The International Consensus for Early TB framework (ICE-TB): Implications from a low-incidence setting.

In recent years, there has been increasing recognition of the public health significance of the spectrum of TB disease presentation, and the existing classification systems of asymptomatic infection and symptomatic TB have been limited in terms of explanatory power. Accordingly, in 2022-2023, a new International Consensus framework for Early TB (ICE-TB) was developed, categorising the spectrum of TB infection and disease into five states based on the presence or absence of macroscopic pathology, host infectiousness, and symptoms and signs.We used the ICE-TB framework to re-analyse existing notification data for 2022 within a low-incidence setting to explore the potential utility and future challenges for its public health application.Existing notification data were sufficient to allow substantial reclassification of currently recognised active disease states, but did not systematically capture Mycobacterium tuberculosis infection or subclinical TB. Fifty percent of existing TB notifications would be classified as 'Clinical, infectious', with the potential need to consider further subclassification.Our exploration highlighted limitations in existing classification systems and diagnostic approaches and should encourage researchers and programmatic implementers to emphasise person-centred and programmatic needs in the development of new tools for TB management..

A Systematic Review of Autistic People and the Criminal Justice System: An Update of King and Murphy (2014).

The purpose of this paper was to determine whether recommendations made by King & Murphy (Journal of Autism and Developmental Disorders 44:2717-2733, 2014) in their review of the evidence on autistic people in contact with the criminal justice system (CJS) have been addressed. Research published since 2013 was systematically examined and synthesised. The quality of 47 papers was assessed using the Mixed Methods Appraisal Tool. Findings suggest a limited amount of good quality research has been conducted that has focused on improving our understanding of autistic people in contact with the CJS since 2013. Methodological limitations make direct comparisons between autistic and non-autistic offenders difficult. Autistic people commit a range of crimes and appear to have unique characteristics that warrant further exploration (i.e., vulnerabilities, motivations for offending).

Annotated normal CT data of the abdomen for deep learning: Challenges and strategies for implementation.

PURPOSE: The purpose of this study was to report procedures developed to annotate abdominal computed tomography (CT) images from subjects without pancreatic disease that will be used as the input for deep convolutional neural networks (DNN) for development of deep learning algorithms for automatic recognition of a normal pancreas. MATERIALS AND METHODS: Dual-phase contrast-enhanced volumetric CT acquired from 2005 to 2009 from potential kidney donors were retrospectively assessed. Four trained human annotators manually and sequentially annotated 22 structures in each datasets, then expert radiologists confirmed the annotation. For efficient annotation and data management, a commercial software package that supports three-dimensional segmentation was used. RESULTS: A total of 1150 dual-phase CT datasets from 575 subjects were annotated. There were 229 men and 346 women (mean age: 45±12years; range: 18-79years). The mean intra-observer intra-subject dual-phase CT volume difference of all annotated structures was 4.27mL (7.65%). The deep network prediction for multi-organ segmentation showed high fidelity with 89.4% and 1.29mm in terms of mean Dice similarity coefficients and mean surface distances, respectively. CONCLUSIONS: A reliable data collection/annotation process for abdominal structures was developed. This process can be used to generate large datasets appropriate for deep learning.

A population-based approach to analyzing pulses in time series of hormone data.

Studies of reproductive physiology involve rapid sampling protocols that result in time series of hormone concentrations. The signature pattern in these times series is pulses of hormone release. Various statistical models for quantifying the pulsatile release features exist. Currently these models are fitted separately to each individual and the resulting estimates averaged to arrive at post hoc population-level estimates. When the signal-to-noise ratio is small or the time of observation is short (e.g., 6 h), this two-stage estimation approach can fail. This work extends the single-subject modelling framework to a population framework similar to what exists for complex pharamacokinetics data. The goal is to leverage information across subjects to more clearly identify pulse locations and improve estimation of other model parameters. This modelling extension has proven difficult because the pulse number and locations are unknown. Here, we show that simultaneously modelling a group of subjects is computationally feasible in a Bayesian framework using a birth-death Markov chain Monte Carlo estimation algorithm. Via simulation, we show that this population-based approach reduces the false positive and negative pulse detection rates and results in less biased estimates of population-level parameters of frequency, pulse size, and hormone elimination. We then apply the approach to a reproductive study in healthy women where approximately one-third of the 21 subjects in the study did not have appropriate fits using the single-subject fitting approach. Using the population model produced more precise, biologically plausible estimates of all model parameters. Copyright © 2017 John Wiley & Sons, Ltd.

