Audit report on the AIM - Jefferson, Keokuk Early Childhood Iowa Area Board, d/b/a Jefferson/Keokuk Early Childhood Iowa Area for the year ended June 30, 2012

Audit report on the AIM - Jefferson, Keokuk Early Childhood Iowa Area Board, d/b/a Jefferson/Keokuk Early Childhood Iowa Area for the year ended June 30, 2012

Ringgold County Early Childhood Iowa Area independent auditor's reports, basic financial statements, schedule of findings, June 30, 2012

Audit report on the Ringgold County Early Childhood Iowa Area for the year ended June 30, 2012

Trends in mortality from leukemia in Europe: an update to 2009 and a projection to 2012.

We considered trends in mortality from leukemia in Europe over the period 1970-2009 using data from the World Health Organization. We computed age-standardized (world population) mortality rates, at all ages and in selected age groups, in 11 selected European countries, the European Union (EU) and, for comparative purposes, in the USA and Japan. For the EU, we also provided projections of the mortality to 2012. Over the period considered, mortality from leukemia steadily declined in most European countries in children and young adults, as well as in western and southern Europe at middle-age (45-69 years); in central/eastern Europe, reductions at ages 45-69 started since the mid-late 1990s. In the EU, annual percent changes were -3.7% in males and -3.8% in females at age 0-14, -2% in both sexes at age 15-44, and -0.6% in males and -1% in females at middle-age and overall. No decline was observed at age 70 or more. Between 1997 and 2007, overall EU rates decreased from 5.4 to 4.8/100,000 males and from 3.4 to 2.9/100,000 females. Declines were from 6.2 to 5.5/100,000 males and from 3.7 to 3.2/100,000 females in the USA and from 3.9 to 3.5/100,000 males and from 2.5 to 2.0/100,000 females in Japan. Projected overall rates in the EU at 2012 are 4.3/100,000 males (-11% compared to 2007) and 2.6/100,000 females (-12%).

Do childhood cancer survivors with physical performance limitations reach healthy activity levels?

BACKGROUND: The extent to which physical performance limitations affect the ability of childhood cancer survivors to reach healthy activity levels is unknown. Therefore this study aims to describe the effect of different types of limitations on activity levels in survivors. PROCEDURE: Within the Swiss Childhood Cancer Survivor Study we sent a questionnaire to all survivors (≥16 years) registered in the Swiss Childhood Cancer Registry, who survived >5 years and were diagnosed 1976-2005 aged <16 years. We measured healthy activity levels using international guidelines and assessed different kinds of performance limitations (visual impairment, weight and endurance problems, cardiorespiratory, musculoskeletal, and neurological problems, pain and fatigue syndromes). RESULTS: The sample included 1,560 survivors (75% response rate), of whom 209 (13.5%) reported they have performance limitations. Forty-two percent of survivors with limitations reached healthy activity levels, compared to 57% of survivors without limitations. Least active were survivors with vision impairments (25% active), weight and endurance problems (27.3%), cardiorespiratory problems (36.4%), and musculoskeletal problems (43.1%). After adjusting for socio-demographic variables and type of cancer, we found that survivors with limitations were 1.4 (95%CI 1.0-2.0; P = 0.047) times more likely to be inactive. CONCLUSIONS: Although many survivors with physical performance limitations maintain healthy activity levels, there is room for improvement. Adapted and targeted physical activity counseling for survivors with performance limitations might help them to raise level of activity and pursue a healthy lifestyle.

Audit report on the Taylor County Early Childhood Iowa Area for the year ended June 30, 2012

Audit report on the Taylor County Early Childhood Iowa Area for the year ended June 30, 2012

La mortalité par tumeur maligne chez les ouvriers d'une fabrique de caoutchouc en Suisse: étude épidémiologique, 1955-1975. [Cancer mortality among the workers of a Swiss rubber goods factory. Epidemiological study, 1955-75].

In an epidemiologic investigation of mortality among workers in a Swiss rubber-goods factory the cancer mortality in the period 1955-1975 has been studied in all male workers active on 1 January 1955 in (a) a rubber-goods factory and (b) a munitions factory, the latter as reference population. The two groups numbered some 1000 each. Both factories were located in the same Central Swiss village where no other industry was present. Mortality in each industry is compared with that in the Swiss population in general (SMR) and the mortalities of the two industries are compared with each other. The results tend to confirm that rubber workers are exposed to a higher risk of cancer mortality. Three particular types of cancer are briefly discussed: cancer of the stomach, of the lower urinary tract, and glioblastoma.

