Clinical surveillance of thrombotic microangiopathies in Scotland, 2003-2005

The prevalence, incidence and outcomes of haemolytic uraemic syndrome (HUS) and thrombotic thrombocytopaenic purpura (TTP) are not well established in adults or children from prospective studies. We sought to identify both outcomes and current management strategies using prospective, national surveillance of HUS and TTP, from 2003 to 2005 inclusive. We also investigated the links between these disorders and factors implicated in the aetiology of HUS and TTP including infections, chemotherapy, and immunosuppression. Most cases of HUS were caused by verocytotoxin-producing Escherichia coli (VTEC), of which serotype O157 predominated, although other serotypes were identified. The list of predisposing factors for TTP was more varied although use of immunosuppressive agents and severe sepsis, were the most frequent precipitants. The study demonstrates that while differentiating between HUS and TTP is sometimes difficult, in most cases the two syndromes have quite different predisposing factors and clinical parameters, enabling clinical and epidemiological profiling for these disorders

Sites of Biosynthesis of Outer and Inner Membrane Proteins of Neurospora crassa Mitochondria

Outer and inner membranes of Neurospora crassa mitochondria were separated by the combined swelling, shrinking, sonication procedure. Membranes were characterized by electron microscopy and by marker enzyme activities. A red carotenoid pigment was found to be concentrated in the outer membrane. The inner mitochondrial membrane was resolved into about 20 protein bands on polyacrylamide gel electrophoresis, whereas the outer membrane shows essentially one single protein band. Only negligible incorporation of radioactive amino acids occurs into outer membrane when isolated mitochondria are synthesizing polypeptide chains. In agreement with this observation labeling of outer membrane protein is almost entirely blocked, when whole Neurospora cells are incubated with radioactive amino acids in the presence of cycloheximide, an inhibitor of cytoplasmic protein synthesis. Finally, the essential electrophoretic protein band from outer membrane does not become labeled when mitochondria are incubated with radioactive amino acids either in vitro or in vivo in the presence of cycloheximide. It is concluded that the vast majority, if not all, of the outer membrane protein is synthesized by the cytoplasmic system and that polypeptide chains formed by the mitochondrial ribosomes are integrated into the inner mitochondrial membrane

Interpolatory methods for H∞\mathcal{H}_\infty model reduction of multi-input/multi-output systems

We develop here a computationally effective approach for producing high-quality $\mathcal{H}_\infty$-approximations to large scale linear dynamical systems having multiple inputs and multiple outputs (MIMO). We extend an approach for $\mathcal{H}_\infty$ model reduction introduced by Flagg, Beattie, and Gugercin for the single-input/single-output (SISO) setting, which combined ideas originating in interpolatory $\mathcal{H}_2$-optimal model reduction with complex Chebyshev approximation. Retaining this framework, our approach to the MIMO problem has its principal computational cost dominated by (sparse) linear solves, and so it can remain an effective strategy in many large-scale settings. We are able to avoid computationally demanding $\mathcal{H}_\infty$ norm calculations that are normally required to monitor progress within each optimization cycle through the use of "data-driven" rational approximations that are built upon previously computed function samples. Numerical examples are included that illustrate our approach. We produce high fidelity reduced models having consistently better $\mathcal{H}_\infty$ performance than models produced via balanced truncation; these models often are as good as (and occasionally better than) models produced using optimal Hankel norm approximation as well. In all cases considered, the method described here produces reduced models at far lower cost than is possible with either balanced truncation or optimal Hankel norm approximation

Correction to: Temporary interruption of baricitinib: characterization of interruptions and effect on clinical outcomes in patients with rheumatoid arthritis

Background In clinical practice, temporary interruption of rheumatoid arthritis (RA) therapy is common for various reasons including side effects, non-compliance, or necessity for surgery. To characterize temporary interruptions of baricitinib and placebo-matched tablets in phase 3 studies of patients with moderate-to-severe rheumatoid arthritis (RA) and describe their impact on efficacy and safety. Methods During 4 baricitinib phase 3 studies, investigators documented timing, reason, and duration of investigator-initiated temporary interruptions of study drug. In 2 studies, patients recorded RA symptoms in daily diaries for 12 weeks. Post hoc analyses investigated changes in symptom scores during interruptions and resumption of treatment. Interruptions were evaluated for reoccurrence of adverse events or laboratory abnormalities after retreatment. Results Across the placebo-controlled studies, interruptions occurred in larger proportions of baricitinib- (2 mg, 18%; 4 mg, 18%) vs placebo-treated (9%) patients in only one study (bDMARD-inadequate responder patients, RA-BEACON). In the active comparator-controlled studies, the lowest rates of interruption were in the baricitinib monotherapy arm (9%) of RA-BEGIN (vs methotrexate monotherapy or combination therapy), and proportions were similar for baricitinib (10%) and adalimumab (9%) in RA-BEAM. Adverse events were the most common reason for interruption, but their reoccurrence after drug restart was infrequent. Most interruptions lasted ≤ 2 weeks. Daily diaries indicated modest symptom increases during interruption with return to pre-interruption levels or better after resumption. Interruptions had no impact on long-term efficacy outcomes. Conclusions Consistent with its pharmacologic properties, brief interruptions of baricitinib during phase 3 studies were associated with minor increases in RA symptoms that resolved following retreatment. This analysis provides useful information for clinicians, as temporary interruption of antirheumatic therapy is common in the care of patients with RA

