Cosmic dust impacts on the Hubble Space Telescope.

Exposure of the Hubble Space Telescope to space in low Earth orbit resulted in numerous hypervelocity impacts by cosmic dust (micrometeoroids) and anthropogenic particles (orbital debris) on the solar arrays and the radiator shield of the Wide Field and Planetary Camera 2, both subsequently returned to Earth. Solar cells preserve residues from smaller cosmic dust (and orbital debris) but give less reliable information from larger particles. Here, we present images and analyses from electron, ion and X-ray fluorescence microscopes for larger impact features (millimetre- to centimetre-scale) on the radiator shield. Validated by laboratory experiments, these allow interpretation of composition, probable origin and likely dimensions of the larger impactors. The majority (~90%) of impacts by grains greater than 50 µm in size were made by micrometeoroids, dominated by magnesium- and iron-rich silicates and iron sulfides, metallic iron-nickel and chromium-rich spinel similar to that in ordinary chondrite meteorites of asteroid origin. Our re-evaluation of the largest impact features shows substantially fewer large orbital debris impacts than reported by earlier authors. Mismatch to the NASA ORDEM and ESA MASTER models of particle populations in orbit may be partly due to model overestimation of orbital debris flux and underestimation of larger micrometeoroid numbers. This article is part of the theme issue 'Dust in the Solar System and beyond'.

One-year outcomes after successful chronic total occlusion percutaneous coronary intervention: The impact of dissection re-entry techniques.

We aimed to determine clinical outcomes 1 year after successful chronic total occlusion (CTO) PCI and, in particular, whether use of dissection and re-entry strategies affects clinical outcomes. Hybrid approaches have increased the procedural success of CTO percutaneous coronary intervention (PCI) but longer-term outcomes are unknown, particularly in relation to dissection and re-entry techniques. Data were collected for consecutive CTO PCIs performed by hybrid-trained operators from 7 United Kingdom (UK) centres between 2012 and 2014. The primary endpoint (death, myocardial infarction, unplanned target vessel revascularization) was measured at 12 months along with angina status. One-year follow up data were available for 96% of successful cases (n = 805). In total, 85% of patients had a CCS angina class of 2-4 prior to CTO PCI. Final successful procedural strategy was antegrade wire escalation 48%; antegrade dissection and re-entry (ADR) 21%; retrograde wire escalation 5%; retrograde dissection and re-entry (RDR) 26%. Overall, 47% of CTOs were recanalized using dissection and re-entry strategies. During a mean follow up of 11.5 ± 3.8 months, the primary endpoint occurred in 8.6% (n = 69) of patients (10.3% (n = 39/375) in DART group and 7.0% (n = 30/430) in wire-based cases). The majority of patients (88%) had no or minimal angina (CCS class 0 or 1). ADR and RDR were used more frequently in more complex cases with greater disease burden, however, the only independent predictor of the primary endpoint was lesion length. CTO PCI in complex lesions using the hybrid approach is safe, effective and has a low one-year adverse event rate. The method used to recanalize arteries was not associated with adverse outcomes. © 2017 Wiley Periodicals, Inc.

Cardiovascular collapse post chronic total occlusion percutaneous coronary intervention due to a compressive left atrial hematoma managed with percutaneous drainage.

This case illustrates a potential complication of the retrograde approach using epicardial collaterals for chronic total occlusion (CTO) percutaneous coronary intervention (PCI). Hypotension post CTO PCI in a patient who has undergone previous cardiac surgery can have multiple causes, one of which is chamber compression from a localized hematoma due to coronary perforation as occurred in this case. This report is the first description of successful nonsurgical management of a left atrial hematoma causing cardiovascular collapse with percutaneous drainage.

Crustal rheology of the Himalaya and Southern Tibet inferred from magnetotelluric data.

The Cenozoic collision between the Indian and Asian continents formed the Tibetan plateau, beginning about 70 million years ago. Since this time, at least 1,400 km of convergence has been accommodated by a combination of underthrusting of Indian and Asian lithosphere, crustal shortening, horizontal extrusion and lithospheric delamination. Rocks exposed in the Himalaya show evidence of crustal melting and are thought to have been exhumed by rapid erosion and climatically forced crustal flow. Magnetotelluric data can be used to image subsurface electrical resistivity, a parameter sensitive to the presence of interconnected fluids in the host rock matrix, even at low volume fractions. Here we present magnetotelluric data from the Tibetan-Himalayan orogen from 77 degrees E to 92 degrees E, which show that low resistivity, interpreted as a partially molten layer, is present along at least 1,000 km of the southern margin of the Tibetan plateau. The inferred low viscosity of this layer is consistent with the development of climatically forced crustal flow in Southern Tibet.