Greater seasonal cycling of 25-hydroxyvitamin D is associated with increased parathyroid hormone and bone resorption.

SUMMARY: This analysis assessed whether seasonal change in 25-hydroxyvitamin D concentration was associated with bone resorption, as evidenced by serum parathyroid hormone and C-terminal telopeptide concentrations. The main finding was that increased seasonal fluctuation in 25-hydroxyvitamin D was associated with increased levels of parathyroid hormone and C-terminal telopeptide. INTRODUCTION: It is established that adequate 25-hydroxyvitamin D (25(OH)D, vitamin D) concentration is required for healthy bone mineralisation. It is unknown whether seasonal fluctuations in 25(OH)D also impact on bone health. If large seasonal fluctuations in 25(OH)D were associated with increased bone resorption, this would suggest a detriment to bone health. Therefore, this analysis assessed whether there is an association between seasonal variation in 25(OH)D and bone resorption. METHODS: The participants were (n = 279) Caucasian and (n = 88) South Asian women (mean (±SD); age 48.2 years (14.4)) who participated in the longitudinal Diet, Food Intake, Nutrition and Exposure to the Sun in Southern England study (2006-2007). The main outcomes were serum 25(OH)D, serum parathyroid hormone (sPTH) and serum C-terminal telopeptide of collagen (sCTX), sampled once per season for each participant. RESULTS: Non-linear mixed modelling showed the (amplitude/mesor) ratio for seasonal change in log 25(OH)D to be predictive of log sPTH (estimate = 0.057, 95 % CI (0.051, 0.063), p < 0.0001). Therefore, individuals with a higher seasonal change in log 25(OH)D, adjusted for overall log 25(OH)D concentration, showed increased levels of log sPTH. There was a corresponding significant ability to predict the range of seasonal change in log 25(OH)D through the level of sCTX. Here, the corresponding parameter statistics were estimate = 0.528, 95 % CI (0.418, 0.638) and p ≤ 0.0001. CONCLUSIONS: These findings suggest a possible detriment to bone health via increased levels of sPTH and sCTX in individuals with a larger seasonal change in 25(OH)D concentration. Further larger cohort studies are required to further investigate these preliminary findings.

Pre-prostatic tissue removed in robotic assisted lymph node dissection for prostate cancer contains lymph nodes.

OBJECTIVE: The on-going discussion about extent and best template for pelvic lymph dissection (PLND) motivated us to analyse pre-prostatic tissue (PPT) for lymph nodes and metastases. MATERIALS AND METHODS: From December 2010 to August 2011 PPT was sent for histopathological evaluation during 80 robotic assisted radical prostatectomies (RARP) and one extended staging lymph node dissection. All patients had either a limited (lPLND, n = 44) or an extended lymph node dissection (ePLND, n = 36). Clinical data were retrospectively analyzed and compared to histopathological findings. RESULTS: Lymph nodes were found in PPT in 10/80 (12.5%) patients after RARP and in the one patient after staging ePLND. Mean number of lymph nodes detected in PPT of them was 1.2 (range 1-3). Clinically no differences were found between patients with or without lymph nodes in PPT. In the standard template of either ePLND or lPLND the average number of lymph nodes was 13 (range 2-56). Herein metastases were found in 10 (12.5%) patients after RARP and in the patient after staging ePLND. A metastasis in PPT was only found after staging ePLND. CONCLUSIONS: Pre-prostatic tissue might contain lymph nodes that potentially harbour metastases. In the intention to perform the most accurate staging this tissue should be considered for histopathological evaluation.

A comparison of methods for analyzing time series of pulsatile hormone data.

Many endocrine systems are regulated by pulsatile hormones - hormones that are secreted intermittently in boluses rather than continuously over time. To study pulsatile secretion, blood is drawn every few minutes for an extended period. The result is a time series of hormone concentrations for each individual. The goal is to estimate pulsatile hormone secretion features such as frequency, location, duration, and amount of pulsatile and non-pulsatile secretion and compare these features between groups. Various statistical approaches to analyzing these data have been proposed, but validation has generally focused on one hormone. Thus, we lack a broad understanding of each method's performance. By using simulated data with features seen in reproductive and stress hormones, we investigated the performance of three recently developed statistical approaches for analyzing pulsatile hormone data and compared them to a frequently used deconvolution approach. We found that methods incorporating a changing baseline modeled both constant and changing baseline shapes well; however, the added model flexibility resulted in a slight increase in bias in other model parameters. When pulses were well defined and baseline constant, Bayesian approaches performed similar to the existing deconvolution method. The increase in computation time of Bayesian approaches offered improved estimation and more accurate quantification of estimation variation in situations where pulse locations were not clearly identifiable. Within the class of deconvolution models for fitting pulsatile hormone data, the Bayesian approach with a changing baseline offered adequate results over the widest range of data.

