The corona contracts in a black-hole transient.

The geometry of the accretion flow around stellar-mass black holes can change on timescales of days to months1-3. When a black hole emerges from quiescence (that is, it 'turns on' after accreting material from its companion) it has a very hard (high-energy) X-ray spectrum produced by a hot corona4,5 positioned above its accretion disk, and then transitions to a soft (lower-energy) spectrum dominated by emission from the geometrically thin accretion disk, which extends to the innermost stable circular orbit6,7. Much debate persists over how this transition occurs and whether it is driven largely by a reduction in the truncation radius of the disk8,9 or by a reduction in the spatial extent of the corona10,11. Observations of X-ray reverberation lags in supermassive black-hole systems12,13 suggest that the corona is compact and that the disk extends nearly to the central black hole14,15. Observations of stellar-mass black holes, however, reveal equivalent (mass-scaled) reverberation lags that are much larger16, leading to the suggestion that the accretion disk in the hard-X-ray state of stellar-mass black holes is truncated at a few hundreds of gravitational radii from the black hole17,18. Here we report X-ray observations of the black-hole transient MAXI J1820+07019,20. We find that the reverberation time lags between the continuum-emitting corona and the irradiated accretion disk are 6 to 20 times shorter than previously seen. The timescale of the reverberation lags shortens by an order of magnitude over a period of weeks, whereas the shape of the broadened iron K emission line remains remarkably constant. This suggests a reduction in the spatial extent of the corona, rather than a change in the inner edge of the accretion disk.

A passion for the profession: a festschrift honoring Erich Meyerhoff.

An introduction to a series of essays honoring Erich Meyerhoff (1919-2015), AHIP, FMLA, who was active in and contributed to the Medical Library Association for generations.

Sub-calcaneal plantar fat pad assessment using dual-energy computed tomography: First experience in the diabetic foot.

BACKGROUND: This study assessed the use of dual-energy computed tomography (CT) to evaluate sub-calcaneal plantar fat pad changes in people with diabetic neuropathy. METHODS: Dual-energy CT scans of people with diabetic neuropathy and non-diabetic controls were retrospectively included. Average CT values (in Hounsfield Units) and thickness (in centimeters) of the sub-calcaneal plantar fat pad were measured in mono-energetic images at two energy levels (40 keV and 70 keV). The CT values measured in patients with diabetic neuropathy were correlated to barefoot plantar pressure measurements performed during walking in a clinical setting. FINDINGS: Forty-five dual-energy CT scans of people with diabetic neuropathy and eleven DECT scans of non-diabetic controls were included. Mean sub-calcaneal plantar fat pad thickness did not significantly differ between groups (diabetes group 1.20 ± 0.34 cm vs. control group 1.21 ± 0.28 cm, P = 0.585). CT values at both 40 keV (-34.7 ± 48.7 HU vs. -76.0 ± 42.8 HU, P = 0.013) and 70 keV (-11.2 ± 30.8 HU vs. -36.3 ± 27.2 HU, P = 0.017) were significantly higher in the diabetes group compared to controls, thus contained less fatty tissue. This elevation was most apparent in patients with Type 1 diabetes. CT values positively correlated with the mean peak plantar pressure. INTERPRETATION: Dual-energy CT was able to detect changes in the plantar fat pad of people with diabetic neuropathy.

Prenatal diagnosis for haemophilia: a nationwide survey among female carriers in the Netherlands.

Carriers of haemophilia face difficult choices regarding prenatal diagnosis, but little is known about the determinants that influence their decisions. The aim of this study was to assess the incidence of prenatal diagnosis and potential determinants affecting the choice for prenatal diagnosis. A nationwide survey was performed among all women who underwent carriership testing for haemophilia in the Netherlands between 1992 and 2004. Prenatal diagnosis was assessed in 207 carriers of haemophilia A or B who had been pregnant. Prenatal diagnosis was categorized into early first trimester (Y-PCR testing or chorionic villus sampling) often intended to prevent the birth of a child with haemophilia, and into late prenatal diagnosis (amniocentesis or ultrasound assessment) aimed at obstetrical management. Of 207 carriers 112 (54%) underwent prenatal diagnosis. Forty-eight women underwent early prenatal diagnosis and 64 women underwent late prenatal diagnosis. In 26 pregnancies early prenatal diagnosis was positive for haemophilia, and in 18 of these pregnancies termination was opted for. The choice for early prenatal diagnosis was associated with a liberal view towards termination of pregnancy (relative risk (RR) 12.5; 95% confidence interval (CI) 3.1-51.2), severe haemophilia in the family (RR 20.2; CI 2.7-153.6), absence of a religion (RR 1.9; CI 1.1-3.1) and older age (RR 2.0; CI 1.0-3.9). The choice for late prenatal diagnosis was associated with birth year after 1970 (RR 2.3; CI 1.5-3.5) and a previous child with haemophilia (RR 2.2; CI 1.4-3.4). More than half of all Dutch haemophilia carriers underwent prenatal diagnosis. Several determinants were strongly associated with prenatal diagnosis.

