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A seven-valent pneumococcal conjugate vaccine (PCV7) was introduced in the Danish childhood immunization program (2+1 schedule) in October 2007, followed by PCV13 starting from April 2010. The nationwide incidence of IPD among children younger than 5 years nearly halved after the introduction of PCV7 in the program, mainly due to a decline in IPD caused by PCV7-serotypes. We report the results from a nationwide population-based cohort study of laboratory confirmed IPD cases in children younger than 5 years during October 1, 2007 to December 31, 2010 and describe the characteristics of children suspected to present with a vaccine failure. The period between April 19 and December 31, 2010 was considered a PCV7/PCV13 transitional period, where both vaccines were offered. We identified 45 episodes of IPD caused by a PCV7 serotype (23% of the total number) and 105 (55%) caused by one of the 6 additional serotypes in PCV13. Ten children had received at least one PCV7 dose before the onset of IPD caused by a PCV7 serotype. Seven children were considered to be incompletely vaccinated before IPD, but only three cases fulfilled the criteria of vaccine failure (caused by serotypes 14, 19F and 23F). One case of vaccine failure was observed in a severely immunosuppressed child following three PCV7 doses, and two cases were observed in immunocompetent children following two infant doses before they were eligible for their booster. None of the IPD cases caused by the additional PCV13 serotypes had been vaccinated by PCV13 and there were therefore no PCV13-vaccine failures in the first 8-months after PCV13 introduction in Denmark.
Citation: Harboe ZB, Valentiner-Branth P, Ingels H, Rasmussen JN, Andersen PHS, Bjerre CC, et al. (2013) Pediatric Invasive Pneumococcal Disease Caused by Vaccine Serotypes following the Introduction of Conjugate Vaccination in Denmark. PLoS ONE 8(1): e51460. https://doi.org/10.1371/journal.pone.0051460
Editor: Ray Borrow, Health Protection Agency, United Kingdom of America
Received: October 24, 2011; Accepted: November 6, 2012; Published: January 24, 2013
Copyright: © 2013 Harboe et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This research was supported by Statens Serum Institut, since data were collected routinely for national surveillance purposes through funding allocated to national surveillance. The funding entity did not have any influence in the study design; collection, analysis, and interpretation of data; writing of the paper; and decision to submit it for publication.
Competing interests: The authors have declared that no competing interests exist.
A seven-valent pneumococcal conjugate vaccine (PCV7) was introduced in the Danish childhood immunization program in October 2007. Shortly after its introduction, the incidence of invasive pneumococcal disease (IPD) declined markedly, in particular among children younger than 2 years, where the incidence halved compared to the pre-vaccination period [1], [2]. The decline was mainly related to a decrease in the incidence of IPD caused by vaccine serotypes (VT-IPD) [2]. These results are consistent with those observed in other industrialized countries and support the high effectiveness of PCV7 against VT-IPD [3]–[6].
Changes in the serotype distribution of invasive pneumococci were described to occur at an early stage in the post-vaccination period in Denmark and non-vaccine serotypes 7F and 1 were found predominantly as a cause of non-VT-IPD in children [7]. However, and similarly to what has been observed in other countries, cases of VT-IPD are still observed in the population during the post-PCV7 period among children for whom vaccination was offered [8], [9].
Cases of VT-IPD raise concerns related to the vaccine's effectiveness and to the possibility of immunological disorders in the affected child. It is well recognized that not all serotypes in the pneumococcal conjugate vaccines (PCV) are equally immunogenic and that the immune response also varies according to the number of doses administered [10]–[12]. Furthermore, incomplete vaccination and co-morbid conditions (such as immunodeficiencies, malignancies, prematurity, and several chronic diseases, among others) have been identified as factors contributing to VT-IPD in vaccinated children [8], [9]. Also, cases of vaccine failure in apparently immunocompetent children have been described [13]–[15].
In October 2007, an enhanced nationwide, population-based surveillance of laboratory confirmed IPD cases in children younger than 5 years was implemented in Denmark in order to identify patients where a vaccine failure could be suspected. This information is considered valuable in order to understand the underlying mechanisms behind a case of vaccine failure and may contribute to identify a subpopulation of children that might need additional immunological investigation.
We hereby report the results from a nationwide population-based cohort study of laboratory confirmed IPD cases in children younger than 5 years of age and describe the characteristics of children with vaccine-type IPD during a 31-month surveillance period.
Materials and Methods
Study Setting and Design
We conducted a nationwide cohort study based on population-based surveillance data on laboratory confirmed IPD in children younger than 5 years of age after the introduction of PCV in the Danish childhood immunization program. Laboratory surveillance data on IPD from October 1, 2007 to December 31, 2010 were linked to the Danish Childhood Vaccination Registry as previously described [2]. Information regarding the patients' clinical course and blood samples for immunological testing were routinely collected by a physician in cases where a vaccine failure was suspected. Since data and samples from patients were collected routinely for national surveillance purposes, no ethical approval or informed consent from patients were required. The study was approved by the Danish Data Protection Agency (no. 2007-41-0229).
Pneumococcal Conjugate Vaccination in Denmark
A PCV has been offered free of charge as a part of the routine childhood immunization program since October 1, 2007 in a reduced 2+1 schedule at the ages of 3, 5, and 12 months. PCV7 started to be offered from October 1, 2007. For an introduction period, children aged 12–17 months at the first vaccination (born after April 30, 2006) were offered a catch-up program of two doses of PCV7 with a minimum interval of two months [16]. The thirteen-valent pneumococcal conjugate vaccine (PCV13) started to be offered on April 19, 2010 [17]. General practitioners were recommended to use their stocks of PCV7 before start using PCV13, and therefore the period following the introduction of PCV13 can only be considered as a transition period, where both PCV7 and PCV13 were administered.
During 2007–2010, approximately 64.000 children were born annually in Denmark (http://www.statistikbanken.dk). The vaccination uptake of PCV7 and the concomitantly administered single shot vaccine against diphtheria, tetanus, acellular pertussis, poliomyelitis and Haemophilus influenzae type b (DTaP-IPV/Hib Statens Serum Institut, Copenhagen, Denmark) has been reported elsewhere [1], [18]. In brief, PCV7's uptake was reported to be approximately two percentage points lower than the uptake of DTaP-IPV/Hib vaccine. The uptake of the primary vaccination program with PCV7 for the birth cohorts 2007–2009 was 81–91% for the first, second and booster doses. The uptake of the catch-up program was lower, 51–76% depending on the age of the child and the number of doses given [18]. No shortages in stockpiles or interruption of the distribution of the vaccines have been reported.
National Surveillance of Pediatric IPD and PCV-Failures
Figure 1 shows the components and setup of the national surveillance system of pediatric IPD and PCV-failures. In brief, all departments of clinical microbiology in Denmark send invasive Streptococcus pneumoniae isolates for determination of serotype to the National Neisseria and Streptococcus Reference Center (NSR), Statens Serum Institut (SSI). The characteristics and completeness of the national surveillance system for IPD have previously been described [19]. Approximately 90% of the isolates are obtained from hospitalized patients [20]. Notification of IPD in children younger than 5 years of age and submission of pneumococcal isolates causing IPD in all age groups became mandatory by law after October 1, 2007 in order to monitor the effectiveness of PCV [21].
