Safety of vaccination against influenza A (H1N1) during pregnancy in the Netherlands: results on pregnancy outcomes and infant's health: cross-sectional linkage study.

OBJECTIVE: This study aims to assess the safety of Influenza A(H1N1), vaccination administered during the second and third trimester and containing MF59 and thiomersal (Focetria(®) ), measured by pregnancy outcomes and infant's health. DESIGN: Cross-sectional linkage study. SETTING AND SAMPLE: A sample of pregnant women, eligible for prenatal screening, were invited to participate. METHODS: Questionnaire data were linked with the Netherlands Perinatal Registry (n = 1920). Information on infant growth, development (n = 1739) and infection-related contacts with the general practitioner (GP) during the first year of life (n = 1671) was obtained. MAIN OUTCOME MEASURES: Multivariate logistic regression was used to assess the association between H1N1 vaccination and small-for-gestational-age infant, preterm delivery and a composite adverse outcome, i.e. low Apgar-score, neonatal intensive care unit admission, neonatal resuscitation or perinatal death. Influence of maternal vaccination on growth, development and GP infection-related contact rates were assessed using multivariate linear mixed modelling and multivariate negative binomial regression, respectively. RESULTS: Response rate was 21%. Though we found differences in characteristics between unvaccinated and vaccinated women, in the multivariate analyses no association was found between H1N1 vaccination and small-for-gestational-age (odds ratio [OR] 0.84; 95% confidence interval [95% CI] 0.50-1.43), preterm delivery (OR 0.98; 95% CI 0.59-1.62) and the composite adverse outcome (OR 0.84; 95% CI 0.44-1.60). We found no differences in weight-for-age (-0.05; 95% CI -0.13 to 0.04), length-for-age (-0.01; 95% CI -0.09 to 0.06), head-circumference-for-age (-0.05; 95% CI -0.13 to 0.03), developmental scores (-0.06; 95% CI -0.28 to 0.17) and infection-related GP contact rates (incidence rate ratio 1.07; 95% CI 0.91-1.28) between infants of unvaccinated and vaccinated mothers. CONCLUSION: Pregnancy outcomes did not differ between H1N1-vaccinated and unvaccinated women. Furthermore, growth, development and GP infection-related contact rates, assessed after the first year of life, were similar in offspring of vaccinated and unvaccinated mothers. TWEETABLE ABSTRACT: No increased risk for adverse pregnancy outcomes and infant's health following influenza vaccination.

Performance of a bedside test for tetanus immunity: results of a cross-sectional study among three EDs in the Netherlands in 2012-2013.

INTRODUCTION: Despite sustained high vaccination coverage and a national guideline by the Health Council (HC-guideline) on tetanus postexposure prophylaxis (T-PEP), tetanus sporadically occurs in the Netherlands. This study aims to assess the added value of a bedside test for tetanus immunity (Tetanos Quick Stick (TQS); Ingen BioSciences Group, France), in the context of routine T-PEP in two adult cohorts: those born before introduction of tetanus toxoid vaccination in the National Immunization Programme (NIP) in 1957 (pre-NIP-cohort; n=196) and those born after (NIP-cohort; n=405). METHODS: Adults included at the time of visiting one of three participating EDs received T-PEP as per routine recommendations. Subsequently, a nurse performed the TQS and filled in a questionnaire. We compared the indication for T-PEP based on TQS results with those based on the HC-guideline and with actually administration of T-PEP, stratified by cohort. RESULTS: Among the pre-NIP and NIP-cohort, 16% and 9%, respectively, received T-PEP, while this was not indicated based on the HC-guideline. Furthermore, 8% and 7%, respectively, did not get T-PEP, although it was indicated by the guideline. Comparing the indication derived from the HC-guideline with TQS result found that 22% (pre-NIP-cohort) and 8% (NIP-cohort) were not eligible for T-PEP according to the HC-guideline but had a negative TQS. Conversely, 36% (pre-NIP-cohort) and 73% (NIP-cohort) were eligible for T-PEP according to the HC-guideline but had positive TQS, indicating sufficient tetanus protection. CONCLUSION: Use of the TQS would allow better targeting of T-PEP. Furthermore, stricter adherence to the HC-guideline can prevent overimmunisation and decrease the risk of tetanus.

