Sacrococcygeal germ-cell tumours - the Red Cross War Memorial Children's hospital experience, 1980 - 1996

Objective. To document the experience of Red Cross War Memorial Children's Hospital in the treatment of sacrococcygeal germ-eell tumours.Patients. Twenty-seven patients with sacrococcygeal germ-cell tumours were treated in our hospital from 1980 to 1996.Design. A retrospective review of these patients' records was undertaken.Results. There were 19 female and 8 male patients. Seventeen (63%) presented in the neonatal period, 13 on the first day of life. Complete surgical resection of the tumour was achieved in all patients with mature or immature teratomas (20 patients) and in 2 neonates with malignant tumours. The first of these 2 neonates, with a malignant teratoma, was not given chemotherapy and remains well 10 years later. The second, with a yolk-sac tumour, also received no initial chemotherapy. He relapsed at the age of 9 months and was successfully treated with repeat excision and chemotherapy. All 5 patients first diagnosed after the age of 1 year had malignant tumours. These patients had incomplete surgical resection (3) or biopsy only (2), and 3 were successfully treated with chemotherapy. One patient relapsed with yolksac tumour after initial complete resection cif a mature teratoma. She was successfully treated with repeat surgery and chemotherapy

To what extent can behaviour change techniques be identified within an adaptable implementation package for primary care? A prospective directed content analysis

Interpreting evaluations of complex interventions can be difficult without sufficient description of key intervention content. We aimed to develop an implementation package for primary care which could be delivered using typically available resources and could be adapted to target determinants of behaviour for each of four quality indicators: diabetes control, blood pressure control, anticoagulation for atrial fibrillation and risky prescribing. We describe the development and prospective verification of behaviour change techniques (BCTs) embedded within the adaptable implementation packages

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Physician attitude toward depression care interventions: Implications for implementation of quality improvement initiatives

<p>Abstract</p> <p>Background</p> <p>Few individuals with depression treated in the primary care setting receive care consistent with clinical treatment guidelines. Interventions based on the chronic care model (CCM) have been promoted to address barriers and improve the quality of care. A current understanding of barriers to depression care and an awareness of whether physicians believe interventions effectively address those barriers is needed to enhance the success of future implementation.</p> <p>Methods</p> <p>We conducted semi-structured interviews with 23 primary care physicians across the US regarding their experience treating patients with depression, barriers to care, and commonly promoted CCM-based interventions. Themes were identified from interview transcripts using a grounded theory approach.</p> <p>Results</p> <p>Six barriers emerged from the interviews: difficulty diagnosing depression, patient resistance, fragmented mental health system, insurance coverage, lack of expertise, and competing demands and other responsibilities as a primary care provider. A number of interventions were seen as helpful in addressing these barriers – including care managers, mental health integration, and education – while others received mixed reviews. Mental health consultation models received the least endorsement. Two systems-related barriers, the fragmented mental health system and insurance coverage limitations, appeared incompletely addressed by the interventions.</p> <p>Conclusion</p> <p>CCM-based interventions, which include care managers, mental health integration, and patient education, are most likely to be implemented successfully because they effectively address several important barriers to care and are endorsed by physicians. Practices considering the adoption of interventions that received less support should educate physicians about the benefit of the interventions and attend to physician concerns prior to implementation. A focus on interventions that address systems-related barriers is needed to overcome all barriers to care.</p

Platelet clearance via shear-induced unfolding of a membrane mechanoreceptor

Mechanisms by which blood cells sense shear stress are poorly characterized. In platelets, glycoprotein (GP)Ib-IX receptor complex has been long suggested to be a shear sensor and receptor. Recently, a relatively unstable and mechanosensitive domain in the GPIba subunit of GPIb-IX was identified. Here we show that binding of its ligand, von Willebrand factor, under physiological shear stress induces unfolding of this mechanosensory domain (MSD) on the platelet surface. The unfolded MSD, particularly the juxtamembrane € Trigger' sequence therein, leads to intracellular signalling and rapid platelet clearance. These results illustrate the initial molecular event underlying platelet shear sensing and provide a mechanism linking GPIb-IX to platelet clearance. Our results have implications on the mechanism of platelet activation, and on the pathophysiology of von Willebrand disease and related thrombocytopenic disorders. The mechanosensation via receptor unfolding may be applicable for many other cell adhesion receptors

Soil Respiration in Relation to Photosynthesis of Quercus mongolica Trees at Elevated CO2

Knowledge of soil respiration and photosynthesis under elevated CO2 is crucial for exactly understanding and predicting the carbon balance in forest ecosystems in a rapid CO2-enriched world. Quercus mongolica Fischer ex Ledebour seedlings were planted in open-top chambers exposed to elevated CO2 (EC = 500 µmol mol−1) and ambient CO2 (AC = 370 µmol mol−1) from 2005 to 2008. Daily, seasonal and inter-annual variations in soil respiration and photosynthetic assimilation were measured during 2007 and 2008 growing seasons. EC significantly stimulated the daytime soil respiration by 24.5% (322.4 at EC vs. 259.0 mg CO2 m−2 hr−1 at AC) in 2007 and 21.0% (281.2 at EC vs. 232.6 mg CO2 m−2 hr−1 at AC) in 2008, and increased the daytime CO2 assimilation by 28.8% (624.1 at EC vs. 484.6 mg CO2 m−2 hr−1 at AC) across the two growing seasons. The temporal variation in soil respiration was positively correlated with the aboveground photosynthesis, soil temperature, and soil water content at both EC and AC. EC did not affect the temperature sensitivity of soil respiration. The increased daytime soil respiration at EC resulted mainly from the increased aboveground photosynthesis. The present study indicates that increases in CO2 fixation of plants in a CO2-rich world will rapidly return to the atmosphere by increased soil respiration

Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS.

Ischaemia-reperfusion injury occurs when the blood supply to an organ is disrupted and then restored, and underlies many disorders, notably heart attack and stroke. While reperfusion of ischaemic tissue is essential for survival, it also initiates oxidative damage, cell death and aberrant immune responses through the generation of mitochondrial reactive oxygen species (ROS). Although mitochondrial ROS production in ischaemia reperfusion is established, it has generally been considered a nonspecific response to reperfusion. Here we develop a comparative in vivo metabolomic analysis, and unexpectedly identify widely conserved metabolic pathways responsible for mitochondrial ROS production during ischaemia reperfusion. We show that selective accumulation of the citric acid cycle intermediate succinate is a universal metabolic signature of ischaemia in a range of tissues and is responsible for mitochondrial ROS production during reperfusion. Ischaemic succinate accumulation arises from reversal of succinate dehydrogenase, which in turn is driven by fumarate overflow from purine nucleotide breakdown and partial reversal of the malate/aspartate shuttle. After reperfusion, the accumulated succinate is rapidly re-oxidized by succinate dehydrogenase, driving extensive ROS generation by reverse electron transport at mitochondrial complex I. Decreasing ischaemic succinate accumulation by pharmacological inhibition is sufficient to ameliorate in vivo ischaemia-reperfusion injury in murine models of heart attack and stroke. Thus, we have identified a conserved metabolic response of tissues to ischaemia and reperfusion that unifies many hitherto unconnected aspects of ischaemia-reperfusion injury. Furthermore, these findings reveal a new pathway for metabolic control of ROS production in vivo, while demonstrating that inhibition of ischaemic succinate accumulation and its oxidation after subsequent reperfusion is a potential therapeutic target to decrease ischaemia-reperfusion injury in a range of pathologies