Temporary interruption of baricitinib: characterization of interruptions and effect on clinical outcomes in patients with rheumatoid arthritis

Background In clinical practice, temporary interruption of rheumatoid arthritis (RA) therapy is common for various reasons including side effects, non-compliance, or necessity for surgery. To characterize temporary interruptions of baricitinib and placebo-matched tablets in phase 3 studies of patients with moderate-to-severe rheumatoid arthritis (RA) and describe their impact on efficacy and safety. Methods During 4 baricitinib phase 3 studies, investigators documented timing, reason, and duration of investigator-initiated temporary interruptions of study drug. In 2 studies, patients recorded RA symptoms in daily diaries for 12 weeks. Post hoc analyses investigated changes in symptom scores during interruptions and resumption of treatment. Interruptions were evaluated for reoccurrence of adverse events or laboratory abnormalities after retreatment. Results Across the placebo-controlled studies, interruptions occurred in larger proportions of baricitinib- (2 mg, 18%; 4 mg, 18%) vs placebo-treated (9%) patients in only one study (bDMARD-inadequate responder patients, RA-BEACON). In the active comparator-controlled studies, the lowest rates of interruption were in the baricitinib monotherapy arm (9%) of RA-BEGIN (vs methotrexate monotherapy or combination therapy), and proportions were similar for baricitinib (10%) and adalimumab (9%) in RA-BEAM. Adverse events were the most common reason for interruption, but their reoccurrence after drug restart was infrequent. Most interruptions lasted ≤ 2 weeks. Daily diaries indicated modest symptom increases during interruption with return to pre-interruption levels or better after resumption. Interruptions had no impact on long-term efficacy outcomes. Conclusions Consistent with its pharmacologic properties, brief interruptions of baricitinib during phase 3 studies were associated with minor increases in RA symptoms that resolved following retreatment. This analysis provides useful information for clinicians, as temporary interruption of antirheumatic therapy is common in the care of patients with RA

Assessment of Load and Energy Reduction Techniques (ALERT) Retrocommissioning Case Study of Two National Renewable Energy Laboratory (NREL) Sites

Portland Energy Conservation Incorporated (PECI) in conjunction with the National Renewable Energy Laboratory (NREL) staff performed an Assessment of Load and Energy Reduction Techniques (ALERT) retrocommissioning evaluation on several buildings located at the South Table Mountain site and National Wind Technology Center site located in Golden, Colorado. The retrocommissioning process involved a coordinated effort between PECI and NREL staff and was completed in November of 2002. Retrocommissioning (RCx), or existing building commissioning, is an event in the life of a building that applies a systematic investigation process for improving and optimizing a building's energy-using equipment such as the HVAC and other mechanical equipment, lighting equipment, and related controls. The investigation phase for this project identified 33 findings. This paper gives an overview of the project and discusses a few of the operations and maintenance (O&M) findings as well as capital improvement recommendations that have the greatest potential for energy savings. An update on the progress of implementation will also be discussed. The combined measures recommended for implementation result in an estimated total annual savings of 572,444 kWh, 54,114 therms, and a total utility cost savings of $44,040, which correspond to a 7.0reduction in annual utility costs. With the measures already implemented, and those in the process thus far, the total estimated savings are 231,924 kWh, 51,550 therms, and$28,920 annual energy savings. Implementation costs were estimated at $56,380, which would result in a 1.9 year average payback. It cost approximately$0.09 per square foot to perform the ALERT RCx assessment. Of the 33 measures identified, energy savings were not calculated for 14 of them due to insufficient data at the time or they are very general and difficult to estimate. Most of the measures focus on O&M improvements, and many of these measures have been implemented, or under evaluation for implementation. It is not unreasonable to assume that the measures under evaluation, if selected for implementation, could account for an additional 1% energy and cost savings

The Importance of Audit Firm Characteristics and the Drivers of Auditor Change in UK Listed Companies

