Can growth in dichorionic twins be monitored with individualized growth assessment?

OBJECTIVE: To characterize fetal growth in dichorionic twins using individualized growth assessment (IGA), a method based on individual growth potential estimates. METHODS: This secondary analysis included 286 fetuses/neonates from 143 dichorionic twin pregnancies that were part of the ESPRiT (Evaluation of Sonographic Predictors of Restricted Growth in Twins) study. The sample was subcategorized according to birth weight into appropriate-for-gestational-age (AGA) (n = 243) and small-for-gestational-age (SGA) (n = 43) cohorts. Serial biometric scans evaluating biparietal diameter, head circumference (HC), abdominal circumference, femur diaphysis length and estimated weight at 2-week intervals were used to evaluate fetal growth, while measurements of birth weight, crown-heel length and HC determined neonatal growth outcome. Six abnormalities (hypoxic ischemic encephalopathy, periventricular leukomalacia, necrotizing enterocolitis, respiratory distress, sepsis and death) constituted the evaluated adverse neonatal outcomes (ANO). IGA was used to: evaluate differences in second-trimester growth velocities between singletons (from a published dataset) and dichorionic twins (138 AGA twins with normal third-trimester growth); describe the degree to which actual third-trimester growth in twins followed expected growth (111 AGA twins, normal fetal growth and neonatal growth outcomes); determine if the fetal growth pathology score 1 (-FGPS1) could detect, quantify and classify twin growth pathology (224 AGA, 42 SGA); and assess the relationship between -FGPS1 and ANO (24 SGA twins with progressive growth restriction confirmed by abnormal neonatal growth outcome). RESULTS: The differences in second-trimester growth velocity between singletons and twins (means and variances) were small and not statistically significant. Percent deviations from the expected third-trimester size trajectories were within the 95% reference ranges derived from singletons at 95.7% (1677/1752) of timepoints studied. Abnormal growth was detected in 37.9% of AGA twins and 85.7% of SGA twins. Growth restriction was more heterogeneous in AGA twins, while in SGA twins progressive growth restriction was the principal type (66.7%). -FGPS1 patterns previously defined in singletons classified 97.5% of pathological twin cases. In our most severe form of growth restriction (progressive), there were only three (12.5%) ANOs related to growth abnormalities, all in cases with -FGPS1 values more negative than -2.0%. Using these criteria, the frequency of ANO was 33%. CONCLUSIONS: With respect to growth, dichorionic twins can be considered as two singletons in the same uterus. Normally growing dichorionic twins have the same growth potential as singletons with normal growth outcome. These twins also follow expected third-trimester growth trajectories with the same precision as do singletons. Third-trimester growth pathology can be detected, quantified and classified using -FGPS1 as in singletons. Limited evidence of a relationship between fetal growth abnormalities and adverse neonatal outcome was found. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Fetoscopic Laser Ablation for Twin-to-Twin Transfusion Syndrome: A 15-year Review of Perinatal Survival.

Objective Twin to twin transfusion syndrome (TTTS) complicates 5-15% of monochorionic twin pregnancies and untreated is associated with a 90% mortality rate. The aim was to present the perinatal survival of patients with TTTS treated with laser ablation, by a national fetal medicine team. Methods This was a review of all cases of TTTS treated with fetoscopic laser ablation performed from March 2006 through to December 2020. All patients treated with fetoscopic laser were identified from the hospital database. The perinatal outcomes for the overall cohort and the individual Quintero stages were determined. Results A total of 155 cases of TTTS underwent fetoscopic laser ablation during the study period. The median gestational age at diagnosis was 19+1 weeks, with a mean growth discordance of 23.6%. The Quintero stage at diagnosis was: Stage 1 6.5% (10/155), Stage 2 49% (76/155), Stage 3 38.7% (60/155), Stage 4 5.8% (9/155). There was at least one survivor in 83.2% (129/155) of pregnancies, with dual survival in 52.9% (82/155). An increase in the rate of any survivor was observed from 75% (2006-2014) to 94% (2014-2020) (p<0.05). Dual survival decreased with increasing Quintero Stage (p<0.05). 80.6% (125/155) of pregnancies delivered prior to 34+6 weeks gestation. Conclusion Fetoscopic laser ablation is the recommended first line treatment for severe TTTS. We observed a survival rate of at least one twin in 83.2% pregnancies which is comparable to internationally published data on single-centre outcomes.