Pertussis resurgence: waning immunity and pathogen adaptation - two sides of the same coin.

Pertussis or whooping cough has persisted and resurged in the face of vaccination and has become one of the most prevalent vaccine-preventable diseases in Western countries. The high circulation rate of Bordetella pertussis poses a threat to infants that have not been (completely) vaccinated and for whom pertussis is a severe, life-threatening, disease. The increase in pertussis is mainly found in age groups in which immunity has waned and this has resulted in the perception that waning immunity is the main or exclusive cause for the resurgence of pertussis. However, significant changes in B. pertussis populations have been observed after the introduction of vaccinations, suggesting a role for pathogen adaptation in the persistence and resurgence of pertussis. These changes include antigenic divergence with vaccine strains and increased production of pertussis toxin. Antigenic divergence will affect both memory recall and the efficacy of antibodies, while higher levels of pertussis toxin may increase suppression of the innate and acquired immune system. We propose these adaptations of B. pertussis have decreased the period in which pertussis vaccines are effective and thus enhanced the waning of immunity. We plead for a more integrated approach to the pertussis problem which includes the characteristics of the vaccines, the B. pertussis populations and the interaction between the two.

Immunity against poliomyelitis in the Netherlands, assessed in 2006 to 2007: the importance of completing a vaccination series.

Europe has been declared polio-free since 2002. Here we describe the seroprotection against poliomyelitis in the Dutch population using banked serum samples. Samples from 1,581 inhabitants of eight municipalities with low vaccination coverage (LVC) and an additional 6,386 samples from a nationwide (NS) group (clinical trial number: ISRCTN20164309; collected in 2006­07) were tested for neutralising antibodies (log² reciprocal titres (GMT); non-protection <3) against all three poliomyelitis serotypes. Demographic and epidemiological data were used for statistical regression analysis. Seroprevalence in the NS was 94.6% (type 1), 91.8% (type 2) and 84.0% (type 3). Infants (0­7 months-old) had ≥80% seroprevalence for all serotypes. The highest seroprevalence was found in children, with type 1 and type 2 in five year-olds and type 3 in nine to 10 year-olds. In the LVC group, orthodox protestants, many of whom refuse vaccination, showed seroprevalence rates of 64.9% (type 1), 61.0% (type 2) and 62.1% (type 3). In the NS group, non-Western immigrants and travellers to non-European continents had higher seroprevalences compared to Western immigrants and travellers within Europe, respectively. The Dutch National Immunisation Programme against poliomyelitis has provided good seroprotection, with high and long-lasting GMTs against all serotypes upon completion. The unvaccinated population remains at risk.

Incidence of multiple sclerosis in the general population in the Netherlands, 1996-2008.

BACKGROUND: We estimated the multiple sclerosis (MS) incidence in the Netherlands for better active monitoring of potential vaccine safety signals. METHODS: A retrospective cohort study (1996-2008) was conducted using a population-based general practice research database containing electronic medical records. Additional information was collected to validate incident probable cases. RESULTS: In the source population (648,656 persons), 146 incident probable MS cases were identified. Overall incidence rate was 6.3/100,000 person years (py; 95% CI, 5.2-7.2). In the subgroup in which MS could be fully validated, the incidence increased from 4/100,000 py (95% CI, 3-5) in 1996-2004 to 9/100,000 py in 2007/8 (95% CI, 6-16). This increase was highest among women, but not statistically significantly different by gender. The median lag time between first recorded symptoms and MS diagnosis decreased from 32 months (<1998) to 2 months (>2005). CONCLUSIONS: MS is rare in the Netherlands. In recent years, there was a slight increase in the incidence especially among women during the fertile age. This increase coincided with a decrease in lag time between symptoms and diagnosis, both for men and women. This trend should be taken into account in the interpretation of MS cases occurring in a population where new vaccinations will be introduced shortly.

