Episodes of particle ejection from the surface of the active asteroid (101955) Bennu.

Active asteroids are those that show evidence of ongoing mass loss. We report repeated instances of particle ejection from the surface of (101955) Bennu, demonstrating that it is an active asteroid. The ejection events were imaged by the OSIRIS-REx (Origins, Spectral Interpretation, Resource Identification, and Security-Regolith Explorer) spacecraft. For the three largest observed events, we estimated the ejected particle velocities and sizes, event times, source regions, and energies. We also determined the trajectories and photometric properties of several gravitationally bound particles that orbited temporarily in the Bennu environment. We consider multiple hypotheses for the mechanisms that lead to particle ejection for the largest events, including rotational disruption, electrostatic lofting, ice sublimation, phyllosilicate dehydration, meteoroid impacts, thermal stress fracturing, and secondary impacts.

The Pluto system: Initial results from its exploration by New Horizons.

The Pluto system was recently explored by NASA's New Horizons spacecraft, making closest approach on 14 July 2015. Pluto's surface displays diverse landforms, terrain ages, albedos, colors, and composition gradients. Evidence is found for a water-ice crust, geologically young surface units, surface ice convection, wind streaks, volatile transport, and glacial flow. Pluto's atmosphere is highly extended, with trace hydrocarbons, a global haze layer, and a surface pressure near 10 microbars. Pluto's diverse surface geology and long-term activity raise fundamental questions about how small planets remain active many billions of years after formation. Pluto's large moon Charon displays tectonics and evidence for a heterogeneous crustal composition; its north pole displays puzzling dark terrain. Small satellites Hydra and Nix have higher albedos than expected.

Mechanism of gain modulation at single neuron and network levels.

Gain modulation, in which the sensitivity of a neural response to one input is modified by a second input, is studied at single-neuron and network levels. At the single neuron level, gain modulation can arise if the two inputs are subject to a direct multiplicative interaction. Alternatively, these inputs can be summed in a linear manner by the neuron and gain modulation can arise, instead, from a nonlinear input-output relationship. We derive a mathematical constraint that can distinguish these two mechanisms even though they can look very similar, provided sufficient data of the appropriate type are available. Previously, it has been shown in coordinate transformation studies that artificial neurons with sigmoid transfer functions can acquire a nonlinear additive form of gain modulation through learning-driven adjustment of synaptic weights. We use the constraint derived for single-neuron studies to compare responses in this network with those of another network model based on a biologically inspired transfer function that can support approximately multiplicative interactions.

Possible induction of systemic lupus erythematosus by human parvovirus.

A 59 year old woman presented with an influenza-like illness preceding signs and symptoms strongly suggestive of systemic lupus erythematosus (SLE), which progressed over several months. Owing to these influenza-like symptoms, a viral cause of her illness was sought. Human parvovirus B19 serology was positive and antibodies to DNA were detected by two different methods. This patient is believed to be the first report of human parvovirus B19 infection coinciding with the onset of SLE. The evidence for B19 virus and the part it plays in autoimmunity and arthritis is discussed.

Patterns of mortality in sickle cell disease in the United Kingdom.

Eighteen of 384 patients entered on the Brent sickle cell disease register died between 1974 and 1989, a mortality of one per 128 years of follow up. Two children died from acute splenic sequestration and a third died from fulminant pneumococcal septicaemia: none was taking prophylactic penicillin. Acute chest syndrome was the cause of death in eight young adults and one child. Three deaths occurred after surgery. Cerebrovascular accidents contributed to the cause of death in three cases and there were two sudden unexplained deaths. Ten of the deaths occurred at home or within 24 hours of admission to hospital. Post mortem examinations were made in 14 cases, but the histological appearances of acute chest syndrome were often not recognised. In most cases for whom information was available, the cause of death (chest syndrome, pneumococcal sepsis, postoperative complications) could have been prevented.

Creatine kinase activity in sickle cell disease.

Creatine kinase activity was measured in 28 patients in the steady state of sickle cell disease and ranged from 4-45 IU/l, comparable with that found in healthy adult caucasians. Creatine kinase activity was also measured in 14 patients admitted consecutively for the treatment of vaso-occlusive sickle cell crises. Creatine kinase activity remained within the normal range in eight of these 14 patients throughout their admission; none had muscle pain or a chest syndrome. In the remaining six, three with muscle pain and three with a chest syndrome, increased activity was found on one or more days. A further 17 patients with vaso-occlusive sickle cell crises, associated with muscle pain, were studied. Creatine kinase activity was significantly raised in all 17, the mean creatine kinase activity for men was 578.8 IU/l and 210.6 IU/l for women, with the highest values (up to 1790 IU/l) found in those who had exercised before admission. Measurement of creatine kinase activity may therefore be a useful marker of muscle perturbation due to sickling.