Third-trimester growth diversity in small fetuses classified as appropriate-for-gestational age or small-for-gestational age at birth.

OBJECTIVE: We have shown previously that third-trimester growth in small fetuses (estimated fetal weight (EFW) < 10th percentile) with birth weight (BW) < 10th percentile is heterogeneous using individualized growth assessment (IGA). We aimed to test our hypothesis that individual growth patterns in small fetuses with BW > 10th percentile are also variable but in different ways. METHODS: This was a study of 191 cases with EFW < 10th percentile and BW > 10th percentile (appropriate-for-gestational-age (AGA) cohort), derived from the PORTO study. Composite size parameters were used to quantify growth pathology at individual third-trimester timepoints (individual composite prenatal growth assessment score (-icPGAS)). The fetal growth pathology score 1 (-FGPS1), calculated cumulatively from serial -icPGAS values, was used to characterize third-trimester growth patterns. Vascular-system evaluation included umbilical artery (UA) and middle cerebral artery (MCA) Doppler velocimetry. Outcome variables were birth age (preterm/term delivery) and BW (expressed as growth potential realization index for weight (GPRIWT ) and percentile). The findings from the AGA cohort were compared with those from small fetuses (EFW < 10th percentile) with BW < 10th percentile (small-for-gestational-age (SGA) cohort). RESULTS: The AGA cohort was found to have 134 fetuses (70%) with normal growth pattern and 57 (30%) with growth restriction based on IGA criteria. Seven growth-restriction -FGPS1 patterns were observed, including the previously defined progressive, late, adaptive and recovering types. The recovering type was the most common growth pattern in the AGA cohort (50.9%). About one-third of fetuses without any evidence of growth restriction had significant unexplained abnormalities in the UA (34%) and MCA (31%) and elevated mean GPRIWT values (113 ± 12.5%). Comparison of the AGA and SGA cohorts indicated a significant difference in the distribution of -FGPS1 growth patterns (P = 0.0001). Compared with the SGA cohort, the AGA cohort had more fetuses with a normal growth pattern (70% vs 38%) and fewer cases with growth restriction (30% vs 62%). While the recovering type was the most common growth-restriction pattern in the AGA cohort (51%), the progressive type was the primary growth-restriction pattern in the SGA cohort (44%). No difference in the incidence of MCA or UA abnormality was found between the SGA and AGA cohorts when comparing subgroups of more than 10 fetuses. CONCLUSIONS: Both normal-growth and growth-restriction patterns were observed in the AGA cohort using IGA, as seen previously in the SGA cohort. The seven types of growth restriction defined in the SGA cohort were also identified in AGA cases, but their distribution was significantly different. In one-third of cases without evidence of growth pathology in the AGA cohort, Doppler abnormalities in the UA and MCA were seen. This heterogeneity underscores the difficulty of accurate classification of fetal and neonatal growth status using conventional population-based methods. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Sonographic markers of fetal adiposity and risk of Cesarean delivery.