Comparison of standardized pre- and postoperative functional pelvic cine-MRI in patients with a bulbourethral composite suspension due to post-prostatectomy incontinence.

OBJECTIVES: To compare functional pelvic cine-MRI in patients with post-prostatectomy incontinence before and after implantation of a bulbourethral composite suspension. PATIENTS AND METHODS: Functional pelvic 1.5 T cine-MRI was performed at rest, under standardized Valsalva pressure and during micturition in six patients with post-prostatectomy incontinence before and 3 months after a bulbourethral composite suspension. Visibility and positioning of the implant as well as membranous urethral length (MUL) and positioning of the bladder neck (BN) in comparison with the pubococcygeal line (PCL) were evaluated. Clinical outcome was measured by patient-reported pad use and standardized questionnaires (ICIQ-UI SF and I-QOL). Paired data were tested with a Wilcoxon signed-ranks test. RESULTS: Surgery was successfully performed in all patients. All patients returned to complete voiding. The ICIQ-UI SF score decreased significantly from median 16.5 to 5 (p = 0.016). I-QOL increased significantly from 70.5 to 93.5 (p = 0.047). Pad use improved from median 2 pads to 0 pads postoperatively (p = 0.031). Four of six patients were completely pad-free, and 2 were failures with persisting urinary incontinence. MRI revealed significant differences of the MUL at rest with median of 8 mm pre- and 13 mm postoperatively (p = 0.016). BN showed a significant elevation with respect to PCL under Valsalva with in median 0.5 to 5 mm postoperatively (p = 0.016). No significant MRI differences were found between patients showing clinical success or failure. CONCLUSIONS: The bulbourethral composite suspension was associated with an increase in urethral length, urethral coaptation zone and bladder neck elevation, implying a non-compressive mode of action.

[Technique of the urethral anastomosis in orthotopic neo-bladder following robot-assisted radical cystectomy (RARC)]. / Technik der urethralen Anastomose bei orthotopem Blasenersatz nach roboterassistierter radikaler Zystektomie (RARC).

The urethral anastomosis in extracorporeally constructed orthotopic neo-bladder following robot-assisted radical cystectomy (RARC) remains a challenge. In principle either pre-posi-tioned single sutures or robotic continuous suture techniques can be applied. In the literature the different techniques are most often not described in detail. In the present work one example for each technique is given and the advantages and disadvantages of both methods are discussed.

Vitamin D deficiency in UK South Asian Women of childbearing age: a comparative longitudinal investigation with UK Caucasian women.

SUMMARY: This is the first 1-year longitudinal study which assesses vitamin D deficiency in young UK-dwelling South Asian women. The findings are that vitamin D deficiency is extremely common in this group of women and that it persists all year around, representing a significant public health concern. INTRODUCTION: There is a lack of longitudinal data assessing seasonal variation in vitamin D status in young South Asian women living in northern latitudes. Studies of postmenopausal South Asian women suggest a lack of seasonal change in 25-hydroxy vitamin D [25(OH)D], although it is unclear whether this is prevalent among premenopausal South Asians. We aimed to evaluate, longitudinally, seasonal changes in 25(OH)D and prevalence of vitamin D deficiency in young UK-dwelling South Asian women as compared with Caucasians. We also aimed to establish the relative contributions of dietary vitamin D and sun exposure in explaining serum 25(OH)D. METHODS: This is a 1-year prospective cohort study assessing South Asian (n = 35) and Caucasian (n = 105) premenopausal women living in Surrey, UK (51° N), aged 20-55 years. The main outcome measured was serum 25(OH)D concentration. Secondary outcomes were serum parathyroid hormone, self-reported dietary vitamin D intake and UVB exposure by personal dosimetry. RESULTS: Serum 25(OH)D <25 nmol/L was highly prevalent in South Asians in the winter (81 %) and autumn (79.2 %). Deficient status (below 50 nmol/L) was common in Caucasian women. Multi-level modelling suggested that, in comparison to sun exposure (1.59, 95 %CI = 0.83-2.35), dietary intake of vitamin D had no impact on 25(OH)D levels (-0.08, 95 %CI = -1.39 to 1.23). CONCLUSIONS: Year-round vitamin D deficiency was extremely common in South Asian women. These findings pose great health threats regarding the adverse effects of vitamin D deficiency in pregnancy and warrant urgent vitamin D public health policy and action.

