In Situ Transmission X-Ray Microscopy of the Lead Sulfate Film Formation on Lead in Sulfuric Acid

Transmission X-ray microscopy is utilized to monitor, in real time, the behavior of the PbSO4 film that is formed on Pb in H2SO4. Images collected from the synchrotron x-rays are coupled with voltammetric data to study the initial formation, the resulting passivation, and the subsequent reduction of the film. It is concluded with support from quartz-crystal-microbalance experiments that the initial formation of PbSO4 crystals occurs as a result of acidic corrosion. In addition, the film is shown to coalesce during the early stages of galvanostatic oxidation and to passivate as a result of morphological changes in the existing film. Finally, it is observed that the passivation process results in the formation of large PbSO4 crystals with low area-to-volume ratios, which are difficult to reduce under both galvanostatic and potentiostatic conditions

Conducting admissions interviews at regional campuses influences applicants’ preferred campus assignment in a statewide system of distributed medical education

There was a strong statistical association between interviewing at the Northwest campus and matriculating at the Northwest campus. This was accompanied by a 22% increase in the number of matriculants who ranked the Northwest campus as their 1st or 2nd choice, as compared to previous years when everyone interviewed at the Indianapolis campus. This suggests that interviewing onsite may have fostered positive attitudes about the Northwest campus. The evidence for Muncie is less compelling. Although there was a statistical association between interviewing and matriculating at the Muncie campus, the percentage of matriculants who highly-ranked the Muncie campus actually dropped by 11% compared to previous years (but not statistically significant)

Pain Medication Management Processes Used by Oncology Outpatients and Family Caregivers Part I: Health Systems Contexts

Context—Oncology patients with persistent pain treated in outpatient settings and their family caregivers have significant responsibility for managing pain medications. However, little is known about their practical, day-to-day experiences with pain medication management. Objective—To describe day-to-day pain medication management from the perspectives of oncology outpatients and their family caregivers who participated in a randomized clinical trial of a psycho-educational intervention called the Pro-Self© Plus Pain Control Program. In this article, we focus on pain medication management by patients and family caregivers in the context of multiple, complex health systems. Methods—We qualitatively analyzed audio-recorded intervention sessions that included extensive dialogue between patients, family caregivers, and nurses about pain medication management during the 10-week intervention. Results—The health systems context for pain medication management included multiple complex systems for clinical care, reimbursement, and regulation of analgesic prescriptions. Pain medication management processes particularly relevant to this context were getting prescriptions and obtaining medications. Responsibilities that fell primarily to patients and family caregivers included facilitating communication and coordination among multiple clinicians, overcoming barriers to access, and serving as a final safety checkpoint. Significant effort was required of patients and family caregivers to insure safe and effective pain medication management. Conclusion—Health systems issues related to access to needed analgesics, medication safety in outpatient settings, and the effort expended by oncology patients and their family caregivers require more attention in future research and healthcare reform initiatives

Pain Medication Management Processes Used by Oncology Outpatients and Family Caregivers Part II: Home and Lifestyle Contexts

Context—Despite the increasing complexity of medication regimens for persistent cancer pain, little is known about how oncology outpatients and their family caregivers manage pain medications at home. Objectives—To describe the day-to-day management of pain medications from the perspectives of oncology outpatients and their family caregivers who participated in a randomized clinical trial (RCT) of a psycho-educational intervention called the Pro-Self © Plus Pain Control Program. In this article, we focus on pain medication management in the context of highly individualized home environments and lifestyles. Methods—This qualitative study was conducted as part of a RCT in which an embedded mixed methods research design was used. Audio-recorded dialogue among patients, family caregivers, and intervention nurses was analyzed using qualitative research methods. Results—Home and lifestyle contexts for managing pain medications included highly individualized home environments, work and recreational activities, personal routines, and family characteristics. Pain medication management processes particularly relevant in these contexts included understanding, organizing, storing, scheduling, remembering, and taking the medications. With the exception of their interactions with the intervention nurses, most study participants had little involvement with clinicians as they worked through these processes. Conclusion—Pain medication management is an ongoing multidimensional process, each step of which has to be mastered by patients and family caregivers when cancer treatment and supportive care is provided on an outpatient basis. Realistic patient- and family-centered skill-building interventions are needed to achieve effective and safe pain medication management in the contexts of individual home environments and lifestyles

