Tollip coordinates Parkin-dependent trafficking of mitochondrial-derived vesicles.

Multiple mitochondrial quality control pathways exist to maintain the health of mitochondria and ensure cell homeostasis. Here, we investigate the role of the endosomal adaptor Tollip during the mitochondrial stress response and identify its interaction and colocalisation with the Parkinson's disease-associated E3 ubiquitin ligase Parkin. The interaction between Tollip and Parkin is dependent on the ubiquitin-binding CUE domain of Tollip, but independent of Tom1 and mitophagy. Interestingly, this interaction is independent of Parkin mitochondrial recruitment and ligase activity but requires an intact ubiquitin-like (UBL) domain. Importantly, Tollip regulates Parkin-dependent endosomal trafficking of a discrete subset of mitochondrial-derived vesicles (MDVs) to facilitate delivery to lysosomes. Retromer function and an interaction with Tom1 allow Tollip to facilitate late endosome/lysosome trafficking in response to mitochondrial stress. We find that upregulation of TOM20-positive MDVs upon mitochondrial stress requires Tollip interaction with ubiquitin, endosomal membranes and Tom1 to ensure their trafficking to the lysosomes. Thus, we conclude that Tollip, via an association with Parkin, is an essential coordinator to sort damaged mitochondrial-derived cargo to the lysosomes.

Performance of a risk factor-based approach in the detection of small for gestational age neonates: A cohort study.

BACKGROUND: Antenatal detection of fetal growth restriction allows the opportunity to increase surveillance and initiate intervention to prevent adverse outcomes. Detection of small for gestational age (SGA) fetuses with risk factor screening and selective ultrasonography is the standard of care in Australia, but evidence regarding performance is lacking. AIMS: To evaluate the diagnostic performance of a risk factor-based screening approach in detection of SGA neonates. MATERIALS AND METHODS: Retrospective cohort study conducted in a metropolitan maternity service, including all consecutive singleton deliveries over 20 weeks gestation from July 2016 to December 2017, and excluding terminations of pregnancy. An SGA neonate was defined by birthweight below the tenth percentile according to Australian reference ranges. Antenatally detected SGA cases were defined by estimated fetal weight or abdominal circumference below the tenth percentile for gestational age, or abnormal symphysio-fundal height. The diagnostic accuracy of the screening protocol was calculated using detection rates and false-positive rates. RESULTS: There were 13 384 singleton pregnancies included. There were 1330 infants (10.0%) who were SGA at birth. Antenatal detection rate of SGA neonates was 39.6% (95% confidence interval (CI) 37.0-42.3%), with a false-positive rate of 10.2% (95% CI 9.6-10.7%). There were 10 266 pregnancies (77.0%) which had at least one risk factor for an SGA infant. Of these, 6650 (64.8%) underwent at least one fetal growth ultrasound after 24 weeks gestation. CONCLUSIONS: Antenatal recognition of poor fetal growth is suboptimal using our current screening protocol. Three-quarters of pregnancies demonstrated risk factors for delivering an SGA infant, but growth ultrasonography may be underutilised.

Effectiveness of a brief form of group dialectical behavior therapy for binge-eating disorder: Case series in a routine clinical setting.

OBJECTIVE: While there is evidence to support the use of group dialectical behavior therapy (DBT) in the treatment of binge-eating disorder (BED), treatment is relatively long compared with other evidence-based treatments. This study explored the effectiveness of brief DBT groups for BED, delivered in a routine community setting. METHOD: Eighty-four adults with BED entered 10-week DBT group treatment in a community eating disorders service. In total, 12 groups were conducted. Patients completed measures of eating disorder pathology, anxiety, depression, and emotional eating at the start and end of treatment, and at 1-month follow-up. Frequency of weekly binges was recorded. RESULTS: Outcomes were similar to those of longer versions of DBT, with an attrition rate of 26%, and significant reductions in eating disorder psychopathology and emotional eating by the end of treatment and at follow-up. Over 50% of patients were abstinent from binge eating by Session 4. DISCUSSION: Group DBT delivered in a 10-session format is clinically equivalent to longer versions of the same treatment. Future research is required to explore patterns of change and to demonstrate replicability under controlled conditions, but these findings are promising for the efficient delivery of effective treatment and reducing waiting times.