Testing the NASA BioSentinel Pixel Dosimeter Using Gamma-ray and Neutron Sources at the LLNL Calibration Lab.

ABSTRACT: The objective of this paper is to evaluate the accuracy of the NASA BioSentinel Pixel Dosimeter (BPD) using gamma-ray and neutron sources in a standard calibration lab. The dosimeter tested here is the ground-based version of the BPD that will be onboard the BioSentinel mission. The BPD was exposed to radiation from 60Co, 137Cs, and 252Cf at selected distances (dose rates) at the Lawrence Livermore National Laboratory (LLNL) Radiation Calibration Laboratory (RCL), and the results were compared with NIST traceable benchmark values. It is recognized that these sources are not analogs for the space environment but do provide direct comparisons between BPD response and well characterized calibration lab values. For gamma rays, the BPD measured absorbed dose agrees to ≤ 3.8% compared with RCL benchmark values. For neutrons, the results show that the BPD is insensitive, i.e., the BPD detected only the gamma-ray dose component from 252Cf. The LET spectra obtained for gamma rays from 60Co and 252Cf are consistent with expectations for these gamma-ray energies, but the LET spectrum from the 137Cs gamma rays differs substantially. The potential causes for this difference are the high dose rate from 137Cs and the lower secondary electron energy produced by 137Cs gamma rays. However, neither of these results in errors in the absorbed dose. Based on comparisons with NIST-traceable standards, it is evident that the BPD can measure absorbed dose accurately from low LET charged particles. The sensor's insensitivity to neutrons is unlikely to be a limitation for the BioSentinel mission due to the expected low secondary neutron fluence.

Quasi-periodic X-ray brightness fluctuations in an accreting millisecond pulsar.

The relativistic plasma flows onto neutron stars that are accreting material from stellar companions can be used to probe strong-field gravity as well as the physical conditions in the supra-nuclear-density interiors of neutron stars. Plasma inhomogeneities orbiting a few kilometres above the stars are observable as X-ray brightness fluctuations on the millisecond dynamical timescale of the flows. Two frequencies in the kilohertz range dominate these fluctuations: the twin kilohertz quasi-periodic oscillations (kHz QPOs). Competing models for the origins of these oscillations (based on orbital motions) all predict that they should be related to the stellar spin frequency, but tests have been difficult because the spins were not unambiguously known. Here we report the detection of kHz QPOs from a pulsar whose spin frequency is known. Our measurements establish a clear link between kHz QPOs and stellar spin, but one not predicted by any current model. A new approach to understanding kHz QPOs is now required. We suggest that a resonance between the spin and general relativistic orbital and epicyclic frequencies could provide the observed relation between QPOs and spin.

Eyes on the prize: reflections on the impact of the evolving digital ecology on the librarian as expert intermediary and knowledge coach, 1969-2009.

OBJECTIVE: The 2009 Janet Doe Lecture reflects on the continuing value and increasing return on investment of librarian-mediated services in the constantly evolving digital ecology and complex knowledge environment of the health sciences. SETTING: The interrelationship of knowledge, decision making based on knowledge, technology used to access and retrieve knowledge, and the important linkage roles of expert librarian intermediaries is examined. METHODOLOGY: Professional experiences from 1969 to 2009, occurring during a time of unprecedented changes in the digital ecology of librarianship, are the base on which the evolving role and value of librarians as knowledge coaches and expert intermediaries are examined. CONCLUSION: Librarian-mediated services linking knowledge and critical decision making in health care have become more valuable than ever as technology continues to reshape an increasingly complex knowledge environment.