The presentation, management and prophylaxis of sickle cell disease.

Sickle cell disease (SCD) is encountered in all parts of the world where plasmodium falciparum has been endemic and has spread by migration to the temperate countries of the world resulting in a heavy caseload in Northern Europe and the United States. These patients in the temperate climates manifest most of the clinical problems associated with SCD in Tropical Africa and the West Indies. There are, however, differences between the groups in both the frequency and presentations of the clinical syndromes. The clinical management of SCD is discussed with particular reference to the potentially fatal sequestration syndromes: splenic, hepatic, 'the girdle syndrome' and 'the chest syndrome'. In all clinical situations encountered in SCD blood transfusions should be by isovolaemic exchange unless there is a marked fall in haematocrit (less than 5 g/dl) as may occur with sequestration and aplasia. The criteria for exchange transfusion in the chest syndrome are a pAO2 of less than 60 mm Hg while breathing air or a rapidly deteriorating clinical picture. Analgesia for vaso-occlusive sickle pain should be adequate and freely available which often requires the parental administration of opiates. We have delineated a small sub-group (6%) of SCD patients, 'the non-copers', who manifest a high demand for analgesia. The prospects for cure, and the techniques and issues for antenatal diagnosis are reviewed demonstrating the importance of education and counselling. The significant reduction in mortality and morbidity of children with SCD taking penicillin prophylaxis is emphasised with the need for its early institution.

Counselling for prenatal diagnosis of sickle cell disease and beta thalassaemia major: a four year experience.

A non-directive programme of prenatal counselling was used during a four year period. Forty-three couples at risk for having a baby with a haemoglobinopathy were identified. Prenatal diagnosis was offered in 19 pregnancies to 14 couples at risk of having a baby with sickle cell anaemia and in two pregnancies in two couples at risk of a baby with beta thalassaemia major, who presented before the 18th week of pregnancy. Six couples at risk for sickle cell anaemia accepted prenatal diagnosis in 10 pregnancies, as did both couples at risk for thalassaemia. Couples who were eligible for prenatal diagnosis but refused it tended not to have been informed about sickle cell disease before counselling, one partner was more frequently absent at the time of the initial counselling session, or they either had no children with sickle cell disease or the children were not severely affected. Other factors influencing their decision included a poor obstetric history and rejection of abortion, mainly on moral grounds. The approximately 50% uptake of prenatal diagnosis in this initial study highlights the complex issues involved. Our experience indicates that with systematic screening and counselling in the antenatal clinic, and with increased awareness of the haemoglobinopathies, couples at risk will be in a better position to make informed decisions.

Alpha-interferon therapy for essential thrombocythaemia.

18 patients with symptomatic essential thrombocythaemia were treated with recombinant alpha interferon (2a or 2b). Subcutaneous dosage regimens, which were well-tolerated, selectively lowered the platelet count and relieved symptoms in all patients, whether previously treated or untreated. Recombinant alpha-interferon may offer a non-leukaemogenic alternative therapy for these patients.

Membrane phenotype and response to deoxycoformycin in mature T cell malignancies.

The adenosine deaminase inhibitor deoxycoformycin was used in low doses to treat 19 patients with clinically aggressive T cell malignancy with a mature membrane phenotype. The patients comprised eight with prolymphocytic leukaemia, two with chronic lymphocytic leukaemia, four with adult T cell leukaemia-lymphoma, three with Sézary syndrome, and two with T cell lymphoma. Two thirds of the patients had been resistant or minimally responsive to combination chemotherapy. Complete remission was obtained in five patients (two with prolymphocytic leukaemia and one each with chronic lymphocytic leukaemia, adult T cell leukaemia-lymphoma, and Sézary syndrome) and partial remission in two others. Unmaintained complete remission lasting more than one year was seen in three patients. Responses were obtained only in patients with CD4+,CD8-membrane markers (seven out of 10), and no responses were recorded in any of the nine patients with a different phenotype. In this series remission appeared to correlate with the membrane phenotype of the neoplastic cell and not with the cytopathological diagnosis. Future studies should establish the biochemical basis for the greater sensitivity of CD4+ lymphoid cells to deoxycoformycin.

Incidence of overt and covert neurological damage in children with sickle cell disease.

