Associations between maternal physical activity in early and late pregnancy and offspring birth size: remote federated individual level meta-analysis from eight cohort studies.

OBJECTIVE: Evidence on the impact of leisure time physical activity (LTPA) in pregnancy on birth size is inconsistent. We aimed to examine the association between LTPA during early and late pregnancy and newborn anthropometric outcomes. DESIGN: Individual level meta-analysis, which reduces heterogeneity across studies. SETTING: A consortium of eight population-based studies (seven European and one US) comprising 72 694 participants. METHODS: Generalised linear models with consistent inclusion of confounders (gestational age, sex, parity, maternal age, education, ethnicity, BMI, smoking, and alcohol intake) were used to test associations between self-reported LTPA at either early (8-18 weeks gestation) or late pregnancy (30+ weeks) and the outcomes. Results were pooled using random effects meta-analyses. MAIN OUTCOME MEASURES: Birth weight, large-for-gestational age (LGA), macrosomia, small-for-gestational age (SGA), % body fat, and ponderal index at birth. RESULTS: Late, but not early, gestation maternal moderate to vigorous physical activity (MVPA), vigorous activity, and LTPA energy expenditure were modestly inversely associated with BW, LGA, macrosomia, and ponderal index, without heterogeneity (all: I2  = 0%). For each extra hour/week of MVPA, RR for LGA and macrosomia were 0.97 (95% CI: 0.96, 0.98) and 0.96 (95% CI: 0.94, 0.98), respectively. Associations were only modestly reduced after additional adjustments for maternal BMI and gestational diabetes. No measure of LTPA was associated with risk for SGA. CONCLUSIONS: Physical activity in late, but not early, pregnancy is consistently associated with modestly lower risk of LGA and macrosomia, but not SGA. TWEETABLE ABSTRACT: In an individual participant meta-analysis, late pregnancy moderate to vigorous physical activity modestly reduced birth size outcomes.

Interaction between nitric oxide signaling and gap junctions: effects on vascular function.

Nitric oxide signaling, through eNOS (or possibly nNOS), and gap junction communication are essential for normal vascular function. While each component controls specific aspects of vascular function, there is substantial evidence for cross-talk between nitric oxide signaling and the gap junction proteins (connexins), and more recently, protein-protein association between eNOS and connexins. This review will examine the evidence for interaction between these pathways in normal and diseased arteries, highlight the questions that remain about the mechanisms of their interaction, and explore the possible interaction between nitric oxide signaling and the newly discovered pannexin channels. This article is part of a Special Issue entitled: The Communicating junctions, composition, structure and characteristics.

An approach for the assessment of risk from chronic radiation to populations of phytoplankton and zooplankton.

A conceptual model of the effects of chronic radiation on a population of phytoplankton and zooplankton in an oceanic nutrient layer is presented. The model shows that there are distinct threshold dose rates at which the different plankton populations become unsustainable. These are 10,400 microGy h(-1) for phytoplankton and 125 microGy h(-1) for zooplankton. Both these values are considerably greater than the current screening values for protection of 10 microGy h(-1). The model highlights the effects of predator-prey dynamics in predicting that when the zooplankton is affected by the radiation dose, the phytoplankton population can increase. In addition, the model was altered to replicate the dose rates to the plankton of a previous ERICA Irish Sea assessment (24 microGy h(-1) for zooplankton and 430 microGy h(-1) to phytoplankton). The results showed only a 10% decrease in the zooplankton population and a 15% increase in the phytoplankton population. Therefore, at this level of dose, the model predicts that although the dose rate exceeds the guideline value, populations are not significantly affected. This result highlights the limitations of a single screening value for different groups of organisms.

An approach to the assessment of risk from chronic radiation to populations of European lobster, Homarus gammarus (L.).

