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Background: Recent studies demonstrate high offer decline and organ non‐utilization rates are associated with increased pediatric heart transplant waitlist mortality. We sought to determine which donor, candidate, and offer specific variables most importantly influenced these decisions using only data available at the time of each offer. Methods: Retrospective review of pediatric (<18 years) heart donor offers made to pediatric candidates in the United States between 2010 and 2020. In addition to standard donor, candidate, and offer data available in UNOS, we extracted objective and qualitative valvar and myocardial function data from all available donor echocardiogram reports. Results: During the study period, 5625 pediatric donor hearts produced 30 156 offers to 4905 unique candidates, of which 88.7% of all offers were declined and 39.2% of organs were not utilized by pediatric waitlisted candidates. Of the 60.8% utilized hearts, 89.7% had a 'cumulatively' normal echocardiogram at the time of offer acceptance; 62.9% of hearts not utilized for a pediatric candidate also had a cumulatively normal final echocardiogram. Random forest and logistic regression modeling demonstrated good predictive performance (AUROC ≥0.83) of likelihood to accept when utilizing donor, candidate, and offer specific variables. SHAP variable importance scores demonstrated number of prior offer declines and candidate institution's prior year acceptance rates as the two most important variables influencing offer decisions. Conclusions: Behavioral economics appear to play a significant role in pediatric heart transplant candidate institutions' acceptance practices, even when considering the arguably healthier pediatric donor population. Removal of prior institution's decisions from DonorNet may help increase donor utilization. [ABSTRACT FROM AUTHOR]

The ability of massive corals to record the impacts of marine heat wave events provides a unique perspective into the variable responses of corals to anthropogenic climate change. In this study, coral cores (Porites spp.) were collected from seven reef sites across the inner‐, mid‐, and outer‐NW shelf of Australia, to examine seasonal patterns of trace element (TE), Sr/Ca and Li/Mg ratios, and extension rate signatures associated with past marine heat waves in the region. TE anomalies and declines in linear extension rate were observed in the records during the late 1990s (two of five records) and more recently during the summers of 2011 (three of seven records) and 2013 (five of seven records), indicating the impacts of marine heat waves have become increasingly widespread in the region. However, for the summers of 2011 and 2013, no significant relationships were observed between the magnitude of these TE ratio anomalies in the core records and maximum thermal stresses predicted at the reef sites from high‐resolution satellite records. We show that the strongest individual reductions in linear extension rates and associated TE ratio anomalies occurred during the 2011 heat wave, rather than during the subsequent and more intense (~1 °C warmer) 2013 event. Together, these observations suggest that at the local reef scale, Porites spp. colonies and their symbionts exhibit differential responses to heat wave events, with the prior exposure to less intense events probably playing an important role in acclimatization. Key Points: Trace element (Sr/Ca and Li/Mg) and linear extension records from Porites cores show distinct coupled signatures of past thermal stressReduced magnitude of trace element anomalies during more severe heat wave event provides new evidence of thermal acclimatisationSignificant inter‐colony relationships between the magnitude of trace element anomalies and linear extension rates [ABSTRACT FROM AUTHOR]

Transplantation is the accepted mode of treatment for patients with end-stage organ disease affecting the heart, lungs, kidney, pancreas, liver and intestine. Long-term outcomes have significantly improved and the aim of management is no longer only long-term survival, but also focuses on quality of life especially in children. Transplantation in Africa faces a number of challenges including wide socioeconomic disparity, lack of legislation around brain death and organ donation in many countries, shortage of skilled medical personnel and facilities, infectious disease burden and insecure access to and monitoring of immunosuppression. Whilst there is a need for transplantation, the establishment and sustainability of transplant programmes require careful planning with national government and institutional support. Legislation regarding brain death diagnosis and organ retrieval/donation; appropriate training of the transplant team; and transparent and equitable criteria for organ allocation are important to establish before embarking on a transplant programme. Establishing sustainable, self-sufficient transplant programmes in Africa with equal access to all citizens is an important step towards curtailing transplant tourism and organ trafficking and has a further beneficial effect in raising the level of medical and surgical care in these countries. [ABSTRACT FROM AUTHOR]

