UK criteria for uterus transplantation: a review.

Absolute uterine factor infertility is the final hurdle for assisted reproductive treatments. Uterus transplant trials are happening worldwide; to advance the debate around uterine transplantation (UTx), this article considers selection criteria for clinical trials from a UK perspective and makes recommendations for future selection criteria for UTx treatment. Recommendations advanced include the use of donor eggs, access for single women and women in same-sex relationships, prohibiting participation of women who are already mothers, and a preference for deceased donors and bioengineered uteri. With UTx treatment on the horizon, it is important to proactively consider future selection criteria. TWEETABLE ABSTRACT: Review of UK selection criteria for clinical trials for uterus transplantation; recommendations for the future.

Neutrophil Gelatinase-associated Lipocalin as a Marker of Postoperative Acute Kidney Injury Following Cardiac Surgery in Patients with Preoperative Kidney Impairment.

INTRODUCTION: Acute kidney injury (AKI) is a serious complication of cardiac surgery. The current 'gold standard' for determining AKI is change in serum creatinine and urine output, however, this change occurs relatively late after the actual injury occurs. Identification of new biomarkers that detect early AKI is required. Recently, new biomarkers, such as the NephroCheck® Test and AKIRisk have also been tested and found to be good indicators of AKI. Neutrophil gelatinase-associated lipocalin (NGAL) has shown promise in paediatric patients but has displayed varied results in adult populations, particularly post cardiac surgery. The aim of this study was to assess the value of urinary NGAL as a biomarker of AKI in patients with pre-existing renal impairment (eGFR >15ml/min to eGFR<60ml/min). METHODS: A post-hoc analysis of urinary NGAL concentrations from 125 patients with pre-existing kidney impairment, who participated in a randomised trial of haemofiltration during cardiac surgery, was undertaken. Urinary NGAL was measured using ELISA at baseline, post-operatively and 24 and 48 hours after surgery, and serum creatinine was measured pre and postoperatively and then at 24, 48, 72 and 96 hours as routine patient care. NGAL concentrations were compared in patients with and without AKI determined by changes in serum creatinine concentrations. A Kaplan-Meier plot compared survival for patients with or without AKI and a Cox proportional hazards analysis was performed to identify factors with the greatest influence on survival. RESULTS: Following surgery, 43% of patients developed AKI (based on KDIGO definition). Baseline urinary NGAL was not found to be significantly different between patients that did and did not develop AKI. Urinary NGAL concentration was increased in all patients following surgery, regardless of whether they developed AKI and was also significant between groups at 24 (p=0.003) and 48 hours (p<0.0001). Urinary NGAL concentrations at 48 hours correlated with serum creatinine concentrations at 48 hours (r=0.477, p<0.0001), 72 hours (r=0.488, p<0.0001) and 96 hours (r=0.463, p<0.0001). Urinary NGAL at 48 hours after surgery strongly predicted AKI (AUC=0.76; P=0.0001). A Kaplan- Meier plot showed that patients with postoperative AKI had a significantly lower 7-year survival compared with those without AKI. Postoperative urinary NGAL at 48 hours >156ng/mL also strongly predicted 7-year survival. However, additive EuroSCORE, age, current smoking and post-operative antibiotics usage were distinctly significantly more predictive of 7-year survival as compared with postoperative urinary NGAL at 48 hours >156ng/mL. CONCLUSIONS: Our study demonstrated that postoperative urinary NGAL levels at 48 hours postsurgery strongly predicts the onset or severity of postoperative AKI based on KDIGO classification in patients with preoperative kidney impairment and were also strongly related to 7-year survival.

Applying shot boundary detection for automated crystal growth analysis during in situ transmission electron microscope experiments.

In situ scanning transmission electron microscopy is being developed for numerous applications in the study of nucleation and growth under electrochemical driving forces. For this type of experiment, one of the key parameters is to identify when nucleation initiates. Typically, the process of identifying the moment that crystals begin to form is a manual process requiring the user to perform an observation and respond accordingly (adjust focus, magnification, translate the stage, etc.). However, as the speed of the cameras being used to perform these observations increases, the ability of a user to "catch" the important initial stage of nucleation decreases (there is more information that is available in the first few milliseconds of the process). Here, we show that video shot boundary detection can automatically detect frames where a change in the image occurs. We show that this method can be applied to quickly and accurately identify points of change during crystal growth. This technique allows for automated segmentation of a digital stream for further analysis and the assignment of arbitrary time stamps for the initiation of processes that are independent of the user's ability to observe and react.

Observation and quantification of nanoscale processes in lithium batteries by operando electrochemical (S)TEM.

