Validity of the SF-36 Health Survey as an outcome measure for trials in people with spinal cord injury

The SF-36 was interviewer-administered to 305 subjects at recruitment. Feasibility, content validity and internal consistency were assessed. We tested a priori hypotheses about discriminative, convergent and divergent validity. Interviewer-assisted administration was feasible. The content validity of several domains (Physical Function, Role Physical, Social Function and Role Emotional) was compromised by the irrelevance of some items and response options. Resultant ceiling and floor effects may limit the SF-36?s ability to detect changes over time. The SF-36 was able to discriminate differences between people with: tetraplegia versus paraplegia (in the Physical Function and Physical Composite scores); injuries that were recent ( 4 years) (in the Vitality, Social Function and Mental Health domain and Mental Composite scores), and who were employed versus unemployed (in the Physical Function, Social Function, Mental Health and Mental Composite scores). It was not able to discriminate between groups dichotomised by age, injury completeness or gender. The convergent and divergent validity of all SF-36 domains was as in other populations, except for correlations involving the Physical Function scale which were poor. Internal consistency was similar to that in other populations (Cronbach?s alpha from 0.75 to 0.92); the SF-36 has sufficient precision for population-based and clinical research in spinal cord injury. The SF-36 is useful for comparing the health status of people with spinal cord injury to that of other populations, but supplementation with a disease-specific health status measure may be necessary for trials of interventions in people with spinal cord injuries.Quality of life, outcome measures, sf-36

Data-driven Soft Sensors in the Process Industry

In the last two decades Soft Sensors established themselves as a valuable alternative to the traditional means for the acquisition of critical process variables, process monitoring and other tasks which are related to process control. This paper discusses characteristics of the process industry data which are critical for the development of data-driven Soft Sensors. These characteristics are common to a large number of process industry fields, like the chemical industry, bioprocess industry, steel industry, etc. The focus of this work is put on the data-driven Soft Sensors because of their growing popularity, already demonstrated usefulness and huge, though yet not completely realised, potential. A comprehensive selection of case studies covering the three most important Soft Sensor application fields, a general introduction to the most popular Soft Sensor modelling techniques as well as a discussion of some open issues in the Soft Sensor development and maintenance and their possible solutions are the main contributions of this work

SOFIA FEEDBACK Survey: The Pillars of Creation in [C II] and Molecular Lines

We investigate the physical structure and conditions of photodissociation regions (PDRs) and molecular gas within the Pillars of Creation in the Eagle Nebula using SOFIA FEEDBACK observations of the [C II] 158 micron line. These observations are velocity resolved to 0.5 km s$^{-1}$ and are analyzed alongside a collection of complimentary data with similar spatial and spectral resolution: the [O I] 63 micron line, also observed with SOFIA, and rotational lines of CO, HCN, HCO$^{+}$, CS, and N$_2$H$^{+}$. Using the superb spectral resolution of SOFIA, APEX, CARMA, and BIMA, we reveal the relationships between the warm PDR and cool molecular gas layers in context of the Pillars' kinematic structure. We assemble a geometric picture of the Pillars and their surroundings informed by illumination patterns and kinematic relationships and derive physical conditions in the PDRs associated with the Pillars. We estimate an average molecular gas density $n_{{\rm H}_2} \sim 1.3 \times 10^5$ cm$^{-3}$ and an average atomic gas density $n_{\rm H} \sim 1.8 \times 10^4$ cm$^{-3}$ and infer that the ionized, atomic, and molecular phases are in pressure equilibrium if the atomic gas is magnetically supported. We find pillar masses of 103, 78, 103, and 18 solar masses for P1a, P1b, P2, and P3 respectively, and evaporation times of $\sim$1-2 Myr. The dense clumps at the tops of the pillars are currently supported by the magnetic field. Our analysis suggests that ambipolar diffusion is rapid and these clumps are likely to collapse within their photoevaporation timescales.Comment: 42 pages, 16 figures. Accepted for publication in The Astronomical Journa

A Phase 1 Study of TRC102, An Inhibitor of Base Excision Repair, and Pemetrexed in Patients with Advanced Solid Tumors

Introduction TRC102 potentiates the activity of cancer therapies that induce base excision repair (BER) including antimetabolite and alkylating agents. TRC102 rapidly and covalently binds to apurinic/apyrimidinic (AP) sites generated during BER, and TRC102-bound DNA causes topoisomerase II-dependent irreversible strand breaks and apoptosis. This study assessed the safety, maximum-tolerated dose (MTD), pharmacokinetics and pharmacodynamics of TRC102 alone and in combination with pemetrexed. Purpose Patients with advanced solid tumors received oral TRC102 daily for 4 days. Two weeks later, patients began standard-dose pemetrexed on day 1 in combination with oral TRC102 on days 1 to 4. The pemetrexed-TRC102 combination was repeated every 3 weeks until disease progression. Methods Twenty-eight patients were treated with TRC102 at 15, 30, 60 or 100 mg/m2/d. The MTD was exceeded at 100 mg/m2/d due to grade 3 anemia in 50 % of patients. TRC102 exposure increased in proportion to dose with a mean t1/2 of 28 h. A pharmacodynamic assay confirmed that TRC102 binds to pemetrexed-induced AP sites at all doses studied. Stable disease or better was achieved in 15 of 25 patients evaluable for response (60 %), including one patient with recurrent metastatic oropharyngeal carcinoma that expressed high levels of thymidylate synthase, who achieved a partial response and was progression free for 14 months. Conclusions When administered with pemetrexed, the maximum tolerated dose of oral TRC102 is 60 mg/m2/d for 4 days. Randomized controlled studies are planned to evaluate the clinical benefit of adding TRC102 to pemetrexed and other agents that induce BER. © 2012 Springer Science+Business Media, LLC

Utilizing small nutrient compounds as enhancers of exercise-induced mitochondrial biogenesis.