Spearman CWN, Goddard E, McCulloch MI, Hairwadzi HN, Sonderup MW, Kahn D, Millar AJW. Pregnancy following liver transplantation during childhood and adolescence. Pediatr Transplantation 2011: 15: 712-717. © 2011 John Wiley & Sons A/S. Abstract: More than 80% of pediatric transplant recipients will survive to reach adulthood, and many will consider having children. We report on outcomes and management of five pregnancies in four women undergoing orthotopic liver transplantation during childhood or adolescence and followed up at our Transplant Center. A retrospective clinical folder audit was performed. Mean age at transplantation was 13.3 ± 3.4 yr (range, 10-18 yr). Mean interval between transplantation and pregnancy was 15.4 ± 4.9 yr (range, 10-22 yr). Mean maternal age at conception was 28 ± 3.5 yr (range, 23-32 yr). Mean gestational age was 36.6 ± 1.7 wk. Mean birth weight was 2672 ± 249 g. Immunosuppression was cyclosporin based in three women and tacrolimus based in one woman. Pregnancy complications necessitating the induction of labor included fetal distress and rising maternal liver enzymes in two women, cholestasis of pregnancy and impaired renal graft function in one woman, fetal distress and preeclampsia in one woman. Modes of delivery were normal vaginal delivery in three women and cesarean section in one woman. No maternal or fetal deaths and no congenital malformations occurred. No episodes of rejection occurred during pregnancy. Two women experienced acute cellular rejection requiring an increase in baseline immunosuppression in the first year, following delivery. No graft losses occurred during a mean follow-up of 44 ± 17.9 months post-delivery. With careful management, pregnancy post-liver transplantation can have a successful outcome. [ABSTRACT FROM AUTHOR]

The need to improve environmental management in Australia is urgent because human health, well-being and social stability all depend ultimately on maintenance of life-supporting ecological processes. Ecological science can inform this effort, but when issues are socially and economically complex the inclination is to wait for science to provide answers before acting. Increasingly, managers and policy-makers will be called on to use the present state of scientific knowledge to supply reasonable inferences for action based on imperfect knowledge. Hence, one challenge is to use existing ecological knowledge more effectively; a second is to tackle the critical unanswered ecological questions. This paper identifies areas of environmental management that are profoundly hindered by an inability of science to answer basic questions, in contrast to those areas where knowledge is not the major barrier to policy development and management. Of the 22 big questions identified herein, more than half are directly related to climate change. Several of the questions concern our limited understanding of the dynamics of marine systems. There is enough information already available to develop effective policy and management to address several significant ecological issues. We urge ecologists to make better use of existing knowledge in dialogue with policy-makers and land managers. Because the challenges are enormous, ecologists will increasingly be engaging a wide range of other disciplines to help identify pathways towards a sustainable future. [ABSTRACT FROM AUTHOR]

Research in central nervous system (CNS) biology and pathology requires in vitro models, which, to recapitulate the CNS in vivo, must have extensive myelin and synapse formation under serum-free (defined) conditions. However, finding such a model has proven difficult. The technique described here produces dense cultures of myelinated axons, with abundant synapses and nodes of Ranvier, that are suitable for both morphological and biochemical analysis. Cellular and molecular events were easily visualised using conventional microscopy. Ultrastructurally, myelin sheaths were of the appropriate thickness relative to axonal diameter (G-ratio). Production of myelinated axons in these cultures was consistent and repeatable, as shown by statistical analysis of multiple experimental repeats. Myelinated axons were so abundant that from one litter of embryonic mice, myelin was produced in amounts sufficient for bulk biochemical analysis. This culture method was assessed for its ability to generate an in vitro model of the CNS that could be used for both neurobiological and neuropathological research. Myelin protein kinetics were investigated using a myelin fraction isolated from the cultures. This fraction was found to be superior, quantitatively and qualitatively, to the fraction recovered from standard cultures of dissociated oligodendrocytes, or from brain slices. The model was also used to investigate the roles of specific molecules in the pathogenesis of inflammatory CNS diseases. Using the defined conditions offered by this culture system, dose-specific, inhibitory effects of inflammatory cytokines on myelin formation were demonstrated, unequivocally. The method is technically quick, easy and reliable, and should have wide application to CNS research. [ABSTRACT FROM AUTHOR]