Right ventricular ejection fraction measured by multigated planar equilibrium radionuclide ventriculography is an independent prognostic factor in patients with ischemic heart disease.

BACKGROUND: The number of studies on the prognostic value of the right ventricular ejection fraction (RVEF) in patients with ischemic heart disease (IHD) is limited, whereas it is widely accepted that the left ventricular ejection fraction (LVEF) is a strong prognostic factor. We assessed whether RVEF measured by multigated planar equilibrium radionuclide ventriculography (RNV) is an independent prognostic factor in patients with IHD. METHODS AND RESULTS: We retrospectively identified 347 consecutive patients with IHD (mean age 71 ± 11 years; 18% women) who underwent multigated planar equilibrium RNV between 2004 and 2008 to determine the LVEF, which also provided the RVEF (mean 44.7% ± 11.0%). We categorized patients according to RVEF in ≥40% (n = 240) and <40% (n = 107). Patients were followed for a median of 826 days (range 3-2,400) for the occurrence of events [all-cause mortality (n = 60), cardiac mortality (n = 33), and cardiac hospitalization (n = 78)]. Cox regression analysis with significant univariate predictors [coronary artery revascularization (P = .003), diuretics (P = .03), and statins (P < .001)] showed that an RVEF <40% was associated with a 2.90 (1.68-5.00)-fold higher risk of all-cause death. Accordingly, a decreased RVEF was associated with a 2.15 (1.34-3.43)-fold increase in the risk of cardiac hospitalization and a 5.11(2.32-11.23)-fold risk of cardiac death. CONCLUSION: RVEF measured by multigated planar equilibrium RNV is an independent prognostic factor in patients with chronic IHD.

[Introduction of pertussis vaccination during pregnancy]. / Invoering van een kinkhoestvaccinatie voor zwangeren.

Pertussis is an endemic disease in the Netherlands. In order to protect infants under 6 months of age, women can be vaccinated during pregnancy with a DTaP(-IPV) booster vaccine. After this so-called maternal vaccination, pertussis antibodies are passed through the placenta to the unborn child, who will be protected after birth. The vaccine is offered as a part of the national vaccination programme (Rijksvaccinatieprogramma, RVP) since 16 December 2019. Children of maternally vaccinated women will follow a different vaccination schedule, namely the 3-5-11-months schedule. This schedule change applies to the DTaP-IPV-HiB-HepB combination vaccine and the 10-valent pneumococcal (PCV10) vaccine. High-risk groups and children of unvaccinated mothers will follow the 2-3-5-11 months schedule. Maternal vaccination is offered from 22 weeks of gestation in the Netherlands. This timing is logistically feasible. We have seen that women already got themselves actively vaccinated during pregnancy before the inclusion of the vaccine in the RVP.

Genotype-phenotype correlation in 21 patients with Wolf-Hirschhorn syndrome using high resolution array comparative genome hybridisation (CGH).

BACKGROUND: The Wolf-Hirschhorn syndrome (WHS) is usually caused by terminal deletions of the short arm of chromosome 4 and is phenotypically defined by growth and mental retardation, seizures, and specific craniofacial manifestations. Large variation is observed in phenotypic expression of these features. In order to compare the phenotype with the genotype, we localised the breakpoints of the 4 pter aberrations using a chromosome 4 specific tiling BAC/PAC array. METHODS: In total, DNA from 21 patients was analysed, of which 8 had a cytogenetic visible and 13 a submicroscopic deletion. RESULTS AND CONCLUSION: In addition to classical terminal deletions sized between 1.9 and 30 Mb, we observed the smallest terminal deletion (1.4 Mb) ever reported in a patient with mild WHS stigmata. In addition, we identified and mapped interstitial deletions in four patients. This study positions the genes causing microcephaly, intrauterine and postnatal growth retardation between 0.3 and 1.4 Mb and further refines the regions causing congenital heart disease, cleft lip and/or palate, oligodontia, and hypospadias.

No evidence found for an increased risk of long-term fatigue following human papillomavirus vaccination of adolescent girls.

