International gestational age-specific centiles for umbilical artery Doppler indices: a longitudinal prospective cohort study of the INTERGROWTH-21st Project.

BACKGROUND: Reference values for umbilical artery Doppler indices are used clinically to assess fetal well-being. However, many studies that have produced reference charts have important methodologic limitations, and these result in significant heterogeneity of reported reference ranges. OBJECTIVES: To produce international gestational age-specific centiles for umbilical artery Doppler indices based on longitudinal data and the same rigorous methodology used in the original Fetal Growth Longitudinal Study of the INTERGROWTH-21st Project. STUDY DESIGN: In Phase II of the INTERGROWTH-21st Project (the INTERBIO-21st Study), we prospectively continued enrolling pregnant women according to the same protocol from 3 of the original populations in Pelotas (Brazil), Nairobi (Kenya), and Oxford (United Kingdom) that had participated in the Fetal Growth Longitudinal Study. Women with a singleton pregnancy were recruited at <14 weeks' gestation, confirmed by ultrasound measurement of crown-rump length, and then underwent standardized ultrasound every 5±1 weeks until delivery. From 22 weeks of gestation umbilical artery indices (pulsatility index, resistance index, and systolic/diastolic ratio) were measured in a blinded fashion, using identical equipment and a rigorously standardized protocol. Newborn size at birth was assessed using the international INTERGROWTH-21st Standards, and infants had detailed assessment of growth, nutrition, morbidity, and motor development at 1 and 2 years of age. The appropriateness of pooling data from the 3 study sites was assessed using variance component analysis and standardized site differences. Umbilical artery indices were modeled as functions of the gestational age using an exponential, normal distribution with second-degree fractional polynomial smoothing; goodness of fit for the overall models was assessed. RESULTS: Of the women enrolled at the 3 sites, 1629 were eligible for this study; 431 (27%) met the entry criteria for the construction of normative centiles, similar to the proportion seen in the original fetal growth longitudinal study. They contributed a total of 1243 Doppler measures to the analysis; 74% had 3 measures or more. The healthy low-risk status of the population was confirmed by the low rates of preterm birth (4.9%) and preeclampsia (0.7%). There were no neonatal deaths and satisfactory growth, health, and motor development of the infants at 1 and 2 years of age were documented. Only a very small proportion (2.8%-6.5%) of the variance of Doppler indices was due to between-site differences; in addition, standardized site difference estimates were marginally outside this threshold in only 1 of 27 comparisons, and this supported the decision to pool data from the 3 study sites. All 3 Doppler indices decreased with advancing gestational age. The 3rd, 5th 10th, 50th, 90th, 95th, and 97th centiles according to gestational age for each of the 3 indices are provided, as well as equations to allow calculation of any value as a centile and z scores. The mean pulsatility index according to gestational age = 1.02944 + 77.7456*(gestational age)-2 - 0.000004455*gestational age3. CONCLUSION: We present here international gestational age-specific normative centiles for umbilical artery Doppler indices produced by studying healthy, low-risk pregnant women living in environments with minimal constraints on fetal growth. The centiles complement the existing INTERGROWTH-21st Standards for assessment of fetal well-being

Demographic and Clinical Characteristics of Human Immunodeficiency Virus-Infected Patients Receiving Dialysis in Portugal: a Nationwide Multicentre Survey

Background: Data on human immunodeficiency virus (HIV) infected patients receiving dialysis in Portugal is scarce. Methods: This nationwide epidemiological survey retrospectively evaluates HIV-infected patients on chronic dialysis in Portugal between 1997 and 2002. Results: Sixty-six patients were evaluated (mean age: 39.1±1.6 years, 47 men, 35 black African). Sixty-two patients started dialysis and 4 patients who were receiving dialysis had HIV seroconversion. Eighty-five percent of patients were treated in Lisbon. The annual incidence of HIV-infected patients on chronic dialysis was 0.5% in 1997 and 0.9% in 2002. Seventy-eight percent of patients were HIV-1 infected , 13% had hepatitis B and 31% hepatitis C. Sexual contact was the mode of transmission of HIV in 53% of cases. Four patients had biopsy-proved HIV-associated nephropathy. Ninety-five percent of patients were on chronic hemodialysis. Fifty percent of patients had acquired immunodeficiency syndrome. At follow-up, 12 patients died. HIV-infected CKD patient survival after starting dialysis was 80% at 3 years. Conclusion: The incidence of HIV-infected patients on chronic dialysis in Portugal has almost doubled. Widespread use of highly active antiretroviral therapy and the increasing number of black Africans from former overseas Portuguese colonies now living in Portugal are possible reasons for this large increase