Renal tuberculosis is relatively uncommon in children. Imaging of renal tuberculosis in children differs from adults in that intravenous urography is rarely performed for urinary symptoms in childhood because of radiation dose considerations. Modern imaging modalities include cross-sectional techniques such as ultrasound, CT and MRI, which successfully show renal, calyceal, ureteric and bladder pathology of renal tuberculosis in children. [ABSTRACT FROM AUTHOR]

Millar AJW, Spearman W, McCulloch M, Goddard E, Raad J, Rode H, Kahn D, Cywes S. Liver transplantation for children – the Red Cross Children's Hospital experience. Pediatr Transplantation 2004: 8: 136–144. © 2004 Blackwell Munksgaard Liver transplantation for infants and children has been available in South Africa at a single centre, the only established service in Sub-Saharan Africa, for more than a decade. Current concerns have shifted from an initial target of early post-transplant survival to quality of life in the long-term. Materials and methods: Since 1985, 225 infants and children have been assessed, with 146 accepted for transplantation. Sixty-nine have had 71 orthotopic liver transplants (OLTx). Biliary atresia was the most frequent diagnosis (54%) followed by acute liver failure (ALF) (15%). Waiting list mortality has remained high (23%), particularly for the ALF group (50%). Forty-three were reduced size transplants with donor: recipient weight ratios ranging from 2:1 to 11:1. Twenty-seven were <10 kg. Results: Fifty (74%) survive 1 month–12 years post-transplant. Actuarial survival after 1996 since HBV core antibody positive donor livers were refused and prophylactic IV ganciclovir used has been >82%. Early post-OLTx mortality was low (5%), one primary non-function, one IVC thrombosis, one PV thrombosis, but late morbidity and mortality (20%) was mainly due to viral infection: de novo hepatitis B (five patients, three deaths), EBV-related post-transplantation lymphoproliferative disease (PTLPD) (eight patients, six deaths) and CMV disease (11 patients, five deaths). Tuberculosis prophylaxis, required in six cases, resulted in major morbidity in two and mortality in one. Poor compliance played a significant role in seven deaths. Hypertension requiring medication along with some compromise of renal function has been present in all but two patients. However, all those of school-going age (25) attend school normally and remain in good health and only three of the survivors have abnormal liver function tests. Conclusions: Successful liver transplantation is possible in a developing country with limited resources. Scarcity of virus-free donors (HBV and HIV) leading to waiting list mortality and infrequent re-transplantation along with long-term consequences of immunosuppression (infection, lymphoma and renal toxicity) remain problems. Intense education of the caregiver and close follow-up, particularly of those living at long distances has partly addressed the compliance problem. [ABSTRACT FROM AUTHOR]

Proteolipid protein (PLP) and its smaller DM20 isoform account for approximately 50% of protein in central nervous system myelin, suggesting an important role in myelination. PLP/DM20-deficient mice generated by gene targeting techniques assemble large amounts of myelin, although it displays a variety of defects at the intraperiod line (IPL) when prepared for conventional electron microscopy. The appearance of the PLP/DM20-deficient myelin prepared by freeze substitution showed a similar range of IPL defects to that prepared by conventional fixation and also included regions containing a normal IPL.