An operando electrochemical stage for the transmission electron microscope has been configured to form a "Li battery" that is used to quantify the electrochemical processes that occur at the anode during charge/discharge cycling. Of particular importance for these observations is the identification of an image contrast reversal that originates from solid Li being less dense than the surrounding liquid electrolyte and electrode surface. This contrast allows Li to be identified from Li-containing compounds that make up the solid-electrolyte interphase (SEI) layer. By correlating images showing the sequence of Li electrodeposition and the evolution of the SEI layer with simultaneously acquired and calibrated cyclic voltammograms, electrodeposition, and electrolyte breakdown processes can be quantified directly on the nanoscale. This approach opens up intriguing new possibilities to rapidly visualize and test the electrochemical performance of a wide range of electrode/electrolyte combinations for next generation battery systems.

A unified model of heading and path perception in primate MSTd.

Self-motion, steering, and obstacle avoidance during navigation in the real world require humans to travel along curved paths. Many perceptual models have been proposed that focus on heading, which specifies the direction of travel along straight paths, but not on path curvature, which humans accurately perceive and is critical to everyday locomotion. In primates, including humans, dorsal medial superior temporal area (MSTd) has been implicated in heading perception. However, the majority of MSTd neurons respond optimally to spiral patterns, rather than to the radial expansion patterns associated with heading. No existing theory of curved path perception explains the neural mechanisms by which humans accurately assess path and no functional role for spiral-tuned cells has yet been proposed. Here we present a computational model that demonstrates how the continuum of observed cells (radial to circular) in MSTd can simultaneously code curvature and heading across the neural population. Curvature is encoded through the spirality of the most active cell, and heading is encoded through the visuotopic location of the center of the most active cell's receptive field. Model curvature and heading errors fit those made by humans. Our model challenges the view that the function of MSTd is heading estimation, based on our analysis we claim that it is primarily concerned with trajectory estimation and the simultaneous representation of both curvature and heading. In our model, temporal dynamics afford time-history in the neural representation of optic flow, which may modulate its structure. This has far-reaching implications for the interpretation of studies that assume that optic flow is, and should be, represented as an instantaneous vector field. Our results suggest that spiral motion patterns that emerge in spatio-temporal optic flow are essential for guiding self-motion along complex trajectories, and that cells in MSTd are specifically tuned to extract complex trajectory estimation from flow.

Factors influencing quantitative liquid (scanning) transmission electron microscopy.

One of the experimental challenges in the study of nanomaterials in liquids in the (scanning) transmission electron microscope ((S)TEM) is gaining quantitative information. A successful experiment in the fluid stage will depend upon the ability to plan for sensitive factors such as the electron dose applied, imaging mode, acceleration voltage, beam-induced solution chemistry changes, and the specifics of solution reactivity. In this paper, we make use of a visual approach to show the extent of damage of different instrumental and experimental factors in liquid samples imaged in the (S)TEM. Previous results as well as new insights are presented to create an overview of beam-sample interactions identified for changing imaging and experimental conditions. This work establishes procedures to understand the effect of the electron beam on a solution, provides information to allow for a deliberate choice of the optimal experimental conditions to enable quantification, and identifies the experimental factors that require further analysis for achieving fully quantitative results in the liquid (S)TEM.

Interfacial ferromagnetism in LaNiO3/CaMnO3 superlattices.

We observe interfacial ferromagnetism in superlattices of the paramagnetic metal LaNiO3 and the antiferromagnetic insulator CaMnO3. LaNiO3 exhibits a thickness dependent metal-insulator transition and we find the emergence of ferromagnetism to be coincident with the conducting state of LaNiO3. That is, only superlattices in which the LaNiO3 layers are metallic exhibit ferromagnetism. Using several magnetic probes, we have determined that the ferromagnetism arises in a single unit cell of CaMnO3 at the interface. Together these results suggest that ferromagnetism can be attributed to a double exchange interaction among Mn ions mediated by the adjacent itinerant metal.

Interfacial ferromagnetism and exchange bias in CaRuO3/CaMnO3 superlattices.

We have found ferromagnetism in epitaxially grown superlattices of CaRuO(3)/CaMnO(3) that arises in one unit cell at the interface. Scanning transmission electron microscopy and electron energy loss spectroscopy indicate that the difference in magnitude of the Mn valence states between the center of the CaMnO(3) layer and the interface region is consistent with double exchange interaction among the Mn ions at the interface. Polarized neutron reflectivity and the CaMnO(3) thickness dependence of the exchange bias field together indicate that the interfacial ferromagnetism is only limited to one unit cell of CaMnO(3) at each interface. The interfacial moment alternates between the 1 µ(B)/interface Mn ion for even CaMnO(3) layers and the 0.5 µ(B)/interface Mn ion for odd CaMnO(3) layers. This modulation, combined with the exchange bias, suggests the presence of a modulating interlayer coupling between neighboring ferromagnetic interfaces via the antiferromagnetic CaMnO(3) layers.