Reduced growth velocity from the mid-trimester is associated with placental insufficiency in fetuses born at a normal birthweight.

BACKGROUND: Fetal growth restriction (FGR) due to placental insufficiency is a major risk factor for stillbirth. While small-for-gestational-age (SGA; weight < 10th centile) is a commonly used proxy for FGR, detection of FGR among appropriate-for-gestational-age (AGA; weight ≥ 10th centile) fetuses remains an unmet need in clinical care. We aimed to determine whether reduced antenatal growth velocity from the time of routine mid-trimester ultrasound is associated with antenatal, intrapartum and postnatal indicators of placental insufficiency among term AGA infants. METHODS: Three hundred and five women had biometry measurements recorded from their routine mid-trimester (20-week) ultrasound, at 28 and 36 weeks' gestation, and delivered an AGA infant. Mid-trimester, 28- and 36-week estimated fetal weight (EFW) and abdominal circumference (AC) centiles were calculated. The EFW and AC growth velocities between 20 and 28 weeks, and 20-36 weeks, were examined as predictors of four clinical indicators of placental insufficiency: (i) low 36-week cerebroplacental ratio (CPR; CPR < 5th centile reflects cerebral redistribution-a fetal adaptation to hypoxia), (ii) neonatal acidosis (umbilical artery pH < 7.15) after the hypoxic challenge of labour, (iii) low neonatal body fat percentage (BF%) reflecting reduced nutritional reserve and (iv) placental weight < 10th centile. RESULTS: Declining 20-36-week fetal growth velocity was associated with all indicators of placental insufficiency. Each one centile reduction in EFW between 20 and 36 weeks increased the odds of cerebral redistribution by 2.5% (odds ratio (OR) = 1.025, P = 0.001), the odds of neonatal acidosis by 2.7% (OR = 1.027, P = 0.002) and the odds of a < 10th centile placenta by 3.0% (OR = 1.030, P < 0.0001). Each one centile reduction in AC between 20 and 36 weeks increased the odds of neonatal acidosis by 3.1% (OR = 1.031, P = 0.0005), the odds of low neonatal BF% by 2.8% (OR = 1.028, P = 0.04) and the odds of placenta < 10th centile by 2.1% (OR = 1.021, P = 0.0004). Falls in EFW or AC of > 30 centiles between 20 and 36 weeks were associated with two-threefold increased relative risks of these indicators of placental insufficiency, while low 20-28-week growth velocities were not. CONCLUSIONS: Reduced growth velocity between 20 and 36 weeks among AGA fetuses is associated with antenatal, intrapartum and postnatal indicators of placental insufficiency. These fetuses potentially represent an important, under-recognised cohort at increased risk of stillbirth. Encouragingly, this novel fetal assessment would require only one additional ultrasound to current routine care, and adds to the potential benefits of routine 36-week ultrasound.

Accuracy of sonographic estimation of weight in fetuses with abdominal wall defects.

BACKGROUND: Accurate estimation of fetal weight is essential in guiding management of fetuses with abdominal wall defects (AWDs), as growth restriction is an important predictor of perinatal morbidity and mortality. Several sonographic formulae are available involving multiple biometric parameters, but abdominal circumference measurements may underestimate weight in fetuses with AWDs. No formula has yet shown superior accuracy. AIMS: The objectives of this study were to evaluate, in fetuses with gastroschisis and omphalocoele, the accuracy of a sonographic estimated fetal weight (EFW) formula proposed by Siemer and colleagues, specifically for use in fetuses with AWDs compared to the commonly used Hadlock IV formula in estimating fetal weight, and detecting small for gestational age (SGA) fetuses. MATERIALS AND METHODS: A retrospective cohort of 113 fetuses with AWDs was identified from an Australian teaching hospital over 13 years. Pregnancy data and sonographic fetal biometry parameters were obtained. The accuracy of each formula in predicting birthweight was compared using Bland-Altman limits of agreement, and the intraclass correlation coefficient between EFW and actual birthweight. Performance of each formula in detecting SGA fetuses was determined. RESULTS: The Siemer and Hadlock formulae have similar accuracies for predicting birthweight in fetuses with AWDs. The Hadlock formula has a higher detection rate for SGA < 10th centile and < 3rd centile compared to the Seimer formula (84% vs 68% and 83% vs 67% respectively), albeit with a higher false-positive rate. CONCLUSION: There is no clear clinical advantage in using the Siemer formula, which is specifically designed for fetuses with AWDs, over the Hadlock formula to estimate weight in fetuses with AWDs.