IL-4-secreting CD4+ T cells are crucial to the development of CD8+ T-cell responses against malaria liver stages.

CD4+ T cells are crucial to the development of CD8+ T cell responses against hepatocytes infected with malaria parasites. In the absence of CD4+ T cells, CD8+ T cells initiate a seemingly normal differentiation and proliferation during the first few days after immunization. However, this response fails to develop further and is reduced by more than 90%, compared to that observed in the presence of CD4+ T cells. We report here that interleukin-4 (IL-4) secreted by CD4+ T cells is essential to the full development of this CD8+ T cell response. This is the first demonstration that IL-4 is a mediator of CD4/CD8 cross-talk leading to the development of immunity against an infectious pathogen

Sustainability and management of groundwater resources in the Minchin Basin, Gansu Province

This project is concerned with a study of the sustainability of irrigation agriculture in the Minqin Basin in Gansu Province, China. In this region agriculture is dependent on water supply from groundwater resources. However, recharge rates from precipitation are very low and surface flow from the Tibetan Plateau is intercepted upstream to provide water for the city ofWuwei and its region. Future climate change may further decrease supply. Already many shallow wells have been exhausted or abandoned because of salinity problems, and new wells are now being drilled to pump water from depths up to 300m

International standards for fetal brain structures based on serial ultrasound measurements from the Fetal Growth Longitudinal Study of the INTERGROWTH-21st Project.

OBJECTIVE: To create prescriptive growth standards for five fetal brain structures, measured by ultrasound, from healthy, well-nourished women, at low risk of impaired fetal growth and poor perinatal outcomes, taking part in the Fetal Growth Longitudinal Study (FGLS) of the INTERGROWTH-21st Project. METHODS: This was a complementary analysis of a large, population-based, multicentre, longitudinal study. We measured, in planes reconstructed from 3-dimensional (3D) ultrasound volumes of the fetal head at different time points in pregnancy, the size of the parieto-occipital fissure (POF), Sylvian fissure (SF), anterior horn of the lateral ventricle (AV), atrium of the posterior ventricle (PV) and cisterna magna (CM). The sample analysed was randomly selected from the overall FGLS population, ensuring an equal distribution amongst the eight diverse participating sites and of 3D ultrasound volumes across pregnancy (range: 15 - 36 weeks' gestation). Fractional polynomials were used to the construct standards. Growth and development of the infants were assessed at 1 and 2 years of age to confirm their adequacy for constructing international standards. RESULTS: From the entire FGLS cohort of 4321 women, 451 (10.4%) were randomly selected. After exclusions, 3D ultrasound volumes from 442 fetuses born without congenital malformations were used to create the charts. The fetal brain structures of interest were identified in 90% of cases. All structures showed increasing size with gestation and increasing variability for the POF, SF, PV and CM. The 3rd , 5th , 50th , 95th and 97th smoothed centile are presented. The 5th centile of POF and SF were 2.8 and 4.3 at 22 weeks and 4.2 and 9.4mm at 32 weeks respectively. The 95th centile of PV and CM were 8.5 and 7.4 at 22 weeks and 8.5 and 9.4mm at 32 weeks respectively. CONCLUSIONS: We have produced prescriptive size standards for fetal brain structures based on prospectively enrolled pregnancies at low risk of abnormal outcomes. We recommend these as international standards for the assessment of measurements obtained by ultrasound from fetal brain structures