OBJECTIVE: Increased fetal size is associated with shoulder dystocia during labor and subsequent need for assisted delivery. We sought to investigate if increased fetal adiposity diagnosed sonographically in late pregnancy is associated with increased risk of operative delivery. METHODS: This secondary analysis of the Genesis Study recruited 2392 nulliparous women with singleton pregnancy in cephalic presentation, in a prospective, multicenter study, to examine prenatal and intrapartum predictors of Cesarean delivery. Participants underwent ultrasound and clinical evaluation between 39 + 0 and 40 + 6 weeks' gestation. Data on fetal biometry were not revealed to patients or to their managing clinicians. A fetal adiposity composite of fetal thigh adiposity and fetal abdominal wall thickness was compiled for each infant in order to determine whether fetal adiposity > 90th centile was associated with an increased risk of Cesarean or operative vaginal delivery. RESULTS: After exclusions, data were available for 2330 patients. Patients with a fetal adiposity composite > 90th centile had a higher maternal body mass index (BMI) (25 ± 5 kg/m2 vs 24 ± 4 kg/m2 ; P = 0.005), birth weight (3872 ± 417 g vs 3585 ± 401 g; P < 0.0001) and rate of induction of labor (47% (108/232) vs 40% (834/2098); P = 0.048) than did those with an adiposity composite ≤ 90th centile. Fetuses with adiposity composite > 90th centile were more likely to require Cesarean delivery than were those with adiposity composite ≤ 90th centile (P < 0.0001). After adjusting for birth weight, maternal BMI and need for induction of labor, fetal adiposity > 90th centile remained a risk factor for Cesarean delivery (P < 0.0001). A fetal adiposity composite > 90th centile was more predictive of the need for unplanned Cesarean delivery than was an estimated fetal weight > 90th centile (odds ratio, 2.20 (95% CI, 1.65-2.94; P < 0.001) vs 1.74 (95% CI, 1.29-2.35; P < 0.001). Having an adiposity composite > 90th centile was not associated with an increased likelihood of operative vaginal delivery when compared with having an adiposity composite ≤ 90th centile (P = 0.37). CONCLUSIONS: Fetuses with increased adipose deposition are more likely to require Cesarean delivery than are those without increased adiposity. Consideration should, therefore, be given to adding fetal thigh adiposity and abdominal wall thickness to fetal sonographic assessment in late pregnancy. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Embolus Analog Trajectory Paths Under Physiological Flowrates Through Patient-Specific Aortic Arch Models.

Atrial fibrillation (AF) is the most common irregular heartbeat among the world's population and is a major contributor to cardiogenic embolisms and acute ischemic stroke (AIS). However, the role AF flow plays in the trajectory paths of cardiogenic emboli has not been experimentally investigated. A physiological simulation system was designed to analyze the trajectory patterns of bovine embolus analogs (EAs) (n = 720) through four patient-specific models, under three flow conditions: steady flow, normal pulsatile flow, and AF pulsatile flow. It was seen that EA trajectory paths were proportional to the percentage flowrate split of 25-31% along the branching vessels. Overall, AF flow conditions increased trajectories through the left- (LCCA) and right (RCCA)-common carotid artery by 25% with respect to normal pulsatile flow. There was no statistical difference in the distribution of clot trajectories when the clot was released from the right, left, or anterior positions. Significantly, more EAs traveled through the brachiocephalic trunk (BCT) than through the LCCA or the left subclavian. Yet of the EAs that traveled through the common carotid arteries, there was a greater affiliation toward the LCCA compared to the RCCA (p < 0.05).

Comparison of bioreactance and echocardiographic non-invasive cardiac output monitoring and myocardial function assessment in primagravida women.

BACKGROUND.: Non-invasive cardiac output monitoring (NICOM) using bioreactance (BRT) in pregnancy is gaining interest but lacks validation. We compared simultaneous cardiac output (CO) measurements obtained using the NICOM ® (BRT-CO) and echocardiography (echo-CO), and assessed the relationship between maternal characteristics and myocardial performance. METHODS.: Paired stroke volume (SV) and CO readings were obtained using NICOM ® and echocardiography, in a group of healthy nulliparous women throughout a 15 min period. Agreement between NICOM ® and echocardiography was assessed using Bland-Altman analysis and the intraclass correlation coefficient (ICC). Left ventricular (LV) function was assessed using systolic strain and tissue Doppler velocities (S', E', and A' waves). RESULTS.: Thirty-five women with a median [interquartile range] age, weight, and gestation of 29 [26-34] yr, 71 [64-79] kg, and 28 [21-29] weeks, respectively, were enrolled. There was good agreement between NICOM ® -measured and echocardiographically measured SV [mean bias 6 ml (limits of agreement -18 to 29); ICC 0.8 (95% confidence interval 0.6-0.9), P <0.001] and CO [mean bias 0.2 litres (limits of agreement -1.3-1.7); ICC 0.8 (95% confidence interval 0.7-0.9), P <0.001; mean percentage error ±26%; coefficient of error (precision)=3.4%]. The mean ( sd ) LV S' was 9.7 (2.3) cm s -1 . The mean ( sd ) LV strain was -18.6 (2.6)%. There was a negative relationship between BMI and LV diastolic function measured using the E':A' ratio ( r = -0.51, P <0.01). CONCLUSIONS.: Stroke volume and CO measurements obtained using NICOM ® were comparable to those obtained using echocardiography, with acceptable limits of agreement. Increased maternal BMI negatively impacts LV diastolic function measured using tissue Doppler imaging.