Energy footprint and carbon emission reduction using off-the-grid solar-powered mixing for lagoon treatment.

Mixing is the driver for the energy footprint of water resource recovery in lagoons. With the availability of solar-powered equipment, one potential measure to decrease the environmental impacts of treatment is to transition to an off-the-grid treatment. We studied the comparative scenarios of an existing grid-powered mixer and a solar-powered mixer. Testing was conducted to monitor the water quality, and to guarantee that the effluent concentrations were maintained equally between the two scenarios. Meanwhile, the energy consumption was recorded with the electrical energy monitor by the wastewater treatment utility, and the carbon emission changes were calculated using the emission intensity of the power utility. The results show that after the replacement, both energy usage and energy costs were significantly reduced, with the energy usage having decreased by 70% and its cost by 47%. Additionally, carbon-equivalent emission from electricity importation dropped by 64%, with an effect on the overall carbon emissions (i.e., including all other contributions from the process) decreasing from 3.8% to 1.5%.

Reduced growth velocity across the third trimester is associated with placental insufficiency in fetuses born at a normal birthweight: a prospective cohort study.

BACKGROUND: While being small-for-gestational-age due to placental insufficiency is a major risk factor for stillbirth, 50% of stillbirths occur in appropriate-for-gestational-age (AGA, > 10th centile) fetuses. AGA fetuses are plausibly also at risk of stillbirth if placental insufficiency is present. Such fetuses may be expected to demonstrate declining growth trajectory across pregnancy, although they do not fall below the 10th centile before birth. We investigated whether reduced growth velocity in AGA fetuses is associated with antenatal, intrapartum and neonatal indicators of placental insufficiency. METHODS: We performed a prospective cohort study of 308 nulliparous women who subsequently gave birth to AGA infants. Ultrasound was utilised at 28 and 36 weeks' gestation to determine estimated fetal weight (EFW) and abdominal circumference (AC). We correlated relative EFW and AC growth velocities with three clinical indicators of placental insufficiency, namely (1) fetal cerebroplacental ratio (CPR; CPR < 5th centile reflects placental resistance, and blood flow redistribution to the brain - a fetal response to hypoxia); (2) neonatal acidosis after the hypoxic challenge of labour (umbilical artery (UA) pH < 7.15 at birth); and (3) low neonatal body fat percentage (BF%, measured by air displacement plethysmography) reflecting reduced nutritional reserve in utero. RESULTS: For each one centile reduction in EFW growth velocity between 28 and 36 weeks' gestation, there was a 2.4% increase in the odds of cerebral redistribution (CPR < 5th centile, odds ratio (OR) (95% confidence interval) = 1.024 (1.005-1.042), P = 0.012) and neonatal acidosis (UA pH < 7.15, OR = 1.024 (1.003-1.046), P = 0.023), and a 3.3% increase in the odds of low BF% (OR = 1.033 (1.001-1.067), P = 0.047). A decline in EFW of > 30 centiles between 28 and 36 weeks (compared to greater relative growth) was associated with cerebral redistribution (CPR < 5th centile relative risk (RR) = 2.80 (1.25-6.25), P = 0.026), and a decline of > 35 centiles was associated with neonatal acidosis (UA pH < 7.15 RR = 3.51 (1.40-8.77), P = 0.030). Similar associations were identified between low AC growth velocity and clinical indicators of placental insufficiency. CONCLUSIONS: Reduced growth velocity between 28 and 36 weeks' gestation among fetuses born AGA is associated with antenatal, intrapartum and neonatal indicators of placental insufficiency. These fetuses potentially represent an important unrecognised cohort at increased risk of stillbirth and may warrant more intensive antenatal surveillance.