Covariant Description of Flavor Conversion in the LHC Era

A simple covariant formalism to describe flavor and CP violation in the left-handed quark sector in a model independent way is provided. The introduction of a covariant basis, which makes the standard model approximate symmetry structure manifest, leads to a physical and transparent picture of flavor conversion processes. Our method is particularly useful to derive robust bounds on models with arbitrary mechanisms of alignment. Known constraints on flavor violation in the K and D systems are reproduced in a straightforward manner. Assumptions-free limits, based on top flavor violation at the LHC, are then obtained. In the absence of signal, with 100 fb^{-1} of data, the LHC will exclude weakly coupled (strongly coupled) new physics up to a scale of 0.6 TeV (7.6 TeV), while at present no general constraint can be set related to Delta t=1 processes. LHC data will constrain Delta F=2 contributions via same-sign tops signal, with a model independent exclusion region of 0.08 TeV (1.0 TeV). However, in this case, stronger bounds are found from the study of CP violation in D-bar D mixing with a scale of 0.57 TeV (7.2 TeV). In addition, we apply our analysis to models of supersymmetry and warped extra dimension. The minimal flavor violation framework is also discussed, where the formalism allows to distinguish between the linear and generic non-linear limits within this class of models.Comment: 24 pages, 6 figures. Some corrections and clarifications; references added. Matches published versio

International Pediatric Otolaryngology Group (IPOG) consensus recommendations: Hearing loss in the pediatric patient

OBJECTIVE To provide recommendations for the workup of hearing loss in the pediatric patient. METHODS Expert opinion by the members of the International Pediatric Otolaryngology Group. RESULTS Consensus recommendations include initial screening and diagnosis as well as the workup of sensorineural, conductive and mixed hearing loss in children. The consensus statement discusses the role of genetic testing and imaging and provides algorithms to guide the workup of children with hearing loss. CONCLUSION The workup of children with hearing loss can be guided by the recommendations provided herei

Study Protocol. ECSSIT – Elective Caesarean Section Syntocinon® Infusion Trial. A multi-centre randomised controlled trial of oxytocin (Syntocinon®) 5 IU bolus and placebo infusion versus oxytocin 5 IU bolus and 40 IU infusion for the control of blood loss at elective caesarean section

<p>Abstract</p> <p>Background</p> <p>Caesarean section is one of the most commonly performed major operations in women throughout the world. Rates are escalating, with studies from the United States of America, the United Kingdom, China and the Republic of Ireland reporting rates between 20% and 25%. Operative morbidity includes haemorrhage, anaemia, blood transfusion and in severe cases, maternal death.</p> <p>The value of routine oxytocics in the third stage of vaginal birth has been well established and it has been assumed that these benefits apply to caesarean delivery as well. A slow bolus dose of oxytocin is recommended following delivery of the baby at caesarean section. Some clinicians use an additional infusion of oxytocin for a further period following the procedure. Intravenous oxytocin has a very short half-life (4–10 minutes) therefore the potential advantage of an oxytocin infusion is that it maintains uterine contractility throughout the surgical procedure and immediate postpartum period, when most primary haemorrhages occur. The few trials to date addressing the optimal approach to preventing haemorrhage at caesarean section have been under-powered to evaluate clinically important outcomes. There has been no trial to date comparing the use of an intravenous slow bolus of oxytocin versus an oxytocin bolus and infusion.</p> <p>Methods and design</p> <p>A multi-centre randomised controlled trial is proposed. The study will take place in five large maternity units in Ireland with collaboration between academics and clinicians in the disciplines of obstetrics and anaesthetics. It will involve 2000 women undergoing elective caesarean section after 36 weeks gestation. The main outcome measure will be major haemorrhage (blood loss >1000 ml). A study involving 2000 women will have 80% power to detect a 36% relative change in the risk of major haemorrhage with two-sided 5% alpha.</p> <p>Discussion</p> <p>It is both important and timely that we evaluate the optimal approach to the management of the third stage at elective caesarean section. Safe operative delivery is now a priority and a reality for many pregnant women. Obstetricians, obstetric anaesthetists, midwives and pregnant women need high quality evidence on which to base management approaches. The overall aim is to reduce maternal haemorrhagic morbidity and its attendant risks at elective caesarean section.</p> <p>Trial registration</p> <p>number: ISRCTN17813715</p