Highly contrasting effects of different climate forcing agents on terrestrial ecosystem services.

Many atmospheric constituents besides carbon dioxide (CO(2)) contribute to global warming, and it is common to compare their influence on climate in terms of radiative forcing, which measures their impact on the planetary energy budget. A number of recent studies have shown that many radiatively active constituents also have important impacts on the physiological functioning of ecosystems, and thus the 'ecosystem services' that humankind relies upon. CO(2) increases have most probably increased river runoff and had generally positive impacts on plant growth where nutrients are non-limiting, whereas increases in near-surface ozone (O(3)) are very detrimental to plant productivity. Atmospheric aerosols increase the fraction of surface diffuse light, which is beneficial for plant growth. To illustrate these differences, we present the impact on net primary productivity and runoff of higher CO(2), higher near-surface O(3), and lower sulphate aerosols, and for equivalent changes in radiative forcing. We compare this with the impact of climate change alone, arising, for example, from a physiologically inactive gas such as methane (CH(4)). For equivalent levels of change in radiative forcing, we show that the combined climate and physiological impacts of these individual agents vary markedly and in some cases actually differ in sign. This study highlights the need to develop more informative metrics of the impact of changing atmospheric constituents that go beyond simple radiative forcing.

Indirect radiative forcing of climate change through ozone effects on the land-carbon sink.

The evolution of the Earth's climate over the twenty-first century depends on the rate at which anthropogenic carbon dioxide emissions are removed from the atmosphere by the ocean and land carbon cycles. Coupled climate-carbon cycle models suggest that global warming will act to limit the land-carbon sink, but these first generation models neglected the impacts of changing atmospheric chemistry. Emissions associated with fossil fuel and biomass burning have acted to approximately double the global mean tropospheric ozone concentration, and further increases are expected over the twenty-first century. Tropospheric ozone is known to damage plants, reducing plant primary productivity and crop yields, yet increasing atmospheric carbon dioxide concentrations are thought to stimulate plant primary productivity. Increased carbon dioxide and ozone levels can both lead to stomatal closure, which reduces the uptake of either gas, and in turn limits the damaging effect of ozone and the carbon dioxide fertilization of photosynthesis. Here we estimate the impact of projected changes in ozone levels on the land-carbon sink, using a global land carbon cycle model modified to include the effect of ozone deposition on photosynthesis and to account for interactions between ozone and carbon dioxide through stomatal closure. For a range of sensitivity parameters based on manipulative field experiments, we find a significant suppression of the global land-carbon sink as increases in ozone concentrations affect plant productivity. In consequence, more carbon dioxide accumulates in the atmosphere. We suggest that the resulting indirect radiative forcing by ozone effects on plants could contribute more to global warming than the direct radiative forcing due to tropospheric ozone increases.

Detection of a direct carbon dioxide effect in continental river runoff records.

Continental runoff has increased through the twentieth century despite more intensive human water consumption. Possible reasons for the increase include: climate change and variability, deforestation, solar dimming, and direct atmospheric carbon dioxide (CO2) effects on plant transpiration. All of these mechanisms have the potential to affect precipitation and/or evaporation and thereby modify runoff. Here we use a mechanistic land-surface model and optimal fingerprinting statistical techniques to attribute observational runoff changes into contributions due to these factors. The model successfully captures the climate-driven inter-annual runoff variability, but twentieth-century climate alone is insufficient to explain the runoff trends. Instead we find that the trends are consistent with a suppression of plant transpiration due to CO2-induced stomatal closure. This result will affect projections of freshwater availability, and also represents the detection of a direct CO2 effect on the functioning of the terrestrial biosphere.

Diaphragmatic pathology: a cause of clinically unexplained death in the perinatal/paediatric age group.

Sudden unexpected death in infancy and childhood requires a 'full' post-mortem investigation. Guidance from the Royal College of Pathologists recommends sampling of all the major organs. However, the diaphragm does not feature in this or in most lists of routine histology. Our aim is to emphasize the importance of sampling the diaphragm for histological examination during autopsy. We describe three autopsy cases of clinically unexplained death in the perinatal and paediatric age group that showed significant pathology of the diaphragm. In Case 1, a previously healthy five-year-old girl collapsed suddenly and died four days later. In Case 2, an eight-month-old infant had repeated episodes of respiratory arrest that culminated in death. Autopsy demonstrated a predominantly diaphragmatic myositis. In Case 3 a female neonate had a respiratory arrest three days after birth and died less than a month later. Autopsy showed multiple large calcified necrotic fibres in the diaphragm. The diaphragm is seldom sampled at autopsy. In the first two cases a predominantly diaphragmatic myositis was either the direct or underlying cause of death. In the third case long-standing diaphragmatic pathology of uncertain cause may have contributed to the original respiratory arrest. Had the diaphragm not been examined histologically, the cause of death would have remained unascertained in these cases. In cases of sudden death in infancy and childhood, failure to reach a diagnosis may lead to undue suspicion falling upon the child's carers. This underscores the need for full histology at post-mortem in child deaths, including diaphragmatic sampling.

