with respect to the latter

Incidence of anogenital warts in Germany: a population-based cohort study

<p>Abstract</p> <p>Background</p> <p>Human papilloma virus (HPV) types 6 and 11 account for 90 percent of anogenital warts (AGW). Assessment of a potential reduction of the incidence of AGW following introduction of HPV vaccines requires population-based incidence rates. The aim of this study was to estimate incidence rates of AGW in Germany, stratified by age, sex, and region. Additionally, the medical practitioner (gynaecologist, dermatologist, urologist etc.) who made the initial diagnosis of AGW was assessed.</p> <p>Methods</p> <p>Retrospective cohort study in a population aged 10 to 79 years in a population-based healthcare insurance database. The database included more than 14 million insurance members from all over Germany during the years 2004-2006. A case of AGW was considered incident if a disease-free period of twelve months preceded the diagnosis. To assess regional variation, analyses were performed by federal state.</p> <p>Results</p> <p>The estimated incidence rate was 169.5/100,000 person-years for the German population aged 10 to 79 years. Most cases occurred in the 15 to 40 years age group. The incidence rate was higher and showed a peak at younger ages in females than in males. The highest incidence rates for both sexes were observed in the city-states Berlin, Hamburg and Bremen. In females, initial diagnosis of AGW was most frequently made by a gynaecologist (71.7%), whereas in males, AGW were most frequently diagnosed by a dermatologist (44.8%) or urologist (25.1%).</p> <p>Conclusions</p> <p>Incidence of AGW in Germany is comparable with findings for other countries. As expected, most cases occurred in the younger age groups. The frequency of diagnoses of AGW differs between sexes and women and men receive treatment by doctors of different specialties.</p

Longitudinal variability of time-location/activity patterns of population at different ages: a longitudinal study in California

<p>Abstract</p> <p>Background</p> <p>Longitudinal time-activity data are important for exposure modeling, since the extent to which short-term time-activity data represent long-term activity patterns is not well understood. This study was designed to evaluate longitudinal variations in human time-activity patterns.</p> <p>Method</p> <p>We report on 24-hour recall diaries and questionnaires collected via the internet from 151 parents of young children (mostly under age 55), and from 55 older adults of ages 55 and older, for both a weekday and a weekend day every three months over an 18-month period. Parents also provided data for their children. The self-administrated diary and questionnaire distinguished ~30 frequently visited microenvironments and ~20 activities which we selected to represent opportunities for exposure to toxic environmental compounds. Due to the non-normal distribution of time-location/activity data, we employed generalized linear mixed-distribution mixed-effect models to examine intra- and inter-individual variations. Here we describe variation in the likelihood of and time spent engaging in an activity or being in a microenvironment by age group, day-type (weekday/weekend), season (warm/cool), sex, employment status, and over the follow-up period.</p> <p>Results</p> <p>As expected, day-type and season influence time spent in many location and activity categories. Longitudinal changes were also observed, e.g., young children slept less with increasing follow-up, transit time increased, and time spent on working and shopping decreased during the study, possibly related to human physiological changes with age and changes in macro-economic factors such as gas prices and the economic recession.</p> <p>Conclusions</p> <p>This study provides valuable new information about time-activity assessed longitudinally in three major age groups and greatly expands our knowledge about intra- and inter-individual variations in time-location/activity patterns. Longitudinal variations beyond weekly and seasonal patterns should be taken into account in simulating long-term time-activity patterns in exposure modeling.</p

Targeted Drug Delivery by Gemtuzumab Ozogamicin: Mechanism-Based Mathematical Model for Treatment Strategy Improvement and Therapy Individualization

Gemtuzumab ozogamicin (GO) is a chemotherapy-conjugated anti-CD33 monoclonal antibody effective in some patients with acute myeloid leukemia (AML). The optimal treatment schedule and optimal timing of GO administration relative to other agents remains unknown. Conventional pharmacokinetic analysis has been of limited insight for the schedule optimization. We developed a mechanism-based mathematical model and employed it to analyze the time-course of free and GO-bound CD33 molecules on the lekemic blasts in individual AML patients treated with GO. We calculated expected intravascular drug exposure (I-AUC) as a surrogate marker for the response to the drug. A high CD33 production rate and low drug efflux were the most important determinants of high I-AUC, characterizing patients with favorable pharmacokinetic profile and, hence, improved response. I-AUC was insensitive to other studied parameters within biologically relevant ranges, including internalization rate and dissociation constant. Our computations suggested that even moderate blast burden reduction prior to drug administration enables lowering of GO doses without significantly compromising intracellular drug exposure. These findings indicate that GO may optimally be used after cyto-reductive chemotherapy, rather than before, or concomitantly with it, and that GO efficacy can be maintained by dose reduction to 6 mg/m2 and a dosing interval of 7 days. Model predictions are validated by comparison with the results of EORTC-GIMEMA AML19 clinical trial, where two different GO schedules were administered. We suggest that incorporation of our results in clinical practice can serve identification of the subpopulation of elderly patients who can benefit most of the GO treatment and enable return of the currently suspended drug to clinic