Cases of IPD caused by a serotype included in PCV7 or one of the additional serotypes included in PCV13 are identified among all IPD cases in children <5 years in order to explore possible cases of vaccine failure. PCV7 was administered in the national childhood immunization program free of charge from October 1, 2007 to April 19, 2010 and then PCV13 was offered. CSF: Cerebrospinal fluid; NSR: National Neisseria and Streptococcus Reference Center, Statens Serum Institut: SSI, MBL: Mannose-Binding Lectin, RTI: Respiratory Tract Infections, WBC: White Blood Cells.
Children who present with IPD due to one of PCV7-serotypes or one of the six additional serotypes included in PCV13 (after PCV13 became available in Denmark) are considered suspects of having a vaccine failure. PCV7 contains the capsular polysaccharide antigens of 7 serotypes (4, 6B, 9V, 14, 18C, 19F, and 23F). Serotypes 1, 3, 5, 6A, 7F, 19A are the six additional serotypes included in PCV13. Clinical information and vaccination status of patients are collected by telephone interview with clinicians in charge of the patient and by verification of discharge diagnoses and medical files (Figure 1). During the transition period when both PCV7 and PCV13 were administered, the vaccine's batch number was used to verify the valence of the vaccine administered to the child, if relevant. If a case fulfills the case definition of vaccine failure, supplementary blood samples from patients are requested for additional immunological investigation, in consultation with the patient's physician (Figure 1). Cases of VT-IPD in vaccinated children, regardless of the number of vaccines they had received, are reported to the Danish Medicines Agency (Lægemiddelstyrelsen) by the Department of Infectious Disease Epidemiology, SSI.
Case Definitions
Invasive Pneumococcal Disease (IPD).
A case of IPD is defined as the occurrence of IPD confirmed by a positive culture for S. pneumoniae from a patient's cerebrospinal fluid (CSF), blood or other sterile site. When both CSF and blood isolates are received from a patient, the case is categorized as meningitis. Patients are considered having a recurrence if a new IPD isolate is obtained within 30 days after the initial incidence, or if a new pneumococcal serotype is isolated within 30 days.
Non-vaccinated, Non-eligible.
Children outside the age group targeted for primary PCV7/PCV13 vaccination or catch-up program with PCV7.
Non-vaccinated, Eligible.
Children within the age group targeted for primary PCV7/PCV13 vaccination or catch-up program who presented an IPD episode before vaccination.
Children who presented an IPD episode after PCV7 immunization, regardless of the number of doses received, the time of onset of illness after vaccination and the age of immunization.
Defined as IPD caused by any of the serotypes included in all the vaccine- doses the child has received, and where one of the following criteria are met: 1) the child is under 13 months of age at IPD onset and has received two doses of PCV7 or PCV13 but not yet the booster dose, and becomes ill more than two weeks after the last dose was given; 2) the child is at least 12 months old at IPD onset, completed the primary vaccination before 12 months of age, and becomes ill more than one week after administration of the booster dose 3) the child is at least 6 months old at IPD onset, received two doses of PCV7 as a part of the catch-up program and becomes ill more than two weeks after the administration of the last dose. Children included in the first two categories were targeted during their primary vaccination and children in the third category were targeted by the catch-up program.
Laboratory Investigations
Pneumococcal Serotyping.
All IPD isolates received are routinely serotyped by using pneumotest latex and/or Quellung reaction using type-specific pneumococcal rabbit-antisera from SSI (SSI-Diagnostica, Copenhagen, Denmark) [2], [22], [23].
Serological Testing.
In cases that fulfilled criteria for PCV-failure, blood samples are requested in order to characterize the patient's antibody response after vaccination and infection. Serum samples are assayed for individual antibodies included in PCV7 or PCV13 according to the immunization schedule. Samples are analyzed by ELISA after absorption with polysaccharide 22F and cell wall polysaccharide and results expressed as concentrations of antibody against each PCV serotype. A serotype specific antibody value of 0.35 µg/mL is considered protective. ELISA assays are carried out at the Pneumococcal Serology Laboratory (SSI) and in this study, at the WHO reference laboratory for Pneumococcal Serology at the UCL Institute of Child Health, London, as previously described [24]–[26]. Functional activity of specific pneumococcal antibodies (PCV7 antibodies+6A) was measured by a opsonophagocytic assay (OPA) at the laboratories in London [27]. Additional immunological testing is carried out according to the child's clinical presentation (Figure 1).
From October 1, 2007 to December 31, 2010, 191 laboratory-confirmed IPD cases in 188 children younger than 5 years were reported, corresponding to an approximate estimated incidence of 14.6 (95% confidence interval (CI) 12.6–16.7) per 100,000 population (Table 1, Figure 2). The median age of children was 20 months (age range 0–59 months), 80% (n = 154) of isolates were obtained from blood, 20% (n = 36) CSF and only one isolate from other sterile sites (<1%). Pneumococcal serotype and vaccination status was available for all patients except in one, presenting with an IPD due to serotype 35F.
Information on pneumococcal serotypes was available for all cases, but not for three cases diagnosed by PCR (not shown in the figure). Vaccination status was available for all patients but one (IPD due to serotype 35F).
We identified 45 IPD episodes (23% of the total number) caused by a PCV7 serotype and 105 (55%) caused by one of the 6 additional serotypes in PCV13 (Table 1). None of the patients presenting IPD due to PCV7 or one of the 6 additional serotypes in PCV13 were vaccinated with PCV13. The most frequent situation was a case of IPD caused by one of the additional serotypes included in PCV13 in a child who had received at least one dose of PCV7 since the beginning of the immunization program. Among these patients, the most frequently isolated serotype was serotype 7F, 19A and 1. Among cases of non-PCV7/PCV13 serotypes after PCV13 started to be used, we identified two cases of 12F-IPD, two cases of 24F-IPD and one case caused by 33F serotype, All these patients received at least 2 doses of PCV7 before IPD.
Three patients (1.6%) presented a recurrent IPD episode: one child presented a 16F and a serotype 14 infection, one presented 6A and 6C infection, and one presented two episodes of 19A bacteremia caused by serotype 19A of MLST type ST994 in both episodes. The child received 2 doses of PCV7 before the first IPD, and had a history of recurrent acute otitis media with no other additional comorbidity. The isolates were sensitive to penicillin (MIC ≤0.1 µg/mL). No further immunological tests were carried out in this child.
IPD Caused by PCV7-Serotypes in Vaccinated Children
Ten children had received at least one PCV7 dose before the onset of IPD caused by a PCV7 serotype (Table 1, Table 2), corresponding to an estimated incidence of 0.8 cases (95% CI 0.3–1.3) per 100.000 population. No fatal cases directly related with the IPD episode were observed in these children.
Seven children were considered to be incompletely vaccinated before IPD onset and did not fulfill the criteria of vaccine-failure. Among them, three children presented important comorbid conditions (Table 2). Three other cases fulfilled the criteria of vaccine failure, two following the second dose and one following the booster dose:
The first case identified as vaccine failure was observed in a 30 month old girl, who presented with pneumococcal bacteremia caused by serotype 14 after she had received a complete immunization with PCV7 at the age of 3, 5 and 12 months. The isolate was susceptible to penicillin. The child was severely immunocompromised at IPD onset; she was admitted to the hospital with febrile leukopenia after chemotherapy due to an acute myeloid leukemia (neutrophil count <200/mm3). The child recovered well after IPD and at 12-months follow-up the child did not present signs of relapse. Due to the critical clinical condition of the child and the severe immunosuppression at IPD onset, no assays for pneumococcal antibodies or additional immunological investigation were conducted.