Becoming an internationalist: reflections on the international activities of Estelle Brodman.

OBJECTIVE: The international consulting and publishing activities of Estelle Brodman, PhD, are placed in the context of Medical Library Association (MLA) international activities. DESCRIPTION: Through multiple consulting engagements in Asia, Dr. Brodman developed an extensive knowledge of the practice and history of health sciences librarianship in countries she visited. International activities in the form of publications, consulting visits, and international meetings occurred sporadically in a career that spanned over forty years and are examined in the context of the international activities of MLA. METHOD: Selected publications and Dr. Brodman's oral history transcript were reviewed. RESULTS/CONCLUSION: Dr. Brodman was a keen observer of the international practice of health sciences librarianship and used her considerable skills in writing and historical research to capture the essence of the cultures she visited. Reports and journal articles form a solid record of scholarship and were complementary to MLA international activities occurring during her career. She approached her assignments with empathy, candor, and respect for the cultures she visited.

The Effect of Obesity on Anti-Xa Concentrations in Bariatric Patients.

BACKGROUND: Morbidly obese patients are at increased risk to develop venous thromboembolism (VTE), especially after bariatric surgery. Adequate postoperative thrombosis prophylaxis is of utmost importance. It is assumed that morbidly obese patients need higher doses of low molecular weight heparin (LMWH) compared to normal-weight patients; however, current guidelines based on relative efficacy in obese populations are lacking. OBJECTIVES: First, we will evaluate the relationship between body weight descriptors and anti-Xa activity prospectively. Second, we will determine the dose-linearity of LMWH in morbidly obese patients. SETTING: This study was performed in a general hospital specialized in bariatric surgery. METHODS: Patients were scheduled for a Roux-en-Y gastric bypass with a total bodyweight (TBW) of ≥ 140 kg. Patients (n = 50, 64% female) received a daily postoperative dose of 5700 IU of nadroparin for 4 weeks. Anti-Xa activity was determined 4 h after the last nadroparin administration. To determine the dose linearity, anti-Xa was determined following a preoperative dose of 2850 IU nadroparin in another 50 patients (52%). RESULTS: TBW of the complete group was 148.5 ± 12.6 kg. Mean anti-Xa activity following 5700 IU nadroparin was 0.19 ± 0.07 IU/mL. Of all patients, 32% had anti-Xa levels below the prophylactic range. Anti-Xa activity inversely correlated with TBW (correlation coefficient - 0.410) and lean body weight (LBW; correlation coefficient - 0.447); 67% of patients with a LBW ≥ 80 kg had insufficient anti-Xa activity concentrations. No VTE events occurred. CONCLUSIONS: In morbidly obese patients, a postoperative dose of 5700 IU of nadroparin resulted in subprophylactic exposure in a significant proportion of patients. Especially in patients with LBW ≥ 80 kg, a higher dose may potentially be required to reach adequate prophylactic anti-Xa levels.

The Mayo brothers and Harvey Cushing: a review of their 39-year friendship through their personal letters.

Mayo Clinic founders, William J. Mayo and Charles H. Mayo, and Harvey W. Cushing were among the most significant pioneers of modem American surgery. A review of their personal correspondence reveals a special relationship among these three individuals, particularly between William Mayo and Cushing. Their interactions within the Society of Clinical Surgery initiated their close personal and professional association, which would endure for 39 years. William Mayo strongly supported Cushing's efforts to develop the specialty of neurological surgery, and Cushing sought Mayo's advice in making important career-related decisions. Their supportive friendship and professional alliance remains an example for future generations of neurological surgeons.

Point-of-Care Knowledge-Based Resource Needs of Clinicians: A Survey from a Large Academic Medical Center.