Fetal brain injury in complicated monochorionic pregnancies: diagnostic yield of prenatal MRI following surveillance ultrasound and influence on prognostic counselling.

OBJECTIVE: This study aimed to determine the additional diagnostic information provided by prenatal (fetal) magnetic resonance imaging (pMRI) following tertiary ultrasound (US) for fetal cranial abnormalities in complicated monochorionic gestations. METHODS: Women with complicated monochorionic gestations complicated by twin-twin transfusion syndrome, co-twin demise (CD), selective intrauterine growth restriction, and/or twin anaemia-polycythaemia sequence who were referred for pMRI after tertiary US were included. Additional diagnostic information by pMRI that changed prognostic counselling was the primary outcome. RESULTS: Thirty-three women with 48 live fetuses had pMRI at a median of 25 weeks (range: 21-29). Three of ten survivors of spontaneous CD, one of eight survivors of CD after twin-twin transfusion syndrome and 1/30 co-survivors had diagnostic information added by pMRI that altered counselling; US was normal in two and in the other three underrepresented parenchymal injury (5/33 = 15%; 95% confidence interval ±0.27-0.03). Additional findings included occipital lobe infarction, hemispheric injury, dural sinus thrombosis, ischaemia-producing polymicrogyria and intraventricular haemorrhage. Another 8/33 women had additional information provided by pMRI that did not alter counselling. CONCLUSION: Prenatal magnetic resonance imaging resulted in changed prognostic counselling in 5/33 pregnancies. Evaluation of incorporation of pMRI into routine surveillance of complicated monochorionic gestations is needed. © 2017 John Wiley & Sons, Ltd.

Identification of Preferential Paths of Fossil Carbon within Water Resource Recovery Facilities via Radiocarbon Analysis.

The Intergovernmental Panel on Climate Change (IPCC) reported that all carbon dioxide (CO2) emissions generated by water resource recovery facilities (WRRFs) during treatment are modern, based on available literature. Therefore, such emissions were omitted from IPCC's greenhouse gas (GHG) accounting procedures. However, a fraction of wastewater's carbon is fossil in origin. We hypothesized that since the fossil carbon entering municipal WRRFs is mostly from soaps and detergents as dissolved organic matter, its fate can be selectively determined during the universally applied separation treatment processes. Analyzing radiocarbon at different treatment points within municipal WRRFs, we verified that the fossil content could amount to 28% in primary influent and showed varying distribution leaving different unit operations. We recorded the highest proportion of fossil carbon leaving the secondary treatment as off-gas and as solid sludge (averaged 2.08 kg fossil-CO2-emission-potential m-3 wastewater treated). By including fossil CO2, total GHG emission in municipal WRRFs increased 13%, and 23% if an on-site energy recovery system exists although much of the postdigestion fossil carbon remained in biosolids rather than in biogas, offering yet another carbon sequestration opportunity during biosolids handling. In comparison, fossil carbon contribution to GHG emission can span from negligible to substantial in different types of industrial WRRFs. With such a considerable impact, CO2 should be analyzed for each WRRF and not omitted from GHG accounting.

Routine Screening for Callosal Dysgenesis in the Second Trimester Is Achievable With Intensive Training.

OBJECTIVES: The purpose of this study was to determine whether routine direct visualization of the corpus callosum is achievable during second-trimester sonography when performed by a large group of sonographers in a general second-trimester sonographic screening program. The secondary aim was to determine the time taken to obtain a sagittal corpus callosum image. METHODS: We conducted a retrospective cohort study of visualization of the corpus callosum before and after intensive training. Images from 150 consecutive second-trimester scans were reviewed before and after training to evaluate the image quality of the corpus callosum. RESULTS: A total of 300 cases were evaluated before and after training. There was a significant increase in the rate of complete visualization of the corpus callosum after intensive training (P < .0001). Before training 35 of 150 cases (23%) had complete visualization of the corpus callosum versus 107 of 150 (71%) after training. The mean time to perform the corpus callosum views was 53.4 seconds before training compared to 56.2 seconds after training. CONCLUSIONS: Assessing the corpus callosum in the sagittal view is difficult and requires appropriate training and patience; however, this view is feasible without adding substantial time to the examination and provides additional information during a routine second-trimester morphologic scan.