Best practice no 178. Examination of the human placenta.

The human placenta is an underexamined organ. The clinical indications for placental examination have no gold standards. There is also inconsistency in the histological reports and the quality is variable. There is great interobserver variability concerning the different entities. Although there are still grey areas in clinicopathological associations, a few mainstream observations have now been clarified. The histopathological examination and diagnosis of the placenta may provide crucial information. It is possible to highlight treatable maternal conditions and identify placental or fetal conditions that can be recurrent or inherited. To achieve optimal benefit from placental reports, it is essential to standardise the method of placenta examination. This article summarises the clinical indications for placenta referral and the most common acknowledged clinicopathological correlations.

Occlusion of arterio-arterial anastomosis manifesting as acute twin-twin transfusion syndrome.

In vivo, ex vivo and modelling studies suggest that arterio-arterial anastomoses (AAAs) protect against haemodynamic imbalance in monochorionic twins and thus the development of TTTS. We report the acute onset of severe TTTS at 34 weeks' gestation in a patient with an antenatally visualized AAA which was shown at injection studies to have been obliterated, presumably by thrombosis. Computer modelling with the relevant clinical data confirmed that occlusion of the AAA alone was sufficient to reproduce the clinical manifestations. A study of the vascular configuration of AAA in the fixed placenta suggested that its small diameter and turbulent flow may have contributed to its occlusion. This case report shows that the unmasking of unbalanced AVA configurations by occlusion of a protective AAA can manifest as TTTS.

Spontaneous intestinal perforation and Candida peritonitis presenting as extensive necrotizing enterocolitis.

UNLABELLED: Spontaneous intestinal perforation (SIP) has been increasingly reported in very-low-birthweight (VLBW) infants, although it is still less common than necrotizing enterocolitis (NEC). In around one-third of cases, SIP is associated with systemic candidiasis. We describe a case of SIP and Candida peritonitis in a VLBW infant, which was mistakenly diagnosed as NEC during the infant's short life. At laparotomy, the bowel surface was black and thought to be necrotic. As the infant was thought to have whole-bowel necrosis due to NEC, her condition was deemed incompatible with survival. At postmortem, however, the bowel wall was found to be healthy apart from a very localized patch of necrosis associated with a single perforation. The bowel was covered by a thick, black, serosal exudate consisting of fungal elements from Candida albicans. CONCLUSION: This case reinforces the fact that a markedly discoloured bowel is not necessarily necrotic and that the discoloration can potentially recover.

Ontogeny of human fetal testicular apoptosis during first, second, and third trimesters of pregnancy.

During spermatogenesis in human adults, testicular germ cells proliferate, differentiate, and die by apoptosis. However, little is known about the temporal or spatial nature of this programmed cell death. Such information may be useful for understanding prenatal developmental biology as well as spermatogenesis during adulthood, particularly in the context of germ cell disorders. We undertook this study to determine 1) whether apoptosis occurred in a cell-specific fashion in the germ cell population and the supporting somatic cells; and 2) whether apoptosis varied with gestational age. We examined human fetal testicular tissues obtained from 17 karyotypically and structurally normal fetuses of mothers who underwent spontaneous or induced abortions. Three gestational ages were defined as follows: group A, 12-13 wk gestation (n = 5); group B, 20-22 wk gestation (n = 7); and group C, 37-40 wk gestation (n = 5). Morphology in conjunction with in situ end labeling was used to identify and quantify apoptotic nuclei in fetal gonadal tissues. The results of this study suggest that gonadal apoptosis occurred in germ cells, Sertoli cells, and Leydig cells at all gestational ages. Apoptotic death was highest in the Leydig cells, followed by germ cells and Sertoli cells. There was a significant positive correlation between the apoptosis of germ cells and Sertoli cells (P < 0.01) and a negative correlation between healthy germ cells and Sertoli cells (P < 0.001). There was also a negative correlation between the intratubular cell number and the gestational age. Specifically, the proportion of Sertoli cells decreased with gestational age, although there was no significant change in the germ cell in relation to gestational age. No such relationship was found in the Leydig cell population, all of which reside outside the seminiferous tubules. These results are the first to suggest that fetal testicular apoptosis begins in the first trimester, occurs in the three major cell types, and continues throughout pregnancy. Our data also suggest that in the fetal gonad, germ and Sertoli cell proliferation and death may be controlled by a genetic program distinct from that of the Leydig cells. This information is relevant to the understanding of abnormal spermatogenesis associated with infertility and to germ cell tumors in adult life.