We studied 25 patients with sickle cell disease (15 with HbSS; 8 with HbSC and 2 with HbS beta degree) using neurological examination as a marker of overt and computed tomographic (CT) scan as a marker of covert neurological damage. Of the 25 patients, 5 (20%) had evidence of cerebral infarcts on CT scan, but only 4 of these 5 patients had neurological signs. Neurological problems were only seen in patients with HbSS. We could not identify any haematological risk factors, but in this small group of HbSS patients a crisis rate greater than 1 per year of follow up was associated with a significant risk of neurological damage.

Acute admissions of patients with sickle cell disease who live in Britain.

All acute admissions of patients with sickle cell disease who lived in the London borough of Brent and attended this hospital were analysed for a period of one year. Sixty three of the 211 patients who were followed up by the haematology department required 161 acute admissions during the year. Most admissions (126) were for the 42 patients with homozygous sickle cell disease; 147 (91%) were for vaso-occlusive episodes, 142 of which were for painful crises, three for cerebrovascular accidents, and two for renal papillary necrosis. Preschool children with sickle cell disease were admitted predominantly with limb pain, whereas in schoolchildren and adults the incidence of trunk pain was higher. Twenty four of the 93 episodes of trunk pain culminated in an episode of severe visceral sequestration usually affecting the lungs, the liver, or the mesenteric circulation. Two patients died: an 18 month old baby with an acute splenic sequestration crisis and a 19 year old man with a severe girdle syndrome (sickling in the mesenteric circulation, liver, and lungs). Infective episodes were rare (11 episodes) but severe: one haemophilus meningitis, two salmonella infections, and three aplastic crises due to parvovirus infections. The average duration of the hospital stay was 7.4 days per admission. It is concluded that because sickle cell disease causes appreciable morbidity in older children, adolescents, and adults a systematic approach to management is needed to deal with acute episodes such as sequestration syndromes.

Haemostatic function and ischaemic heart disease: principal results of the Northwick Park Heart Study.

The Northwick Park Heart Study (NPHS) has investigated the thrombotic component of ischaemic heart disease (IHD) by the inclusion of measures of haemostatic function. Among 1511 white men aged between 40 and 64 at the time of recruitment, 109 subsequently experienced first major events of IHD. High levels of factor VII coagulant activity and of plasma fibrinogen were associated with increased risk, especially for events occurring within 5 years of recruitment. These associations seemed to be stronger than for cholesterol, elevations of one standard deviation in factor VII activity, fibrinogen, and cholesterol being associated with increases in the risk of an episode of IHD within 5 years of 62%, 84%, and 43% respectively. Multiple regression analyses indicated independent associations between each of the clotting factor measures and IHD but not between the blood cholesterol level and IHD incidence. The risk of IHD in those with high fibrinogen levels was greater in younger than in older men. Much of the association between smoking and IHD may be mediated through the plasma fibrinogen level. The biochemical disturbance leading to IHD may lie at least as much in the coagulation system as in the metabolism of cholesterol.

Measurement of regional cerebral blood flow, blood volume and oxygen metabolism in patients with sickle cell disease using positron emission tomography.

Regional cerebral blood flow, blood volume, fractional oxygen extraction and oxygen consumption were measured by positron emission tomography in six patients with sickle cell disease to see how oxygen delivery to the brain is maintained in the presence of both anemia and a low oxygen affinity hemoglobin. Both regional cerebral blood flow and blood volume were found to be markedly increased compared to values obtained from 14 normal subjects in the same age range. The mean fractional oxygen extraction was not significantly different in the two groups. Mean oxygen consumption in the two groups was also not significantly different but low values in individual patients with sickle cell disease and the presence of atrophy on the CT-scans of three of them were suggestive of some neuronal loss in patients without any history of nervous system involvement. In view of the known high values of cerebral blood flow and metabolism in childhood, it is suggested that when compounded by anemia and abnormal red cells, a hypercirculatory state may make patients in this age-group particularly prone to ischemic infarction.

Red cell alloimmunization in sickle cell disease.

Alloimmunization to red cell antigens contributes to morbidity in transfused patients. It has been recommended that blood for sickle cell patients need not be matched for antigens other than ABO and Rh(D), as there is no greater incidence of antibody production than in other multitransfused patient populations. Post transfusion alloimmunization was studied in a group of 34 sickle cell disease patients attending a U.K. haemoglobinopathy clinic. Red cell antibodies were formed in 17.6% of the transfused patients and Rhesus and Kell antibodies accounted for 66% of this total. In order to reduce alloimmunization, a policy of performing extended red cell phenotyping on the patients, and providing blood matched for Kell, and in certain circumstances the Rhesus antigens other than Rh(D), is recommended.