A unique CO-like micrometeorite hosting an exotic Al-Cu-Fe-bearing assemblage - close affinities with the Khatyrka meteorite.

We report the discovery of a unique micrometeorite, containing an exotic Al-Cu-Fe alloy composed of two intermixed phases: khatyrkite (CuAl2) and stolperite (CuAl) and both containing minor Fe (<1.4 wt%). These phases are dendritic and rapidly co-crystallized at the binary system's peritectic (~550 °C). The host micrometeorite is an otherwise typical S-type micro-porphyritic cosmic spherule containing relict olivine (Fo76-90, Cr2O3: 0.01-0.56 wt%, MnO: 0.03-0.32 wt% and CaO: 0.09-0.22 wt%) and a cumulate layered texture. These properties suggest the micrometeorite is derived from a carbonaceous chondrite (best matched to a CO chondrite) and entered the atmosphere a high speed (~16 kms-1), implying an origin from a highly eccentric orbit. This particle represents the second independent discovery of naturally occurring intermetallic Al-Cu-Fe alloys and is thus similar to the previously reported Khatyrka meteorite - a CV chondrite containing near-identical alloys and the only known natural quasicrystals. We did not observe quasicrystalline phases in this micrometeorite, likely due to the low amounts of Fe in the alloy, insufficient to stabilize quasicrystals. Our discovery confirms the existence of Al-Cu-Fe intermetallic alloys on chondritic parent bodies. These unusual phases require a currently unexplained formation process, we tentatively suggest this could represent the delivery of exotic interstellar material to the inner solar system via impact.

Urgent in-patient coronary angiography: a comparison of centres with and without cardiac catheter facilities.

OBJECTIVES: To review the referral of patients to a tertiary centre for urgent angiography and to determine if there are differences in invasive treatment strategies for patients with acute coronary syndrome (ACS). METHODS: There were 2 parts to the study, a retrospective part over 3.5 years from a computerised cardiac laboratory booking data base and a prospective part over 3 months. RESULTS: There were 1190 urgent in-patient angiograms performed with 499 (42%) admitted initially to the tertiary centre while the remaining 691 (58%) were admitted to district general hospitals (DGH), with no on-site access to a cardiac laboratory, and subsequently transferred to the tertiary centre. Once referred, DGH patients waited longer for their angiogram (2.7 +/- 3.2 vs 2.0 +/- 2.8 days, p < 0.0001). Interestingly, DGH patients appear to spend an average of 4 days in hospital prior to referral for angiography. DGH patients were more likely to have a higher Thrombosis in Myocardial Infarction (TIMI) risk score at presentation and following angiography were more likely to have coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI) and less likely to have angiographically normal arteries. CONCLUSIONS: Our findings are consistent with previous studies demonstrating that access to coronary angiography varies considerably between hospitals. However, we have demonstrated that patients in DGHs wait on average 4 days before referral for coronary angiography suggesting that there may be triage based on initial responses to medical therapy. Further research is needed to determine whether this has a direct effect on outcomes.

Cytokinetic definition of acute and chronic breast cancer.

The purpose of this paper is to report the extant observations at the Ellis Fischel State Cancer Hospital-Cancer Research Center and in the literature on the gross rates of growth of human mammary cancer as measured for primary cancers in the breast by mammography and for metastatic cancer in the skin and lymph nodes by direct measurements. From these measurements, the gross or net rates of growth for the cancers have been calculated and reported as actual doubling times. Cytokinetic variables contribute to the observed growth, and the data are used to estimate the potential acuteness or chronicity of breast cancer.

Geometry, growth rates, and duration of cancer and carcinoma in situ of the breast before detection by screening.

The purpose of this study is to report the time elapsing between the moment a breast cancer reaches threshold size that would permit detection and the size at actual detection defined as sojourn time (STt) using data from the Breast Cancer Detection and Demonstration Project (Louisville data and reported composite data from 27 centers) by dividing prevalence rates by incidence rates. The number of cellular generations (n) required to produce cancers of different volumes was calculated at threshold (nt), at detection (nd), and the difference between the two (nd - nt). By dividing the difference (nd - nt) into STt, the average actual or net tumor volume doubling time (DTact) in this interval have been estimated. The STt value for carcinoma in situ was 557 and for cancer it was 538. At ages 35-39, STt ranged from 365-456 days, by ages 70-74, 942-1383 days. The average DTact similarly varied with age, carcinoma in situ, cancer with negative axillary nodes, and cancer with positive axillary nodes over a range of 28-732 days (95% confidence). The estimated DTact in the predetectable period was manyfold less than the DTact measured for mammographically visible cancers, in keeping with the predictions of decelerating growth. Models of the cytokinetic and clinical behavior of breast cancer are discussed.