INTRODUCTION: In 2013, the Netherlands Pharmacovigilance Center Lareb published an overview of reports of long-lasting fatigue following bivalent HPV-vaccination (2vHPV). After an update of this overview in 2015, concerns regarding the safety of 2vHPV was picked up by the media, which led to further reports of long-lasting fatigue. Therefore, the Dutch National Institute for Public Health and the Environment (RIVM) investigated a possible association between HPV-vaccination and long-term fatigue. METHODS: In this retrospective cohort study conducted in the Integrated Primary Care Information database, we investigated the occurrence of chronic fatigue syndrome (CFS), fatigue ≥6 months and 3-6 months in all girls born in 1991-2000 during the follow-up period January 1st 2007-December 31st 2014 (2007-2008 pre-vaccination and 2009-2014 post-vaccination). Patients with certain fatigue ≥6 m were asked for consent to link their primary care information with vaccination data. Incidence rates per 10,000 person years (PY) for 12-16-year-old girls were compared between pre- and post-HPV-vaccine era. A self-controlled case series (SCCS) analysis was performed using consenting vaccinated cases. A primary high-risk period of 12 months after each dose was defined. RESULTS: The cohort consisted of 69,429 12-16-year-old girls accounting for 2758 PY pre-vaccination and 57,214 PY post-vaccination. Differences between pre- and post-vaccination incidences (CFS: 3.6 (95% CI 0.5-25.7)/10,000 PY and 0.9 (0.4-2.1); certain fatigue ≥6 m: 7.3 (1.8-29.0) and 19.4 (16.1-23.4); certain fatigue 3-6 m: 0.0 and 16.6 (13.6-20.3), respectively) were not statistically significant. SCCS analyses in 16 consenting vaccinated cases resulted in an age-adjusted RR of 0.62 (95%CI 0.07-5.49). CONCLUSIONS: Fatigue ≥6 m and 3-6 m was frequently found among adolescent girls, but CFS was rarely diagnosed. No statistically significant increased incidence rates were found post-vaccination compared to similar age groups of girls pre-vaccination. The SCCS analysis included a low number of cases but revealed no elevated risk of certain fatigue ≥6 m in the high-risk period.

Emerging patterns of cryptic chromosomal imbalance in patients with idiopathic mental retardation and multiple congenital anomalies: a new series of 140 patients and review of published reports.

BACKGROUND: Chromosomal abnormalities are a major cause of mental retardation and multiple congenital anomalies (MCA/MR). Screening for these chromosomal imbalances has mainly been done by standard karyotyping. Previous array CGH studies on selected patients with chromosomal phenotypes and normal karyotypes suggested an incidence of 10-15% of previously unnoticed de novo chromosomal imbalances. OBJECTIVE: To report array CGH screening of a series of 140 patients (the largest published so far) with idiopathic MCA/MR but normal karyotype. RESULTS: Submicroscopic chromosomal imbalances were detected in 28 of the 140 patients (20%) and included 18 deletions, seven duplications, and three unbalanced translocations. Seventeen of 24 imbalances were confirmed de novo and 19 were assumed to be causal. Excluding subtelomeric imbalances, our study identified 11 clinically relevant interstitial submicroscopic imbalances (8%). Taking this and previously reported studies into consideration, array CGH screening with a resolution of at least 1 Mb has been undertaken on 432 patients with MCA/MR. Most imbalances are non-recurrent and spread across the genome. In at least 8.8% of these patients (38 of 432) de novo intrachromosomal alterations have been identified. CONCLUSIONS: Array CGH should be considered an essential aspect of the genetic analysis of patients with MCA/MR. In addition, in the present study three patients were mosaic for a structural chromosome rearrangement. One of these patients had monosomy 7 in as few as 8% of the cells, showing that array CGH allows detection of low grade mosaicisims.

The t(4;8) is mediated by homologous recombination between olfactory receptor gene clusters, but other 4p16 translocations occur at random.