Recurrent competition explains temporal effects of attention in MSTd.

Navigation in a static environment along straight paths without eye movements produces radial optic flow fields. A singularity called the focus of expansion (FoE) specifies the direction of travel (heading) of the observer. Cells in primate dorsal medial superior temporal area (MSTd) respond to radial fields and are therefore thought to be heading-sensitive. Humans frequently shift their focus of attention while navigating, for example, depending on the favorable or threatening context of approaching independently moving objects. Recent neurophysiological studies show that the spatial tuning curves of primate MSTd neurons change based on the difference in visual angle between an attentional prime and the FoE. Moreover, the peak mean population activity in MSTd retreats linearly in time as the distance between the attentional prime and FoE increases. We present a dynamical neural circuit model that demonstrates the same linear temporal peak shift observed electrophysiologically. The model qualitatively matches the neuron tuning curves and population activation profiles. After model MT dynamically pools short-range motion, model MSTd incorporates recurrent competition between units tuned to different radial optic flow templates, and integrates attentional signals from model area frontal eye fields (FEF). In the model, population activity peaks occur when the recurrent competition is most active and uncertainty is greatest about the relative position of the FoE. The nature of attention, multiplicative or non-multiplicative, is largely irrelevant, so long as attention has a Gaussian-like profile. Using an appropriately tuned sigmoidal signal function to modulate recurrent feedback affords qualitative fits of deflections in the population activity that otherwise appear to be low-frequency noise. We predict that these deflections mark changes in the balance of attention between the priming and FoE locations.

A neural circuit for robust time-to-contact estimation based on primate MST.

Time-to-contact (TTC) estimation is beneficial for visual navigation. It can be estimated from an image projection, either in a camera or on the retina, by looking at the rate of expansion of an object. When expansion rate (E) is properly defined, TTC = 1/E. Primate dorsal MST cells have receptive field structures suited to the estimation of expansion and TTC. However, the role of MST cells in TTC estimation has been discounted because of large receptive fields, the fact that neither they nor preceding brain areas appear to decompose the motion field to estimate divergence, and a lack of experimental data. This letter demonstrates mathematically that template models of dorsal MST cells can be constructed such that the output of the template match provides an accurate and robust estimate of TTC. The template match extracts the relevant components of the motion field and scales them such that the output of each component of the template match is an estimate of expansion. It then combines these component estimates to provide a mean estimate of expansion across the object. The output of model MST provides a direct measure of TTC. The ViSTARS model of primate visual navigation was updated to incorporate the modified templates. In ViSTARS and in primates, speed is represented as a population code in V1 and MT. A population code for speed complicates TTC estimation from a template match. Results presented in this letter demonstrate that the updated template model of MST accurately codes TTC across a population of model MST cells. We conclude that the updated template model of dorsal MST simultaneously and accurately codes TTC and heading regardless of receptive field size, object size, or motion representation. It is possible that a subpopulation of MST cells in primates represents expansion in this way.

Differential effects of antiepileptic drugs on neonatal outcomes.

Offspring of women with epilepsy (WWE) on AEDs are at increased risks for major congenital malformations and reduced cognition. They may be at risk for other adverse neonatal outcomes. Women with epilepsy on carbamazepine (CBZ), lamotrigine (LTG), phenytoin (PHT), or valproate (VPA) monotherapy were enrolled in a prospective, observational, multicenter study of the neurodevelopmental effects of AEDs. The odds ratio for small for gestational age (SGA) was higher for VPA vs. PHT, VPA vs. LTG, and CBZ vs. PHT. Microcephaly rates were elevated to 12% for all newborns and at 12 months old, but normalized by age 24 months. Reduced Apgar scores occurred more frequently in the VPA and PHT groups at 1 min, but scores were near normal in all groups at 5 min. This study demonstrates increased risks for being born SGA in the VPA and CBZ groups, and transiently reduced Apgar scores in the VPA and PHT groups. Differential risks among the AEDs can help inform decisions about AED selection for women during childbearing years.

Investigating the electronic structure of fluorite-structured oxide compounds: comparison of experimental EELS with first principles calculations.