The second case of vaccine failure was observed in a 12-month old girl, who received primary immunization with PCV7 at 4 and 6 months of age. The child was admitted to the hospital due to febrile illness, blood cultures demonstrated S. pneumoniae serotype 19F, susceptible to penicillin. The child was discharged from the hospital shortly after admission with the clinical diagnosis of acute otitis media and received phenoxymethylpenicillin for oral treatment. The child was previously healthy, and had no clinical history of recurrent infections. The child did not have specific testing for pneumococcal antibodies or immunologic deficiencies conducted after the clinicians' consideration.
The third case of vaccine failure was observed in an 8-month old boy, who presented with pneumococcal meningitis caused by serotype 23F after 2 doses of PCV7 given at 3 and 5 months of age. The isolate was sensitive to penicillin. The child was considered as immune competent by the clinicians in charge of the patient. The full blood count including white blood cells differential, the levels of immunoglobulins (IgG, IgA, and IgM), the Mannose-Binding lectin level, and the antibody titers to tetanus, H. influenzae type b, and diphtheria toxin were within normal ranges. The antibody response to PCV7 and OPA profiles are shown in Table 3. The GMC for all PCV7 serotypes but 23F were over the protective threshold, for 23F the concentration was below the threshold (0.06 µg/mL). The OPA analysis confirmed that there was incomplete (poor) killing activity for 23F. On the follow-up after 6 months the child was clinically well with no signs or symptoms of underlying medical conditions, no other episodes of invasive bacterial disease and no evidence of recurrent respiratory tract infections. The child recovered from the episode without neurological sequelae.
Results from our population-based cohort study support that PCV7 has been effective in preventing IPD caused by vaccine serotypes in the context of a 2+1 PCV program in Denmark. PCV7-type IPD in <5 year-olds occurred mainly in unvaccinated children, with only seven cases in those who received at least one dose of PCV7 (less than 1 case per 100.000 person-years) and only three cases of true vaccine failures due to serotypes 14, 19F and 23F. Among these cases, one case of vaccine failure was observed in a severely immunosuppressed child following three PCV7 doses, and two cases were observed in immunocompetent children following two infant doses before they were eligible for their booster. In addition, none of the IPD cases caused by the additional PCV13 serotypes had been observed in children vaccinated with PCV13. Thus no PCV13-vaccine failures have been observed in the first 8-months after PCV13 was started to be used in Denmark.
Concomitantly with the decrease of PCV7 serotypes observed shortly after PCV7's introduction [2], the six additional serotypes included in PCV13 were found to be the predominant cause of pediatric IPD in our cohort of patients, similarly to what has been reported from other countries [28]. However, following the introduction of PCV13 in the program, it is not clear from our data whether further benefit in preventing IPD in children under 5 years could potentially be achieved by including additional serotypes in a pediatric vaccine, since no additional serotypes have been shown to be clearly dominating the pneumococcal population causing replacement disease. This observation could be both related to differences in the invasive potential of pneumococci and characteristics of the population [29], [30]. Nevertheless, the surveillance period after PCV7/PCV13 introduction is relatively short (8 months), and serotype replacement has to be closely followed in the future in order to evaluate replacement disease in children.
During the surveillance period immediately following the introduction of PCV7, we found that nearly one-fourth of IPD cases (n = 45/191) were caused by a serotype included in PCV7, but only 10 children were partially or completely vaccinated with PCV7 before IPD, and only 3 cases fulfilled criteria of vaccine failure (Table 1, Table 2). Comorbid conditions were identified in one-third of vaccinated children with IPD due to PCV7 serotypes, regardless of the number of doses administered (Table 2). Similar results have been reported from the US, where children belonging to moderate and high-risk groups are recommended to receive PCV-vaccination [28]. We have previously reported an approximated 8% prevalence of comorbid conditions in a nationwide cohort of patients with pediatric IPD in Denmark [20]. However, the methods used for collecting data on comorbidity and estimating the prevalence of such conditions differ greatly between the two studies (by calculation of the Charlson index vs. telephonic interviews with physicians), which make direct comparison of the findings difficult. In any case, our findings underline the importance of continued vigilance for pneumococcal disease in febrile children with comorbidity or other risk factors that make them more susceptible to the disease even after immunization with PCV.
The first case identified as a vaccine failure was due to a serotype 14 infection, a serotype which has been otherwise considered to be quite immunogenic [11], [14], [31]. A case of serotype 14-vaccine failure has previously been described in a patient enrolled in the efficacy trial carried out among Navajo and White Mountain Apache children in the US [14]. In contrast to this case, our patient was severely immunosuppressed before IPD onset. In the case from the US, the child was not known to have underlying medical conditions and had a high concentration of antibodies against serotype 14, which were also found to be functional in the OPA assay. The authors suggest that serotype-specific correlates of protection based on the ELISA cut-off values from population-based vaccine efficacy studies are not necessarily adequate to predict the level of protection at the individual level. Due to the critical clinical condition of the patient in our cohort, it was considered inappropriate to collect samples for immunological testing in this patient and they would probably be of limited value.
Serotype 19F has been found to be the most frequent serotype causing pneumococcal meningitis in PCV7-vaccinated children in France [32]. In spite of its good immunogenicity, serotype 19F has been described to induce antibodies of lower avidity that decline faster compared to other antibodies induced by the vaccine [31]. A case of vaccine failure due to serotype 19F has previously been described in the literature, in a child who presented with pneumococcal meningitis in spite of three PCV7 doses and who was considered immunocompetent [15]. In our case, the clinical course was not severe; the child was discharged shortly after admission to the hospital with oral antibiotics. The clinicians decided not to investigate the antibody profile after IPD and had no clinical suspicion of immunosuppression in this patient.
Although the infant we described with 23F vaccine failure had received only 2 doses of PCV7, the antibody response to all the vaccine serotypes except serotype 23F was satisfactory, both measured by ELISA and OPA assay (Table 2). The child was considered to be immunocompetent. A lower vaccine response to this serotype has previously been reported, with the protective threshold for antibodies to this serotype (alike serotype 6B) being reached only after the booster dose [12].
Recommendations regarding clinical management and revaccination of children presenting vaccine failures must be tailored to the individual child in different clinical settings. Probably, an additional vaccine-dose followed by antibody responses and OPA measurements are suitable recommendations, since it is well documented that in some cases of vaccine failures the patient remains refractory to responses to the invading serotype despite further doses after the infection [5], [29], [31].
Concerning IPD caused by PCV7 serotypes in non-vaccinated patients, we found that nearly 40% of children were eligible for vaccination but presented with IPD before the first dose, mainly children who were targeted by the catch-up program. It has also been described that the coverage of PCV7 is slightly lower than the coverage of DTaP-IPV/Hib, and particularly for the catch-up program. The reasons for this difference are currently unknown [1]. Still, PCV7's uptake achieved in Denmark is one of the highest in Europe, where large differences in PCV7 vaccination schemes and use of PCV7 between regions have been reported [33].