The basic principles underlying a four-discrete age group, logistic, growth model for the European lobster Homarus gammarus are presented and discussed at proof-of-concept level. The model considers reproduction, removal by predation, natural death, fishing, radiation and migration. Non-stochastic effects of chronic low linear energy transfer (LET) radiation are modelled with emphasis on (99)Tc, using three endpoints: repairable radiation damage, impairment of reproductive ability and, at higher dose rates, mortality. An allometric approach for the calculation of LD(50/30) as a function of the mass of each life stage is used in model calibration. The model predicts that at a dose rate of 1 Gy day(-1), lobster population reproduction and survival become severely compromised, leading eventually to population extinction. At 0.01 Gy day(-1), the survival rate of an isolated population is reduced by 10%, mainly through loss of fecundity, comparable to natural migration losses. Fishing is the main ecological stress and only dose rates in the range 0.03-0.1 Gy day(-1) can achieve discernible effects above it. On the balance of radiation and other ecological stresses, a benchmark value of 0.01 Gy day(-1) is proposed for the protection of lobster populations. This value appears consistent with available information on radiation effects in wildlife.

Laboratory and field studies of polonium and plutonium in marine plankton.

Uptake experiments were successfully undertaken for polonium and plutonium in the marine diatom Skeletonema costatum. Experiments were complemented with a field study which yielded concentration factors for these radionuclides for plankton samples collected in the eastern Irish Sea. The uptake experiment produced uptake half times of 0.8 and 0.6 days for plutonium and polonium, respectively. Concentration factors of 3.1 x 10(5) l kg(-1) for plutonium and 2.4 x 10(5) l kg(-1) for polonium were consistent with those suggested by the IAEA for phytoplankton. Concentration factors derived from the field study were 2 x 10(3) l kg(-1) for plutonium and 1.4 x 10(4) l kg(-1) for polonium and were more consistent with IAEA values for zooplankton rather than phytoplankton. The maximum calculated dose rate due to Po and Pu in plankton sampled in the field was 0.12 microGyh(-1). In applying the laboratory-derived phytoplankton CF values for Po and Pu, higher dose rates, in the range 6-11 microGyh(-1), were calculated. The latter values are well below the UNSCEAR and IAEA review value of 400 microGyh(-1), and are also below the Environment Agency marine action level of 40 microGyh(-1).

Dynamic model for the assessment of radiological exposure to marine biota.

A generic approach has been developed to simulate dynamically the uptake and turnover of radionuclides by marine biota. The approach incorporates a three-compartment biokinetic model based on first order linear kinetics, with interchange rates between the organism and its surrounding environment. Model rate constants are deduced as a function of known parameters: biological half-lives of elimination, concentration factors and a sample point of the retention curve, allowing for the representation of multi-component release. The new methodology has been tested and validated in respect of non-dynamic assessment models developed for regulatory purposes. The approach has also been successfully tested against research dynamic models developed to represent the uptake of technetium and radioiodine by lobsters and winkles. Assessments conducted on two realistic test scenarios demonstrated the importance of simulating time-dependency for ecosystems in which environmental levels of radionuclides are not in equilibrium.

Sea to land transfer of anthropogenic radionuclides to the North Wales coast, Part I: external gamma radiation and radionuclide concentrations in intertidal sediments, soil and air.

Previous projects specifically aimed at performing radiological assessments in the vicinity of North Wales, investigating the presence and transfer of radionuclides from sea to land, were in 1986 and 1989. Since then, changes have occurred in the radioactive discharges from the British Nuclear Group Sellafield site. Annual discharges of (137)Cs, (238)Pu, (239,340)Pu and (241)Am have decreased markedly whereas, up until recent years, discharges of (99)Tc have increased. It is therefore desirable to quantify current transfer processes of radionuclides in the North Wales region and thus provide an update on 15-year-old studies. A field campaign was conducted collecting soil samples from 10 inland transects and air particulates on air filters from three High Volume Air Samplers, along the northern coast of Wales at Amlwch, Bangor Pier and Flint. Complementary field data relating to external gamma dose rates were collected at the soil sites. The field data generated for (137)Cs, (238)Pu, (239,340)Pu and (241)Am were consistent with what had been reported 15 years previously. Therefore, there has been no increase in the supply of these Sellafield-derived radionuclides to the terrestrial environment of the North Wales coast. The (99)Tc data in sediments were consistent with reported values within annual monitoring programmes, however, a relatively high activity concentration was measured in one sediment sample. This site was further investigated to determine the reason why such a high value was found. At present there is no clear evidence as to why this elevated concentration should be present, but the role of seaweed and its capacity in accumulating (99)Tc and transferring it to sediment is of interest. The analysis of the field samples for (99)Tc, (137)Cs, (238)Pu, (239,240)Pu and (241)Am has provided a data set that can be used for the modelling of the transfer of anthropogenic radionuclides from sea to land and its subsequent radiological implications and is reported in an accompanying paper.