Direct Effect of Birth Weight on Childhood Blood Pressure: a Causal Mediation Analysis

Background: Numerous studies have shown a negative association between birth weight (BW) and blood pressure (BP) later in life. To estimate the direct effect of BW on BP, it is conventional to condition on current weight (CW). However, such conditioning can induce collider stratification bias in the estimate of the direct effect. Objective: To bound the potential bias due to U, an unmeasured common cause of CW and BP, on the estimate of the (controlled) direct effect of BW on BP. Methods: Data from a school based study in Switzerland were used (N = 4,005; 2,010 B/1,995 G; mean age: 12.3 yr [range: 10.1-14.9]). Measured common causes of BW-BP (SES, smoking, body weight, and hypertension status of the mother) and CW-BP (breastfeeding and child's physical activity and diet) were identified with DAGs. Linear regression models were fitted to estimate the association between BW and BP. Sensitivity analyses were conducted to assess the potential effect of U on the association between BW and BP. U was assumed 1) to be a binary variable that affected BP by the same magnitude in low BWand in normal BW children and 2) to have a different prevalence in low BW children and in normal BW children for a given CW. Results: A small negative association was observed between BW and BP [beta: -0.3 mmHg/kg (95% CI: -0.9 to 0.3)]. The association was strengthened upon conditioning for CW [beta: -1.5 mmHg/kg (95% CI: -2.1 to -0.9)]. Upon further conditioning on common causes of BW-BP and CW-BP, the association did not change substantially [beta: -1.4 mmHg/kg (95% CI: -2.0 to -0.8)]. The negative association could be explained by U only if U was strongly associated with BP and if there was a large difference in the prevalence of U between low BWand normal BW children. Conclusion: The observed negative association between BW and BP upon adjustment for CW was not easily explained by an unmeasured common cause of CWand BP.

A Mutation in CALM1 Encoding Calmodulin in Familial Idiopathic Ventricular Fibrillation in Childhood and Adolescence.

OBJECTIVES: This study aimed to identify the genetic defect in a family with idiopathic ventricular fibrillation (IVF) manifesting in childhood and adolescence. BACKGROUND: Although sudden cardiac death in the young is rare, it frequently presents as the first clinical manifestation of an underlying inherited arrhythmia syndrome. Gene discovery for IVF is important as it enables the identification of individuals at risk, because except for arrhythmia, IVF does not manifest with identifiable clinical abnormalities. METHODS: Exome sequencing was carried out on 2 family members who were both successfully resuscitated from a cardiac arrest. RESULTS: We characterized a family presenting with a history of ventricular fibrillation (VF) and sudden death without electrocardiographic or echocardiographic abnormalities at rest. Two siblings died suddenly at the ages of 9 and 10 years, and another 2 were resuscitated from out-of-hospital cardiac arrest with documented VF at ages 10 and 16 years, respectively. Exome sequencing identified a missense mutation affecting a highly conserved residue (p.F90L) in the CALM1 gene encoding calmodulin. This mutation was also carried by 1 of the siblings who died suddenly, from whom DNA was available. The mutation was present in the mother and in another sibling, both asymptomatic but displaying a marginally prolonged QT interval during exercise. CONCLUSIONS: We identified a mutation in CALM1 underlying IVF manifesting in childhood and adolescence. The causality of the mutation is supported by previous studies demonstrating that F90 mediates the direct interaction of CaM with target peptides. Our approach highlights the utility of exome sequencing in uncovering the genetic defect even in families with a small number of affected individuals.

Health-related quality of life in long-term survivors of relapsed childhood acute lymphoblastic leukemia.