Ultrasound-guided umbilical cord occlusion using bipolar diathermy for Stage III/IV twin-twin transfusion syndrome.

OBJECTIVES: To evaluate bipolar diathermy as a technique for selective fetocide in the treatment of advanced (Stage III/IV) twin-twin transfusion syndrome (TTTS). METHODS: A prospective observational study in two tertiary referral fetal medicine centres: Queen Charlotte's Hospital, London, UK and Haemek Hospital, Afula, Israel. Fifteen cases of TTTS (14 twins and one triplet pregnancy) were treated by selective occlusion of either the donor (n=8) or recipient's (n=7) umbilical cord using ultrasound-guided bipolar diathermy. Following each procedure, patients were scanned serially for fetal growth, liquor volume and umbilical Doppler measurements. Procedural complications and obstetric outcome were recorded. Postnatal placental injection studies were performed. RESULTS: Overall co-twin survival in Stage III/IV TTTS was 13/14 (93%). There were no treatment failures. The incidence of preterm prelabour rupture of membranes (PPROM) within 3 weeks of the procedure was 3/15 (20%). In those cases where pre-procedure umbilical artery Dopplers were abnormal, the Doppler findings normalised post-procedure in all non-cord-occluded fetuses. Growth velocities of surviving donors were similar to those of surviving recipients. CONCLUSIONS: Bipolar diathermy appears an effective technique for the selective reduction of monochorionic twins complicated by severe as well as preterminal TTTS, with recipient and donor fetuses being equally appropriate choices for fetocide. We suggest that for advanced-stage disease where the parents can contemplate this option, cord occlusion as a single preemptive procedure maximises the opportunity for intact survival of a single survivor.

Reducing medication errors.

This article describes initiatives one institution developed to improve systems for detecting and preventing adverse medication events. Our discussion focuses on issues regarding the frequency and incidence of medication errors, the trials of traditional versus anonymous incident reporting, and the efforts to improve systems rather than placing blame and punishment on individuals. Initiatives such as improved documentation of pediatric patient weights and hepatic and renal function, increase of direct physician order entry into our Medical Information System (MIS), elimination of nonemergent verbal orders, and new and improved MIS ordering matrices (incorporating medical protocols and pathways) have led to more rational and efficient practices. Improved error prevention and critical incident review have identified on-going opportunities for improvement. Although the direct impact on patient outcomes is not yet measurable, numerous positive results have allowed for improved clinical decision making, streamlining of processes, increased regulatory compliance, and a positive culture change.

Intrauterine rescue transfusion in monochorionic multiple pregnancies with recent single intrauterine death.

To assess the role of fetal blood sampling and intrauterine transfusion in monochorionic (MC) multiple pregnancy complicated by single intrauterine death (IUD), we reviewed ten cases over a 4-year period in a tertiary referral centre which underwent fetal blood sampling within 24 h of death of its MC co-twin. Intrauterine rescue transfusion was performed in all seven anaemic fetuses (hematocrit; Hct < 30%) to raise the fetal Hct to > or = 40%. The rationale was to prevent death and/or brain injury. Two fetuses, which were severely acidaemic at blood sampling, died in utero within 24 h of the procedure. In two cases, the surviving twins manifested abnormal sonographic findings of the fetal brain 2-5 weeks later and underwent late termination. In two cases, the pregnancies continued uneventfully until delivery at 35 and 40 weeks' gestation with good neonatal outcome. In one case the co-twin delivered 1 week later at 29 weeks but died within 12 h. Fetuses without anaemia were not transfused and had normal clinical outcomes. We suggest that intrauterine rescue transfusion before the development of severe acidaemia in anaemic surviving MC co-twins may prevent fetal death, but does not necessarily prevent brain injury. Until its role becomes clearer, we recommend that its use be restricted to situations in which the parents and the local jurisdiction allow late termination as an option if brain injury subsequently manifests on ultrasound.