Clap and fling mechanism with interacting porous wings in tiny insect flight.

The aerodynamics of flapping flight for the smallest insects such as thrips is often characterized by a 'clap and fling' of the wings at the end of the upstroke and the beginning of the downstroke. These insects fly at Reynolds numbers (Re) of the order of 10 or less where viscous effects are significant. Although this wing motion is known to augment the lift generated during flight, the drag required to fling the wings apart at this scale is an order of magnitude larger than the corresponding force acting on a single wing. As the opposing forces acting normal to each wing nearly cancel during the fling, these large forces do not have a clear aerodynamic benefit. If flight efficiency is defined as the ratio of lift to drag, the clap and fling motion dramatically reduces efficiency relative to the case of wings that do not aerodynamically interact. In this paper, the effect of a bristled wing characteristic of many of these insects was investigated using computational fluid dynamics. We performed 2D numerical simulations using a porous version of the immersed boundary method. Given the computational complexity involved in modeling flow through exact descriptions of bristled wings, the wing was modeled as a homogeneous porous layer as a first approximation. High-speed video recordings of free-flying thrips in take-off flight were captured in the laboratory, and an analysis of the wing kinematics was performed. This information was used for the estimation of input parameters for the simulations. Compared with a solid wing (without bristles), the results of the study show that the porous nature of the wings contributes largely to drag reduction across the Re range explored. The aerodynamic efficiency, calculated as the ratio of lift to drag coefficients, was larger for some porosities when compared with solid wings.

Precise mid-trimester placenta localisation: does it predict adverse outcomes?

BACKGROUND: A low-lying placenta detected at the mid-pregnancy ultrasound is commonly reported to warn against potential morbidity associated with placenta praevia. There is no information on what distance away from the internal cervical os is safe. AIMS: We examined whether a low-lying placenta not overlapping the cervical os in the second trimester increases the risk of obstetric complications and whether there is a cut-off point at which that increase occurs. METHODS: Adverse perinatal outcomes were examined prospectively in a cohort of women with a placenta 0-30 mm from the internal cervical os ('low-lying') at the routine mid-trimester ultrasound and compared to those with a placenta further away. Two composite outcomes of 'major' and 'minor' adverse events were predefined as primary outcome measures, requiring a sample size of 480 women with a low-lying placenta. Chi-square and Fisher's exact tests were used for statistical analysis. RESULTS: In 1662 pregnancies ('low-lying': n = 484; 'normal': n = 1178), there was no increase in composite adverse outcomes with a low-lying placenta and no cut-off distance within 30 mm from the cervical os at which risks increased. Postpartum haemorrhage ≥ 1000 mL was more frequent with a low-lying placenta (7.6% vs 4.7%, P < 0.05). CONCLUSIONS: Women with a low-lying placenta, not overlapping the cervical os, in mid-pregnancy are at no higher risk of adverse outcomes than those with a normally located placenta, except postpartum haemorrhage. This suggests that the high-risk label can be removed from pregnancies with a low-lying placenta not overlapping the cervical os in mid-pregnancy, reducing anxiety and resource utilisation.

Therapeutic strategies targeting inflammation and immunity in atherosclerosis: how to proceed?

Atherosclerosis is a chronic inflammatory disease of the arterial wall, characterized by the formation of plaques containing lipid, connective tissue and immune cells in the intima of large and medium-sized arteries. Over the past three decades, a substantial reduction in cardiovascular mortality has been achieved largely through LDL-cholesterol-lowering regimes and therapies targeting other traditional risk factors for cardiovascular disease, such as hypertension, smoking, diabetes mellitus and obesity. However, the overall benefits of targeting these risk factors have stagnated, and a huge global burden of cardiovascular disease remains. The indispensable role of immunological components in the establishment and chronicity of atherosclerosis has come to the forefront as a clinical target, with proof-of-principle studies demonstrating the benefit and challenges of targeting inflammation and the immune system in cardiovascular disease. In this Review, we provide an overview of the role of the immune system in atherosclerosis by discussing findings from preclinical research and clinical trials. We also identify important challenges that need to be addressed to advance the field and for successful clinical translation, including patient selection, identification of responders and non-responders to immunotherapies, implementation of patient immunophenotyping and potential surrogate end points for vascular inflammation. Finally, we provide strategic guidance for the translation of novel targets of immunotherapy into improvements in patient outcomes.