BACKGROUND: Relapses occur in about 20% of children with acute lymphoblastic leukemia (ALL). Approximately one-third of these children can be cured. Their risk for late effects is high because of intensified treatment, but their health-related quality of life (HRQOL) was largely unmeasured. Our aim was to compare HRQOL of ALL survivors with the general population, and of relapsed with non-relapsed ALL survivors. METHODOLOGY/PRINCIPAL FINDINGS: As part of the Swiss Childhood Cancer Survivor Study (SCCSS) we sent a questionnaire to all ALL survivors in Switzerland who had been diagnosed between 1976-2003 at age <16 years, survived ≥5 years, and were currently aged ≥16 years. HRQOL was assessed with the Short Form-36 (SF-36), which measures four aspects of physical health and four aspects of mental health. A score of 50 corresponded to the mean of a healthy reference population. We analyzed data from 457 ALL survivors (response: 79%). Sixty-one survivors had suffered a relapse. Compared to the general population, ALL survivors reported similar or higher HRQOL scores on all scales. Survivors with a relapse scored lower in general health perceptions (51.6) compared to those without (55.8;p=0.005), but after adjusting for self-reported late effects, this difference disappeared. CONCLUSION/SIGNIFICANCE: Compared to population norms, ALL survivors reported good HRQOL, even after a relapse. However, relapsed ALL survivors reported poorer general health than non-relapsed. Therefore, we encourage specialists to screen for poor general health in survivors after a relapse and, when appropriate, specifically seek and treat underlying late effects. This will help to improve patients' HRQOL.

Expression of O⁶-methylguanine-DNA methyltransferase in childhood medulloblastoma.

Medulloblastomas (MB) are the most common malignant brain tumors in childhood. Alkylator-based drugs are effective agents in the treatment of patients with MB. In several tumors, including malignant glioma, elevated O(6)-methylguanine-DNA methyltransferase (MGMT) expression levels or lack of MGMT promoter methylation have been found to be associated with resistance to alkylating chemotherapeutic agents such as temozolomide (TMZ). In this study, we examined the MGMT status of MB and central nervous system primitive neuroectodermal tumor (PNET) cells and two large sets of primary MB. In seven MB/PNET cell lines investigated, MGMT promoter methylation was detected only in D425 human MB cells as assayed by the qualitative methylation-specific PCR and the more quantitative pyrosequencing assay. In D425 human MB cells, MGMT mRNA and protein expression was clearly lower when compared with the MGMT expression in the other MB/PNET cell lines. In MB/PNET cells, sensitivity towards TMZ and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) correlated with MGMT methylation and MGMT mRNA expression. Pyrosequencing in 67 primary MB samples revealed a mean percentage of MGMT methylation of 3.7-92% (mean: 13.25%, median: 10.67%). Percentage of MGMT methylation and MGMT mRNA expression as determined by quantitative RT-PCR correlated inversely (n = 46; Pearson correlation r (2) = 0.14, P = 0.01). We then analyzed MGMT mRNA expression in a second set of 47 formalin-fixed paraffin-embedded primary MB samples from clinically well-documented patients treated within the prospective randomized multicenter trial HIT'91. No association was found between MGMT mRNA expression and progression-free or overall survival. Therefore, it is not currently recommended to use MGMT mRNA expression analysis to determine who should receive alkylating agents and who should not.

Little evidence that hepatitis C virus leads to a higher risk of mortality in the absence of cirrhosis and excess alcohol intake: the Swiss Hepatitis C Cohort Study.

The objective of this study was to describe the all-cause mortality of participants in the Swiss Hepatitis C Cohort compared to the Swiss general population. Patients with hepatitis C virus (HCV) infection attending secondary and tertiary care centres in Switzerland. One thousand six hundred and forty-five patients with HCV infection were followed up for a mean of over 2 years. We calculated all-cause standardized mortality ratios (SMR) and 95% confidence intervals (CI) using age, sex and calendar year-specific Swiss all-cause mortality rates. Multivariable Poisson regression was used to model the variability of SMR by cirrhotic status, HCV genotype, infection with hepatitis B virus or HIV, injection drug use and alcohol intake. Sixty-one deaths were recorded out of 1645 participants. The crude all-cause SMR was 4.5 (95% CI: 3.5-5.8). Patients co-infected with HIV had a crude SMR of 20 (95% CI: 11.1-36.1). The SMR of 1.1 (95% CI: 0.63-2.03) for patients who were not cirrhotic, not infected with HBV or HIV, did not inject drugs, were not heavy alcohol consumers (<or=40 g/day) and were not genotype 3, indicated no strong evidence of excess mortality. We found little evidence of excess mortality in hepatitis C infected patients who were not cirrhotic, in the absence of selected risk factors. Our findings emphasize the importance of providing appropriate preventive advice, such as counselling to avoid alcohol intake, in those infected with HCV.