Sea to land transfer of anthropogenic radionuclides to the North Wales coast, Part II: aerial modelling and radiological assessment.

Modelling calculations have been performed to predict the radiological impact of the sea to land transfer pathway to members of the public in North Wales from 1952 to 2004. The radionuclides of interest were (99)Tc, (137)Cs, (239,240)Pu and (241)Am and the exposure routes considered were food consumption, external and inhalation. The consumption of locally grown terrestrial food in the early to mid 1980s was the most significant source of exposure to all of the groups considered, with (239,240)Pu being the radionuclide contributing most to the dose. A maximum dose of 1.46microSvy(-1) was calculated for adult members of the critical consumption group in 1985, with doses for 2004 reducing to 0.59microSvy(-1). Despite the conservative approach of the dose calculations, the dose rate values are very low, less than 0.15% of the annual limit of 1000microSvy(-1) for the UK public from controlled radiation sources (excluding medical).

Allometric methodology for the calculation of biokinetic parameters for marine biota.

Biological half-lives of elimination (T(B1/2)) and concentration factors (CF) for different radionuclides and marine organisms were analysed. Tests were carried out in order to investigate the cases in which these parameters can be described by a simple power equation as a function of the volume of the organism, to verify the hypothesis of allometric scaling. Statistically significant trends were found for the CF of plutonium and americium and the T(B1/2) of technetium and radiocaesium across organisms. Some of these trends satisfy the theoretical expectation that allometric relations are a power function of the volume of the organism. For the CF, which relates to retention of a radionuclide, the mean exponent of the power function, -0.29+/-0.02, is close to the theoretical value of -0.25. For the T(B1/2) the mean exponent of the power function is lower at 0.16+/-0.01. The work improves the understanding of the metabolism of radionuclides within organisms for which no direct biokinetic information exists. The allometric relationships derived can be applied to calculate a T(B1/2) for caesium or technetium and a CF for plutonium and americium for any marine species. For the elements N, K, Np and Cm, the same allometric relationships as those derived for their analogues (99)Tc, (137)Cs, (239,240)Pu and (241)Am, respectively, can be applied, when no other data are available.

Uptake and depuration of 131I from labelled diatoms (Skeletonema costatum) to the edible periwinkle (Littorina littorea).

Uptake and depuration of (131)I into winkles through consumption of the diatom Skeletonema costatum is described. The work follows on from previous studies that investigated the uptake of iodine into winkles from seawater and seaweed. Incorporation of (131)I in S. costatum from labelled seawater followed linear first-order kinetics with an uptake half-time of 0.40 days. Iodine uptake in winkles from labelled S. costatum also followed linear first-order kinetics, with a calculated equilibrium concentration (C(infinity)) of 42Bqkg(-1) and a transfer factor (TF) of 1.1x10(-4) with respect to labelled diatom food. This TF is lower than that observed for uptake of (131)I in winkles from labelled seaweed. For the depuration stage, a biphasic sequence with biological half-lives of 1.3 and 255 days was determined. The first phase is biokinetically important, given that winkles can lose two-thirds of their activity during that period. This study shows that, whilst winkles can obtain radioactive iodine from phytoplankton consumption, they do not retain the majority of that activity for very long. Hence, compared with other exposure pathways, such as uptake from seawater and macroalgae, incorporation from phytoplankton is a relatively minor exposure route.