Energy loss spectra from fluorite-structured ZrO(2), CeO(2), and UO(2) compounds are compared with theoretical calculations based on density functional theory (DFT) and its extensions, including the use of Hubbard-U corrections (DFT + U) and hybrid functionals. Electron energy loss spectra (EELS) were obtained from each oxide using a scanning transmission electron microscope (STEM). The same spectra were computed within the framework of the full-potential linear augmented plane-wave (FLAPW) method. The theoretical and experimental EEL spectra are compared quantitatively using non-linear least squares peak fitting and a cross-correlation approach, with the best level of agreement between experiment and theory being obtained using the DFT + U and hybrid computational approaches.

Effects of fetal antiepileptic drug exposure: outcomes at age 4.5 years.

OBJECTIVE: To examine outcomes at age 4.5 years and compare to earlier ages in children with fetal antiepileptic drug (AED) exposure. METHODS: The NEAD Study is an ongoing prospective observational multicenter study, which enrolled pregnant women with epilepsy on AED monotherapy (1999-2004) to determine if differential long-term neurodevelopmental effects exist across 4 commonly used AEDs (carbamazepine, lamotrigine, phenytoin, or valproate). The primary outcome is IQ at 6 years of age. Planned analyses were conducted using Bayley Scales of Infant Development (BSID at age 2) and Differential Ability Scale (IQ at ages 3 and 4.5). RESULTS: Multivariate intent-to-treat (n = 310) and completer (n = 209) analyses of age 4.5 IQ revealed significant effects for AED group. IQ for children exposed to valproate was lower than each other AED. Adjusted means (95% confidence intervals) were carbamazepine 106 (102-109), lamotrigine 106 (102-109), phenytoin 105 (102-109), valproate 96 (91-100). IQ was negatively associated with valproate dose, but not other AEDs. Maternal IQ correlated with child IQ for children exposed to the other AEDs, but not valproate. Age 4.5 IQ correlated with age 2 BSID and age 3 IQ. Frequency of marked intellectual impairment diminished with age except for valproate (10% with IQ <70 at 4.5 years). Verbal abilities were impaired for all 4 AED groups compared to nonverbal skills. CONCLUSIONS: Adverse cognitive effects of fetal valproate exposure persist to 4.5 years and are related to performances at earlier ages. Verbal abilities may be impaired by commonly used AEDs. Additional research is needed.

A motion pooling model of visually guided navigation explains human behavior in the presence of independently moving objects.

Humans accurately judge their direction of heading when translating in a rigid environment, unless independently moving objects (IMOs) cross the observer's focus of expansion (FoE). Studies show that an IMO on a laterally moving path that maintains a fixed distance with respect to the observer (non-approaching; C. S. Royden & E. C. Hildreth, 1996) biases human heading estimates differently from an IMO on a lateral path that gets closer to the observer (approaching; W. H. Warren & J. A. Saunders, 1995). C. S. Royden (2002) argued that differential motion operators in primate brain area MT explained both data sets, concluding that differential motion was critical to human heading estimation. However, neurophysiological studies show that motion pooling cells, but not differential motion cells, in MT project to heading-sensitive cells in MST (V. K. Berezovskii & R. T. Born, 2000). It is difficult to reconcile differential motion heading models with these neurophysiological data. We generate motion sequences that mimic those viewed by human subjects. Model MT pools over V1; units in model MST perform distance-weighted template matching and compete in a recurrent heading representation layer. Our model produces heading biases of the same direction and magnitude as humans through a peak shift in model MSTd without using differential motion operators, maintaining consistency with known primate neurophysiology.

A retrospective study examining thrombolysis for occluded femoro-popliteal grafts - is it worthwhile?

AIM: To assess the effectiveness of catheter directed thrombolysis (CDT) in the treatment of acute graft occlusion. METHODS: Tissue prothrombin activator (rt-PA) was the sole agent used for thrombolysis. This was infused through a 4F straight 65 cm catheter placed under ultrasound guidance. Following a pre-CDT angiogram, a catheter was placed just proximal to the distal anastomosis. An infusion of rt-PA was given over 24 h. An assessment of acute clinical success, limb salvage rates, patency rates and complication rates were made over a period of one year. RESULTS: 80% (20/25) of grafts were successfully reopened immediately. 4/5 (80%) of the unsuccessful CDT cases required amputation within a few weeks. 60% (12/20) of successful CDT cases had an underlying stenotic lesion which required angioplasty. Limb salvage rate was 72% (18/25) at 12 months. There was no CDT related mortality. Secondary patency rate at 9 months was 76% (13/17). CONCLUSION: CDT can achieve reasonable results in this group of challenging patients and may be seen as a useful accessory in the vascular toolkit. However, precise indications for its use need further clarification.