OBJECTIVE: To better understand the literature searching preferences of clinical providers we conducted an institution-wide survey assessing the most preferred knowledge searching techniques. MATERIALS AND METHODS: A survey regarding literature searching preferences was sent to 1862 unique clinical providers throughout Mayo Clinic. The survey consisted of 25 items asking respondents to select which clinical scenarios most often prompt literature searches as well as identify their most preferred knowledge resources. RESULTS: A total of 450 completed surveys were returned and analyzed (24% response rate). 48% of respondents perform literature searches for more than half of their patient interactions with 91% of all searches occurring either before or within 3 hours of the patient interaction. When a search is performed 57% of respondents prefer synthesized information sources as compared to only 13% who prefer original research. 82% of knowledge searches are performed on a workstation or office computer while just 10% occur on a mobile device or at home. CONCLUSION: Providers in our survey demonstrate a need to answer clinical questions on a regular basis, especially in the diagnosis and therapy domains. Responses suggest that most of these searches occur using synthesized knowledge sources in the patient care setting within a very short time from the patient interaction.

Variation in circumferential resection margin: Reporting and involvement in the South-Netherlands.

BACKGROUND: Since the introduction of total mesorectal surgery the outcome of rectal cancer patients has improved significantly. Involvement of the circumferential resection margin (CRM) is an important predictor of increased local recurrence, distant metastases and decreased overall survival. Abdomino perineal excision (APE) is associated with increased risk of CRM involvement. Aim of this study was to analyze reporting of CRM and to identify predictive factors for CRM involvement. METHODS: A population-based dataset was used selecting 2153 patients diagnosed between 2008 and 2013 with primary rectal cancer undergoing surgery. Variation in CRM reporting was assessed and predictive factors for CRM involvement were calculated and used in multivariate analyses. RESULTS: Large variation in CRM reporting was found between pathology departments, with missing cases varying from 6% to 30%. CRM reporting increased from 77% in 2008 to 90% in 2012 (p < 0.001). CRM involvement significantly decreased from 12% to 6% over the years (p < 0.001). In multivariate analysis type of operation, low anterior resection or APE, did not influence the risk of CRM involvement. Clinical T4-stage [odds ratio (OR) = 3.51; 95% confidence interval (CI) = 1.85-6.65) was associated with increased risk of CRM involvement, whereas neoadjuvant treatment (5 × 5 gray radiotherapy [OR 0.39; CI 0.25-0.62] or chemoradiation therapy [OR 0.30; CI 0.17-0.53]) were associated with significant decreased risk of CRM involvement. CONCLUSION: Although significant improvements are made during the last years there still is variation in reporting of CRM involvement in the Southern Netherlands. In multivariate analysis APE was no longer associated with increased risk of CRM involvement.

Risk estimation for healthy women from breast cancer families: new insights and new strategies.

Risk estimation in breast cancer families is often estimated by use of the Claus tables. We analyzed the family histories of 196 counselees; compared the Claus tables with the Claus, the BRCA1/2, the BRCA1/2/ models; and performed linear regression analysis to extend the Claus tables with characteristics of hereditary breast cancer. Finally, we compared the Claus extended method with the Claus, the BRCA1/2, and the BRCA1/2/u models. We found 47% agreement for Claus table versus Claus model; 39% agreement for Claus table versus BRCA1/2 model; 48% agreement for Claus table versus BRCA1/2/u model; 37% agreement for Claus extended method versus Claus model; 44% agreement for Claus extended model versus BRCA1/2 model; and 66% agreement for Claus extended method versus BRCA1/2/u model. The regression formula (Claus extended method) for the lifetime risk for breast cancer was 0.08 + 0.40 (*) Claus Table + 0.07 (*) ovarian cancer + 0.08 (*) bilateral breast cancer + 0.07 (*) multiple cases. This new method for risk estimation, which is an extension of the Claus tables, incorporates information on the presence of ovarian cancer, bilateral breast cancer, and whether there are more than two affected relatives with breast cancer. This extension might offer a good alternative for breast cancer risk estimation in clinical practice.

Fetal endocrine responses to prolonged reduced uterine blood flow are altered following bilateral sectioning of the carotid sinus and vagus nerves.