The t(4;8)(p16;p23) is the second most common constitutional chromosomal translocation and is caused by an ectopic meiotic recombination between the olfactory receptor gene clusters (ORGC), located on chromosome 4p and 8p. Given that ORGCs are scattered across the genome and make-up about 0.1% of the human genome we reasoned that translocations between 4p16 and other chromosomes might be mediated by ectopic recombination between different ORGC. In 13 patients, we mapped the breakpoints of either a balanced or unbalanced translocation between chromosome 4p16 and different chromosomes. For all four t(4;8) cases, the breakpoints fall within the 4p and 8pter ORGC, confirming that non-allelic homologous recombination (NAHR) between the ORGC is the main mechanism of the t(4;8) formation. For the nine other translocations, the breakpoints on chromosome 4 mapped to different loci, one of them within the ORGC and in two flanking the ORGC. In these three cases, the translocation breakpoint at the reciprocal chromosome did not contain ORGC sequences. We conclude that only the t(4;8) is mediated by NAHR between ORGC.

Breast irradiation with brachytherapy: approved techniques and new concepts.

Among surgery and chemotherapy, radiotherapy has an important role in the treatment of breast cancer patients. But not only external beam radiotherapy (EBRT) treatment is an established method for treatment of breast cancer, also brachytherapy (BT) is an approved method. BT is well known for boost irradiation in combination with EBRT, but new indications as re-irradiation for local recurrences or partial breast irradiation offer new aspects in the field of BT for breast cancer treatment. Because of modern CT based 3-D treatment planning systems and the possibility of intensity modulated brachytherapy (IMBT) has getting more potential. In the future for selected patient's re-irradiation of the breast using IMBT after local relapse and second breast conserving surgery might be an alternative instead of mastectomy. Even partial breast BT following breast conservative operation as a new treatment option is getting more and more interesting and is widely investigated in several studies. Due to the approved techniques and the new indications BT is and will be an attractive alternative and extension in the field of breast cancer treatment. But we need five better ten years results for definite conclusions at least.

[Safety surveillance in the National Vaccination Programme; fewer adverse events with the DTP-IPV-Hib vaccine after the transition to an acellular pertussis component in 2005]. / Veiligheidsbewaking van Rijksvaccinatieprogramma; minder bijwerkingen van DKTP-Hib-combinatievaccin sinds overgang in 2005 naar vaccin met acellulaire kinkhoestcomponent.

OBJECTIVE: To determine the adverse reactions to the combined vaccine against diptheria, acellular pertussis, tetanus, poliomyelitis and Haemophilus Infuenzae type B (DTP-IPV-Hib) before and after the introduction of an acellular pertussis component. DESIGN: Descriptive. METHOD: Safety surveillance of the Dutch National Vaccination Programme is performed by the National Institute for Public Health and Environment (RIVM). It is based on an enhanced passive reporting system and complemented by targeted survey-based studies. The data obtained were analysed. RESULTS: The passive surveillance system showed a large increase in reports in 2004, probably linked to increased media attention on the efficacy and safety of the whole-cell DTP-IPV-Hib vaccine. The Health Council recommended transitioning to the use of a DTP-IPV-Hib vaccine with an acellular pertussis component, which was implemented in January 2005. The number of reports dropped sharply in 2005 to a level below that of 2002-2003. Results of a survey study on adverse events following DTP-IPV-Hib vaccination that began in late 2003 and continued in 2005 confirmed the wide coverage ofthe enhanced passive surveillance system and revealed low rates of underreporting of rare adverse events, such as collapse and convulsions. CONCLUSION: This study confirms the data from the passive surveillance system, which show that the newly introduced acellular DTP-IPV-Hib vaccine is associated with fewer adverse events than the whole-cell vaccine that was used previously.

Severe underestimation of pertussis related hospitalizations and deaths in the Netherlands: A capture-recapture analysis.

