Hanbury-Brown and Twiss exchange and non-equilibrium-induced correlations in disordered, four-terminal graphene-ribbon conductor.

We have investigated current-current correlations in a cross-shaped conductor made of graphene. The mean free path of charge carriers is on the order of the ribbon width which leads to a hybrid conductor where there is diffusive transport in the device arms while the central connection region displays near ballistic transport. Our data on auto and cross correlations deviate from the predictions of Landauer-Büttiker theory, and agreement can be obtained only by taking into account contributions from non-thermal electron distributions at the inlets to the semiballistic center, in which the partition noise becomes strongly modified. The experimental results display distinct Hanbury - Brown and Twiss (HBT) exchange correlations, the strength of which is boosted by the non-equilibrium occupation-number fluctuations internal to this hybrid conductor. Our work demonstrates that variation in electron coherence along atomically-thin, two-dimensional conductors has significant implications on their noise and cross correlation properties.

Long-term clinical and economic outcomes in previously untreated paediatric patients with severe haemophilia A: A nationwide real-world study with 700 person-years.

AIM: For previously untreated patients (PUPs) with severe haemophilia A in Finland for the past 2 decades, the standard practice has been to start early primary prophylaxis. We evaluated the long-term clinical outcomes and costs of treatment with high-dose prophylaxis in PUPs from birth to adolescence, including immune tolerance induction (ITI). METHODS: From the medical records of all PUPs born between June 1994 and May 2013 in Finland, we retrospectively extracted data on clinical outcomes and healthcare use. Using linear mixed models, we analysed longitudinal clinical outcome data. To analyse skewed cost data, including zero costs, we applied hurdle regression. RESULTS: All 62 patients received early regular prophylaxis; totally, they have had treatment for nearly 700 patient-years. The median age of starting home treatment was 1.1 years. The mean (SD) annual treatment costs (€ per kg) were 4391€ (3852). For ages 1-3, ITI comprised over half of the costs; in other groups, prophylactic FVIII treatment dominated. With these high costs, however, clinical outcomes were desirable; median (IQR) ABR was low at 0.19 (0.07-0.46) and so was AJBR at 0.06 (0-0.24). Thirteen (21%) patients developed a clinically significant inhibitor, 10 (16%) with a high titre. All ITIs were successful. The mean costs for ITI were 383 448€ (259 085). The expected ITI payback period was 1.81 (95% CI 0.62-12.12) years. CONCLUSIONS: Early high-dose prophylaxis leads to excellent long-term clinical outcomes, and early childhood ITI therapy seems to turn cost-neutral generally already in 2 years.

Inhibitor development in previously untreated patients with severe haemophilia A: a nationwide multicentre study in Finland.

INTRODUCTION: Currently the most serious treatment complication of haemophilia is the inhibitor development (ID), i.e. neutralizing antibody development. AIM: This nationwide multicentre study in Finland evaluated the incidence and risk factors of ID in previously untreated patients (PUPs) with severe haemophilia A (FVIII:C < 0.01 IU mL(-1) ). METHODS: We enrolled all PUPs (N = 62) born between June 1994 and May 2013 with at least 75 exposure days (EDs) to screen ID during follow-up extending to September 2013. RESULTS: Thirteen ID (21% of 62) occurred; 10 (16% of 62) with high titre. Fifty-one patients (82%) were on primary prophylaxis (regular prophylaxis before the age of 2 and before the first joint bleed) from the median age of 11.4 months, 90% via a central venous access device. The initial product was rFVIII in 63% and pd-FVIII in 37%, moreover in 24% pd-FVIII was switched to rFVIII concentrate during the 75 EDs. Non-transient inhibitors developed in 9/51 (17.6%; 13.7% high titre) children with primary and in 4/11 (36.4%; 27.3% high titre) patients with secondary prophylaxis (P = 0.24). Overall, 74% had a high-risk genotype similarly distributed among the prophylaxis groups. The history of a major bleed enhanced ID (aHR, 4.0; 95% CI, 1.2-13.7), whereas FVIII treatment intensity or source and early implantation of ports did not increase ID risk. CONCLUSION: The cumulative incidence of ID was low notwithstanding prevalent high-risk mutations. Despite patient-related risk factors, our management involving early intensive primary prophylaxis via ports helps to prevent bleeds and lower the incidence of inhibitors.