The present study examines the effect of carotid sinus/vagosympathetic denervation on fetal endocrine responses to prolonged reduced uterine blood flow (RUBF). Fetal sheep had vascular catheters inserted following bilateral sectioning of the carotid sinus and vagus nerves (denervated, n = 7) or sham denervation (intact, n = 7). Uterine blood flow was mechanically restricted at 126.1 +/- 0.7 days (mean +/- S.E.M.) for 24 h, decreasing arterial oxygen saturation by 47.3 +/- 2.6% (P < 0.01). Fetal plasma samples were obtained at -1, 3, 6, 12 and 24 h for subsequent analyses of arginine vasopressin (AVP), angiotensin II and catecholamines. The AVP response to prolonged RUBF was markedly attenuated in denervated fetuses (15.6 +/- 3.6 to 34.9 +/- 6.0 pg/ml) when compared with intact (10.0 +/- 1.4 to 127.3 +/- 28.4 pg/ml). In contrast, intact fetuses demonstrated no change in plasma angiotensin II concentrations with RUBF whereas denervated fetuses demonstrated a marked increase from 47.5 +/- 18.9 to 128.7 +/- 34.2 pg/ml. The norepinephrine and epinephrine responses to prolonged RUBF were attenuated in denervated fetuses (950.1 +/- 308.9 and 155.8 +/- 58.5 to 1268.3 +/- 474.6 and 290.6 +/- 160.2 pg/ml respectively) when compared with intact (1558.3 +/- 384.4 and 547.3 +/- 304.7 pg/ml to 3289.2 +/- 1219.8 and 896.8 +/- 467.8 pg/ml respectively). These results support a role for the peripheral chemoreceptors in mediating fetal endocrine responses to prolonged RUBF, which may in part lead to the altered cardiovascular responses observed in denervated fetuses under these conditions.

Pulmonary blood flow. A potential factor in the pathogenesis of pulmonary edema.

The purpose of this study is to examine the hemodynamics of the pulmonary circulation and the potential role of pulmonary blood flow in the pathogenesis of cardiogenic pulmonary edema. To do so, the pulmonary circulation was isolated and controlled such that, within a closed circuit, pulmonary blood flow and left atrial pressure (LAP) could be regulated independently: the first by a constant flow pump, the second by a variable height reservoir. The effect of pulmonary blood flow on pulmonary artery pressure and intravascular blood volume was then determined at different LAPs. Contrary to our expectations, the results indicate that (1) pulmonary vascular resistance does not change appreciably as flow increases, (2) the microcirculation comprises the major capacitance vessels of the lung, and (3) increased pulmonary flow in the normal lung causes little change in intravascular pulmonary blood volume, whereas, by contrast, major changes in pulmonary blood volume occur as LAP rises. Next, the effect of pulmonary blood flow on edema formation in the lungs was examined. Below a critical level of LAP (15 mm Hg in these experiments), pulmonary blood flow up to 5 L/min did not produce pulmonary edema. Above this level, however, such an effect was clear. Thus, at an LAP of 20 mm Hg, edema did not develop if pulmonary flow was low (0.7 L/min) but did if flow was increased to 2 L/min. As well, if the LAP was 17.5 mm Hg and pulmonary flow 3.5 L/min, severe pulmonary edema also resulted.

Initiation of pulmonary gas exchange by fetal sheep in utero.

The role of umbilical cord occlusion in the initiation of breathing at birth was investigated using unanesthetized fetal sheep that were provided with access to a tracheal supply of hyperoxic air. Near-term fetuses were studied in utero to eliminate extraneous sensory stimuli. Gasping movements began 1.4 +/- 0.1 min after cord occlusion. Breathing was irregular for several minutes before continuous breathing (greater than or equal to 40 min-1) began 6 +/- 1 min after cord occlusion (n = 10). Arterial PO2 rose significantly from 18 +/- 2 mmHg before occlusion and was 115 +/- 15 mmHg immediately before cord release at 15 or 30 min. Breathing continued even during high-voltage electrocortical activity. Cord release caused the breathing rate to decrease from 77 +/- 13 min-1 during the last 5 min of cord occlusion to 5 +/- 3 min-1 10 min after cord release (P less than 0.002; n = 7). Results indicate the change from placental to lung gas exchange can occur in the absence of sensory and thermal changes normally present at birth and that the transition is reversible.

The adenosine A(1)-receptor antagonist 8-CPT reverses ethanol-induced inhibition of fetal breathing movements.