The ACS Fornax Cluster Survey VII. Half-Light Radii of Globular Clusters in Early-Type Galaxies

We measure the half-light radii of globular clusters (GCs) in 43 galaxies from the ACS Fornax Cluster Survey (ACSFCS). We use these data to extend previous work in which the environmental dependencies of the half-light radii of GCs in early type galaxies in the ACS Virgo Cluster Survey (ACSVCS) were studied, and a corrected mean half-light radius (corrected for the observed environmental trends) was suggested as a reliable distance indicator. This work both increases the sample size for the study of the environmental dependencies, and adds leverage to the study of the corrected half-light radius as a possible distance indicator (since Fornax lies at a larger distance than the Virgo cluster). We study the environmental dependencies of the size of GCs using both a Principal Component Analysis as well as 2D scaling relations. We largely confirm the environmental dependencies shown in Jordan et al. (2005), but find evidence that there is a residual correlation in the mean half-light radius of GC systems with galaxy magnitude, and subtle differences in the other correlations - so there may not be a universal correction for the half-light radii of lower luminosity galaxy GC systems. The main factor determining the size of a GC in an early type galaxy is the GC color. Red GCs have = 2.8+/-0.3 pc, while blue GCs have = 3.4+/-0.3 pc. We show that for bright early-type galaxies (M_B < -19 mag), the uncorrected mean half-light radius of the GC system is by itself an excellent distance indicator (with error ~11%), having the potential to reach cosmologically interesting distances in the era of high angular resolution adaptive optics on large optical telescopes.Comment: ApJ in press, 19 pages, 16 figures

Thrombolytic removal of intraventricular haemorrhage in treatment of severe stroke: results of the randomised, multicentre, multiregion, placebo-controlled CLEAR III trial

Background: Intraventricular haemorrhage is a subtype of intracerebral haemorrhage, with 50% mortality and serious disability for survivors. We aimed to test whether attempting to remove intraventricular haemorrhage with alteplase versus saline irrigation improved functional outcome. Methods: In this randomised, double-blinded, placebo-controlled, multiregional trial (CLEAR III), participants with a routinely placed extraventricular drain, in the intensive care unit with stable, non-traumatic intracerebral haemorrhage volume less than 30 mL, intraventricular haemorrhage obstructing the 3rd or 4th ventricles, and no underlying pathology were adaptively randomly assigned (1:1), via a web-based system to receive up to 12 doses, 8 h apart of 1 mg of alteplase or 0·9% saline via the extraventricular drain. The treating physician, clinical research staff, and participants were masked to treatment assignment. CT scans were obtained every 24 h throughout dosing. The primary efficacy outcome was good functional outcome, defined as a modified Rankin Scale score (mRS) of 3 or less at 180 days per central adjudication by blinded evaluators. This study is registered with ClinicalTrials.gov, NCT00784134. Findings: Between Sept 18, 2009, and Jan 13, 2015, 500 patients were randomised: 249 to the alteplase group and 251 to the saline group. 180-day follow-up data were available for analysis from 246 of 249 participants in the alteplase group and 245 of 251 participants in the placebo group. The primary efficacy outcome was similar in each group (good outcome in alteplase group 48% vs saline 45%; risk ratio [RR] 1·06 [95% CI 0·88–1·28; p=0·554]). A difference of 3·5% (RR 1·08 [95% CI 0·90–1·29], p=0·420) was found after adjustment for intraventricular haemorrhage size and thalamic intracerebral haemorrhage. At 180 days, the treatment group had lower case fatality (46 [18%] vs saline 73 [29%], hazard ratio 0·60 [95% CI 0·41–0·86], p=0·006), but a greater proportion with mRS 5 (42 [17%] vs 21 [9%]; RR 1·99 [95% CI 1·22–3·26], p=0·007). Ventriculitis (17 [7%] alteplase vs 31 [12%] saline; RR 0·55 [95% CI 0·31–0·97], p=0·048) and serious adverse events (114 [46%] alteplase vs 151 [60%] saline; RR 0·76 [95% CI 0·64–0·90], p=0·002) were less frequent with alteplase treatment. Symptomatic bleeding (six [2%] in the alteplase group vs five [2%] in the saline group; RR 1·21 [95% CI 0·37–3·91], p=0·771) was similar. Interpretation: In patients with intraventricular haemorrhage and a routine extraventricular drain, irrigation with alteplase did not substantially improve functional outcomes at the mRS 3 cutoff compared with irrigation with saline. Protocol-based use of alteplase with extraventricular drain seems safe. Future investigation is needed to determine whether a greater frequency of complete intraventricular haemorrhage removal via alteplase produces gains in functional status