Clinical delivery system for intraperitoneal hyperthermic chemotherapy.

A 35-year-old man was treated for pseudomyxoma peritonei by surgery and by thermal infusion and chemotherapy with a machine designed specifically for the treatment of cancers of serosal surfaces. After extensive abdominal resection and closure, the patient's peritoneal cavity was instilled with 2.5 liters of 5% lactated Ringer's solution. He was then attached to hyperthermic perfusion system which elevated the i.p. temperature by warming (to 42 degrees) and recirculating the effusion solution. When the 42 degrees i.p. temperature was attained (after 1.5 hr), chemotherapy was added to the recirculating effusion. A second procedure followed 8 days later. The patient's postoperative course was uneventful except for minor pulmonary atelectasis with bacteremia. Hyperthermic perfusion was tolerated well and was evaluated as safe for intracavitary cancer treatment.

Hyperthermic peritoneal perfusion system in canines.

The thermal infusion filtration system was designed to manage malignant effusions and treat metastatic cancers of the intracavitary serosa. Hyperthermia, chemotherapy, and cell and debris filtration were administered by a dynamic fluid flow. Preclinical evaluations of surgical procedure, temperature studies, fluid dynamics, and physiology were carried out in 15 dogs (17.2 to 25.4 kg) with peritoneal perfusion at 41 degrees C and 10 liters/hr flow. Results suggest that the dynamics of flow achieves total intracavitary equilibrium in 7 min. The time essential to elevate animal body mass temperature from ambient to 41 degrees varied as a function of mass. The hyperthermia induced expected nonlethal responses in physiology. The system was determined to be safe for clinical procedure.

Hybrid approach improves success of chronic total occlusion angioplasty.

OBJECTIVES: Treatment options for coronary chronic total occlusions (CTO) are limited, with low historical success rates from percutaneous coronary intervention (PCI). We report procedural outcomes of CTO PCI from 7 centres with dedicated CTO operators trained in hybrid approaches comprising antegrade/retrograde wire escalation (AWE/RWE) and dissection re-entry (ADR/RDR) techniques. METHODS: Clinical and procedural data were collected from consecutive unselected patients with CTO between 2012 and 2014. Lesion complexity was graded by the Multicentre CTO Registry of Japan (J-CTO) score, with ≥2 defined as complex. Success was defined as thrombolysis in myocardial infarction 3 flow with <30% residual stenosis, subclassified as at first attempt or overall. Inhospital complications and 30-day major adverse cardiovascular events (MACEs, death/myocardial infarction/unplanned target vessel revascularisation) were recorded. RESULTS: 1156 patients were included. Despite high complexity (mean J-CTO score 2.5±1.3), success rates were 79% (first attempt) and 90% (overall) with 30-day MACE of 1.6%. AWE was highly effective in less complex lesions (J-CTO ≤1 94% success vs 79% in J-CTO score ≥2). ADR/RDR was used more commonly in complex lesions (J-CTO≤1 15% vs J-CTO ≥2 56%). Need for multiple approaches during each attempt increased with lesion complexity (17% J-CTO ≤1 vs 48% J-CTO ≥2). Lesion modification ('investment procedures') at the end of unsuccessful first attempts increased the chance of subsequent success (96% vs 71%). CONCLUSIONS: Hybrid-trained operators can achieve overall success rates of 90% in real world practice with acceptable MACE. Use of dissection re-entry and investment procedures maintains high success rates in complex lesions. The hybrid approach represents a significant advance in CTO treatment.

Transcription rates of SERCA and phospholamban genes change in response to chronic stimulation of skeletal muscle.

Chronic low frequency stimulation of predominantly fast-twitch skeletal muscles decrease the levels of SERCA1 (fast-twitch sarco(endo)plasmic reticulum Ca2+-ATPase) mRNA, and increase the levels of SERCA2 (slow-twitch sarco(endo)plasmic reticulum Ca2+-ATPase) and phospholamban mRNAs. To assess the role of transcription in these changes in mRNA levels, nuclei were isolated from chronically stimulated canine latissimus dorsi muscles and transcription rates were estimated by nuclear run-on assays. Decreases in the rates of SERCA1 gene transcription matched the fall in its mRNA level and increases in the rates of SERCA2 and phospholamban gene transcription matched the increases in their mRNAs.

Dissociation between early recovery of regional function and purine nucleotide content in postischaemic myocardium in the conscious dog.

