Separation sign: novel ultrasound sign for ruling out diagnosis of placenta accreta spectrum.

OBJECTIVE: To assess the performance of the 'separation sign' as a predictor of normal placental separation in a large cohort of women at risk for placenta accreta spectrum (PAS) and in a high-risk subgroup with placenta previa or anterior low-lying placenta and at least one previous Cesarean delivery. METHODS: This was a prospective study of women at risk for PAS referred to a specialist clinic at between 22 and 38 weeks' gestation. All women underwent ultrasound assessment for the presence of the separation sign, which detects the difference in elasticity between the myometrium and the placenta, characterized by different rates of rebound after an ultrasound probe is used to apply pressure over the uteroplacental interface. When the sign is positive, the placenta appears to move relative to the myometrium, leading to the appearance or enhancement of the clear zone. The predictive performance of the separation sign for normal spontaneous placental separation at delivery was assessed. RESULTS: Of the 194 included women, 163 had a positive separation sign, all of whom went on to have normal placental separation at delivery. Of the 24 women with a negative separation sign, three (12.5%) had normal placental separation and 21 (87.5%) were diagnosed with PAS. This yielded a sensitivity of 98.2% (95% CI, 94.8-99.6%) and specificity of 100% (95% CI, 83.9-100%). In the high-risk cohort (n = 35), a positive separation sign remained a reliable predictor of normal placental separation, with a positive predictive value of 100%, sensitivity of 88.9% (95% CI, 65.3-98.6%) and specificity of 100% (95% CI, 80.5-100%). CONCLUSIONS: The separation sign could be a useful tool in women considered to be at risk for PAS, as it can facilitate the prediction of normal placental separation at delivery. This may prevent overtreatment, the associated iatrogenic morbidity and unnecessary allocation of clinical resources. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Impact of placenta previa with placenta accreta spectrum disorder on fetal growth.

OBJECTIVES: To evaluate fetal growth in pregnancies complicated by placenta previa with or without placenta accreta spectrum (PAS) disorder, compared with in pregnancies with a low-lying placenta. METHODS: This was a multicenter retrospective cohort study of singleton pregnancies complicated by placenta previa with or without PAS disorder, for which maternal characteristics, ultrasound-estimated fetal weight and birth weight were available. Four maternal-fetal medicine units participated in data collection of diagnosis, treatment and outcome. The control group comprised singleton pregnancies with a low-lying placenta (0.5-2 cm from the internal os). The diagnosis of PAS and depth of invasion were confirmed at delivery using both a predefined clinical grading score and histopathological examination. For comparison of pregnancy characteristics and fetal growth parameters, the study groups were matched for smoking status, ethnic origin, fetal sex and gestational age at delivery. RESULTS: The study included 82 women with placenta previa with PAS disorder, subdivided into adherent (n = 35) and invasive (n = 47) PAS subgroups, and 146 women with placenta previa without PAS disorder. There were 64 controls with a low-lying placenta. There was no significant difference in the incidence of small-for-gestational age (SGA) (birth weight ≤ 10th percentile) and large-for-gestational age (LGA) (birth weight ≥ 90th  percentile) between the study groups. Median gestational age at diagnosis was significantly lower in pregnancies with placenta previa without PAS disorder than in the low-lying placenta group (P = 0.002). No significant difference was found between pregnancies complicated by placenta previa with PAS disorder and those without for any of the variables. Median estimated fetal weight percentile was significantly lower in the adherent compared with the invasive previa-PAS subgroup (P = 0.047). Actual birth weight percentile at delivery did not differ significantly between the subgroups (P = 0.804). CONCLUSIONS: No difference was seen in fetal growth in pregnancies complicated by placenta previa with PAS disorder compared with those without and compared with those with a low-lying placenta. There was also no increased incidence of either SGA or LGA neonates in pregnancies with placenta previa and PAS disorder compared with those with placenta previa with spontaneous separation of the placenta at birth. Adverse neonatal outcome in pregnancies complicated by placenta previa and PAS disorder is linked to premature delivery and not to impaired fetal growth. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

High prevalence of Legionella in non-passenger merchant vessels.