An additional bolus of rapid-acting insulin to normalise postprandial cardiovascular risk factors following a high-carbohydrate high-fat meal in patients with type 1 diabetes: A randomised controlled trial.

AIM: To evaluate an additional rapid-acting insulin bolus on postprandial lipaemia, inflammation and pro-coagulation following high-carbohydrate high-fat feeding in people with type 1 diabetes. METHODS: A total of 10 males with type 1 diabetes [HbA1c 52.5 ± 5.9 mmol/mol (7.0% ± 0.5%)] underwent three conditions: (1) a low-fat (LF) meal with normal bolus insulin, (2), a high-fat (HF) meal with normal bolus insulin and (3) a high-fat meal with normal bolus insulin with an additional 30% insulin bolus administered 3-h post-meal (HFA). Meals had identical carbohydrate and protein content and bolus insulin dose determined by carbohydrate-counting. Blood was sampled periodically for 6-h post-meal and analysed for triglyceride, non-esterified-fatty acids, apolipoprotein B48, glucagon, tumour necrosis factor alpha, fibrinogen, human tissue factor activity and plasminogen activator inhibitor-1. Continuous glucose monitoring captured interstitial glucose responses. RESULTS: Triglyceride concentrations following LF remained similar to baseline, whereas triglyceride levels following HF were significantly greater throughout the 6-h observation period. The additional insulin bolus (HFA) normalised triglyceride similarly to low fat 3-6 h following the meal. HF was associated with late postprandial elevations in tumour necrosis factor alpha, whereas LF and HFA was not. Fibrinogen, plasminogen activator inhibitor-1 and tissue factor pathway levels were similar between conditions. CONCLUSION: Additional bolus insulin 3 h following a high-carbohydrate high-fat meal prevents late rises in postprandial triglycerides and tumour necrosis factor alpha, thus improving cardiovascular risk profile

Contemporary Art and Transitional Justice in Northern Ireland: The Consolation of Form

Abstract Contemporary artworks in Northern Ireland are explored here as critical constellations, in Walter Benjamin’s sense, that engage the cultural processes of transition through their problematisation of it. It is argued that the artworks become sites in which the assumptions of transition are opened up for critical reflection, requesting attention to the foreclosing of the meanings of memory, of past-and-future, of community. A mode of critical questioning of the present renders the present problematic not in terms of exclusions nor with reference to a past that cannot or will not be erased, but in terms of the present’s inability to be conceived through a linear conception of time. That is, the past and its relation to both the present and to the future are set in oscillation as artworks explore the complex temporalities of a present self-consciously attempting to narrate itself away from the past. The artworks, ‘without the bigotry of conviction’ as Seamus Deane put it, suggest that the task of dealing with the past is flawed wherever the past is conceived as a history that can be rendered present to be judged by subjects who are thereby placed beyond it. That is the illusion of a present ‘no-time’ that dovetails with the desires of commercial enterprise and neo-liberal conceptions of freedom. If this suggests an unceasing restlessness, the consolation is that this questioning does take a form, not as judgement or political decision but as artworks which by definition, remain open to reinterpretation and new understandings. These issues are discussed with reference to the work of four artists in Northern Ireland: the paintings of Rita Duffy, the photography and installation work of Anthony Haughey, and the sculptural works of Philip Napier and Mike Hogg

Comprehensive preclinical evaluation of human-derived anti-poly-GA antibodies in cellular and animal models of C9ORF72 disease