Administration of either ethanol or adenosine inhibits fetal breathing movements (FBM), eye movements, and low-voltage electrocortical activity (LV ECoG). The concentration of adenosine in ovine fetal cerebral extracellular fluid increases during ethanol-induced inhibition of FBM. The purpose of this study was to determine the effect of a selective adenosine A(1)-receptor antagonist, 8-cyclopentyltheophylline (8-CPT) on the incidence of FBM during ethanol exposure. After a 2-h control period, seven pregnant ewes received a 1-h intravenous infusion of ethanol (1 g/kg maternal body wt), followed 1 h later by a 2-h fetal intravenous infusion of either 8-CPT (3.78 +/- 0.08 microg. kg(-1). min(-1)) or vehicle. Ethanol reduced the incidence of FBM from 44.0 +/- 10.4 to 2.7 +/- 1.3% (P < 0.05) and 51.2 +/- 7.6 to 11.9 +/- 5.0% (P < 0.05) in fetuses destined to receive 8-CPT or vehicle, respectively. In the vehicle group, FBM remained suppressed for 7 h. In contrast, during the first hour of 8-CPT infusion, FBM returned to baseline (31 +/- 11%) and was not different from control throughout the rest of the experiment. Ethanol also decreased the incidence of both low-voltage electrocortical activity and eye movements, but there were no differences in the incidences of these behavioral parameters between the 8-CPT and vehicle groups throughout the experiment. These data are consistent with the hypothesis that adenosine, acting via A(1) receptors, may play a role in the mechanism of ethanol-induced inhibition of FBM.

Increased cerebral extracellular adenosine and decreased PGE2 during ethanol-induced inhibition of FBM.

Adenosine and PGE2 are neuromodulators, both of which inhibit fetal breathing movements (FBM). Although circulating PGE2 has been implicated as a mediator of ethanol-induced inhibition of FBM in the late-gestation ovine fetus, a role for adenosine has not been examined. The objective of this study was to determine the effect of maternal ethanol infusion on ovine fetal cerebral extracellular fluid adenosine and PGE2 concentrations by using in utero microdialysis and to relate any changes to ethanol-induced inhibition of FBM. Dialysate samples were obtained from the fetal parietal cortex over 70 h after surgery to determine steady-state extracellular fluid adenosine and PGE2 concentrations. On each of postoperative days 3 and 4, after a 2-h baseline period, ewes received a 1-h infusion of ethanol (1 g/kg maternal body wt) or an equivalent volume of saline, and the fetus was monitored for a further 11 h with 30-min dialysate samples collected throughout. Immediately after surgery, dialysate PGE2 and adenosine concentrations were 3.7 +/- 0.7 and 296 +/- 127 nM, respectively. PGE2 did not change over the 70 h, whereas adenosine decreased to 59 +/- 14 nM (P < 0.05) at 4 h and then remained unchanged. Ethanol decreased dialysate PGE2 concentration for 2 h (3.3 +/- 0.3 to 1.9 +/- 0.4 nM; P < 0.05) and increased adenosine concentration for 6 h (87 +/- 13 to a maximum of 252 +/- 59 nM, P < 0.05). Ethanol decreased FBM incidence from 47 +/- 7 to 16 +/- 5% (P < 0.01) for 8 h. Saline infusion did not change dialysate adenosine or PGE2 concentrations or FBM incidence. These data are consistent with the hypothesis that fetal cerebral adenosine, and not PGE2, is the primary mediator of ethanol-induced inhibition of FBM at 123 days of gestation in sheep.

Regional brain blood flow in the ovine fetus during transition to the low-voltage electrocortical state.

Sequential changes in cerebral blood flow and regional distribution were studied in nine chronically catheterized fetal sheep during the transition to the low-voltage ECOG (REM) state to determine the time course for blood flow change within the brain and whether executive centres for REM state generation might thus be identified. Blood flows were measured during the first, second and third minutes after the transition to the low-voltage ECOG state and during the third minute of the subsequent high-voltage ECOG (NREM) state using the radioactive labelled microsphere technique. Blood flow to the brain was increased during the low-voltage REM state when compared to that of the high-voltage NREM state, with the increase evident when measured during the first minute after the state transition and with no sequential change thereafter. Regional blood flow increases during the low-voltage state were greatest to those areas variously associated with the generation of REM state activity, but were again remarkably stable through the first 3 minutes after the state transition. This rapid increase in blood flow within the brain and the regional hierarchy for such, supports the participation of multiple anatomical areas which are highly integrated and act in concert to give rise to what is known as the REM state.