There is a paucity of information on the risk from potable water in non-passenger merchant vessels (NPMVs) particularly with regard to Legionella and other bacteria. This retrospective study examined water samples from 550 NPMVs docked in eight UK ports. A total of 1027 samples from 412 NPMVs were examined for total aerobic colony counts (ACC), coliforms, Escherichia coli and enterococci; 41% of samples yielded ACC above the action level (>1 × 103 c.f.u./ml) and 4·5% contained actionable levels (>1 c.f.u./100 ml) of faecal indicator bacteria. Eight hundred and three samples from 360 NPMVs were cultured specifically for Legionella and 58% of vessels proved positive for these organisms with 27% of samples showing levels greater than the UK upper action limit of 1 × 103 c.f.u./l. Cabin showers (49%) and hospital shower (45%) were frequently positive. A subset of 106 samples was analysed by quantitative polymerase chain reaction for Legionella and identified a further 11 Legionella-positive NPMVs, returning a negative predictive value of 100%. There was no correlation between NPMV age or size and any microbial parameters (P > 0·05). Legionella pneumophila serogroup 1 was isolated from 46% of NPMVs and sequence-based typing of 17 isolates revealed four sequence types (STs) previously associated with human disease. These data raise significant concerns regarding the management of microbial and Legionella risks on board NPMVs and suggest that better guidance and compliance are required to improve control.

Heated birthing pools as a source of Legionnaires' disease.

In June 2014 Public Health England confirmed a case of Legionnaires' disease (LD) in a neonate following birth at home in a hired birthing pool incorporating a heater and a recirculation pump which had been filled in advance of labour. The case triggered a public health investigation and a microbiological survey of an additional ten heated birthing pools hired or recently hired to the general public across England. The birthing pool used by the parent of the confirmed case was identified as the source of the neonate's infection following detection of Legionella pneumophila ST48 in both patient and environmental samples. Legionella species were detected by quantitative polymerase chain reaction but not culture in a further three pools together with other opportunistic pathogens identified by culture and matrix-assisted laser desorption ionization-time of flight (MALDI-ToF) mass spectrometry. A Patient Safety Alert from NHS England and Public Health England was issued stating that heated birthing pools filled in advance of labour should not be used for home births. This recommendation remains in place. This investigation in conjunction with other recent reports has highlighted a lack of awareness regarding the microbiological safety of heated birthing pools and their potential to be a source of LD and other opportunistic infections. Furthermore, the investigation raised important considerations with regards to microbiological sampling and testing in such incidents. Public health authorities and clinicians should consider LD in the differential diagnosis of severe respiratory infection in neonates within 14 days of a water birth.

Grassland to shrubland state transitions enhance carbon sequestration in the northern Chihuahuan Desert.

The replacement of native C4 -dominated grassland by C3 -dominated shrubland is considered an ecological state transition where different ecological communities can exist under similar environmental conditions. These state transitions are occurring globally, and may be exacerbated by climate change. One consequence of the global increase in woody vegetation may be enhanced ecosystem carbon sequestration, although the responses of arid and semiarid ecosystems may be highly variable. During a drier than average period from 2007 to 2011 in the northern Chihuahuan Desert, we found established shrubland to sequester 49 g C m(-2) yr(-1) on average, while nearby native C4 grassland was a net source of 31 g C m(-2) yr(-1) over this same period. Differences in C exchange between these ecosystems were pronounced--grassland had similar productivity compared to shrubland but experienced higher C efflux via ecosystem respiration, while shrubland was a consistent C sink because of a longer growing season and lower ecosystem respiration. At daily timescales, rates of carbon exchange were more sensitive to soil moisture variation in grassland than shrubland, such that grassland had a net uptake of C when wet but lost C when dry. Thus, even under unfavorable, drier than average climate conditions, the state transition from grassland to shrubland resulted in a substantial increase in terrestrial C sequestration. These results illustrate the inherent tradeoffs in quantifying ecosystem services that result from ecological state transitions, such as shrub encroachment. In this case, the deleterious changes to ecosystem services often linked to grassland to shrubland state transitions may at least be partially offset by increased ecosystem carbon sequestration.

Influence of power Doppler gain setting on Virtual Organ Computer-aided AnaLysis indices in vivo: can use of the individual sub-noise gain level optimize information?

OBJECTIVES: To demonstrate the influence of gain setting on the calculated Virtual Organ Computer-aided AnaLysis (VOCAL(™)) three-dimensional (3D) indices and define a point, the sub-noise gain (SNG), at which maximum information is available without noise artifact. METHODS: Pregnant women were recruited at the time of their pregnancy-dating scan. Five identical static 3D power Doppler volumes of the placenta were acquired using identical machine settings apart from altering the power Doppler gain setting. The gain settings included the individualized SNG setting (determined by increasing gain until noise artifact was visible, then reducing it until the artifact just disappeared). The data were analyzed using VOCAL II. Vascularization index (VI), flow index (FI) and vascularization flow index (VFI) were calculated for the same sample at five different power Doppler gain levels. The relationship between the values calculated for the VOCAL indices and the gain value was explored using linear regression analysis. RESULTS: Results from 50 women were analyzed. The percentage difference in VI and VFI from that observed at the SNG level in each woman was significantly linearly related to the gain setting relative to that at the SNG point (VI: r(2) = 0.68, P < 0.0001; VFI: r(2) = 0.72, P < 0.0001), with the values produced for VI and VFI decreasing as the gain was turned down. There was a distinct 'turning point' at the SNG level with linear relationships above and below, but with significantly different gradients (P ≤ 0.001). This relationship was not demonstrated for FI. CONCLUSION: The SNG setting appears to represent each individual's optimum gain level. Using this may improve meaningful comparisons of VI and VFI between patients.