Bilateral congenital pulmonary airway malformation in an extremely preterm infant.

We present the case of a baby boy, with antenatal finding of bilateral enlarged echogenic lungs, who developed severe postnatal respiratory failure. Two important differential diagnoses, which have an impact on antenatal and postnatal management, are discussed. Fetal ultrasound, MRI and postmortem MRI images are presented and findings correlated with the autopsy findings.

Accelerated fetal growth velocity across the third trimester is associated with increased shoulder dystocia risk among fetuses who are not large-for-gestational-age: A prospective observational cohort study.

OBJECTIVE: To investigate whether fetuses with accelerated third trimester growth velocity are at increased risk of shoulder dystocia, even when they are not large-for-gestational-age (LGA; estimated fetal weight (EFW) >95th centile). METHODS: Fetal growth velocity and birth outcome data were prospectively collected from 347 nulliparous women. Each had blinded ultrasound biometry performed at 28 and 36 weeks' gestation. Change in EFW and abdominal circumference (AC) centiles between 28-36 weeks were calculated, standardised over exactly eight weeks. We examined the odds of shoulder dystocia with increasing EFW and AC growth velocities among women with 36-week EFW ≤95th centile (non-LGA), who went on to have a vaginal birth. We then examined the relative risk (RR) of shoulder dystocia in cases of accelerated EFW and AC growth velocities (>30 centiles gained). Finally, we compared the predictive performances of accelerated fetal growth velocities to 36-week EFW >95th centile for shoulder dystocia among the cohort planned for vaginal birth. RESULTS: Of the 226 participants who had EFW ≤95th centile at 36-week ultrasound and birthed vaginally, six (2.7%) had shoulder dystocia. For each one centile increase in EFW between 28-36 weeks, the odds of shoulder dystocia increased by 8% (odds ratio (OR [95% Confidence Interval (CI)]) = 1.08 [1.04-1.12], p<0.001). For each one centile increase in AC between 28-36 weeks, the odds of shoulder dystocia increased by 9% (OR[95%CI] = 1.09 [1.05-1.12], p<0.001). When compared to the rest of the cohort with normal growth velocity, accelerated EFW and AC velocities were associated with increased relative risks of shoulder dystocia (RR[95%CI] = 7.3 [1.9-20.6], p = 0.03 and 4.8 [1.7-9.4], p = 0.02 respectively). Accelerated EFW or AC velocities predicted shoulder dystocia with higher sensitivity and positive predictive value than 36-week EFW >95th centile. CONCLUSIONS: Accelerated fetal growth velocities between 28-36 weeks' gestation are associated with increased risk of shoulder dystocia, and may predict shoulder dystocia risk better than the commonly used threshold of 36-week EFW >95th centile.

Enabling Biological Nitrogen Fixation for Cereal Crops in Fertilized Fields.

Agricultural productivity relies on synthetic nitrogen fertilizers, yet half of that reactive nitrogen is lost to the environment. There is an urgent need for alternative nitrogen solutions to reduce the water pollution, ozone depletion, atmospheric particulate formation, and global greenhouse gas emissions associated with synthetic nitrogen fertilizer use. One such solution is biological nitrogen fixation (BNF), a component of the complex natural nitrogen cycle. BNF application to commercial agriculture is currently limited by fertilizer use and plant type. This paper describes the identification, development, and deployment of the first microbial product optimized using synthetic biology tools to enable BNF for corn (Zea mays) in fertilized fields, demonstrating the successful, safe commercialization of root-associated diazotrophs and realizing the potential of BNF to replace and reduce synthetic nitrogen fertilizer use in production agriculture. Derived from a wild nitrogen-fixing microbe isolated from agricultural soils, Klebsiella variicola 137-1036 ("Kv137-1036") retains the capacity of the parent strain to colonize corn roots while increasing nitrogen fixation activity 122-fold in nitrogen-rich environments. This technical milestone was then commercialized in less than half of the time of a traditional biological product, with robust biosafety evaluations and product formulations contributing to consumer confidence and ease of use. Tested in multi-year, multi-site field trial experiments throughout the U.S. Corn Belt, fields grown with Kv137-1036 exhibited both higher yields (0.35 ± 0.092 t/ha ± SE or 5.2 ± 1.4 bushels/acre ± SE) and reduced within-field yield variance by 25% in 2018 and 8% in 2019 compared to fields fertilized with synthetic nitrogen fertilizers alone. These results demonstrate the capacity of a broad-acre BNF product to fix nitrogen for corn in field conditions with reliable agronomic benefits.