Acceleration of global warming due to carbon-cycle feedbacks in a coupled climate model.

The continued increase in the atmospheric concentration of carbon dioxide due to anthropogenic emissions is predicted to lead to significant changes in climate. About half of the current emissions are being absorbed by the ocean and by land ecosystems, but this absorption is sensitive to climate as well as to atmospheric carbon dioxide concentrations, creating a feedback loop. General circulation models have generally excluded the feedback between climate and the biosphere, using static vegetation distributions and CO2 concentrations from simple carbon-cycle models that do not include climate change. Here we present results from a fully coupled, three-dimensional carbon-climate model, indicating that carbon-cycle feedbacks could significantly accelerate climate change over the twenty-first century. We find that under a 'business as usual' scenario, the terrestrial biosphere acts as an overall carbon sink until about 2050, but turns into a source thereafter. By 2100, the ocean uptake rate of 5 Gt C yr(-1) is balanced by the terrestrial carbon source, and atmospheric CO2 concentrations are 250 p.p.m.v. higher in our fully coupled simulation than in uncoupled carbon models, resulting in a global-mean warming of 5.5 K, as compared to 4 K without the carbon-cycle feedback.

Doppler detection of arterio-arterial anastomoses in monochorionic twins: feasibility and clinical application.

The accuracy of in-vivo detection of arterio-arterial anastomoses (AAA) in monochorionic (MC) twins and its predictive value for twin-twin transfusion syndrome (TTTS) was assessed in 105 consecutive MC twins scanned at fortnightly intervals. AAA were sought using spectral and colour energy Doppler and ultrasound findings were compared with placental injection studies. AAA were identified in vivo in 59 (56%) pregnancies and at injection study in 68 (65%). The overall sensitivity and specificity was 85 and 97.3% respectively for the detection of AAA. Detection rates were higher at later gestations, with anterior placentae and with larger diameter AAA. The median insonation time to detect an AAA was 10 min (range 1-30). Where an AAA was identified, 15% of pregnancies (nine of 59) developed TTTS compared to 61% (28 of 46) when no AAA was seen (odds ratio 8.6). We conclude that AAA can be detected in vivo with high sensitivity and specificity without undue prolongation of scanning times and have a role in risk stratification in the antenatal assessment of MC twins.

Asymptomatic maternal myasthenia as a cause of the Pena-Shokeir phenotype.

We report six sibs with arthrogryposis multiplex congenita and a Pena-Shokeir phenotype, born to a healthy woman who was discovered to have asymptomatic myasthenia gravis (MG). This is the first report of anti-acetylcholine receptor (AChR) antibodies causing fetal akinesia/hypokinesia sequence in the offspring of an asymptomatic mother.

MURCS association with encephalocele: report of a second case.

We report a female fetus with occipital encephalocele, dysraphism of the cervical spine, right renal agenesis and Mullerian agenesis. Additional findings included posterior cleft palate, absent left umbilical artery and Meckel's diverticulum. This fetus had the features of MURCS association with occipital encephalocele. This is the second report of encephalocele with MURCS association.

Immunohistochemical detection of myocardial necrosis in stillbirth and neonatal death.

The aims of this study were to determine whether immunohistochemical staining for C9 can demonstrate myocardial necrosis in the fetus and neonate. Hearts from cases of stillbirth or neonatal death with confirmed myocardial necrosis (in neonates) or with ischemic lesions outside the heart (in neonates and stillborns) were stained immunohistochemically with antibodies to C9. All five cases with confirmed myocardial infarction showed positive immunohistochemical staining for C9, largely localized to the infarcted areas. The youngest subject was born at 24 weeks gestation and died at 4 days of age. One of two neonates without myocardial necrosis on H&E staining but with pathological evidence of ischemic lesions elsewhere showed staining of scattered fibers. Six out of ten hearts from macerated stillborn infants showed varying degrees of positive staining. Immunohistochemical staining for C9 detects myocardial necrosis in neonates of a gestational age of 24 weeks or more. C9 is also demonstrable immunohistochemically in macerated stillborns, and this is likely to represent myocardial necrosis. The method is of great potential value in the investigation of cardiac ischemia in the fetal and perinatal period.