Inapplicability of fractional moving blood volume technique to standardize Virtual Organ Computer-aided AnaLysis indices for quantified three-dimensional power Doppler.

OBJECTIVE: To determine whether the technique of fractional moving blood volume (FMBV) is applicable to Virtual Organ Computer-aided AnaLysis II (VOCAL II™)-based indices to quantify three-dimensional power Doppler ultrasound (3D-PDU) by investigating the effect of gain level on the indices measured at a possible reference point for standardization. METHODS: Ten women with singleton pregnancy between 33+3 and 37+5 weeks' gestation were recruited. The optimal position for 3D acquisition of cord insertion into the placenta was identified and static 3D-PDU volumes were acquired using consistent machine configurations. Without moving the probe or the participant changing position, successive 3D volumes were stored at -3, -5, -7 and -9 dB and at the individualized sub-noise gain (SNG) level. Volumes were excluded if flash artifact was present, in which case all five volumes were reacquired. Using 4D View software, the cord insertion was magnified and the smallest sphere possible was used to measure vascularization index (VI), flow index (FI) and vascularization flow index (VFI). The associations between VOCAL indices and gain level were assessed using Pearson's correlation coefficient. RESULTS: VOCAL indices for cord insertion correlated poorly with gain level, whether fundamental or relative to SNG level (R(2) = 0.07 and 0.04, respectively). VI was consistently 100% and mean FI and VFI were 99.5 (SD, 0.57), with all values > 97 irrespective of gain level. CONCLUSIONS: Whilst previous work has shown that gain correlates well with placental tissue VOCAL indices, the correlation between gain level and VOCAL indices in an area of 100% vascularity at the cord insertion is poor. Regions of 100% vascularity appear to be artificially assigned a value approaching 100% for all VOCAL indices irrespective of gain level. This precludes using the technique of VOCAL indices from large vessels to standardize power Doppler measurements and the FMBV index is therefore not applicable to image analysis using VOCAL.

Measurement of spiral artery jets: general principles and differences observed in small-for-gestational-age pregnancies.

OBJECTIVE: To investigate whether the jets of blood from the mouths of the spiral arteries could be measured reliably, as well as their relationship with the uterine artery (UtA) and any differences in small-for-gestational-age (SGA) pregnancies. METHODS: Participants underwent serial ultrasound scans, from 11 weeks' gestation. Pulsatility index (PI) and resistance index (RI) of jets into the intervillous space (IVS) and UtA were recorded at every visit. Intra- and interobserver variability studies were performed. Customized birth weight centiles were calculated and SGA was defined as < 10(th) centile. Linear mixed model analysis was used to allow for the longitudinal nature of the data. RESULTS: Sixty-six women were recruited; 58 remained normotensive and delivered at term. Of these, six women delivered SGA newborns and 52 delivered appropriate-for-gestational-age newborns. All had pulsatile jets until 20 weeks' gestation. The PI and RI of the jets decreased with advancing gestation, following a trend similar to that of the UtAs. There was no correlation between the jets and UtA waveforms when gestational age was controlled for. For intraobserver variability the intraclass correlation coefficient was 0.9. The interobserver study showed no significant difference between the observers. Mixed model analysis demonstrated that PI and RI of jets were different in SGA pregnancies (P < 0.06). This difference was not seen for the UtAs (P = 0.8). CONCLUSION: This technique enables examination of characteristics of the jets of blood flowing from spiral arteries into the IVS. It is both precise and reproducible, with biologically plausible results. Further work is required to assess differences in pregnancies with adverse outcomes.

Volume and vascularity: Using ultrasound to unlock the secrets of the first trimester placenta.

Fetal growth restriction (FGR) is a major cause of perinatal morbidity and mortality. Identifying which pregnancies are at risk of FGR facilitates enhanced surveillance and early delivery before fetal demise can ensue. However, existing risk stratification strategies yield an unacceptably low detection rate. A robust and reliable first trimester screening test for FGR would not only enable high-risk women to be appropriately monitored but would facilitate future trials for possible interventions to enhance fetal growth. Both the volume and vascularity of the first trimester placenta has been demonstrated to be linked to adverse pregnancy outcomes including FGR and pre-eclampsia. The investigation of novel ultrasound markers for FGR are discussed along with the development of methods for fully automatic placental volume estimation which has the potential for use as part of a multi-variable population-based screening test.