The neuropathology of 20 German shepherd dogs and five German shepherd dog crosses with chronic degenerative radiculomyelopathy were analysed by conventional techniques, immunocytochemistry and electron microscopy. There were previously unrecognised changes in brain nuclei. In the spinal cord, both motor and sensory tracts were involved, principally in their more distal regions. Wallerian degeneration affected the corticorubrospinal pathways in the lateral columns and the ventral funiculi, predominantly in the caudal thoracic and lumbar segments, although more cranial involvement was also observed. The dorsal columns were affected in the caudal lumbar region and the cervical fasciculus gracilis. The regional distribution was variable between cases. Within the brain, abnormalities, including chromatolysis, gliosis and neuronal loss were observed in the red nucleus, lateral vestibular nucleus and, occasionally, in the dentate nucleus. The changes in brain nuclei were compared with those found in dogs at various times after a focal spinal injury. The neuronal changes in the brain may be related to the primary site of damage, and possible aetiological mechanisms are discussed. [ABSTRACT FROM PUBLISHER]

Background Infants with heart failure remain at significant risk for wait list mortality, despite mechanical circulatory support (MCS). It is unclear if the outcomes are influenced by modality of support or underlying diagnosis. We sought to compare the outcomes of infants <10 kg, focusing on modality of support and underlying diagnosis. Methods and Results Using the Pediatric Heart Transplant Society database, we evaluated survival following first MCS device in children <10 kg who were listed for heart transplant between 2010 and 2018. There were 2049 children <10 kg, with the predominant diagnosis being congenital heart disease (CHD) (59.8% [n=1226]) and 28.1% (n=577) requiring MCS. Extracorporeal membrane oxygenation (ECMO) was the most common form of MCS at listing, with ventricular assist device (VAD) more common after listing. There was no difference in the use of ECMO at or after listing for cardiomyopathy versus CHD (8.9% versus 7.2%; P =0.2; 5.4% versus 6.4%; P =0.4). However, there was a significant difference in the use of VAD both at listing (8% versus 2.4%; P <0.001) and after (22.8% versus 5.1%; P <0.001) between the 2 groups. When comparing these groups, patients with CHD were smaller and younger and had a higher proportion with previous cardiac surgery. Survival at 3 months demonstrated better survival for VAD therapy compared with ECMO (74.3% versus 48.6%; P <0.001). In patients <5 kg, survival did not differ between ECMO and VAD ( P =0.01) for the CHD or the cardiomyopathy group ( P =0.38), but patients with cardiomyopathy demonstrated better survival on both forms of support. Conclusions Survival for patients <10 kg on ECMO is inferior compared with VAD. Patients with cardiomyopathy <5 kg had better survival with both modes of MCS compared with those with CHD. These findings support the need for small, durable devices for neonates and infants, with particular focus in patients with CHD.

We investigated proliferation of sensory cell precursors in the rat vomeronasal organ (VNO) at various postnatal ages from birth (P1) to P666. In the rat, which continues to grow during most of its adult life, proliferation might be related to growth and/or replacement. Proliferating cells were labelled by BrdU injection, and histological sections of the VNO were evaluated after immunohistochemical detection of BrdU. Proliferation density (number of proliferating cells/section) decreased dramatically from 115 at P1 to 27.2 at P21, although the area increased. Adult values were reached at P66-P333 (10.3 cells/section); at P400-P666 the value was 8.6 cells/section. Distribution of labelled cells changed considerably with age: in neonates the cells were nearly equally distributed throughout the sensory epithelium, whereas from P21 onwards most proliferating cells were concentrated in clusters near the boundaries with non-sensory epithelium. Labelled cells in the sensory neuronal layer were adjacent to the undulating basement membrane-bordering capillaries that intrude into the sensory epithelium, indicating that they were true basal cells. The volume of the sensory epithelium increased between P1 and P66, and remained constant thereafter, although the length still increased. Length and volume of the sensory epithelium were related to body size, not to sex; males and females of the same body size had the same VNO size. The complex changes in proliferation pattern during postnatal development indicate differential growth and replacement. We suggest that in adults the labelled cell clusters near the boundaries are a pool for growth, whereas proliferation in the central parts represents a replacement pool.