Effect of maternal facial oxygen on neonatal behavioural scores during elective Caesarean section with spinal anaesthesia.

BACKGROUND AND OBJECTIVE: For many, the administration of additional oxygen to the women receiving regional anaesthesia for Caesarean section is traditional, but for others it is controversial because of doubts about its efficacy. The aim of our study was to determine if beneficial effects of maternal oxygen therapy on the fetus could be revealed using a neonatal behavioural scoring system. METHODS: Sixty women with a normal singleton pregnancy beyond 36 weeks gestation, undergoing elective Caesarean section under spinal anaesthesia were randomized into two groups: Group 1 received air and oxygen mixture through a Hudson style face mask (FiO2 of 0.21-0.25). Group 2 received FiO2 of 0.40-0.60 through an identical Hudson style face mask. Neurologic Adaptive Capacity Score on all the infants within 5 min of birth and between 10 and 24 h after the Caesarean delivery was performed. Apgar score, umbilical venous blood oxygen tension and umbilical artery standardized base excess were recorded. RESULTS: Initial Neurologic Adaptive Capacity Scores at birth in Groups 1 and 2 were 32.6 (SD 4.6) and 31.3 (SD 4.3), respectively. Latter scores were 36.0 (SD 3.0) and 36.5 (SD 1.9), respectively. Neither were statistically significant. There were no significant differences between the groups for any of the recorded variables. CONCLUSIONS: Administering maternal oxygen using a standard commercial Hudson style face mask does not appear to significantly improve oxygen delivery to, nor does it influence acidosis or behavioural effects in, the normal neonate at elective Caesarean delivery with spinal anaesthesia.

Equivalent dose of ephedrine and phenylephrine in the prevention of post-spinal hypotension in Caesarean section.

BACKGROUND: Comparative studies of ephedrine and phenylephrine in prevention of hypotension after spinal anaesthesia for Caesarean section have lacked a consensus on dose equivalence. The aim of this study was to determine the minimum vasopressor dose for each of these drugs to calculate the dose ratio for clinical equivalence in the prevention of hypotension. METHODS: Patients with a normal singleton pregnancy beyond 36 weeks gestation undergoing elective Caesarean section under spinal anaesthesia were randomized into two groups. The first patient in Group A received 50 mg of ephedrine in saline 0.9% w/v, 500 ml, at 999 ml h(-1), the maximum rate possible on the pump and the first patient in Group B received 500 microg of phenylephrine in saline 0.9% w/v, 500 ml, at the same rate. The initial dose for dilution was an arbitrary choice. The dose of vasopressor in the saline bag for every subsequent patient was established by the efficacy of the dose in preventing hypotension in the previous patient according to the technique of up-down sequential allocation. Minimum vasopressor dose for each drug was determined according to the Dixon-Massey formula. RESULTS: The minimum vasopressor dose in saline 500 ml was 532.9 microg (95% CI 506.0-559.8) for phenylephrine and 43.3 mg (95% CI 39.2-47.3) for ephedrine. The concentration needed for equivalence at an infusion rate of 999 ml h(-1) was 1.07 microg ml(-1) for phenylephrine and 86.66 microg ml(-1) for ephedrine. Mean (sd) dose used for phenylephrine was 496.45 (78.3) microg and for ephedrine 39.64 (6.33) mg. CONCLUSION: This study demonstrates a potency ratio of 81.2 (95% CI 73.0-89.7) for equivalence between phenylephrine and ephedrine in prevention of hypotension after spinal anaesthesia for Caesarean section.

Update on the prenatal diagnosis and treatment of congenital adrenal hyperplasia due to 11beta-hydroxylase deficiency.