Health conditions associated with metabolic syndrome after cancer at a young age: A nationwide register-based study.

PURPOSE: Childhood cancer survivors are at risk for developing metabolic syndrome (MetS), which subsequently leads to cardiovascular morbidity and excess mortality. Our aim was to investigate the purchases of medications associated with MetS among 7551 early onset cancer patients compared to siblings. METHODS: Our nationwide Finnish population-based registry study analyzed the drug purchase of medication among early onset cancer patients diagnosed with cancer below the age of 35 years between 1994 and 2004 compared to siblings by linkage to the drug purchase registry, allowing for a maximal follow-up of 18 years. RESULTS: The hazard ratios (HRs) for purchasing antihypertensives and diabetes drugs were higher after both childhood (HR 4.6, 95%CI 3.1-7.0; HR 3.0, 95%1.5-6.1) and young adulthood (YA) cancer (HR 1.5, 95%CI 1.3-1.8; HR 1.6, 95%CI 1.1-2.2) compared to siblings. The HRs for purchasing lipid-lowering drugs were elevated both after childhood (HR 4.3,95%CI 0.9-19.5) and YA cancer (HR 1.6, 95%CI 1.04-2.5), but only reached significance in YA cancer patients. Among specific cancer diagnosis groups, highest HR values for antihypertensives were found in childhood acute lymphoblastic leukemia (ALL) (HR 6.1, 95%CI 3.7-10.3) and bone tumor (HR 4.3, 95%CI 1.9-9.4), and YA ALL (HR 4.8, 95%CI 3.1-7.0) and acute myeloid leukemia (AML) (HR 3.4, 95%CI 2.5-5.1) patients. Moreover, childhood ALL (HR 6.3, 95%CI 2.7-14.8), AML (HR 7.6, 95%CI 1.9-24.5) and central nervous system (CNS)-tumor (HR 3.5, 95%CI 1.3-9.2) and YA ALL (HR 3.7, 95%CI 1.2-9.5) patients showed the strongest likelihood of purchasing diabetes drugs compared to siblings. CONCLUSION: The purchase of medications associated with MetS was increased after early onset cancer and highly dependent on the age at cancer diagnosis and the cancer diagnosis. Prevention strategies are imperative for reducing potentially life-threatening cardiovascular complications after early onset cancer.

Cardiovascular medication after cancer at a young age in Finland: A nationwide registry linkage study.

Despite improved survival rates, childhood and young adult (YA) cancer survivors face elevated risks for life-threatening morbidities, especially cardiovascular complications. Our nationwide Finnish registry study investigated the purchases of cardiovascular medication from 1993 to 2011 in patients diagnosed with cancer aged below 35 years (N = 8,197) between 1993 and 2004 compared to siblings (N = 29,974) via linkage to the drug purchase registry. The cumulative incidence for purchasing cardiovascular medications was higher in childhood and YA cancer patients compared to siblings with a rising trend over time. After childhood cancer, the highest hazard ratio (HR) was found for purchasing anticoagulants (HR 19.8, 95% CI 8.5-45.9). The HRs for any cardiovascular medication (HR 7.2, 95% CI 5.1-10.1) and cardiac medication (HR 4.8, 95% CI 3.3-6.9) were markedly elevated after childhood cancer as well. Regarding YA cancer patients, the respective HRs were 2.5 (95% CI 2.0-3.2) for anticoagulants, HR 1.7 (95% CI 1.5-1.9) for any cardiovascular medication and HR 1.5 (95% CI 1.3-1.7) for cardiac medication. Among cancer patients, highest HRs for cardiovascular medication were observed after childhood acute lymphoblastic leukemia (ALL) and bone tumors (HR 10.2, 95% CI 6.8-15.5 and HR 7.4, 95% CI 4.0-13.7) and YA ALL and acute myeloid leukemia (HR 5.1, 95% CI 3.5-7.1 and HR 2.8, 95% CI 1.8-4.0). Our study demonstrated increased HRs for purchasing cardiovascular medication after early-onset cancer compared to siblings reflecting elevated cardiovascular morbidity. Thus, the implementation of long-term cardiovascular disease screening is imperative to prevent, detect and adequately treat cardiovascular late effects after cancer at a young age.