Identification of arterio-venous anastomoses in vivo in monochorionic twin pregnancies: preliminary report.

OBJECTIVE: To determine whether it is possible to identify in vivo placental arterio-venous anastomoses (AVAs) by color Doppler flow mapping. METHODS: Three monochorionic twin pregnancies (one with and two without twin-to-twin transfusion syndrome) underwent placental mapping by color Doppler ultrasound. Placental vessels along the chorionic plate were recorded together with the direction of blood flow and their location in relation to the cord insertions and to superficial arterio-arterial anastomoses. Suggestive AVAs were mapped topographically and results were compared with the findings of formal postnatal placental injection studies. RESULTS: An AVA was identified in each of the three cases. Injection studies showed multiple AVAs. Each antenatally identified AVA was confirmed at placental injection study. Their placental location correlated to other landmarks as predicted by ultrasound. CONCLUSIONS: This preliminary report demonstrates that AVAs can be identified using color Doppler ultrasound. This may facilitate planning for highly selective ablation of AVAs, and shorter procedure times. Formal studies are now indicated to determine the accuracy of this technique.

Early-onset fetal hydrops and muscle degeneration in siblings due to a novel variant of type IV glycogenosis.

We report on 3 consecutive sib fetuses, presenting at 13, 12, and 13 weeks of gestation, respectively, with fetal hydrops, limb contractures, and akinesia. Autopsy of the first fetus showed subcutaneous fluid collections and severe degeneration of skeletal muscle. Histologic studies demonstrated massive accumulation of diastase-resistant periodic acid-Schiff-positive material in the skeletal muscle cells and epidermal keratinocytes of all 3 fetuses. Enzyme studies of fibroblasts from the 3rd fetus showed deficient activity of glycogen brancher enzyme, indicating that this is a new, severe form of glycogenosis type IV with onset in the early second trimester.

High failure rate of umbilical vessel occlusion by ultrasound-guided injection of absolute alcohol or enbucrilate gel.

The success rate for injected umbilical vascular occlusion in the published literature exceeds 85 per cent. In this study we assessed the efficacy of two forms of injected sclerosants in achieving umbilical vessel occlusion. 12 cases of attempted ultrasound-guided occlusion over a 2 1/2 year period were reviewed. These were monochorionic (MC) twins (n=6), dichorionic twins (n=3) and singletons (n=3) undergoing fetocide for severe anomalies, or impending fetal demise. Absolute alcohol (n=6), enbucrilate gel (n=5) or both (n=1) were used in an attempt to achieve vascular occlusion. Complete vessel occlusion was achieved in only a third of cases (4/12), three with absolute alcohol and one with enbucrilate gel. In MC twins occlusion was successful in two of six cases. In contrast to previously published data, this large series, containing more cases than the total previously reported, shows considerably poorer success rates for injected umbilical vascular occlusion. Injection of currently available sclerosants can no longer be recommended for umbilical vascular occlusion in human fetuses.

Expression of amyloid precursor protein (beta-APP) in the neonatal brain following hypoxic ischaemic injury.

Perinatal hypoxic ischaemic brain injury (HII) is a major cause of neonatal mortality and long-term neurological morbidity. An understanding of the molecular events which follow HII may lead to novel treatments to improve the final outcome for affected infants. The beta-amyloid precursor protein (beta-APP) is a widely expressed transmembrane protein whose proposed functions include stabilization of neuronal calcium fluxes, inhibition of the clotting cascade and cell-cell or cell-matrix adhesion. Normally present at low levels in neurons its expression is induced as part of the acute response of the adult brain to HII. This study aimed to determine whether beta-APP is also part of the acute adaptive response of the infant brain to HII. Immunohistochemistry and Western blotting were used to assess cerebral beta-APP expression in 14-day-old rat pups subjected to unilateral HII, and in 10 term human infants, who died between 12 h and 16 months after severe perinatal HII. In the rat pups beta-APP expression was increased by 2 h post-injury, peaked, fourfold above control levels, at 24 h and gradually declined over the following 4 days. Expression was induced bilaterally, but was greater on the side of injury. In the human infants, increased, predominantly neuronal expression of beta-APP, was detectable immunohistochemically within 24 h of injury and was greatest in those infants dying within 3 days. Expression was particularly strong in the areas showing histological evidence of injury, but was also seen in apparently undamaged areas. We conclude that beta-APP induction is part of the the acute adaptive response of the neonatal brain to HII.