Hexanucleotide G4C2 repeat expansions in the C9ORF72 gene are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Dipeptide repeat proteins (DPRs) generated by translation of repeat-containing RNAs show toxic effects in vivo as well as in vitro and are key targets for therapeutic intervention. We generated human antibodies that bind DPRs with high affinity and specificity. Anti-GA antibodies engaged extra- and intracellular poly-GA and reduced aggregate formation in a poly-GA over-expressing human cell line. However, antibody treatment in human neuronal cultures synthesizing exogenous poly-GA resulted in the formation of large extracellular immune complexes and did not affect accumulation of intracellular poly-GA aggregates. Treatment with antibodies was also shown to directly alter the morphological and biochemical properties of poly-GA and to shift poly-GA/antibody complexes to more rapidly sedimenting ones. These alterations were not observed with poly-GP and have important implications for accurate measurement of poly-GA levels including the need to evaluate all centrifugation fractions and disrupt the interaction between treatment antibodies and poly-GA by denaturation. Targeting poly-GA and poly-GP in two mouse models expressing G4C2 repeats by systemic antibody delivery for up to 16 months was well-tolerated and led to measurable brain penetration of antibodies. Long term treatment with anti-GA antibodies produced improvement in an open field movement test in aged C9ORF72450 mice. However, chronic administration of anti-GA antibodies in AAV-(G4C2)149 mice was associated with increased levels of poly-GA detected by immunoassay and did not significantly reduce poly-GA aggregates or alleviate disease progression in this model. Significance Immunotherapy has been proposed for neurodegenerative disorders including Alzheimer’s or Parkinson’s diseases. Recent reports using antibodies against poly-GA or active immunization suggested similar immunotherapy in ALS/FTD caused by repeat expansion in the C9ORF72 gene (1, 2). Here, we systematically characterized human antibodies against multiple DPR species and tested the biological effects of antibodies targeting poly-GA in different cellular and mouse models. Target engagement was shown in three independent cellular models. Anti-GA antibodies reduced the number of intracellular poly-GA aggregates in human T98G cells but not in cultured human neurons. Whereas chronic anti-GA treatment in BAC C9ORF72450 mice did not impact poly-GA levels and modestly improved one behavioral phenotype, poly-GA levels detected by immunoassays were increased and disease progression was unaltered in AAV-(G4C2)149 mice

Early neonatal vitamin A supplementation and infant mortality: an individual participant data meta-analysis of randomised controlled trials

Background Biannual vitamin A supplementation is a well-established survival tool for preschool children 6 months and older in vitamin A deficient populations but this schedule misses the opportunity to intervene on most young infant deaths. Randomised trials of neonatal vitamin A supplementation (NVAS) in the first few days of life to assess its impact on under 6-month mortality in low/middle-income countries have had varying results. Methods Investigators of 11 published randomised placebo-controlled NVAS trials (n=163 567 children) reanalysed their data according to an agreed plan and pooled the primary outcomes of mortality from supplementation through 6 and 12 months of age using random effects models and meta-regression. One investigator withdrew but allowed use of the data. Findings Overall there was no effect of NVAS on infant survival through 6 (risk ratio (RR) 0.97; 95% CI 0.89 to 1.06) or 12 months of age (RR 1.00; 95% CI 0.93 to 1.08) but results varied by study population characteristics. NVAS significantly reduced 6-month mortality among the trials conducted in Southern Asia (RR 0.87; 95% CI 0.77 to 0.98), in contexts with moderate or severe vitamin A deficiency (defined as 10% or higher proportion of women with serum retinol 32% mothers had no schooling (RR 0.88; 95% CI 0.80 to 0.96). NVAS did not reduce mortality in the first 6 months of life in trials conducted in Africa, in contexts characterised by a low prevalence of vitamin A deficiency, lower rates of infant mortality and where maternal education was more prevalent. There was a suggestion of increased infant mortality in trials conducted in Africa (RR 1.07; 95% CI 1.00 to 1.15). Individual-level characteristics such as sex, birth weight, gestational age and size, age at dosing, parity, time of breast feeding initiation, maternal education and maternal vitamin A supplementation did not modify the impact of NVAS. Conclusion NVAS reduced infant mortality in South Asia, in contexts where the prevalence of maternal vitamin A deficiency is moderate to severe and early infant mortality is high; but it had no beneficial effect on infant survival in Africa, in contexts where the prevalence of maternal vitamin A deficiency is lower, early infant mortality is low