Complications associated with central venous access device in children with haemophilia: a nationwide multicentre study in Finland.

Children with haemophilia require venous access for regular infusion of coagulation factors. A central venous access device (CVAD) ensures long-term access but associates with infectious and non-infectious complications with proposed risk factors of young age at initial CVAD implantation and presence of an inhibitor. Our aim was to evaluate the incidence and risk factors for complications associated with CVAD usage in a retrospective nationwide multicentre study in five Finnish Paediatric Haemophilia Treatment Centers. Our study investigated 106 CVADs in 58 patients with 137 971 CVAD days. The median access survival was 1159 CVAD days, and most often a malfunction led to CVAD removal after a long survival (median of 1640 CVAD days). We detected a very low bloodstream infection rate (0.12/1000 CVAD days). The presence of neutralizing inhibitor was a significant risk factor for infection. Heparin vs. saline flushing did not influence the CVAD outcome. We detected a lower infection rate than previously reported, although 90% of the patients were very young (<2 years) at first insertion (median age = 1.02 year). Port access was frequent after initial implantation: six patients (10%) used the port daily for immune tolerance induction therapy and 74% at least twice weekly for prophylaxis. Young age did not increase the risk of infections, as 59% of the CVAD-related infections were recorded in children over 6 years of age. Our national experience confirms the safety of prophylactic factor concentrate administration via ports even in very young children.

Cooper pair splitting by means of graphene quantum dots.

A split Cooper pair is a natural source for entangled electrons which is a basic ingredient for quantum information in the solid state. We report an experiment on a superconductor-graphene double quantum dot (QD) system, in which we observe Cooper pair splitting (CPS) up to a CPS efficiency of ∼10%. With bias on both QDs, we are able to detect a positive conductance correlation across the two distinctly decoupled QDs. Furthermore, with bias only on one QD, CPS and elastic cotunneling can be distinguished by tuning the energy levels of the QDs to be asymmetric or symmetric with respect to the Fermi level in the superconductor.

Cardiovascular morbidity in long-term survivors of early-onset cancer: a population-based study.

Improvements in cancer therapy have resulted in an expanding population of early-onset cancer survivors. In contrast to childhood and adolescent cancer survivors, there is still a lack of data concerning late morbidities among young adult (YA) cancer survivors. Thus, our aim was to investigate cardiac and vascular morbidity among early-onset cancer survivors with a special interest in YA cancer survivors. In a population-based setting, we explored the risk of cardiovascular disease in early-onset cancer survivors compared to healthy siblings. Patients diagnosed with cancer below 35 years of age since 1975 were identified from the Finnish Cancer Registry, and 5-year survivors were included in our study (N = 13,860). Information on cardiovascular morbidity was collected from the national hospital discharge registry. Compared to siblings, cancer survivors aged 0-19 and 20-34 at diagnosis had significantly elevated hazard ratios (HRs) for the studied outcomes: HR 13.5 (95% CI 8.9-20.4) and 3.6 (95% CI 2.8-4.6) for cardiomyopathy/cardiac insufficiency; HR 3.4 (95% CI 2.3-5.1) and 1.7 (95% CI 1.4-2.0) for atherosclerosis/brain vascular thrombosis; HR 3.3 (95% CI 1.7-6.5) and 1.8 (95% CI 1.5-2.1) for myocardial infarction/cardiac ischemia and HR 1.7 (95% CI 1.2-2.6) and 1.4 (95% CI 1.2-1.7) for cardiac arrhythmia. In both groups, depending on the outcome, the HR for adverse events was highest among lymphoma, brain tumor, leukemia and testicular malignancy survivors. Our results regarding late effects of childhood cancer survivors confirmed previous findings. Additionally, our study provides novel information concerning the YA cancer survivor population. Hence, our data may help in planning the risk-based long-term follow-up of early-onset cancer survivors.