11beta-Hydroxylase deficiency is a common form of congenital adrenal hyperplasia causing virilization of the female fetus and hypertension. DNA analysis of the gene (CYP11B1) encoding 11beta-hydroxylase has been reported previously to be effective in the prenatal diagnosis of one affected female fetus. In that case, prenatal treatment with dexamethasone resulted in normal female genitalia. We now report five new pregnancies that underwent prenatal diagnosis for 11beta-hydroxylase deficiency. In the first family, the proband is homozygous for a T318M mutation and all fetuses from four subsequent pregnancies are carriers. In a second family, the mother is homozygous for a A331V mutation and was started on dexamethasone, but identification of a homozygous normal fetus led to the discontinuation of treatment. In another family, the fetus was a male homozygous for R384Q and treatment was discontinued. Lastly, a novel G444D mutation in exon 8 was identified and proven to reduce 11beta-hydroxylase activity.

The natural history and genotype-phenotype nonconcordance of HLA identical siblings with the same mutations of the 21-hydroxylase gene.

The correlation of genotype to phenotype in congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency has been investigated thoroughly since the mapping of the CYP21 gene to the short arm of chromosome 6. In most instances, it is possible to accurately predict the phenotype based on genoytpe; however, in a small number of patients, individuals with identical mutations demonstrate variable phenotypes. We report two HLA-identical brothers who represent a striking case of genotype-phenotype nonconcordance in CAH. Molecular genetic analysis showed both patients had mutations in intron 2 and exon 10 of CYP21. Both brothers underwent salt-deprivation tests at similar ages over three separate hospital admissions. Patient 1 was diagnosed with simple virilizing CAH and was able to maintain sodium balance during salt deprivation tests. Patient 2, 3 years younger, was diagnosed with salt-wasting CAH and was unable to maintain sodium balance but progressively increased his aldosterone secretion with age.

Uptake and depuration of 131I by the edible periwinkle Littorina littorea: uptake from labelled seaweed (Chondrus crispus).

Uptake and depuration experiments of (131)I from labelled seaweed (Chondrus crispus) by the edible periwinkle Littorina littorea have been performed. Radioiodine concentrations in winkles during uptake followed first-order kinetics with an uptake half-time of 1 day, and a calculated equilibrium concentration (C(infinity)) of 21 000 Bq kg(-1) resulting in a transfer factor of 0.07 with respect to the labelled seaweed used as food. For depuration, a biphasic sequence with biological half-lives of 1 and 24 days was determined. The results suggest that in general, iodine turnover in periwinkles is slower than observed for other molluscs (monophasic biological half-lives in the order of 2-3 days). Both environmental media, food and seawater, can be significant sources of radioiodine for the winkle.

Uptake and depuration of 131I by the edible periwinkle Littorina littorea: uptake from seawater.

Uptake and depuration experiments for the edible periwinkle Littorina littorea have been performed using 131I-labelled seawater. Throughout the experimental phase the winkles were fed on unlabelled Chondrus crispus. 131I concentrations in winkles during uptake followed linear first-order kinetics with an uptake half-time of 11 days, whereas for depuration a triphasic sequence with biological half-lives of 4, 23 and 56 days was determined. In general, iodine turnover in winkles via labelled seawater appears to be slower than observed for other molluscs (2-3 days). Most of the activity prior to and after depuration is found to be in the shell, with indications that shell and soft parts accumulate and depurate 131I at a similar rate. The operculum displays the highest specific activity of all fractions with a concentration factor of 750 l kg(-1). Concentration factors for whole winkle, shell, soft parts and digestive gland are in the order of 40-60 l kg(-1), higher than the IAEA recommended CF value for iodine in molluscs of 10 l kg(-1). The 131I CF in winkles is closer to that of the conservative radionuclides 99Tc and 137Cs than the CF of the particle reactive radionuclides (239,240)Pu and 241Am.

Which patients spend more than 4 hours in the Accident and Emergency department?