[The urethral anastomosis in orthotopic neobladder following robot-assisted radical cystectomy (RARC) at German-speaking centres]. / Urethrale Anastomose bei orthotopem Blasenersatz nach roboterassistierter radikaler Zystektomie (RARC) an deutschsprachigen Robotikzentren.

INTRODUCTION: Following robot-assisted radical cystectomy (RARC) and extracorporeal reconstruction, robotic continuous suture techniques and those using open or robotically pre-positioned single sutures are used for the urethroneovesical anastomosis. METHODS: 62 German-speaking robotic centres were asked in an online questionnaire whether they carried out RARC. Following an affirmative answer further questions were put to the form of the neobladder and the technique of the urethrovesical anastomosis. RESULTS: 80% of the online questionnaires were answered. 44% (n=22) of these centres perform the RARC. According to the answers, given all of the centres but one perform an extracorporeal construction of the neobladder [Studer bladder 73% (n=16), Hautmann bladder 18% (n=4), others 9% (n=2)]. After reconstruction 36% (n=8) of the teams perform a completely open surgical anastomosis with pre-positioned sutures, 24% (n=5) close the anastomosis in a single knot technique using robotically pre-positioned sutures and 40% (n=9) use continuous sutures during the intracorporeal reconstruction or after re-docking the robot. CONCLUSION: According to this questionnaire to German-speaking centres the most common anastomotic technique following extracorporeal reconstruction, mostly a Studer bladder, is that of the pre-positioned single knot sutures. This offers the advantage that a re-docking of the robotic cart is unnecessary. In contrast, however, to robotically performed suturing, there must be enough space in the open procedure to surgically tie-off the sutures of the anastomosis.

Complications of a buried penis in an extremely obese patient.

The buried penis syndrome in adults is a rare condition of different aetiologies. Today extreme obesity is considered as a major contributor. We present a case of a 30-year-old extremely obese patient (BMI 65 kg/m(2)) with purulent infection of the penile cavity, a phlegmon of the mons pubis and urinary retention due to a buried penis. Whereas acute complications of a buried penis in obese patients include local infection and urinary retention, chronic problems are undirected voiding, disturbed vaginal penetration and erectile dysfunction. Even though several surgical techniques are described, weight reduction should be primarily preferred.

Trastuzumab and lapatinib modulation of HER2 tyrosine/threonine phosphorylation and cell signaling.

Cell surface transmembrane signaling receptors EGFR, HER3, and HER4 are activated by ligand-binding-mediated dimerization and phosphorylation. In contrast, HER2 amplification promotes signaling by increasing homo/heterodimerization and ligand binding. Trastuzumab or lapatinib therapy of HER2 amplicon-positive breast cancer cells induces growth inhibition and intracellular growth pathway signaling modulation. The mechanism(s) by which trastuzumab, an IgG1 humanized antibody, induces modification of cell signaling upon binding to an extracellular determinant on a ligand-less "receptor" membrane protein remains unexplained. Using immune detection methodology comprised of antibodies detecting three distinct domains of HER and five tyrosine/threonine phosphorylation sites, the effects of trastuzumab and lapatinib were defined during steady state growth inhibition. Here, we show that lapatinib markedly reduces HER2 tyrosine phosphorylation, while in contrast, no change in tyrosine phosphate levels is detected during trastuzumab-mediated cell growth inhibition. As trastuzumab treatment does not change either the steady state HER2 protein levels or HER2 mRNA, these findings argue against an antibody-dependent alteration in internalization kinetics. We further show a sequenced relationship between lapatinib-induced blockage of phosphorylation (6-8 h) and induction of delayed cell death (5-6 days), while trastuzumab-treated cells showed no evidence of cell death up to 9 days. Taken together, these results demonstrate that inhibition of HER2 phosphorylation by lapatinib is sufficient to induce apoptosis while trastuzumab binding to the extracellular HER2 domain may function by sterically modulating the detection of phosphate moieties by cytoplasmic signal transducers. This investigation also detected a 20 kD protein, which is down-regulated by lapatinib, further demonstrating the complexity of this signal transduction system.