Among the strengths of our study, we can mention that we were able to report high-quality data collected through an enhanced surveillance system based on collaboration between NSR, the Department of Epidemiology, the departments of clinical microbiology and clinicians across the country (Figure 1). The register of pediatric IPD due to PCV7 serotypes or to one of the six serotypes included in PCV13 includes complete clinical, epidemiological and laboratory information on patients, which will allow us to closely monitor and improve our understanding on cases of vaccine failure. Among the needs and opportunities for our surveillance system in the future we envisage the collection of information on vaccination history from IPD-cases due to other serotypes than those included in the vaccines. This would allow us to investigate whether certain groups of children are at higher risk of getting IPD and directly assess the effectiveness of the vaccines using the indirect cohort method [5], [34].
The results of our study may be limited by several factors. We present the results from a relatively short surveillance period (39 months) which followed the introduction of PCV7 in the immunization program. This may be of importance in terms of evaluation of replacement disease among vaccinated children, considering that pneumococcal populations are highly dynamic over time and susceptible to external factors such as conjugate vaccination pressure [35]. Also, children in the study population have recently been vaccinated with PCV and a large part of the population is still incompletely vaccinated, limiting the extrapolation of these results in the long term.
A selection bias may also be present in our study, since we used a highly specific case definition including only culture confirmed IPD cases in a setting were blood- and CSF-cultures are almost exclusively obtained in hospital settings. Furthermore, we were not able to investigate the immunological status after IPD in all children with vaccine failure, which could have contributed to the understanding the underlying mechanisms.
In summary, IPD in children younger than 5 years of age was a rare event and occurred mainly in unvaccinated children in our cohort of patients. Only three cases of PCV7-failure were confirmed during a 31-month surveillance period. Seven additional IPD cases due to PCV7- serotypes were observed in incompletely vaccinated children. So far, no PCV13-vaccine failure cases have been observed, however the surveillance period was short. Children with confirmed or suspected immunosuppression should be closely monitored and assessed on an individual basis.
We would like to thank the departments of clinical microbiology in Denmark for routinely sending pneumococcal isolates for surveillance. We acknowledge the dedicated work of the staff performing the serotyping of the isolates and entering the data at the NSR Center and the staff performing serological testing of the samples at the Pneumococcal Serology Center, SSI. We thank Bente Gahrn-Hansen (Department of clinical microbiology, Odense) for the submission of isolates to NSR and critical reading of the manuscript. The contents of the article are solely the responsibility of the authors and do not necessarily represent the official views of Statens Serum Institut.
Members of the Danish Pneumococcal Surveillance Collaborating group 2007–2010 follow: Participants from SSI: Department of Infectious Disease Epidemiology: Peter H. Andersen, Steffen Glismann, Michael Howitz, Jeppe Rasmussen, Palle Valentiner-Branth. Department of Microbiological Surveillance and Research: Jens Jørgen Christensen, Zitta B. Harboe, Steen Hoffmann, Helene Ingels, Helle B. Konradsen, Lotte Lambertsen. Department of Microbiological Diagnostics: Charlotte S. Jørgensen. Participants from Departments of Clinical Microbiology in Denmark: Ram B. Dessau (Slagelse, Nykøbing F, Næstved), Poul Kjældgaard (Sønderborg), Jenny Dahl Knudsen (Hvidovre), Brian Kristensen (Skejby), Lene Leerbeck (Hillerød), Steen Lomborg (Herning), Jørgen Prag (Viborg), Per Schouenborg (Vejle), Henrik C. Schønheyder (Aalborg), Robert Skov (SSI), Michael Tvede (Rigshospitalet), Christian Østergaard (Herlev). Participants from Clinical Departments: Jon Helgestad (Pediatric Department Aalborg), Thomas Benfield (Infectious Diseases Department, Hvidovre), Mette Rokkjær (Pediatric Department, Syddanmark), Birgitte Lausen (Pediatric Department, Rigshospitalet).
Author Contributions
Culture, identification and submission of isolates and clinical samples from the departments of clinical microbiology across the country to the Neisseria and Streptococci Reference Center, Statens Serum Institut: Danish Pneumococcal Surveillance Collaborating Group. Conceived and designed the experiments: ZBH PVB PHA DG HBK LL. Performed the experiments: ZBH PVB HI PHA JNR DG LA MH LL HBK. Analyzed the data: ZBH PVB HI JNR PHA CCB DG LA MH HBK LL. Contributed reagents/materials/analysis tools: Danish Pneumococcal Surveillance Collaborating Group. Wrote the paper: ZBH PVB.
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- 19. Harboe ZB, Valentiner-Branth P, Benfield TL, Christensen JJ, Hjuler T, et al. (2008) Estimated effect of pneumococcal conjugate vaccination on invasive pneumococcal disease and associated mortality, Denmark 2000–2005. Vaccine 26(29–30): 3765–71.
- 20. Harboe ZB, Thomsen RW, Riis A, Valentiner-Branth P, Christensen JJ, et al. (2009) Pneumococcal serotypes and mortality following invasive pneumococcal disease: a population-based cohort study. PLoS Med 6(5): e1000081.
- 21.
Bekendtgørelse om ændring af bekendtgørelse om lægers anmeldelse af smitsomme sygdomme m.v. (BEK nr 1102 af 20/09/2007). Sundhedsstyrelsen, den 20. september 2007.
- 22. Henrichsen J (1995) Six newly recognized types of Streptococcus pneumoniae. J Clin Microbiol 33(10): 2759–62.
- 23. Sorensen UB (1993) Typing of pneumococci by using 12 pooled antisera. J Clin Microbiol 31(8): 2097–100.
- 24. Konradsen HB, Sorensen UB, Henrichsen J (1993) A modified enzyme-linked immunosorbent assay for measuring type-specific anti-pneumococcal capsular polysaccharide antibodies. J Immunol Methods 164(1): 13–20.
- 25. Skovsted IC, Kerrn MB, Sonne-Hansen J, Sauer LE, Nielsen AK, et al. (2007) Purification and structure characterization of the active component in the pneumococcal 22F polysaccharide capsule used for adsorption in pneumococcal enzyme-linked immunosorbent assays. Vaccine 25(35): 6490–500.
- 26. Wernette CM, Frasch CE, Madore D, Carlone G, Goldblatt D, et al. (2003) Enzyme-linked immunosorbent assay for quantitation of human antibodies to pneumococcal polysaccharides. Clin Diagn Lab Immunol 10(4): 514–9.
- 27. Rose CE, Romero-Steiner S, Burton RL, Carlone GM, Goldblatt D, et al. (2011) Multilaboratory comparison of Streptococcus pneumoniae opsonophagocytic killing assays and their level of agreement for the determination of functional antibody activity in human reference sera. Clin Vaccine Immunol 18(1): 135–42.
- 28. Hsu K, Pelton S, Karumuri S, Heisey-Grove D, Klein J (2005) Population-based surveillance for childhood invasive pneumococcal disease in the era of conjugate vaccine. Pediatr Infect Dis J 24(1): 17–23.
- 29. Dagan R (2009) Serotype replacement in perspective. Vaccine 27(Supplement 3): C22–C24.
- 30. Weinberger DM, Malley R, Lipsitch M (2011) Serotype replacement in disease after pneumococcal vaccination. Lancet 378(9807): 1962–73.
- 31. Ekström N, Ahman H, Verho J, Jokinen J, Väkeväinen M, et al. (2005) Kinetics and Avidity of Antibodies Evoked by Heptavalent Pneumococcal Conjugate Vaccines PncCRM and PncOMPC in the Finnish Otitis Media Vaccine Trial. Infect Immun 73(1): 369–77.