OBJECTIVES: The NHS Plan has a target that no patient should spend longer than 4 hours in Accident and Emergency (A & E) by the end of 2004. The aim of this study is to describe the attendance characteristics of patients spending less than and more than 4 hours total time in A & E. METHODS: Data were collected from 10 A & E departments in the West Midlands NHS region for the period 1 April 2001 to 31 March 2002. Patients were split into three groups; those spending less than 4 hours, between 4 and 8 hours and over 8 hours in A & E. The groups were compared in terms of their attendance characteristics, these being demography, temporal patterns, arrival mode and disposal. The data were also entered into a multinomial logistic regression using SPSS. RESULTS: Overall, 83.0 per cent (range 76.7 - 94.0 per cent) of patients spent less than 4 hours in A & E ; 3.6% per cent (range 0.3-8.6 per cent) spent longer than 8 hours in A & E. The risk factors for spending over 4 hours in A & E were requiring admission, arriving by ambulance, arriving during the night, increasing age and higher levels of deprivation. Being admitted had the greatest effect on time spent in A & E, with a patient being 2.64 times more likely to spend 4-8 hours and 4.84 times more likely to spend over 8 hours in the department. CONCLUSIONS: This study points to admission and service provision at night as factors leading to long periods in A & E. However, these results can only act as a guide as the problems are different in different Trusts and each should analyse their problem before taking action.

Influence of material deprivation on hospital admissions for gynaecologic infections.

This study was conducted to examine the relationship between age, material deprivation, and hospital admissions for selected gynaecologic infections in an English health region. Data from hospital episode statistics relating to hospital admissions for pelvic inflammatory disease (PID), infections of the uterus, and infections of the cervix, vagina, and vulva were obtained. Townsend deprivation scores (based on 1991 census data) were allocated by linking postcodes of cases to enumeration districts (EDs) and then assigning the EDs to appropriate quintiles of material deprivation. Both single variable and multivariable (Poisson regression) analyses were performed. For women with PID, the risk of hospitalisation increased with increasing deprivation (P<0.0001), and women in the most deprived quintile were at increased risk (relative risk [RR] 1.31; 95% confidence interval [95%CI] 1.24-1.39) for hospitalisation. Multivariable analysis identified an elevated risk of hospital admission in women aged 25-44 years for PID (RR 2.03; 95%CI 0.84-4.87) and infections of the cervix, vagina, and vulva (RR 1.47; 95%CI 1.16-1.87), and the incidence of both conditions increased significantly with age. In summary, the results obtained suggest that women from the most deprived areas are at greatest risk of hospitalisation for gynaecologic infections, particularly PID. Preventive measures together with earlier diagnostic, treatment, and referral procedures are required to reduce morbidity.

A novel semiquantitative polymerase chain reaction/enzyme digestion-based method for detection of large scale deletions/conversions of the CYP21 gene and mutation screening in Turkish families with 21-hydroxylase deficiency.

21-Hydroxylase deficiency is a recessively inherited disorder resulting from mutations in the CYP21 gene. The CYP21 gene is located along with the CYP21P pseudogene in the human leukocyte antigen major histocompatibility complex region on chromosome 6. Molecular diagnosis is difficult due to the 98% similarity of CYP21 and CYP21P genes and the fact that almost all frequently reported mutations reside on the pseudogene. Allele-specific PCR for the 8 most frequently reported point mutations was performed in 31 Turkish families with at least a single 21-hydroxylase-deficient individual. The allele frequencies of the point mutations were as follows: P30L, 0%; IVS2 (AS,A/C-G,-13), 22.5%; G110delta8nt, 3.2%; I172N, 11.4%; exon 6 cluster (I236N, V237E, M239K), 3.2%; V281L, 0%; Q318X, 8%; and R356W, 9.6%. Large deletions and gene conversions were detected by Southern blot analysis, and the allele frequencies were 9.6% and 22.5%, respectively. Sequence analysis of the gene, performed on patients with only 1 mutated allele, revealed 2 missense mutations (R339H and P435S). A novel semiquantitative PCR/enzyme digestion-based method for the detection of large scale deletions/conversions of the gene was developed for routine diagnostic purposes, and its accuracy was shown by comparison with the results of Southern blot analysis.