Postnatal MRI Brain in Infants Treated for Twin-Twin Transfusion Syndrome.

Untreated twin-twin transfusion syndrome (TTTS) is associated with significant mortality and neurological impairment. Fetoscopic laser surgery (FLS) is the treatment of choice. We sought to assess intracranial abnormalities in TTTS twins following treatment. In this prospective, blinded study MRI scans were performed on 3 groups; (1) monochorionic diamniotic (MCDA) twins with TTTS who had undergone FLS (n = 10), (2) MCDA twins without TTTS (n = 8) and (3) dichorionic twins (n = 8). Scans were scored as either normal or abnormal. The primary outcome was a composite of abnormal MRI brain or intrauterine fetal demise. The primary outcome occurred in 6/10 (60%) of the TTTS group versus 3/8 (37.5%) in the MCDA group. The primary outcome was significantly different across all study groups [p = 0.029; X2 = 7.112]. We found that twins treated for TTTS are more likely to have abnormalities on MRI brain at term than other twin groups. This group merits term-corrected MRI as part of their postnatal assessment.

Umbilical and fetal middle cerebral artery Doppler reference ranges in a twin population followed longitudinally from 24 to 38 weeks' gestation.

OBJECTIVE: To construct monochorionic diamniotic (MCDA) and dichorionic diamniotic (DCDA) twin reference ranges for umbilical artery (UA) pulsatility index (PI), UA resistance index (RI), fetal middle cerebral artery (MCA) PI and peak systolic velocity (PSV) and cerebroplacental ratio (CPR) from 24 weeks' to 38 weeks' gestation and compare these with published normal values for singleton pregnancies. METHODS: This prospective multicenter cohort study included 1028 unselected twin pairs recruited over a 2-year period. Participants with dichorionic twins underwent fortnightly ultrasound surveillance from 24 weeks' gestation, with monochorionic twins being followed every 2 weeks from 16 weeks until delivery. A total of 7536 fetal Doppler examinations in 618 twin pregnancies were included in the analysis, with reference ranges for MCDA and DCDA pregnancies constructed for each of the Doppler indices using multilevel modeling. RESULTS: UA-PI and UA-RI appear to be higher in twins than in singletons, and MCA-PI and MCA-PSV appear to be lower. The CPR also appears to be lower in twins than in singletons. Similar MCA indices were observed in MCDA and DCDA twins. CONCLUSION: We have established longitudinal reference ranges for UA-PI and UA-RI, MCA-PI and MCA-PSV and CPR in twin pregnancies, which appear to differ from those in singleton pregnancies. The derived twin-specific reference ranges may be more appropriate in the surveillance of these high-risk pregnancies. Applying the singleton CPR cut-off of ≤ 1.0 may lead to a large number of false-positive diagnoses of cerebral redistribution in twin fetuses.

Changing trends in diabetes mellitus in pregnancy.

The purpose of this study was to identify any changing trends in the incidence and caesarean section (CS) rate of pre-gestational diabetes mellitus (DM) and gestational diabetes mellitus (GDM) over a 10- year period, between 1999 and 2008. Although the incidence of pre-gestational DM has not significantly changed over the course of the last 10 years, there is an obvious rising trend in the incidence of GDM. Despite an increase in the overall CS rate during this time period, a parallel increase in the CS rate has not been observed among women whose pregnancies are complicated either by gestational or by pre-gestational diabetes (PGD).

Platelet reactivity changes significantly throughout all trimesters of pregnancy compared with the nonpregnant state: a prospective study.