- 32. Bingen E, Levy C, Varon E, de La Rocque F, Boucherat M, et al. (2008) Pneumococcal meningitis in the era of pneumococcal conjugate vaccine implementation. Eur J Clin Microbiol Infect Dis 27(3): 191–9.
- 33. De Carvalho GH, Muscat M, Monnet DL, Giesecke J, Lopalco PL (2009) Use of seven-valent pneumococcal conjugate vaccine (PCV7) in Europe, 2001–2007. Euro Surveill 14(12). pii: 19159.
- 34. Miller E, Andrews NJ, Waight PA, Slack MP, George RC (2011) Effectiveness of the new serotypes in the 13-valent pneumococcal conjugate vaccine. Vaccine 29(49): 9127–31.
- 35. Hausdorff WP, Feikin DR, Klugman KP (2005) Epidemiological differences among pneumococcal serotypes. Lancet Infect Dis 5(2): 83–93.


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More of Quianna Canada's
Top 10 Spoken Word Videos for November 2016
Spoken word is an oral art that focuses on the aesthetics of word play and intonation and voice inflection. It is a 'catchall' that includes any kind of poetry recited aloud, including hip-hop, jazz poetry, poetry slams, traditional poetry readings and can include comedy routines and 'prose monologues.'
10. Christopher Martinez
"An Untitled Brown Poem"
Christopher "Rooster" Martinez is a poet from San Antonio's west side. He co-founded the Blah Blah Blah Poetry Spot, an open mic venue in San Antonio that maintains a focus on community outreach, as well as in assisting with the creative development of new poets and performers. Over the years, Christopher has developed a number of national and regional slam teams. He has competed at Texas Grand Slam, as well as conducted workshops at a number of high schools, universities, and community centers. In 2014 he earned the title of San Antonio Grand Slam Champion, leading a team of poets to represent the city at the at the National Poetry Slam Competition in Oakland, California. Christopher is an organizer for Fresh Ink Youth Slam, San Antonio's only under 21 poetry writing and performance workshops for all ages, MC'ing and organizing open mic readings and poetry slams. Christopher writes in a personal narrative style. He has extensive experience competing across the country as a slam poet. He graduated from the University of Texas at San Antonio with a degree in English.

subset: commoncrawl


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Four-time major champion Rory McIlroy crashed out of the U.S. Open after two rounds, carding a double bogey on his 36th hole of the tournamnet to fall below the cut line. McIlroy was on the verge of a huge comeback after posting a 77 in his first round, but he fell apart on the third green with a stunning four-putt before his costly mistake at No. 9.
McIlroy addressed his result on Twitter Sunday - and he's reading his mentions.
Disappointing week to say the least. Fighting my swing a bit at the minute but working hard to get back on track. Happy Father's Day!— Rory McIlroy (@McIlroyRory) June 19, 2016
More from FoxSports
Best of luck to @ShaneLowryGolf today... Bring that trophy back to these shores and give Brendan the best Father's Day gift of all! ☘🏆— Rory McIlroy (@McIlroyRory) June 19, 2016


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We are proud to announce that our nutritional expert here at DIAKADI, Manuel Villacorta, was recently appointed to a three-year term as national media spokesperson for the American Dietetic Association (ADA)!
The ADA's nationwide volunteer spokesperson network consists of 30 registered dietitians who annually conduct more than 2,000 print, TV, radio, and online interviews about nutrition and healthful eating on behalf of the organization. These registered dietitians who represent the 25 largest media markets as well as specialty nutrition areas are considered some of the country's leading experts in nutrition.
Manuel has so much to offer as one of the leading weight loss and behavior and lifestyle modification specialists in the country! As a part of the ADA, Manuel is one of only two male ADA spokespersons nationwide, and the only male spokesperson on the West Coast. "I feel very honored and privileged to have been chosen by the ADA to fill one of these important positions," says Manuel. "I look forward to communicating important messages about wholesome food, proper nourishment, and sensible weight management to people across America and throughout the world starting immediately and through 2013."
We are confident that Manuel will support the ADA's vision to "optimize the nation's health through food and nutrition." We are so honored to have him on our team and be a part of his great achievements!
Author: CJ Murfey, DIAKADI Intern


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Hamas says will respond Saturday to truce proposalFebruary 6th, 2009 - 2:56 am ICT by IANS
Gaza, Feb 6 (DPA) An official in the Islamist movement Hamas said Thursday that the movement would give its final answer on Saturday to a possible Egyptian-brokered truce with Israel, but said that Israeli proposals for an agreement were vague.Hamas Gaza spokesman in Gaza Fawzi Barhoum said that "a deal on a truce was not reached" because Israel had linked ending its blockade on the Gaza Strip and opening the border crossings - a key Hamas demand - with the release of Gilad Shalit, an Israeli soldier held captive in the Strip for over two-and-a-half years.
Barhoum said Israel was offering only a partial opening of the Gaza crossings, an offer which was " totally rejected". Other issues needed clarifications, he said.
"Egypt would need time to prepare the Israeli answers to Hamas' questions, then Hamas would take the Israeli answers for consultations with its leadership inside and outside the Palestinian territories," he said.
The talks between Egypt and Hamas would resume on Saturday, he added.
The Hamas delegation, which included three officials from Gaza and two from Damascus, where the leadership-in-exile sits, has held intensive talks with senior Egyptian security officials over the past four days in an effort to finalize a long-term truce with Israel, to replace the ceasefires declared Jan 18 ending a three-week-long Israeli offensive in the salient.
Earlier reports had indicated that Hamas and other Palestinian factions were slated to declare a one-year ceasefire with Israel Thursday.
- Egypt confirms Israeli-Palestinian prisoners swap deal - Oct 12, 2011
- Seize Israeli soldiers to swap for Palestinian prisoners: Hamas - Oct 07, 2011
- Israeli-Palestinian prisoner swap deal to start Tuesday - Oct 15, 2011
- Hamas says it accepts one-year truce with Israel - Feb 02, 2009
- Egyptian parliamentary delegation visits Gaza - Mar 29, 2012
- Hamas hails decision to permanently open Rafah border crossing - May 27, 2011
- Israeli planes attack Hamas sites in Gaza - Feb 26, 2011
- Hamas calls on Palestinians to abduct Israelis - Apr 18, 2012
- Israel to harden conditions of imprisoned Palestinians - Jun 24, 2011
- Five Palestinians killed in Israeli airstrike - Oct 30, 2011
- Dozens of Palestinians wounded in clashes with Israeli soldiers - Mar 31, 2012
- Israeli defence minister, Mubarak meet in Egypt - Jan 27, 2010
- Demands in exchange for Shalit will grow: Hamas - Jun 28, 2010
- Palestinian reconciliation unlikely in 2012: Hamas official - Mar 31, 2012
- Israel inner cabinet meets to discuss prisoner swap deal - Dec 21, 2009
Tags: blockade, border crossings, ceasefire, clarifications, damascus, fawzi, final answer, gaza strip, gilad shalit, hamas, intensive talks, islamist movement, israeli proposals, israeli soldier, movement hamas, palestinian factions, palestinian territories, security officials, truce, two and a half years


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NetPremise® transmits high-speed data through the electrical cables already available in any building and sends it out either wirelessly or through the wired Ethernet Ports on the device.
This makes Wi-Fi deployment or extension easy and cost-effective; and as there is no need of installing new structural data cable it minimizes business disruption, downtime and offers great user experience.