Diagnostic criteria and yield of real-time transcranial Doppler monitoring of intra-arterial reperfusion procedures.

BACKGROUND AND PURPOSE: Intra-arterial (IA) rescue procedures are increasingly used to treat acute ischemic stroke. We implemented continuous transcranial Doppler (TCD) monitoring during these procedures to detect any potentially harmful flow changes. Here, we report diagnostic criteria and yield of TCD monitoring. METHODS: We studied consecutive acute stroke patients who underwent IA reperfusion procedures. TCD flow signatures during these procedures were analyzed and any abnormal findings were documented. RESULTS: Patients were included only if there was successful insonation through the skull; of 56 eligible patients, 51 were included. IA procedures included IA tissue plasminogen activator, use of the Merci retriever, the Penumbra system, balloon angioplasty, and stenting. On TCD monitoring, contrast injections produced high-intensity signals and increased the mean flow velocity (MFV). Deployment of the Merci device appeared as high-intensity, short-duration signals with a transient MFV decrease of 11.5%. The Penumbra system produced lower-intensity signals with a greater transient decrease in MFV during aspiration. IA tissue plasminogen activator significantly increased MFV by 7.5% over Merci and Penumbra flow velocity changes. Power motion Doppler-TCD detected reocclusion in 13 patients, artery-to-artery embolization in 2 patients, air embolism in 2 patients, and hyperperfusion in 6 patients. Overall, the yield of TCD monitoring was positive in 23 (49%) patients who received IA reperfusion procedures. CONCLUSIONS: Our velocity, intensity, and flow signatures criteria for TCD monitoring of IA reperfusion procedures detect reocclusion, hyperperfusion, or thromboembolism and air embolism in nearly half of all procedures. This hemodynamic information can be particularly helpful when neurological assessment is limited or delayed.

Within-wingbeat damping: dynamics of continuous free-flight yaw turns in Manduca sexta.

Free-flight body dynamics and wing kinematics were collected from recordings of continuous, low-speed, multi-wingbeat yaw turns in hawkmoths (Manduca sexta) using stereo videography. These data were used to examine the effects of rotational damping arising from interactions between the body rotation and flapping motion (flapping counter-torque, FCT) on continuous turning. The moths were found to accelerate during downstroke, then decelerate during upstroke by an amount consistent with FCT damping. Wing kinematics related to turning were then analysed in a simulation of hawkmoth flight; results were consistent with the observed acceleration-deceleration pattern. However, an alternative wing kinematic which produced more continuous and less damped accelerations was found in the simulation. These findings demonstrate that (i) FCT damping is detectable in the dynamics of continuously turning animals and (ii) FCT-reducing kinematics do exist but were not employed by turning moths, possibly because within-wingbeat damping simplifies control of turning by allowing control systems to target angular velocity rather than acceleration.

Appropriate-for-gestational-age infants who exhibit reduced antenatal growth velocity display postnatal catch-up growth.