OBJECTIVE: Platelets play an important role in the pathophysiology of uteroplacental disease and platelet reactivity may be an important marker of uteroplacental disease activity. However, platelet reactivity has not been evaluated comprehensively in normal pregnancy. We sought to evaluate platelet reactivity using a number of agonists at defined time points in pregnancy using a novel platelet assay and compare these with a nonpregnant cohort. DESIGN: Prospective longitudinal study. SETTING: Outpatient department of a large tertiary referral centre. SAMPLE: Eighty participants with 30 nonpregnant women and 50 pregnant women assessed longitudinally. METHODS: This was a prospective cohort study performed longitudinally throughout uncomplicated singleton pregnancies with participants recruited before 15 weeks of gestation. They were controlled for a number of factors known to affect platelet reactivity. Blood samples were obtained in each trimester. Thirty nonpregnant healthy female volunteers also had a platelet assay performed. A modification of standard light transmission aggregometry was used to assess platelet function, with light absorbance measured following the addition of five different agonists at submaximal concentrations. Dose-response curves were plotted for each agonist for the nonpregnant cohort and in each trimester for the pregnant cohort. MAIN OUTCOME MEASURES: Dose-response curves and median effective concentration. RESULTS: When compared with the nonpregnant controls a significant reduction was demonstrated in platelet reactivity to collagen during the first trimester of pregnancy (P < 0.0001). Platelet aggregation increased significantly from the first to third trimesters in response to collagen and arachidonic acid. CONCLUSION: Platelet reactivity varies according to pregnancy state, gestational age and agonist. The finding that platelet reactivity is reduced in the first trimester of pregnancy may be useful for the interpretation of further studies examining the role of platelet reactivity in the first trimester of pregnancies that develop uteroplacental disease.

A retrospective cohort study of the characteristics of unsuccessful operative vaginal deliveries.

INTRODUCTION: Unsuccessful operative vaginal delivery (OVD) is associated with high rates of materno-fetal morbidity. We aimed to examine institutional rates of unsuccessful OVDs (uOVD) and compare them with successful OVD (sOVD) in order to identify factors to aid patient selection and education. METHODS: A 6-month retrospective cohort study was performed on all unsuccessful and successful OVDs in a tertiary level maternity hospital in the Republic of Ireland. Maternal demographics and obstetric factors were assessed to evaluate potential underlying risk factors for unsuccessful operative vaginal delivery versus successful vaginal delivery. RESULTS: There were 4,191 births during the study period with an OVD rate of 14.2% (n = 595) with 28 (4.7% of OVDs) being unsuccessful. Unsuccessful OVD were predominately nulliparous (25; 89.2%) with a mean maternal age of 30.1 years (range 20-42), with more than half (n = 15, 53.5%) being induced. The most common indication for induction was prolonged rupture of membranes (PROM) (n = 7, 25%) which was significantly different from the successful OVD group. A senior obstetrician was significantly more likely to be the primary operator in uOVD when compared to sOVD. (82.1 % V 54.1% p < 0.01). The majority of unsuccessful OVD were vacuum deliveries (n = 17; 60.7%), with a significantly higher mean birthweight when compared to successful OVD (3.695 kg V 3.483 kg; p < 0.01). Following an unsuccessful OVD, women were more likely to have a postpartum haemorrhage (64.2 % V 31.5% p < 0.01) and their infant was more likely to require admission to the neonatal intensive care unit (NICU) (32.1 % V 5.8% p < 0.01) when compared with successful OVD. CONCLUSION: Risk factors for unsuccessful OVD were higher birth weight and induction of labour. There was a higher incidence of postpartum haemorrhage and NICU admission when compared with successful OVD.

Congenital anomalies: Impact of prenatal diagnosis on mode of delivery.

An important aspect of prenatal diagnosis is the avoidance of emergency caesarean delivery (CD) where the abnormality is considered lethal and the infant will not survive. A consecutive cohort of 211,163 women delivered of infants weighing 500 grams or more in three tertiary referral centers from 01/95 to 12/04, was analyzed for perinatal death attributed to congenital malformations. In the group that died in the neonatal period, the emergency CD rate was significantly lower where anomaly was detected versus undetected (17.5% versus 31%). Further, in contrast to undiagnosed anomalies, the indication for emergency CD was more often maternal in the diagnosed group (42% versus 19%, p=0.019). When a diagnosis of lethal congenital anomaly has been made in the prenatal period, the reduction in the emergency CD rate by almost half in this study supports a pivotal role for prenatal diagnosis in optimizing maternal care.

Maintaining quality assurance for sonographic nuchal translucency measurement: lessons from the FASTER Trial.