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KALLYAS is a multi-purpose theme, which also takes care of e-commerce niche and the required features and functionalities for it. It's a popular product at ThemeForest, and it comes with tons of integration of premium tools and plugins like BuddyPress, bbPress, WPML, Slider Revolution, MailChip, Google Translate, WooCommerce, etc. The theme is regularly updated, and features are always on their way to make the deal even sweeter.
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City Sport
Student Offer
20% off 12 week student membership
City Student promo code XN9BAK
Other Student promo code XNBTFB
CitySport is the sports and fitness centre of City University London, offering a very different experience from traditional gym chains. CitySport is open to students, staff and alumni, as well as the public.
Watch this video to take a virtual tour of the centre.


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Plating Live Rock
Date Added: 07/18/2012 by Charlie Littlechild
Just wanted to say how lovely my the rock i got is, i got 9kg of branch rock and 6kg of plate rock i...
Date Added: 03/12/2010 by mark temple
Very pleased great rock very pleased. Thank you. Martin Temple.
Date Added: 01/30/2010 by Cath Parrington
Bought a plate which was absolutly fantastic in apperance, even better now it started to sprout. Wil...
Date Added: 01/29/2010 by David Rowe
Recieved my rock the other day, I order some plates and Fijian and some branch. It is all extremely ...
Copyright © 2018 Rock'N'Critters


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Lor Mee..........
Going down to old Airport road for breakfast,there is no way you can miss this stall.With one of the longest queue,it might be mistaken for some freebies.
It's advisable to go early or normal time.Sorry it's hard to avoid the queue.
Try avoid going near to finishing time.....
Served with barished pork belly,half a egg(whole egg for $4.00),shredded fried fish(used to be big chucks of shredded fish) Ngoh hiangs are missing nowadays.
Taste wise to me,this stall has one of the best lor mee sauce,smooth,not too thick nor too thin,very flavourful, old fashion taste.
I love to have my dishes with bit more of the ingredients.Lately I seem to notice,a snitch in the serving portion .I had the $3.00 and $4.00,with not being much of a different.The $3.00 seem to be a better value.
Still a crowd puller after all these years,this lor mee must be doing something right(the sauce).
Over all,though disappointed with the missing ingredients and the serving portion.
It is still gives me some kind of a pleasure,when I eat this lor mee.To me it's still very special.....
Xin Mei Xiang
Stall #01-116
Old Airport Road Food Centre
7.00a.m-13.00p.m(or till sold out.
Closed on Monday


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Saturday, June 31, 6pm-10pm
Chungking Studio
975 Chung King Road, Los Angeles, CA 90012
It is our privilege to invite you to attend "ÉTRANGERS" an art exhibition by Gareth Maguire and Ugo Nonis at the Chungking Studio in Chinatown, LA.
This show is a rare opportunity to see the collision of artistic styles of two internationally recognized artists bringing their latest creations
together for your pleasure at a one night only event at the Chungking Studio.
French artist Nonis's passion for curves and shapes are highlighted throughout this body of work. Mostly inspired by early 90's video games visuals, Ugo's work is based on the simplification of form to connect with his emotions and the world. At times depicted in soft monotones and other times vivid colors, the current compositions are layered with stories. The curves, abstracted shapes, layers of color and symbols combine together to create a truly unforgettable finished product.
Irish artist Maguire works primarily in neo-expressionist style paintings and prints with a focus on social dichotomies that range from simple and humorous to insightful and highly provocative. The work is punctuated with phrases and doodles from his daughters, to poetry and words from his favorite authors. Colorful yet blacker than black, unique yet familiar Maguire's work is truly a unification of the obscure and the obvious.
Claudia French
"Growing Collages"
Art exhibit
Chungking Studio
975 Chung King Road
Los Angeles, CA 90012
Closing Reception
Saturday, December 16 2017, 6pm-9pm
By Peter Frank
The medium of collage can be said to be the quintessential art form of the modern era. Certainly, the aesthetic it promulgates – of rapid, jagged juxtaposition, of quick change and interior contradiction – has dominated the mental and visual patterns of society since the early 20th century. But there is another side to collage, a gentle, contemplative, and even restfully coherent side, that persists in our time as well. For all the wit, vigor, and even disruption that manifest in the work of Claudia French, for instance, it is the "rational" side of collage upon which she draws to assemble her elements into forthright, starkly described images of self-possessed gravity. Employing a medium prized for its discontinuity, French conjures stark apparitions of ponderous solidity – apparitions, however, whose features shimmer with the electricity collage brings to a surface.
The collage aesthetic dominates French's entire oeuvre. Even her series of quasi-traditional religious icons (based equally on the opulent but austere Eastern Orthodox votives she grew up with in her native Romania and on the florid depictions of La Virgin de Guadalupe and other saints that recur throughout the Mexican culture now surrounding her in southern California) have been built up out of myriad diverse segments. Indeed, French treats collage as if it were a direct descendant of mosaic art. A body of collage work from the beginning of the 2000s, for instance, seems at first to present diverse, or broadly related, images in rolling cascades, the appropriated pictures attached to one another obsessively rather than logically. But French's hand gently guides the myriad elements into a coherent structure – not a "whole" per se, as she deliberately maintains the quick cuts and jumps of the collage aesthetic, but a rhythmic continuity that covers its ground with wit and brio.
In her recent series, French pays homage to nature, finding in some of its most representative factors – trees above all, but also geological strata, the occasional animal, and the qualities of decay – a sensual field no less than an ecological presence. The renditions of trees range from the nearly naturalistic to the highly stylized and almost abstract; but the fact that, regardless of picture size, they are all composed of collaged segments of paper unifies them into a statement as well as into a format. With few exceptions (exceptions that seem quite deliberately to prove the rule), the tree rises from the soil, defines the vertical center of the image, and, somewhere just north of the picture's epicenter, breaks into myriad branches and, often, foliage (as well as, less often, fruit). The formulaic armature allows for a great deal of variation, dictated as much – but only as much – by French's own fantasy as by the species of tree depicted in each work. In all cases, no matter how varied in form, color, or visual texture, the work is constructed of so many (relatively) small collage elements, laid in side by side with others of their ilk to create skies or tree trunks or other pictorial surfaces. It is a visual reasoning, again, that descends directly from ancient mosaic art. It gives the treeworks a multiple quality: that of paintings, that of stonework, that of a cultivated garden, and that of paper, almost of a page. The medium disappears behind the message by alluding to many media. French's is an art of observation, but equally of construction.
The work immediately preceding the trees set the tone for that series by exploring even more directly the possibilities and ramifications of collage technique. A series of small, colorful abstractions, featuring an icon-like form (or compounded forms) framed by so many undulating rectangles, set a playful tone that is never entirely absent from the tree images. These eccentric presences, decidedly organic but otherwise unidentifiable, hop and writhe like marionettes on an invisible string. Their palette, similarly vivacious, is almost fructose in its sweetness. While working on these, French also realized a contrasting series of collage works composed similarly of many small strips of paper, but this time hewing towards a worn and earthy palette. These materials were in fact harvested from old books, including bibles, atlases, and sheet music, capitalizing on their evocative texts as well as textures. They invite closer inspection, which reveals their discontinuity as much as their antiquity, bringing them into modern form. They constitute not simply a recycling of the old into a newer modality but a kind of eidetic nostalgia, a quiet celebration of the forms knowledge once took. Such forms are at once revealed and disrupted – but never quite destroyed – by French's recycling activity.