Since abnormalities in regional myocardial function and nucleotide metabolism persist for a prolonged period after a brief coronary occlusion the temporal relation between the resolution of myocardial dysfunction and repletion of nucleotide pools in postischaemic myocardium was studied in conscious mildly sedated animals. In a second experiment 5-amino-4-imidazolecarboxamide riboside (AICAriboside) was infused in an attempt to influence myocardial function by altering the rate of adenine nucleotide synthesis. Conscious dogs mildly sedated with morphine underwent coronary occlusion for 15 min followed by reperfusion for 30 min or 12 h, at which time a myocardial sample was obtained for nucleotide analysis. Segment shortening averaged 62% of control values at 15 min of reperfusion and increased to 81% of control by 12 h of reperfusion (p less than 0.05). Adenine nucleotide content was 75(5)% of control after 30 min of reperfusion and did not change significantly over the next 12 h of reperfusion. Thus the early return of systolic function was not accompanied by a detectable increase in total adenine nucleotide content. In the second experiment a pronounced stimulation of the proximal purine nucleotide synthetic pathway occurred as evidenced by a 13-fold to 25-fold increase in inosine monophosphate content. One branch of the distal purine pathway was also stimulated as evidenced by complete repletion of guanine nucleotide pools, but the product of the other branch (adenine nucleotides) did not increase significantly. These results indicate a selective limitation of the distal adenine nucleotide synthetic pathway in postischaemic myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)

Impact of proctoring on success rates for percutaneous revascularisation of coronary chronic total occlusions.

OBJECTIVE: To assess the impact of proctoring for chronic total occlusion (CTO) percutaneous coronary intervention (PCI) in six UK centres. METHODS: We retrospectively analysed 587 CTO procedures from six UK centres and compared success rates of operators who had received proctorship with success rates of the same operators before proctorship (pre-proctored) and operators in the same institutions who had not been proctored (non-proctored). There were 232 patients in the pre-proctored/non-proctored group and 355 patients in the post-proctored group. Complexity was assessed by calculating the Japanese CTO (JCTO) score for each case. RESULTS: CTO PCI success was greater in the post-proctored compared with the pre-proctored/non-proctored group (77.5% vs 62.1%, p<0.0001). In more complex cases where JCTO≥2, the difference in success was greater (70.7% vs 49.5%, p=0.0003). After proctoring, there was an increase in CTO PCI activity in centres from 2.5% to 3.5%, p<0.0001 (as a proportion of total PCI), and the proportion of very difficult cases with JCTO score ≥3 increased from 15.3% (35/229) to 29.7% (105/354), p<0.0001. CONCLUSIONS: Proctoring resulted in an increase in procedural success for CTO PCI, an increase in complex CTO PCI and an increase in total CTO PCI activity. Proctoring may be a valuable way to improve access to CTO PCI and the likelihood of procedural success.

Systemic blockade of the endothelin-B receptor increases peripheral vascular resistance in healthy men.

Endothelin-1 (ET-1) is an important mediator of vascular tone in humans, and a number of endothelin receptor antagonists are currently in clinical development as vasodilator agents. While the vasoconstrictor role of the ETA receptor is undisputed, the role of the ETB receptor remains unclear. Hemodynamic effects of systemic doses of the ETB-selective antagonist BQ-788 were investigated in 5 healthy male volunteers (age range, 33 to 48 years) in a placebo-controlled, four-way crossover study. After a 15-minute infusion of BQ-788 (3, 30, or 300 nmol/min) or placebo, plasma ET-1 and big ET-1, blood pressure, heart rate, cardiac index, and stroke index were measured. Total peripheral vascular resistance was calculated from cardiac index and mean arterial pressure. Hemodynamic data are expressed as maximum, placebo-corrected, percentage change from baseline following BQ-788 (300 nmol/min) and were examined by ANOVA. Plasma ET-1 increased by 3.7+/-1.2 pg/mL (maximum at 15 minutes, P=0.02), whereas there was no significant change in plasma big ET-1. Although BQ-788 had no effect on mean arterial pressure, there was a reduction in heart rate (13+/-7% at 50 minutes; P=0.002), cardiac index (17+/-5% at 40 minutes; P<0. 0001), and stroke index (8+/-4% at 40 minutes; P=0.002) and an increase in total peripheral vascular resistance (24+/-5% at 40 minutes; P<0.0001). The selective ETB receptor antagonist BQ-788 causes peripheral vasoconstriction in healthy volunteers, suggesting that the overall balance of effects of endogenous ET-1 at the vascular ETB receptor favors vasodilatation. Further investigation is now clearly required to address whether selective ETA or combined ETA/ETB receptor blockade will be more effective in the clinical setting.