OBJECTIVE: To evaluate nuchal translucency measurement quality assurance techniques in a large-scale study. METHODS: From 1999 to 2001, unselected patients with singleton gestations between 10 + 3 weeks and 13 + 6 weeks were recruited from 15 centers. Sonographic nuchal translucency measurement was performed by trained technicians. Four levels of quality assurance were employed: (1) a standardized protocol utilized by each sonographer; (2) local-image review by a second sonographer; (3) central-image scoring by a single physician; and (4) epidemiological monitoring of all accepted nuchal translucency measurements cross-sectionally and over time. RESULTS: Detailed quality assessment was available for 37 018 patients. Nuchal translucency measurement was successful in 96.3% of women. Local reviewers rejected 0.8% of images, and the single central physician reviewer rejected a further 2.9%. Multivariate analysis indicated that higher body mass index, earlier gestational age and transvaginal probe use were predictors of failure of nuchal translucency measurement and central image rejection (P = 0.001). Epidemiological monitoring identified a drift in measurements over time. CONCLUSION: Despite initial training and continuous image review, changes in nuchal translucency measurements occur over time. To maintain screening accuracy, ongoing quality assessment is needed.

gammadeltaT cells are involved in liver transplant tolerance.

The role of nonconventional T cells in innate and adaptive immunity is just emerging; gammadeltaT cells play important roles in anti-tumor and anti-infectious diseases. The involvement of gammadeltaT cells in immunologic responses to hematopoietic cell transplantation remains controversial; divergent results have been reported depending on the murine strains and model systems. Whether gammadeltaT cells are involved in solid organ transplantation is understudied. We have characterized the gammadeltaT cells in mouse livers and spleens to evaluate their contributions to liver transplant tolerance posttransplantation using a murine allogeneic liver transplant model which induces spontaneous T regulatory cell (Treg)-dependent tolerance. Our studies revealed that gammadeltaT cells comprised about 20% of the population of liver nonparenchymal cells (NPCs). In naïve C3H mice they were CD4, CD8, and NK1.1 negative. The percentage of gammadeltaT cells decreased in spontaneously tolerated liver grafts posttransplantation from 20% in naïve C3H livers to <10% in allografts throughout the time course. In contrast, they increased in liver grafts with rejection induced by anti-CTLA4 plus anti-CD25 mAb administration. CD4 and CD8 expression on gammadeltaT cells dramatically increased in the tolerated but not rejected livers posttransplantation to >20% of CD4(+) and 30% of CD8(+). Our results suggested that gammadeltaT cells are involved in allogeneic immune responses. Whether gammadeltaT cells function as the causal or the effector cells in allograft tolerance rejection warrants further investigation.

Parameter estimation and simulations of a mathematical model of Corynebacterium pseudotuberculosis transmission in sheep.

Caseous lymphadenitis (CLA) is an infectious disease of sheep caused by Corynebacterium pseudotuberculosis. It is prevalent in most sheep producing countries and was introduced into the UK sheep population in 1991. The pathogen invades the host through epithelium and forms an abscess in the local draining lymph node. Typically, disease presents as clinical, with overt (externally visible) swollen lymph nodes (the parotid, submandibular, prefemoral, prescapular, popliteal or mammary) or sub-clinical, with abscesses in the lungs and associated thoracic (bronchial and mediastinal) lymph nodes. We present a mathematical model in which disease is categorised as overt and/or respiratory (sub-clinical), using the above groupings. In both situations sheep may be infected and may or may not be infectious. In the model, overt abscesses may resolve and respiratory abscesses are considered to be present for life. Using the location of the abscesses, three routes of transmission are postulated: overt to overt, respiratory to overt and respiratory to respiratory. Data from four naturally infected flocks were used to describe populations of sheep with epidemic CLA and to estimate transmission coefficients for each of the postulated transmission routes. The infection process parameters were derived from literature where possible. Parameters were estimated using maximum likelihood methods and compared to the data using a multinomial distribution. The distribution of abscesses in the flocks was similar to endemic data reported in other studies. In the model most infected sheep developed abscesses, and approximately 36% of sheep with overt abscesses recovered from infection. The average time for respiratory abscesses to become infectious was 41 days. In these data, overt to overt transmission was the most frequent route of transmission since it had the highest coefficient in the model compared with respiratory to overt and respiratory to respiratory transmission. Transmission coefficients specific for each flock significantly (P<0.05) improved the model fit to the data. In simulations using values of best-fitting parameter combinations, the proportion of sheep infected was between 0.39 and 0.60 at equilibrium. This is the first mathematical model of C. pseudotuberculosis infection, the parameter estimates indicate that aspects of the infection process could be utilised to design control strategies.