Claudia French has lived in and through the extremes of European culture and those of American. Her use of collage embraces her experience on both continents and her pictorial sensibility reveals a natural link between the two places. In this respect her oeuvre argues for the commonality of human insight; even as her work derives from and contributes to the visual culture of Western civilization, its breadth and symbolic ambition – ultimately resting on that universal signifier, the tree – point outward from Europe and America. French has found her fertile ground in collage, and from it her cultivations show us the world.
Los Angeles
May 2017
A Featured MOPLA Event (Month of Photography Los Angeles)
Exhibition Dates January 7 – February 11
Opening Reception January 12, 8:30-11pm
Pre-opening: January 7, 7-10pm
Directions to Chungking Studio
The earth's landscapes are both eternal and ever-changing. Human activity in the Anthropocene has reworked the character of the topography in majestic, surreal, and troubling ways. Salt flats, strip mines, and the cracks of dry lake beds offer mysterious, often painterly surfaces that tether the universe to intimate experience. Dust on the horizon, in the air, and under our feet catches the light, refracts and radiates. These three artists use photography and photogenic means to both depict and evoke the visual and geological territory of the new terrestrial normal.
–Shana Nys Dambrot
Chungking Studio: www.chungkingstudio.com
Cristopher Cichocki: www.cristophersea.com
Jay Mark Johnson: www.jaymarkjohnson.com
Osceola Refetoff: www.ospix.com
Please RSVP on our Facebook event page:
Bill Leigh Brewer & Osceola Refetoff
Curated by Shana Nys Dambrot
A Featured MOPLA Event (Month of Photography Los Angeles)
TWO DAYS ONLY April 18-19 12-5pm
Opening Reception April 18 7-10pm
Magic, truth, objectivity, reality. What differentiates photography from other visual art forms is its indelible, inescapably direct relationship to the external world. This tether is both a semiotic and technological constriction, a challenge that has given rise to a seemingly endless debate about photography's status as a "fine art" rather than say, an "applied art" -- and is ultimately also the source of its unique, evolving appeal.
The pairing of work by photographers Bill Leigh Brewer and Osceola Refetoff -- contemporaries working independently -- explores photography's paradoxical capacity to simultaneously document and interpret the world around us, to elicit fresh details and construct new experiences and narratives from its raw materials. The interaction between their work is particularly well suited to exploring this dynamic, because Brewer and Refetoff are uncannily drawn to many of the same specific topographies of desert and industry, yet they return with vastly different works of art.
Some of these differences result from the intentionality of how they work. Brewer could be said to work somewhat loosely, guided more by cultivated serendipity than by an agenda -- his camera functioning as an extension of an intuitive attention, his series grouped by evocative formal or narrative suggestions in a subsequent process sorting the harvest of his wanderlust. Refetoff, for his part, sets out in a nearly cinematic quest for certain specific stories he feels require telling, set against and among the details and vistas of an archetypal set of lands -- speaking directly to how humans have historically manipulated these lands throughout the mythology of the American West.
By considering them together, it is our hope that not only will further facets of their individual practices be highlighted, but so will certain fundamental circumstances of their shared medium's paradoxical ability to preserve evidence of actual events while sustaining personal interpretation, in so doing reconciling documentation and invention, experience and imagination -- and, by somehow showing more than can be seen, to reconcile magic and realism. –Shana Nys Dambrot
Please RSVP on our Facebook event page
For inquiries please contact Kristine Schomaker at Shoebox PR Visual Artist Marketing shoeboxpr.com T: 661.317.1069
A museum for animal lovers of all ages, the new National Museum of Animals and Society is hosting a two-part Fundraiser Exhibition:
The mission of the exhibit, curated by Peter Frank and Delia Cabral, is to raise awareness about our relationship with rabbits, both the animals and what they have come to symbolize in our human experience. Prepare yourself for the cute, the grotesque, the beautiful...and everything in between! The exhibit will explore our perceptions of rabbits as individual beings, muses, companions, and as dynamic cultural symbols.
Peter Frank, Los Angeles Art Critic
Delia Cabral, Exhibit Producer
Adonna Khare, Bibi Davidson, Bogdan Dumitrica, Brian Duda , Corrie Gregory, Dana Feagin, Daniela Schweitzer, Dave Ghilarducci , Debra Broz, Doug Uyesaka, Georgie Flood, Gretchen Ryan, Heather Mattoon, Inge Dehenin, Jane O'Hara, Karen Florito, Karrie Ross, Kathryn Pitt, Kim McCarty, Kim Tucker, Lara Regan, Marina Hebert, Mark Gleason, Mary McGilli, Michelle Page, Michelle Waters, Moniuque Rebelle, NAMAAK Collective, Nancy Lane, Nina Salerno (aka: Perfect Reject), Osceola Refetoff, Paul W Evans, Paula De La Cruz, Penny Collins, Rafael Perea De la Cabada, Raul Contreras, Rebecca Midford, Rhea Korito, Rikki Niehaus, Sally Ann Field, Salomon Huerta, Sarah Hardt, Sarah Stone, Susan Coates, Suzanne Walsh, Trine Churchill, Valerie Daval
Stay up to date by visiting our Facebook event page:
Or the museum's website:
Or on:
Contact: Delia Cabral, (310) 770-2525, email@example.com
© Corrie Gregory


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My sweet Hannah Riley turned two today. She has grown so much this year. She was just a baby last year, and now she's a little lady full of thoughts and emotions, likes and dislikes and now she can effectively communicate the difference between the two. For example, she currently loves cheese above all other foods. Her favorites are mozzarella and cheddar, or in her terminology, white and orange cheese. She absolutely loathes pickles. She can't even stand the smell of pickle juice. She is truly my girl and loves all things pretty, pink, sparkly, baby-related or involving princesses or mermaids. And no, I have in no way had to nurture or even encourage this girlishness. In the words (but not the meaning) of Lady Gaga, she was born this way. She has little to no interest in any of Gabe's "boy" toys. She won't sit through Wall-E or Megamind. She asks to watch Princess and the Frog, The Little Mermaid or Beauty and the Beast at least once a day. And so, in recognizing the joy that all the fun, pretty girly things bring her, it brings me great happiness to try to give her the girliest birthday I could manage. Also, as a grown woman, it would be abnormal for me to throw myself a princess party, so as one of the many great perks of being a mom I get to live vicariously through my little two year old and throw her a party I would love as a little girl....or for my next birthday...just kidding...sort of.
|The presents and cake.
|Hanging with Nicole.
|Enjoying time with Grandma M.
|Waiting for the food.
|Yum. Fresh squeezed mint limeade. Thank you to my many squeezers.
|Monkey see.
|Monkey do...
|One strand at a time.
|Um, is it on there mom?
|Crazy kid.
|"Nana, close your eyes..."
|"Now open them." And they both laugh as if something very funny just took place.
Present Time!
|From the aunts and uncles, an awesome princess Barbie and...
|An awesome princess giant bouncy ball.
|A Dora doll, some coloring books and regular books from Mama.
|And a baby Ariel doll from Mama. The Disney princesses as babies. It's a strange concept and highly illogical, but I get where the marketers were coming from. It combines Hannah's two favorite loves, princesses and babies.
|An adorable outfit from Grandma Smith which Hannah wanted to put on immediately.
|A pillow pet from Daddy.
|And some summer dresses and sandals from Mama and Daddy.
|From Grandma M. and Grandpa Doug, a box of candy and...
|"Hannah, what's this?" "I don't know. Paper?" "Yes, it is paper."
|And a sweet 4-wheeler from Grandma Kathy and Granddaddy.