Reproducibility of pulse wave velocity and augmentation index measured by pulse wave analysis.

OBJECTIVE: The aim of this study was to determine the reproducibility of pulse wave velocity (PWV) and augmentation index (AIx) measured using pulse wave analysis (PWA), prior to its use in large-scale clinical trials. METHODS: Arterial pressure waveforms were recorded and analysed using an established technique (Sphygmocor). Subjects with and without a range of recognized cardiovascular risk factors were studied to provide a wide range of values. Measurements were made after a brief introduction to the technique in a clinical setting. Two observers recorded aortic and brachial PWV in 24 subjects, each on two occasions, in a random order. In a separate study, two different observers used PWA to determine AIx in 33 subjects, each on two occasions, in a random order. Data were analysed using Bland-Altman plots and presented as mean +/- SD. RESULTS: Brachial PWV was 8.65+/-1.58 m/s (range 6.16-10.95 m/s) and aortic PWV was 8.15+/-3.01 m/s (5.01-17.97 m/s). Within-observer variability was 0.14+/-0.82 m/s for brachial PWV and 0.07+/-1.17 m/s for aortic PWV. Corresponding between-observer values were -0.44+/-1.09 m/s and -0.30+/-1.25 m/s. AIx ranged from -15.0 to +45.0%, with a group mean of +19.6+/-12.0%. The within-observer difference was 0.49+/-5.37% and between-observer difference 0.23+/-3.80%. CONCLUSION: PWA is a simple and reproducible technique with which to measure PWV and AIx. Reproducibility accords with that reported by other workers using different methodologies. PWA may, therefore, be suitable for large-scale population and intervention studies investigating the clinical relevance of vascular stiffness.

Systemic ETA receptor antagonism with BQ-123 blocks ET-1 induced forearm vasoconstriction and decreases peripheral vascular resistance in healthy men.

1. The effect on systemic haemodynamics of BQ-123, a selective endothelin A (ETA) receptor antagonist, was investigated in healthy men by giving, on separate occasions, ascending intravenous doses of 100, 300, 1000 and 3000 nmol min(-1) BQ-123, each for 15 min, in a randomized, placebo-controlled, double-blind study. The response of forearm blood flow to brachial artery infusion of endothelin-1 (ET-1; 5 pmol min(-1) for 90 min) was also studied using bilateral forearm plethysmography, after systemic pre-treatment, on separate occasions, with one of two doses of BQ-123 (300 and 1000 nmol min(-1) for 15 min) or placebo. 2. Systemic BQ-123 dose-dependently decreased systemic vascular resistance (P<0.01 for all doses vs placebo) and mean arterial pressure (P<0.05 for 300 nmol min(-1) and P<0.01 for 1000 and 3000 nmol min(-1)) during the 60 min following infusion. There were concurrent increases in heart rate and cardiac index. BQ-123, when infused systemically for 15 min, appeared to reach a maximum effect at 1000 nmol min(-1). 3. Intra-brachial ET-1 infusion, after pre-treatment with placebo, caused a slow onset progressive forearm vasoconstriction without systemic effects. This vasoconstriction was attenuated by pre-treatment with BQ-123 at 300 nmol min(-1) and abolished by BQ-123 at 1000 nmol min(-1) (P<0.01 vs placebo). 4. These effects occurred at concentrations of BQ-123 in the plasma (510+/-64 nmol l(-1)) that were ETA receptor selective, and were not accompanied by an increase in plasma ET-1 that would have indicated ETB receptor blockade. 5. We conclude that ETA-mediated vascular tone contributes to the maintenance of basal systemic vascular resistance and blood pressure in healthy men.

The prognostic value of measuring the gross linear radial growth of pulmonary metastases and primary pulmonary cancers.

The gross rates of growth of pulmonary cancers and pulmonary metastases may be reduced to clinically useful nomograms and graphs. The constructs are feasible because most neoplasms growing in the lung are observed only during a limited segment of their life history, often being observed too few times to permit the identification of the growth curve of best fit. Consequently, the parameter that can be calculated most quickly, namely linear growth rate in mm./day, may be most useful. The linear radial growth rates are plotted against observed survival. The nomograms permit easy approximation of the volume doubling time and the exponential radial growth rate in mm./mm./day. The mean of the log normal frequency distributions of doubling times for common primary and metastatic cancers found growing in the lung is plotted on one nomogram to put the information in perspective. The more widespread reporting and tabulation of such data should lead to a highly useful kinetic staging and treatment evaluation system.