Hepatoblastoma in the Nordic countries.

Little is known about the etiology of hepatoblastoma. Because of the young age at diagnosis, several studies have looked at various birth characteristics. The purpose of our study was to investigate the incidence of hepatoblastoma in the Nordic countries and the association between selected birth characteristics and hepatoblastoma. Data from national cancer registries and birth registries in Denmark, Sweden, Norway and Finland 1985-2006 was used. Overall, 155 children with hepatoblastoma aged 0-14 years were included and individually matched to five controls drawn randomly from national population registries. The incidence rate of hepatoblastoma was 1.7 per million person-years with a predominance of boys (1.5:1). Incidence rate was highest before the age of 1 year (8.3 per million person-years). A higher risk of hepatoblastoma was found in children with birth weight <1,500 g [odds ratio (OR) = 9.5; 95% confidence interval (CI): 2.3-38.2], born preterm in week 22-32 (OR = 4.5; CI: 1.8-11.5) and Apgar scores <7 after 1 min (OR = 3.1; CI: 1.3-7.1) and 5 min (OR = 7.5; CI: 1.8-32.4). A doubling in risk was found in children who were large for gestational age (OR = 2.3; CI: 1.0-5.3). No associations were found with birth order, maternal age or maternal smoking. Our study indicates that intrauterine and/or neonatal factors are associated with increased risk of hepatoblastoma. These may include low birth weight and asphyxia leading to neonatal intensive care. Alternatively, the factors may be a consequence of hepatoblastoma developing in utero.

Infectious exposure in the first years of life and risk of central nervous system tumours in children: analysis of birth order, childcare attendance and seasonality of birth.

BACKGROUND: An infective, mostly viral basis has been found in different human cancers. To test the hypothesis of a possible infectious aetiology for central nervous system (CNS) tumours in children, we investigated the associations with proxy measures of exposure to infectious disease. METHODS: In a large case-control study nested in the populations of Denmark, Norway, Sweden, and Finland of 4.4 million children, we studied the association of birth order and seasonal variation of birth with subsequent risk for CNS tumours. We identified 3983 children from the national cancer registries, and information on exposure was obtained from the high-quality national administrative health registries. We investigated the association between childcare attendance during the first 2 years of life and the risk for CNS tumours in a subset of Danish children with CNS tumours, using information from the Danish Childcare database. RESULTS: We observed no association between birth order and risk of CNS tumours overall (odds ratio (OR) for second born or later born vs first born, 1.03; 95% confidence interval (CI), 0.96-1.10) or by histological subgroup, and children with CNS tumours did not show a seasonal variation of birth that was distinct from that of the background population. Childcare attendance compared with homecare showed a slightly increased OR (1.29; 95% CI, 0.90-1.86) for CNS tumours, with the highest risk observed in children attending a crèche. The strongest association was observed for embryonal CNS tumours. We found no effect of age at enrolment or duration of enrolment in childcare. CONCLUSION: These results do not support the hypothesis that the burden of exposure to infectious disease in early childhood has an important role in the aetiology of paediatric CNS tumours.

Male reproductive health after childhood cancer.