Assessment of pain on injection of the emulsified formulation of di-isopropylphenol (propofol, 'Diprivan') was undertaken in 120 unpremedicated patients and comparison made with thiopentone. A high incidence of pain (37.5%) was found using dorsal hand veins, but use of forearm veins showed only a 2.5% incidence of pain. The use of intravenous lignocaine immediately before propofol injection only partially reduced the incidence of pain using dorsal hand veins (17.5%). A degree of cardiorespiratory depression accompanied induction but the incidence of other side effects was low.

1. In rat isolated tail arteries and atria in which transmitter stores are labelled with (3H)-noradrenaline, isoprenaline in low concentrations facilitates the stimulation-induced efflux of tritium. 2. This effect is dependent on the frequency and duration of electrical stimulation, being observed only at low frequency (2 Hz) and short duration (10 s in atria and 30 s in arteries) or at high frequency (5 Hz) and long duration (1 min in atria and 4 min in arteries). 3. In atria, phenotlamine enchances tritium efflux with stimulation at 5 Hz for 1 min but not at 2 Hz for 10 s. Conversely, propranolol reduces tritium efflux with stimulation at 2 Hz for 10 s but not at 4 Hz for 1 min. 4. The results can be interpreted in terms of the selective operation, depending on the frequency and duration of electrical stimulation, of inhibitory and facilitatory feedback loops for transmitter release involving prejunctional alpha -and beta-adrenoceptors, respectively.

The effects of clonidine, oxymetazoline and thirteen substituted phenyliminoimidazolidine analogues of clonidine were studied and compared on postjunctional alpha-adrenoceptors in guinea-pig and rabbit aorta and on prejunctional alpha-adrenoceptors in guinea-pig atria. In the aorta all compounds were partial agonists at postjunctional alpha-adrenoceptors. Correlation of agonist potency with various combinations of their physicochemical parameters showed that, with the present series of compounds, physicochemical parameters alone determined 92% of the variance in the data with potency being primarily and highly correlated with pKa. Similarly in atria, all compounds, with the possible exceptions of St 95 and St 1943, appeared to be partial agonists at prejunctional alpha-adrenoceptors; transmitter noradrenaline release could either be inhibited (field stimulation at 1 Hz for 5 s) or enhanced (5 Hz for 30 s). The results indicate that 2,6-substitution in the phenyl ring appears to be a specific non-physicochemical activity-enhancing factor at prejunctional but not postjunctional alpha-adrenoceptors. A comparison with data in the literature giving the acute hypotensive potencies of the compounds suggests that central alpha-adrenoceptors may more closely resemble atrial prejunctional alpha-adrenoceptors than aortic postjunctional alpha-adrenoceptors. Quantitative correlations between centrally-mediated hypotensive and peripheral vasoconstrictor effects of clonidine-like imidazolidines do not provide a sufficiently sensitive method of distinguishing between alpha-adrenoceptor subtypes.

1. The effects of noradrenaline, adrenaline, isoprenaline, dopamine and the N-methyl and alpha-methyl homologoues of dopamine were studied on tritium release and on vasoconstrictor responses to sympathetic nerve stimulation in isolated arteries of the rabbit ear after labelling noradrenergic transmitter stores with 3H-noradrenaline. These observations were made in the presence of cocaine (100 muM). 2. Noradrenaline (0-5 and 5 muM) inhibited transmitter release and abolished vasoconstrictor responses. A concentration of 0-05 muM had no effect on transmitter release, although the vasoconstrictor response was reduced and there was sometimes a vasodilator response. 3. Adrenaline in concentrations of 0-05, 0-5 and 5 muM decreased transmitter release and vasoconstrictor responses; sometimes there was a vasodilator response. 4. Isoprenaline in concentrations of 0-05, 0-5 and 5 muM did not affect transmitter release. Vasoconstrictor responses were either unaffected or enhanced by all concentrations of isoprenaline when infusions had been in progress for 15 min; but immediately after beginning the infusion of 5 muM isoprenaline, the response was reduced. 5. Dopamine (0-05, 0-5 and 5 muM) produced a concentration-dependent decrease in transmitter release, but vasoconstrictor responses were not reduced with infusions of 0-05 or 0-5 muM; during infusions of 5 muM, stimulation produced a vasodilator response.