OJECTIVE: Despite vaccination, pertussis has remained endemic, sometimes leading to severe disease. We aimed to quantify the completeness of reporting (CoR) of pertussis hospitalizations and deaths in the Netherlands. STUDY DESIGN: CoR was estimated using capture-recapture analyses. Hospitalizations (2007-2014) from the National Registration Hospital Care (hospital data) were matched to the notifiable Infectious Disease case registry (notifications) providing (month and) year of birth, gender and postal code. Deaths (1996-2014) from Statistics Netherlands (death registry) were matched to notifications using gender, age, year of death and notification date. Cases <2years (y) and ≥2y were analysed separately. Chao's estimator estimated the total population, which was used to calculate CoR. RESULTS: Using strict matching criteria, we found 461 matches among 876 (hospital data) and 757 (notifications) hospitalizations <2y. The population estimate of hospitalized infants was 1446, resulting in CoR between 52% and 61%. For hospitalizations ≥2y (246; hospital data and 264; notifications) 43 matches were found, with a population estimate of 1512 and CoR between 16.5% and 22%. Among thirteen (death registry) and eight (notifications) deaths <2y, seven cases overlapped. The population estimate was 16. CoR of the two sources was 50-81%. With two (death registry) and eight (notifications) deaths ≥2y without overlap, the population estimate was 26 and CoR 8-31%. CONCLUSION: Results showed substantial underestimation of pertussis hospitalizations and deaths. This has to be taken into account in evaluation of current and future immunization programs.

Molecular karyotyping of patients with MCA/MR: the blurred boundary between normal and pathogenic variation.

Molecular karyotyping has revealed that microdeletions/duplications in the human genome are a major cause of multiple congenital anomalies associated with mental retardation (MCA/MR). The identification of a de novo chromosomal imbalance in a patient with MCA/MR is usually considered causal for the phenotype while a chromosomal imbalance inherited from a phenotypically normal parent is considered as a benign variation and not related to the disorder. Around 40% of imbalances in patients with MCA/MR in this series is inherited from a healthy parent and the majority of these appear to be (extremely) rare variants. As some of these contain known disease-causing genes and have also been found to be de novo in MCA/MR patients, this challenges the general view that such familial variants are innocent and of no major phenotypic consequence. Rather, we argue, that human genomes can be tolerant of genomic copy number variations depending on the genetic and environmental background and that different mechanisms play a role in determining whether these chromosomal imbalances manifest themselves.

Carcinosarcomas--a retrospective analysis of 21 patients.

BACKGROUND: Carcinosarcomas (CS) are mixed epithelial and stromal tumours with both components being malignant. Twenty-one patients with carcinosarcomas who were treated at the University of Saarland, Germany, are presented. PATIENTS AND METHODS: The hospital records of all patients were reviewed. RESULTS: The mean age range for homologue CS (homCS) was 60.7 years and for heterologue CS (hetCS) 68.4 years. Post-menopausal bleeding and abdominal pain were the main symptoms. Treatment modalities included surgery, adjuvant radiation therapy and various chemotherapy regimens. The median follow-up time was 17.6 months (homCS) and 31.1 months (hetCS). The 1-year survival rate was 55.6% (hetCS 58.3%) and the 5-year survival rate was 11.1% (hetCS 8.3%). CONCLUSION: Carcinosarcoma is a uterine sarcoma with a poor prognosis. Treatment includes surgery and adjuvant chemotherapy, whereas radiotherapy does not necessarily lead to a benefit. Treatment with trastuzumab might be a new approach in the therapy of HER-2/neu-positive CS.

[Infection prevention in newborns through maternal vaccination: current insights and developments]. / Infectiepreventie bij zuigelingen door maternale vaccinatie.

- In the first few months of life, newborns are vulnerable to infections.- Vaccination of the pregnant mother leads to transplacental antibody transfer, resulting in the best possible protection of the newborn.- Maternal vaccination has long been given for the prevention of tetanus in developing countries, and for the prevention of pertussis and influenza in developed countries, such as the United States, England and Belgium. These vaccinations give newborns good protection and, to date, no adverse effects are known for the foetus or the pregnancy.- Currently, phase 3 trials during pregnancy are ongoing following maternal vaccination against group B streptococci and respiratory syncytial virus. Here, again, no risks to mother or child have been reported.- Recently, the Dutch Health Council advised that all pregnant women in the Netherlands be vaccinated against pertussis in a vaccination programme.- This paper gives an overview of effectiveness, safety and practicalities of maternal vaccination.