AIM: Twenty-five male patients were investigated to elucidate the correlation of semen parameters and other related parameters in the assessment of spermatogenesis after childhood cancer treatment. METHODS: Evaluation of given cancer treatment, anthropometric and testicular size measurements, semen analysis, and measurement of gonadotrophins, testosterone, sex hormone-binding globulin (SHBG), and inhibin B were performed according to a protocol. RESULTS: Median (range) sperm concentration (SC) was 35.5 (0-273)x10(6)/mL, and percentage of motile sperm 56 (0-86)%. Testicular size (r=0.73, p<0.001) and the level of inhibin B (r=0.66, p<0.001) correlated strongly to SC. SC correlated negatively to FSH (r=0.46, p=0.03). Only testicular size predicted SC significantly (p=0.03). Inhibin B showed highest area under ROC curve (0.83, 95%CI 0.67-0.99) in showing SC<20x10(6)/mL. Body mass index (BMI) did not correlate with SC, but negative correlation between BMI and SHBG was found (r=-0.41, p=0.04). CONCLUSION: Although semen analysis is a useful instrument for fertility assessment in men, it is often difficult to get these samples from childhood cancer survivors. Thus, indirect methods are needed in prediction of possible sperm count impairment in postpubertal adolescents after cancer treatment. When combined with the data on testicular size and follicle-stimulating hormone (FSH) level, inhibin B gives valuable addition to the estimations of spermatogenesis.

Scholastic achievements of children with brain tumors at the end of comprehensive education: a nationwide, register-based study.

BACKGROUND: Cancer treatment may affect school performance. Scholastic achievements after childhood brain tumors have not been previously reported on the level of actual grades. PATIENTS AND METHODS: Patients with brain tumor (n = 300) were identified from the Finnish Cancer Registry. Population controls (n = 1,473) were matched for age, gender, and place of living. Their ninth grade school reports were obtained from Statistics Finland. Age at diagnosis and cranial irradiation (CRT) were considered in analyses, and the level of parental education was taken into model as a covariate. RESULTS: Six percent of patients did not finish their comprehensive school at the usual age. Patients had lower overall averages than their controls (95% CI for the difference -0.30, -0.16). Girls differed from their controls independently of the age at diagnosis or CRT. Boys treated with CRT at school age, but not before school age, had poorer results than their controls (95% CI -0.65, -0.18). The grades of patients were significantly lower in each school subject, and differed most in foreign language. Young girls with CRT had greatest differences from their controls (95% CI -1.73, -0.86) in this subject. In mathematics, patients diagnosed before school age had greatest difference from their controls. In their mother tongue, patients differed less from their controls. CONCLUSIONS: Few patients with brain tumor missed the ninth grade certificate at the age of 16. Grades in foreign language (representing verbal performance) were most affected. However, the patients fared poorer than controls in each subject. The difference was most pronounced among girls. Girls were more sensitive to the adverse effects of irradiation.

The siblings of childhood cancer patients need early support: a follow up study over the first year.

BACKGROUND AND METHODS: In a 1 year follow up study, we assessed the life situation of 33 siblings of childhood cancer patients and 357 healthy controls. The hypothesis was that siblings have more behavioural and health related problems just after the cancer diagnosis. Validated assessment methods were used. RESULTS: Siblings below school age tended to have conduct problems, psychosomatic problems, and a mixed group of other behavioural problems, when assessed 3 months after the cancer diagnosis. These symptoms became less evident during follow up. Among the school aged siblings, however, conduct problems, learning problems, psychosomatic problems, impulsive-hyperactive symptoms, and other behavioural symptoms remained unchanged during follow up. In their self assessments, the school aged siblings showed both state and trait anxiety more often than controls at the first assessment, but later these symptoms settled to the same level as the controls. The overall Children's Depression Inventory (CDI) depression scores did not show differences between the study groups. CONCLUSIONS: The ratings of the parents were in keeping with the self assessment of the school aged siblings only in a few aspects; the emphasis of findings can be changed when proxies are used. The siblings have symptoms and adverse feelings which probably could be relieved by targeted, early information about the illness, and possibly by group discussions or activities, soon after the cancer diagnosis. In order to obtain necessary support for the siblings with educational problems, school personnel need to be informed about the sibling distress.

The life situation of parents over the first year after their child's cancer diagnosis.