Fetoscopic laser treatment of twin-to-twintransfusion syndrome (TTTS).

The aim of this study was to report the results of the first 10 cases of fetoscopic laser surgery for twin-to-twin transfusion syndrome by the Rotunda Hospital Fetal Treatment Programme. All cases of severe TTTS managed by our team from 2006 to 2007 were included. All fetoscopic laser surgeries were performed by a single specialist in fetal medicine. All pregnancies were followed up to pregnancy completion and a minimum of six weeks neonatal life. Laser surgeries were performed with ultrasound guidance and percutaneously using local anaesthesia via a 2.8mm rigid fetoscope. Selective laser ablation of placental vessels was accomplished with a neodymium:YAG laser. The first 10 cases of severe TTTS managed by our team are reported. Laser ablation of placental vessels was accomplished successfully in all cases. Two pregnancies were complicated by preterm premature rupture of membranes before 22 weeks and both pregnancies were lost. Of the remaining 16 fetuses, one was diagnosed with significant ventriculomegaly postoperatively and underwent selective termination in the United Kingdom. The overall intact neonatal survival rate was 65%. Fetoscopic laser ablation of placental vessels for severe twin-to-twin transfusion syndrome is now available in Ireland, and our programme has delivered results that are in keeping with international best practices in this regard.

The Mechanical Characterisation of Bovine Embolus Analogues Under Various Loading Conditions.

Embolus Analogues (EAs) can provide understanding of the mechanical characteristics of blood clots of cardiac origin. Bovine EAs (n = 29) were fabricated with varying concentrations of thrombin (0-20 NIHU/ml blood). Histological staining confirmed that EA composition compared sufficiently with human samples reported in literature. EAs were mechanically described under seven testing conditions: tensile, compression, shear wave ultrasound elastography (SWE), parallel plate rheometry, indentation, creep and relaxation. The Young modulus of bovine EAs in tension varied from 7 kPa (5% strain) to 84 kPa (50% strain). The compressive Young modulus increased with increasing thrombin concentration, which was in agreement with the SWE results. There was no significant difference in Young modulus throughout the clot (p < 0.05). The EAs displayed a non-linear response under parallel plate rheometry, creep and stress relaxation. The 3rd order Mooney-Rivlin constitutive equation and Standard Linear Solid model were used to fit the non-linear stress-strain response and time-dependent properties, respectively. This is the first study in which bovine EAs, with and without addition of thrombin, are histologically and mechanically described with corresponding proposed constitutive equations. The equations and experimental data determined can be applied for future numerical and experimental testing of mammalian EAs and cardiac source clots.

Prolonged anorexia and elevated plasma cytokine levels following myeloablative allogeneic hematopoietic cell transplant.

Myeloablative conditioning regimens commonly lead to prolonged anorexia and poor oral intake. In a prospective study of 147 patients receiving CY, total body irradiation and allogeneic hematopoietic cells, we determined the extent of decline in oral intake and assessed plasma cytokine levels and development of acute GVHD as explanations for protracted anorexia. For each patient, daily oral caloric intake was expressed as a percent of estimated basal requirements, calculated as basal energy expenditure, through day 20. Oral caloric intake was significantly reduced in 92% of patients and remained low. The nadir in oral intake occurred at days 10-12, when median oral caloric intake was 3% of basal energy requirements. Plasma cytokines known to affect appetite (IL2, IL6, tumor necrosis factor-alpha) were significantly elevated above normal following conditioning therapy (P<0.001 for each cytokine). Acute GVHD did not appear to affect oral intake to transplant day 20 in this cohort of patients; however, plasma levels of IL6 rose steeply before the clinical onset of GVHD. Persistent fever occurred with the greatest frequency in patients with most profound reduction in oral intake. We conclude that prolonged alterations in oral intake following this myeloablative regimen may be related to circulating cytokines known to alter eating behavior.