A proposal for standardized magnetic resonance imaging (MRI) descriptors of abnormally invasive placenta (AIP) - From the International Society for AIP.

Abnormally invasive placenta (AIP) is used to describe a placenta that does not separate naturally after delivery and cannot be extirpated without causing abnormally high blood loss. Recently, the use of a standardized terminology for descriptors of AIP signs seen on ultrasound has been prosed but to date no such unified descriptors have been developed for magnetic resonance imaging (MRI). The purpose of this paper is to propose a unified terminology based on a consensus opinion from the members of the International Society for AIP (IS-AIP) that include obstetricians, gynecologists, radiologists, pathologists, anesthesiologists and basic science researchers. We assume that using these standardized MRI descriptors for AIP will be useful for clinical use, education, teaching and future research projects, thus assumably improving care of patients with this condition. In addition, using a uniform terminology for AIP should become the first step of a standardized MRI report.

Soil net nitrogen mineralisation across global grasslands.

Soil nitrogen mineralisation (Nmin), the conversion of organic into inorganic N, is important for productivity and nutrient cycling. The balance between mineralisation and immobilisation (net Nmin) varies with soil properties and climate. However, because most global-scale assessments of net Nmin are laboratory-based, its regulation under field-conditions and implications for real-world soil functioning remain uncertain. Here, we explore the drivers of realised (field) and potential (laboratory) soil net Nmin across 30 grasslands worldwide. We find that realised Nmin is largely explained by temperature of the wettest quarter, microbial biomass, clay content and bulk density. Potential Nmin only weakly correlates with realised Nmin, but contributes to explain realised net Nmin when combined with soil and climatic variables. We provide novel insights of global realised soil net Nmin and show that potential soil net Nmin data available in the literature could be parameterised with soil and climate data to better predict realised Nmin.

mTORC2 signalling regulates M2 macrophage differentiation in response to helminth infection and adaptive thermogenesis.

Alternatively activated macrophages (M2) have an important function in innate immune responses to parasitic helminths, and emerging evidence also indicates these cells are regulators of systemic metabolism. Here we show a critical role for mTORC2 signalling in the generation of M2 macrophages. Abrogation of mTORC2 signalling in macrophages by selective conditional deletion of the adaptor molecule Rictor inhibits the generation of M2 macrophages while leaving the generation of classically activated macrophages (M1) intact. Selective deletion of Rictor in macrophages prevents M2 differentiation and clearance of a parasitic helminth infection in mice, and also abrogates the ability of mice to regulate brown fat and maintain core body temperature. Our findings define a role for mTORC2 in macrophages in integrating signals from the immune microenvironment to promote innate type 2 immunity, and also to integrate systemic metabolic and thermogenic responses.

Mechanisms of immune suppression in patients with head and neck cancer: presence of CD34(+) cells which suppress immune functions within cancers that secrete granulocyte-macrophage colony-stimulating factor.

Production of granulocyte-macrophage colony-stimulating factor (GM-CSF) by murine tumors has been shown to induce immune suppressive cells having homology with GM progenitor cells. The purpose of this study was to determine if human head and neck cancers secrete GM-CSF, if this is associated with an intratumoral presence of similar cells expressing the hematopoietic progenitor cell antigen CD34, and if such CD34(+) cells suppress functions of intratumoral T cells. This was evaluated with fresh head and neck cancers, and in some instances regional lymph nodes and control tissue. Ten of the 14 squamous cell carcinomas (SCCs) studied secreted greater than 5 ng GM-CSF/g tissue. GM-CSF was not secreted in significant levels by either the other cancer types or by control normal muscle. Each of the high GM-CSF-secreting SCCs, but none of the cancers that did not secrete GM-CSF, contained cells expressing the hematopoietic progenitor cell antigen CD34 that had the capacity to grow into colonies in soft agar. Available regional lymph nodes from patients with high GM-CSF-producing cancers also contained CD34(+) cells. Depletion of CD34(+) cells from dissociated cancers increased interleukin 2 secretion by the intratumoral lymphocytes while addition of the CD34(+) cells to dissociated cancers reduced interleukin 2 production, indicating that the presence of CD34(+) cells within GM-CSF-producing head and neck SCCs results in suppressed functional competence of lymphocytes within the SCCs. These results show that GM-CSF-secreting SCCs contain cells expressing the hematopoietic antigen CD34 which are inhibitory to the capacity of lymphocytes within the SCCs to secrete interleukin 2.