Right and left heart failure in severe H1N1 influenza A infection.

Influenza infection can affect cardiac function. The recent pandemic of H1N1 influenza A provided an opportunity to study echocardiographic findings in critically ill infected patients. We hypothesised that critically ill patients with H1N1 infection would have a higher incidence of right and left heart failure than is seen in unselected populations of patients with septic shock and/or acute respiratory distress syndrome (ARDS). We retrospectively studied all patients admitted to four intensive care units at three hospitals in Salt Lake County, UT, USA, with laboratory-confirmed H1N1 infection in whom a clinical echocardiogram was available. 23 out of 48 patients had qualifying echocardiograms. Right ventricular (RV) dilatation (50-80%) and at least moderate systolic impairment (23%) were common, higher than the range described in general populations with ARDS. Left ventricular systolic dysfunction was present in 17% of patients. No single echocardiographic parameter was associated with 28-day mortality or ventilator-free days to 28 days. Critically ill patients with H1N1 infection frequently exhibit right heart dilatation and failure. RV basal dilatation was extremely common. These patients have less left heart failure than expected on the basis of prior descriptions of influenza myopericarditis or of general populations of septic patients.

The effects of aerobic exercise on metabolic risk, insulin sensitivity and intrahepatic lipid in healthy older people from the Hertfordshire Cohort Study: a randomised controlled trial.

AIMS/HYPOTHESIS: We sought to determine the effect of an aerobic exercise intervention on clustered metabolic risk and related outcomes in healthy older adults in a single-centre, explanatory randomised controlled trial. METHODS: Participants from the Hertfordshire Cohort Study (born 1931-1939) were randomly assigned to 36 supervised 1 h sessions on a cycle ergometer over 12 weeks or to a non-intervention control group. Randomisation and group allocation were conducted by the study co-ordinator, using a software programme. Those with prevalent diabetes, unstable ischaemic heart disease or poor mobility were excluded. All data were collected at our clinical research facility in Cambridge. Components of the metabolic syndrome were used to derive a standardised composite metabolic risk score (zMS) as the primary outcome. Trial status: closed to follow-up. RESULTS: We randomised 100 participants (50 to the intervention, 50 to the control group). Mean age was 71.4 (range 67.4-76.3) years. Overall, 96% of participants attended for follow-up measures. There were no serious adverse events. Using an intention-to-treat analysis, we saw a non-significant reduction in zMS in the exercise group compared with controls (0.07 [95% CI -0.03, 0.17], p = 0.19). However, the exercise group had significantly decreased weight, waist circumference and intrahepatic lipid, with increased aerobic fitness and a 68% reduction in prevalence of abnormal glucose metabolism (OR 0.32 [95% CI 0.11-0.92], p = 0.035) compared with controls. Results were similar in per-protocol analyses. CONCLUSIONS/INTERPRETATION: Enrolment in a supervised aerobic exercise intervention led to weight loss, increased fitness and improvements in some but not all metabolic outcomes. In appropriately screened older individuals, such interventions appear to be safe. TRIAL REGISTRATION: Controlled-trials.com ISRCTN60986572 FUNDING: Medical Research Council.

Neonatal 6-hydroxydopamine lesions of the frontal cortex in rats: persisting effects on locomotor activity, learning and nicotine self-administration.

Dopaminergic innervation of the frontal cortex in adults is important for a variety of cognitive functions and behavioral control. However, the role of frontal cortical dopaminergic innervation for neurobehavioral development has received little attention. In the current study, rats were given dopaminergic lesions in the frontal cortex with local micro-infusions of 6-hydroxydopamine (6-OHDA) at 1 week of age. The long-term behavioral effects of neonatal frontal cortical 6-OHDA lesions were assessed in a series of tests of locomotor activity, spatial learning and memory, and i.v. nicotine self-administration. In addition, neurochemical indices were assessed with tissue homogenization and HPLC in the frontal cortex, striatum, and nucleus accumbens of neonatal and adult rats after neonatal 6-OHDA lesions. In neonatal rats, frontal 6-OHDA lesions as intended caused a significant reduction in frontal cortical dopamine without effects on frontal cortical 5-HT and norepinephrine. The frontal cortical dopamine depletion increased 5-HT and norepinephrine levels in the nucleus accumbens. Locomotor activity assessment during adulthood in the figure-8 maze showed that lesioned male rats were hyperactive relative to sham-lesioned males. Locomotor activity of female rats was not significantly affected by the neonatal frontal 6-OHDA lesion. Learning and memory in the radial-arm maze was also affected by neonatal frontal 6-OHDA lesions. There was a general trend toward impaired performance in early maze acquisition and a paradoxical improvement at the end of cognitive testing. Nicotine self-administration showed significant lesion x sex interactions. The sex difference in nicotine self-administration with females self-administering significantly more nicotine than males was reversed by neonatal 6-OHDA frontal cortical lesions. Neurochemical studies in adult rats showed that frontal cortical dopamine and DOPAC levels significantly correlated with nicotine self-administration in the 6-OHDA-lesioned animals but not in the controls. Frontal cortical 5-HT and 5HIAA showed inverse correlations with nicotine self-administration in the 6-OHDA-lesioned animals but not in the controls. These results show that interfering with normal dopamine innervation of the frontal cortex during early postnatal development has persisting behavioral effects, which are sex-specific.