Tolerability of 2 doses of pandemic influenza vaccine (Focetria®) and of a prior dose of seasonal 2009-2010 influenza vaccination in the Netherlands.

In the Netherlands, people indicated for seasonal influenza vaccination are divided in 3 risk groups, i.e. those less than 60 y (y) with comorbidity and those 60 y and over with and without comorbidity. Those risk groups were also eligible for pandemic vaccination during the 2009 influenza A(H1N1) pandemic. We assessed tolerability of seasonal influenza vaccination and 2 doses of pandemic influenza A(H1N1) vaccine, adjuvanted with MF-59, administered 2 and 5 weeks after seasonal 2009-2010 vaccination among adults. Vaccinees were asked to return questionnaires on local and systemic adverse events (AEs) after each of 3 consecutive vaccinations given at the office of their General Practitioner. Sex- and risk group-specific AE-frequencies were calculated. Generalized Linear Mixed Model with seasonal vaccination as reference was used to calculate odds ratios (ORs) for AEs of the 2 pandemic doses. 5553 questionnaires (3251 vaccinees) were returned. Vaccinees reported any local AE after seasonal vaccination and both pandemic doses in 34%, 23%, and 18%, respectively. These percentages were 29%, 25%, and 16% for any systemic AE. Men reported fewer local and systemic AEs then women (p<0.0001). The risk of local (OR range 0.34-0.63) and systemic (OR range 0.39-0.99) AEs (overall, stratified by risk group and by sex) was lower after both pandemic doses compared to seasonal vaccination. This decreased risk was more pronounced after the second pandemic dose than after the first. Therefore, we conclude that MF59-adjuvanted pandemic vaccine given after seasonal vaccination was well tolerated.

The del(2)(q32.2q33) deletion syndrome defined by clinical and molecular characterization of four patients.

We report four patients with an interstitial deletion of chromosome 2q32-->2q33. They presented similar clinical findings including pre- and postnatal growth retardation, distinct facial dysmorphism, thin and sparse hair and fair built, micrognathia, cleft or high palate, relative macroglossia, dacrocystitis, persisting feeding difficulties, inguinal hernia and broad based gait. All were severely mentally retarded. Three patients had a specific behavioral phenotype with hyperactivity and motor restlessness, chaotic behavior, happy-personality but with periods of aggression and anxiety, sleeping problems and self-mutilation. (head-banging). Array CGH and fluorescence in situ hybridization (FISH) allowed us to delineate the deletion size and showed that the four patients share a 8.1 Mb minimal deleted region. Reviewing additional nine case reports of patients with similar deletions showed striking phenotypic similarities which enabled the delineation of the 2q32.2q33 syndrome. Deletion of 2q32 has been also associated with the wrinkly skin syndrome (WWS) and isolated cleft palate. Although the patients presented here shared many aspects of WWS, they did not had the wrinkly skin. All patients had a cleft or high palate, most likely as a result of hemizygosity for SATB2. A potential commonly deleted interval of the three patients with behavioral problems, excluding the deletion in the patient without behavioral problems, is at most 0.5 Mb in size harboring only two genes.

Roles of methanogens on volatile organic sulfur compound production in anaerobically digested wastewater biosolids.

Land application of wastewater biosolids is both economical and beneficial to resource recycling. However, this environmentally friendly practice can be at risk due to odor complaints. Volatile organic sulfur compounds (VOSCs) including methanethiol, dimethyl sulfide, and dimethyl disulfide, have been identified as major contributors to biosolids odor. In this study, methanogens were shown to play a key role in removing VOSCs and reducing odors, and methane production was related to reduced VOSC production. Factors influencing the growth of methanogens such as the shear during dewatering and storage temperature showed a strong impact on net odor production. Examination of the microbial communities of both bacteria and archaea indicated a simplified archaeal community in biosolids, which is susceptible to environmental perturbations. Therefore, one possible odor control strategy is the preservation and enhancement of the methanogenic population during biosolids storage.