AIM: To evaluate the impact of childhood cancer on the life of the parents. METHOD: A 1-y follow-up study, with two time points for questionnaires, was completed in 21 out of 26 eligible families, and there were 46 control families matched by mothers' educational status. RESULTS: Half of the mothers worked outside home during the first year of their child's illness. The perceived amount of lost family income was high during the first few months. The attitudes of the parents were fairly positive as their family life and spouse relations were concerned. Feelings of being under strain or stressed were, by the mothers, described as intolerable in the beginning. However, standardized anxiety assessment failed to show an increase in feelings of anxiety. Own health was rated significantly negative by cancer parents. CONCLUSIONS: Despite good family relationships, a need for supportive measures exists, especially during the first few months, and in-depth interviews by psychologists or special nurses might be a way of finding out possible anxiety. The perceived feelings of own health may also be an indicator of the level of distress. Parent support groups could also do more to offer opportunities of physical activities for the parents, not merely disease-related information and group discussions.

Childhood cancer patients at school.

The aim of this study was to assess the school-related problems of childhood cancer patients. A cross-sectional questionnaire study for school-aged children with extracranial malignancies, in the area of Turku University Hospital serving around 1000000 people. Siblings, healthy pupils and teachers were studied as controls. 43 patients responded. None of the patients or controls was placed in special educational programmes. However, 30.8% of the patients, 15.7% of the controls and 3.7% of the siblings had required extra tutoring. The patients' results differed statistically from both the siblings' (P=0.022) and the controls' (P=0.041) results. The school marks in mathematics (P=0.05) and in foreign languages (P=0.06) tended to be worse for the patients than for the healthy controls. Bullying was reported by 31.7% of the patients, 10.9% of controls (P=0.0012) and 8.3% of the siblings (P=0.056). The biggest problem faced by the cancer patients was bullying-the patients reported approximately 3 times as much bullying as the healthy children did. It seems that there are still several aspects which need to be reconsidered when these children return to school or start their school-life as survivors of childhood cancer. Some proposals are presented.

Cholesterol-lowering effect of spreads enriched with microcrystalline plant sterols in hypercholesterolemic subjects.

BACKGROUND: Plant sterols have been shown to reduce serum lipid concentrations. The effectiveness is highly dependent on the physical state of the plant sterols. By means of a new crystallizing method, plant sterols can be added into dietary fats and oils homogeneously. In this fat ingredient, plant sterols are in a microcrystalline form. AIMS OF THE STUDY: We investigated the cholesterol-lowering effect and possible side effects of vegetable oil-based spreads fortified with two different doses of microcrystalline plant sterols. METHODS: This double-blind randomized, placebo-controlled study consisted of a 6-wk run-in and a 6-month experimental period. During the run-in period, all 155 hypercholesterolemic subjects received rapeseed oil-based control spread. In the beginning of the experimental period subjects were randomly assigned into one of three experimental groups. The control group continued to use control spread, and the two test groups used spreads with added plant sterols of either 1.5 g/d or 3.0 g/d. The subjects consumed test spreads as a part of their normal diet without any restrictions in lifestyle and diet. RESULTS: Plasma total- and LDL-cholesterol concentrations were significantly reduced by 7.5-11.6% (0.46-0.62 mmol/1) in groups consuming margarine enriched with free plant sterols, compared with the control group. The effects were similar between the two groups consuming either 1.5g or 3.0 g plant sterols per day. No effect on HDL-cholesterol or triacylglycerol concentrations occurred. The test spreads did not induce any adverse effects in blood clinical chemistry, hematology or decreases in serum concentrations of lipid soluble vitamins. CONCLUSIONS: Microcrystalline plant sterols are effective in lowering serum total- and LDL-cholesterol concentrations without obvious side effects. The daily dose of 1.5 g plant sterols is enough to reach the maximum effect.

Ovarian function during use of vaginal rings delivering three different doses of Nestorone.