Pediatric jejunoileitis: a severe Crohn's disease phenotype that requires intensive nutritional management.

BACKGROUND: Jejunoileitis (JI) is an unusual manifestation of Crohn's disease (CD) that has been associated with high morbidity and the frequent need for surgical intervention. Although the disease has been well-described in adults, the true prevalence and clinical phenotype in children is unknown. AIM: To compare the clinical course and nutritional impact of CD in children with and without proximal small bowel involvement. METHODS: Patients with either Crohn's jejunitis or JI with or without colonic involvement were identified through a clinical database (1996--2002). All radiologic studies were reviewed by an experienced radiologist blinded to the clinical diagnosis. Thirty-six patients with CD without histologic or radiologic signs of proximal small bowel involvement were used for comparison. All medical, surgical, and hematologic parameters were compared in both disease groups. RESULTS: Among the 134 patients with CD, 23 (17%) had radiologic signs of JI, including intestinal fold thickening (57%), luminal narrowing (31%), and skip lesions (13%). Enteric fistula (6%) and strictures (6%) were less common. Patients with JI were likely to be stunted at the time of diagnosis, require surgical intervention (P < 0.03) and nutritional therapy in the form of nasogastric tube feeds (P < 0.03). Nutritional therapy was also associated with an improvement in height in patients with proximal small bowel disease (OR:5.87). DISCUSSION: JI is a relatively common disease phenotype in children with CD that requires aggressive nutritional and surgical intervention. Future studies are required to determine if the early detection and use of immune modulators may lessen the morbidity associated with proximal small bowel disease.

Glove powder's carrying capacity for latex protein: analysis using the ASTM ELISA test.

Glove donning powders carry latex proteins and disperse them into the workplace environment. We have used the ASTM D6499 ELISA to quantify the amount of latex antigen bound to and carried by glove powders. We could differentiate between a small amount of protein actually bound to the powders and a larger amount carried by the powder. Enhanced binding of a major allergen, Hev b 5, to the starch powders was demonstrated by Western blot. The D6499 ELISA is able to measure total latex antigen, soluble and powder bound, simultaneously without the need to centrifuge the samples.

Macrophage inhibitory cytokine-1 in gestational tissues and maternal serum in normal and pre-eclamptic pregnancy.

Macrophage inhibitory cytokine-1 (MIC-1), a divergent member of transforming growth factor-beta superfamily, has been recently shown to be produced by the human placenta with detectable levels in maternal serum. In this study, using immunohistochemistry, we have localized MIC-1 in placenta, decidua and foetal membranes across pregnancy and, using an enzyme-linked immunoassay, measured MIC-1 in maternal serum in normal pregnancy, in association with labour and pre-eclampsia. In the placenta MIC-1 was principally localized to the syncytiotrophoblast while in the foetal membranes MIC-1 was present in the amniotic epithelium, chorionic trophoblasts and adherent decidual cells. There were no differences in MIC-1 staining distribution or intensity in the placentae between women in labour and not in labour, or between healthy and pre-eclamptic pregnancies. MIC-1 staining in the foetal membranes was slightly stronger after a labour and delivery compared to those delivered by elective Caesarean section. MIC-1 levels in the maternal serum increased with advancing gestation but there were no significant differences in maternal serum levels associated with either labour or pre-eclampsia.These observations would be consistent with MIC-1 having roles at the maternal-foetal interface, perhaps in the establishment and/or maintenance of pregnancy. Our data argue against MIC-1 having a significant role in the regulation of labour or in the pathophysiology of pre-eclampsia.