BACKGROUND: Postnatally, small-for-gestational-age (SGA; birthweight <10th centile) infants who are growth restricted due to uteroplacental insufficiency (UPI) demonstrate 'catch-up growth' to meet their genetically-predetermined size. Infants who demonstrate slowing growth during pregnancy are those that cross estimated fetal weight centiles at serial ultrasound examinations. These infants that slow in growth but are born appropriate-for-gestational-age (AGA; ≥10th centile), exhibit antenatal, intrapartum and postnatal indicators of UPI. Here, we examine if and when these infants (labelled as AGA-FGR) also demonstrate catch-up growth like SGA infants, when compared with AGA infants with normal antenatal growth velocity (AGA-NG). METHODS: We followed-up the infants of women who had previously undergone ultrasound assessment of fetal size at 28- and 36-weeks' gestation, enabling calculation of antenatal growth velocity. To assess postnatal growth, we asked parents to send their infant's growth measurements, up to two years post-birth, which are routinely collected through the state-wide Maternal-Child Health service. Infants with medical conditions affecting postnatal growth were excluded from the analysis. From the measurements obtained we calculated age-adjusted z-scores for postnatal weight, length and body mass index (BMI; weight(kg)/height(m2)) at birth and 4, 8, 12, 18 and 24 months. We used linear spline regression modelling to predict mean weight, length and BMI z-scores at intervals post birth. Predicted mean age-adjusted z-scores were then compared between three groups; SGA, AGA with low antenatal growth (AGA-FGR; loss of >20 customised estimated fetal weight centiles), and AGA-NG to determine if catch-up growth occurred. In addition, we compared the rates of catch-up growth (defined as an increase in weight age-adjusted z-score of ≥0.67 over 1 year) between the groups with Fisher's exact tests. RESULTS: Of 158 (46%) infant growth records received, 146 were AGA, with low antenatal growth velocity occurring in 34/146 (23.2%). Rates of gestational diabetes and SGA birthweight were higher in those lost to follow-up. Compared to AGA-NG infants, AGA-FGR infants had significantly lower predicted mean weight (p<0.001), length (p = 0.04) and BMI (p = 0.001) z-scores at birth. These significant differences were no longer evident at 4 months, suggesting that catch-up growth had occurred. As expected, the catch-up growth that occurred among the AGA-FGR was not as great in magnitude as that demonstrated by the SGA. When assessed categorically, there was no significant difference between the rate of catch-up growth among the AGA-FGR and the SGA. Catch-up growth was significantly more frequent among both the AGA-FGR and the SGA groups compared to the AGA-NG. CONCLUSIONS: AGA infants that have exhibited reduced antenatal fetal growth velocity also exhibit significant catch-up growth in the first 12 months of life. This finding represents further evidence that AGA fetuses that slow in growth during pregnancy do so due to UPI.

Prevalence and risk factors associated with reversed Robin Hood syndrome in acute ischemic stroke.

BACKGROUND AND PURPOSE: Early deterioration can occur after acute stroke for a variety of reasons. We describe a hemodynamic steal and associated neurological deterioration, the reversed Robin Hood syndrome (RRHS). We aimed to investigate the frequency and factors associated with RRHS. METHODS: Consecutive patients with acute cerebral ischemia underwent serial National Institutes of Health Stroke Scale and bilateral transcranial Doppler monitoring with breathholding. Steal magnitude (%) was calculated from transient mean flow velocity reduction in the affected arteries at the time of velocity increase in normal vessels. Excessive sleepiness and likelihood of sleep apnea were evaluated by the Epworth Sleepiness Scale and Berlin Questionnaire. RESULTS: Among 153 patients (age, 61+/-14 years; 48% women; 21% transient ischemic attack) admitted within 48 hours from symptom onset, 21 (14%) had steal phenomenon (median steal magnitude, 20%; interquartile range, 11%; range, 6% to 45%), and 11 (7%) had RRHS. RRHS was most frequent in patients with proximal arterial occlusions (17% versus 1%; P<0.001). The following factors were independently (P<0.05) associated with RRHS (multivariate logistic regression model): male gender, younger age, persisting arterial occlusions, and excessive sleepiness (P<0.001). A 1-point increase in the Epworth Sleepiness Scale was independently related to an increased likelihood of RRHS of 36% (95% CI, 7% to 73%). CONCLUSIONS: RRHS and hemodynamic steal can be found in 7% and 14%, respectively, of consecutive patients with stroke without other known causes for deterioration. Patients with persisting arterial occlusions and excessive sleepiness can be particularly vulnerable to the steal.