This paper explores the importance of audit firm characteristics and the factors motivating auditor change based on questionnaire responses from 210 listed UK companies (a response rate of 70%). Twenty-nine potentially desirable auditor characteristics are identified from the extant literature and their importance elicited. Exploratory factor analysis reduces these variables to eight uncorrelated underlying dimensions: reputation/quality; acceptability to third parties; value for money; ability to provide non-audit services; small audit firm; specialist industry knowledge; non-Big Six large audit firm; and geographical proximity. Insights into the nature of 'the Big Six factor' emerge. Two thirds of companies had recently considered changing auditors; the main reasons cited being audit fee level, dissatisfaction with audit quality and changes in top management. Of those companies that considered change, 73% did not actually do so, the main reasons cited being fee reduction by the incumbent and avoidance of disruption. Thus audit fee levels are both a key precipitator of change and a key factor in retaining the status quo

Australian long-term care personnel's knowledge and attitudes regarding palliative care for people with advanced dementia.

This study aimed to describe Australian long-term care (LTC) personnel's knowledge and attitudes concerning palliative care for residents with advanced dementia, and explore relationships with LTC facility/personnel characteristics. An analysis was undertaken of baseline data from a cluster randomised controlled trial of facilitated family case conferencing for improving palliative care of LTC residents with advanced dementia (the 'IDEAL Study'). Participants included any LTC personnel directly involved in residents' care. Knowledge and attitudes concerning palliative care for people with advanced dementia were measured using the questionnaire on Palliative Care for Advanced Dementia. Univariate and multivariate analyses explored relationships between personnel knowledge/attitudes and facility/personnel characteristics. Of 307 personnel in the IDEAL Study, 290 (94.5%) from 19/20 LTCFs provided sufficient data for inclusion. Participants included 9 (2.8%) nurse managers, 59 (20.5%) registered nurses, 25 (8.7%) enrolled nurses, 187 (64.9%) assistants in nursing/personal care assistants and 9 (3.1%) care service employees. In multivariate analyses, a facility policy not to rotate personnel through dementia units was the only variable associated with more favourable overall personnel knowledge and attitudes. Other variables associated with favourable knowledge were a designation of nursing manager or registered or enrolled nurse, and having a preferred language of English. Other variables associated with favourable attitudes were tertiary level of education and greater experience in dementia care. Like previous international research, this study found Australian LTC personnel knowledge and attitudes regarding palliative care for people with advanced dementia to be associated with both facility and personnel characteristics. Future longitudinal research is needed to better understand the relationships between knowledge and attitudes, as well as between these attributes and quality of care

Potentially Inappropriate Prescribing in Australian Nursing Home Residents with Advanced Dementia: A Substudy of the IDEAL Study

© 2018, Mary Ann Liebert, Inc. Background: Prescribing medications for nursing home residents with advanced dementia should focus on optimizing function and comfort, reducing unnecessary harms and aligning care goals with a palliative approach. Objective: The aim of the study was to estimate the proportion of Australian nursing home residents with advanced dementia receiving potentially inappropriate medications, and identify those most commonly prescribed and factors associated with their use. Design: Data were collected through retrospective audit of medication charts. Setting/Subjects: Two hundred eighteen nursing home residents with advanced dementia from 20 nursing homes participated in a cluster-randomized controlled trial of case conferencing (the IDEAL Study) from June 2013 to December 2014. Measurements: Inappropriate drug use was defined as medications classified as "never appropriate" by the Palliative Excellence in Alzheimer Care Efforts (PEACE) program criteria. Generalized linear mixed models were used to identify variables predicting use of "never" appropriate medications. Results: Over a quarter (n = 65, 30%) of residents received at least one medication classed as "never" appropriate, the most common being lipid-lowering agents (n = 38, 17.4%), antiplatelet agents (n = 18, 8.3%), and acetylcholinesterase inhibitors (n = 16, 7.3%). Residents who had been at the nursing home for ≤10 months (odds ratio [OR] 5.60, 95% confidence interval [CI] 1.74-18.06) and 11-21 months (OR 5.41, 95% CI 1.67-17.75) had significantly greater odds of receiving a never appropriate medication compared with residents who had been at the nursing home for >5 years. Conclusions: Use of potentially inappropriate medications in Australian nursing home residents with advanced dementia is common. A greater understanding of the rationale that underpins prescribing of medications is required

Science and Film-making

The essay reviews the literature, mostly historical, on the relationship between science and film-making, with a focus on the science documentary. It then discusses the circumstances of the emergence of the wildlife making-of documentary genre. The thesis examined here is that since the early days of cinema, film-making has evolved from being subordinate to science, to being an equal partner in the production of knowledge, controlled by non-scientists