Contraceptive vaginal rings delivering various progestins alone or in combination with estrogen have been previously studied, showing adequate steroid vaginal absorption and acceptability by the users. Nestorone progestin (NES) is a potent 19-nor-progesterone derivative, inactive by the oral route, but an excellent option for vaginal delivery. The purpose of this study was to evaluate ovarian function during 6 months of continuous use of progestin-only vaginal rings delivering 3 different doses of NES: 50, 75, and 100 microg per day. Blood samples were taken twice a week for 5 consecutive weeks during a control cycle and on months 1, 3 and 6 of use, for the measurement of estradiol (E2), progesterone (P), and NES. A total of 87 volunteers randomly received each of the 3 doses. After an initial peak, NES serum levels remained fairly constant throughout the duration of the study at about 125, 200 and 250 pmol/L, respectively, decreasing slightly with time. Luteal activity occurred very rarely (1.2-2.6% of sampling periods) with no apparent difference between doses. Low E2 levels (< or =100 pmol/L) in all samples of a run were rare (5%) and only with the high dose ring (100 microg/day). E2 remained within normal levels (101-1500 pmol/L) in most of the segments studied. We conclude that the 50 and 75 microg/day NES rings provide adequate ovulation inhibition without hypoestrogenism, while the 100 microg/day ring may deliver an unnecessarily high dose.

Cognitive functions of adolescent childhood cancer survivors assessed by event-related potentials.

BACKGROUND: Neurophysiological methods were applied to examine subtle central nervous system (CNS) adverse effects for adolescent childhood cancer survivors. We analyzed auditory event-related potentials (ERPs)-P300 and MMN/P3a complex-to find out whether there was impaired attention orientation in asymptomatic cancer survivors, and whether these ERP methods could be used as more objective tools in detecting those survivors who might need academic testing. Previous clinical studies of P300 have focused on leukemia survivors. MMN for cancer survivors has not been reported. PROCEDURE: The subjects were survivors of childhood leukemia (n=11) and solid tumors (n=8), as well as healthy controls (n=10). The mean age was 15.5 years for survivors and 15.9 years for controls. Pure sine-wave tones (500 and 553 Hz, 100 ms) were used as stimuli in an oddball paradigm. The ERPs to frequency change were measured. MMN recordings were performed in a passive non-attended situation where the subject was watching a voiceless video cartoon. P300 was produced thereafter, but in an active attend situation, by the same auditory oddball paradigm as MMN. RESULTS: A significant difference was detected between the groups for the latency of P300 at electrodes Cz (P = 0.03) and C4 (P = 0.05). The cancer survivors had prolonged P300 latencies as an indication of prolonged short-term memory processing. The area and latency parameters of MMN did not differ significantly between the study groups, but in cancer survivors, the area and the mean amplitude of the subsequent P3a wave were diminished. The results indicate that the discrimination process was not as easy for the survivors as for the controls. However, it seems that in cancer survivors the basic mechanism starting attention shift to novel stimuli is not impaired. CONCLUSIONS: These results indicate that it is important to carefully evaluate the proper methods for the teaching of children who are survivors of malignancies. The auditory information may not always lead to the best possible learning results.

The possible role of enterohepatic cycling on bioavailability of norethisterone and gestodene in women using combined oral contraceptives.

Using steady-state conditions we aimed to test if administration of oral activated charcoal affects the bioavailability of norethisterone acetate (NET Ac) and gestodene (GEST) by inhibiting their enterohepatic recirculation. Thirteen volunteers received, in a randomized order, Minulet (75 microg GEST and 30 microg ethinylestradiol [EE(2)]) and Econ/30 (1 mg NET Ac and 30 microg EE(2)), each for 4 months. Serum GEST and norethisterone (NET) levels were evaluated with respect to C(max,) t(max) and 24-h area under the curve (AUC(0-24h)) in the middle of the control (3rd) cycle and the charcoal treatment (4th) cycle during both pill treatments. No statistically significant difference was seen in any of the aforementioned variables between the control and charcoal treatment cycles of either pill. Neither was a difference seen in the bioavailability of GEST and NET as evaluated by the ratios of two 24-h AUCs calculated in the control and charcoal cycles of each pill treatment (p = 0.29). The results suggest that enterohepatic circulation of GEST and NET is not of clinical importance. We conclude that women on oral contraceptives can take activated charcoal for the treatment of diarrhea when administered 3 h after and at least 12 h before pill intake.