Hannah checking out her 4-wheeler video will be inserted here.
Cake Time!
A blowing out of the candles video will be inserted here.
|I love my girl.
|My girl loves princesses.


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October 11, 2017—The Centers for Medicare & Medicaid Services should "stand down and rescind its deleterious proposal" to slash what Medicare pays 340B hospitals for many of the most expensive medicines in use today, a co-founder of the U.S. House GOP Doctors Caucus says.
In a recent commentary in the Capitol Hill newspaper The Hill, former Rep. Phil Gingrey (R-Ga.) writes that if he were still serving in the House, he would have teamed up with the bipartisan group of 228 members who signed a letter asking CMS Administrator Seema Verma to withdraw its proposal to cut Medicare Part B drug reimbursement to hospitals in the 340B drug discount program by nearly 30 percent. A bipartisan group of 57 senators sent Verma a similar letter the day after Gingrey's article ran. CMS's proposed cuts would cover expensive treatments for cancer, age-related macular degeneration, and rheumatoid arthritis, among other physician-administered drugs.
You must be registered to read complete articles (it's quick, easy, and 100% free). Click here to register. Already registered? Click here to login. (340B Health members, Drug Discount Monitor subscribers, and 340B Coalition conference attendees: Use your existing username and password.)


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Lembaga Penelitian di Brighton, United Kingdom
Library Road, University of Sussex, Falmer, Brighton BN1 9RE, UK
The Institute of Development Studies (IDS) is an international development research institute. IDS acts to influence policy makers through research, by working with partner organisations in developing countries, and communicating with international policy makers. IDS is based at the University of Sussex.
Bidang studi: Pengembangan Internasional
Lembaga induk: University of Sussex
4 hasil.


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A Sound Of Thunder Ranks On The Following Lists:
Time Travel Books(Ranked 25 out of 67)
Time travel books are one of those genre-bending subgenres of science fiction that could easily be fantasy. It's certainly Speculative Fiction. Time Travel Science Fiction features stores where time ...MORE
Best Time Travel Books(Ranked 8 out of 79)
A list of publicly ranked Time Travel Books
How Would You Rate A Sound Of Thunder? (leave blank if you just want to comment on the book and not review it):


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Quotes About And Michelangelo
Even Michelangelo on his deathbed thought he'd done nothing to ennoble art. He wanted to destroy his work-the Pieta! And this from the greatest artist who ever lived. Of course I am not comparing my work to Michelangelo's. But this eternal dissatisfaction of the artist is what I was talking about.Send Quote
Take a Nicodemus and put a Joseph Smith's spirit in him, and what do you have? Take a Da Vinci or a Michelangelo or a Shakespeare and give him a total knowledge of the plan of salvation of God and personal revelation and cleanse him and take a look at the statues he will carve and the murals he will paint and the masterpieves he will produce. Take a handel with his purposeful effort, his superb talent, his earnest desire to properly depict the story, and give him inward vision of the whole true story and revelation, and what a master you will have!Send Quote
But the great artists like Michelangelo and Blake and Tolstoi--like Christ whom Blake called an artist because he had one of the most creative imaginations that ever was on earth--do not want security, egoistic or materialistic. Why, it never occurs to them. "Be not anxious for the morrow," and "which of you being anxious can add one cubit to his stature?" So they dare to be idle, i.e. not to be pressed and duty-driven all the time. They dare to love people even when they are very bad, and they dare not to try and dominate others to show them what they must do for their own good.Send Quote
If an artist may say nothing except what he has invented by his own sole efforts, it stands to reason he will be poor in ideas. If he could take what he wants wherever he could find it, as Euripides and Dante and Michelangelo and Shakespeare and Bach were free, his larder would always be full, and his cookery might be worth tasting.Send Quote
I hope and dream the time will come when serious artists will make marvelous pictures that will love and live in life-like manner and be far more interesting and wonderful than pictures you now see on canvas. I think if Michelangelo was alive today he would immediately see the wonders...The artist can make his scenes and characters live instead of stand still on canvas in art museums.Send Quote
The great artist Michelangelo claimed that his sculptures were already present in the stone, and all he had to do was carve away everything else. Our understanding of identity is often similar: Beneath the many layers of shoulds and shouldn'ts that cover us, there lies a constant, single, true self that is just waiting to be discovered.Send Quote
The feat of superbly imitating a muscle, as Michelangelo did, or a face, as Raphael did, created neither progress nor a hierarchy in art. Because these artists of the sixteenth century imitated human forms, they were not superior to the artists of the high periods of Egyptian, Chaldean, Indochinese, Roman, and Gothic art who interpreted and stylized form but did not imitate it.Send Quote
Every great artist raises art to a science, and every great scientist raises science to an art, hence we have Michelangelo's David and Einstein's Theory of Relativity.Send Quote
I like the little chess match of how people move through space. I'm not comparing myself to Michelangelo with this analogy, but he said when he sculpts it's like finding the sculpture within. It feels that way when you are with actors, too. There's a natural way to do this with a natural language that flows and feels like real people talking. And you've just got to find it. So I enjoy that part of the process.Send Quote
Perhaps dirt is the necessary condition of beauty.... Perhaps hygiene and art can never be bedfellows. No Verdi, after all, without spitting into trumpets. No Duse without a crowd of malodorous bourgeois giving one another their coryzas. And think of the inexpugnable retreats for microbes prepared by Michelangelo in the curls of Moses' beard!Send Quote
Michelangelo is a constructor, and Rafael an artist who, great as he is, is always limited by the model. When he tries to be thoughtful he falls below the niveau of his great rival.Send Quote
Personal style, be it that of Michelangelo, or that of Tintoretto... has always been that peculiar personal rapport which has developed between an artist and his medium.Send Quote
Put yourself in the position of an up-and-coming artist living in early-sixteenth-century Italy. Now imagine trying to distinguish yourself from the other artists living in your town: Michelangelo, Raphael, Leonardo, or Titian. Is it any wonder that the Italian High Renaissance lasted only 30 years?Send Quote
There [is] a feeling of recognition, as of meeting an old friend, which comes to us all in the face of great artistic experiences. I had the same experience when I first heard an English folksong, when I first saw Michelangelo's Day and Night, when I suddenly came upon Stonehenge or had my first sight of New York City - the intuition that I had been there already.Send Quote
Painting dissolves the forms at its command, or tends to; it melts them into color. Drawing, on the other hand, goes about resolving forms, giving edge and essence to things. To see shapes clearly, one outlines them--whether on paper or in the mind. Therefore, Michelangelo, a profoundly cultivated man, called drawing the basis of all knowledge whatsoever.Send Quote
I don't think there is a 'gay lifestyle.' I think that's superficial crap, all that talk about gay culture. A couple of restaurants on Castro Street and a couple of magazines do not constitute culture. Michelangelo is culture. Virginia Woolf is culture. So let's don't confuse our terms. Wearing earrings is not culture ...Send Quote
Be an artist at whatever you do. Even if you are a street sweeper, be the Michelangelo of street sweepers.Send Quote
Even Michelangelo got paid for doing the Sistine Chapel. To those artists who say they're doing it for the love of art, I say: Get real.Send Quote
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