Endurance exercise, when performed regularly as part of a training program, leads to increases in whole-body and skeletal muscle-specific oxidative capacity. At the cellular level, this adaptive response is manifested by an increased number of oxidative fibers (Type I and IIA myosin heavy chain), an increase in capillarity and an increase in mitochondrial biogenesis. The increase in mitochondrial biogenesis (increased volume and functional capacity) is fundamentally important as it leads to greater rates of oxidative phosphorylation and an improved capacity to utilize fatty acids during sub-maximal exercise. Given the importance of mitochondrial biogenesis for skeletal muscle performance, considerable attention has been given to understanding the molecular cues stimulated by endurance exercise that culminate in this adaptive response. In turn, this research has led to the identification of pharmaceutical compounds and small nutritional bioactive ingredients that appear able to amplify exercise-responsive signaling pathways in skeletal muscle. The aim of this review is to discuss these purported exercise mimetics and bioactive ingredients in the context of mitochondrial biogenesis in skeletal muscle. We will examine proposed modes of action, discuss evidence of application in skeletal muscle in vivo and finally comment on the feasibility of such approaches to support endurance-training applications in humans

The cytolinker plectin regulates nuclear mechanotransduction in keratinocytes.

The transmission of mechanical forces to the nucleus is important for intracellular positioning, mitosis and cell motility, yet the contribution of specific components of the cytoskeleton to nuclear mechanotransduction remains unclear. In this study, we examine how crosstalk between the cytolinker plectin and F-actin controls keratin network organisation and the 3D nuclear morphology of keratinocytes. Using micro-patterned surfaces to precisely manipulate cell shape, we find that cell adhesion and spreading regulate the size and shape of the nucleus. Disruption of the keratin cytoskeleton through loss of plectin facilitated greater nuclear deformation, which depended on acto-myosin contractility. Nuclear morphology did not depend on direct linkage of the keratin cytoskeleton with the nuclear membrane, rather loss of plectin reduced keratin filament density around the nucleus. We further demonstrate that keratinocytes have abnormal nuclear morphologies in the epidermis of plectin-deficient, epidermolysis bullosa simplex patients. Taken together, our data demonstrate that plectin is an essential regulator of nuclear morphology in vitro and in vivo and protects the nucleus from mechanical deformation.This work was funded by the Biotechnology and Biological Sciences Research Council (BBSRC) [grant number BB/J000914/1]; and by the Barts and the London Charity [grant number 442/1032]

Emerin Caps the Pointed End of Actin Filaments: Evidence for an Actin Cortical Network at the Nuclear Inner Membrane

X-linked Emery-Dreifuss muscular dystrophy is caused by loss of emerin, a LEM-domain protein of the nuclear inner membrane. To better understand emerin function, we used affinity chromatography to purify emerin-binding proteins from nuclear extracts of HeLa cells. Complexes that included actin, αII-spectrin and additional proteins, bound specifically to emerin. Actin polymerization assays in the presence or absence of gelsolin or capping protein showed that emerin binds and stabilizes the pointed end of actin filaments, increasing the actin polymerization rate 4- to 12-fold. We propose that emerin contributes to the formation of an actin-based cortical network at the nuclear inner membrane, conceptually analogous to the actin cortical network at the plasma membrane. Thus, in addition to disrupting transcription factors that bind emerin, loss of emerin may destabilize nuclear envelope architecture by weakening a nuclear actin network

Probiotics [LGG-BB12 or RC14-GR1] versus placebo as prophylaxis for urinary tract infection in persons with spinal cord injury [ProSCIUTTU]: a randomised controlled trial

© 2019, The Author(s). Study design: Randomised double-blind factorial-design placebo-controlled trial. Objective: Urinary tract infections (UTIs) are common in people with spinal cord injury (SCI). UTIs are increasingly difficult to treat due to emergence of multi-resistant organisms. Probiotics are efficacious in preventing UTIs in post-menopausal women. We aimed to determine whether probiotic therapy with Lactobacillus reuteri RC-14+Lactobacillus GR-1 (RC14-GR1) and/or Lactobacillus rhamnosus GG+Bifidobacterium BB-12 (LGG-BB12) are effective in preventing UTI in people with SCI. Setting: Spinal units in New South Wales, Australia with their rural affiliations. Methods: We recruited 207 eligible participants with SCI and stable neurogenic bladder management. They were randomised to one of four arms: RC14-GR1+LGG-BB12, RC14-GR1+placebo, LGG-BB12+ placebo or double placebos for 6 months. Randomisation was stratified by bladder management type and inpatient or outpatient status. The primary outcome was time to occurrence of symptomatic UTI. Results: Analysis was based on intention to treat. Participants randomised to RC14-GR1 had a similar risk of UTI as those not on RC14-GR1 (HR 0.67; 95% CI: 0.39–1.18; P = 0.17) after allowing for pre-specified covariates. Participants randomised to LGG-BB12 also had a similar risk of UTI as those not on LGG-BB12 (HR 1.29; 95% CI: 0.74–2.25; P = 0.37). Multivariable post hoc survival analysis for RC14-GR1 only vs. the other three groups showed a potential protective effect (HR 0.46; 95% CI: 0.21–0.99; P = 0.03), but this result would need to be confirmed before clinical application. Conclusion: In this RCT, there was no effect of RC14-GR1 or LGG-BB12 in preventing UTI in people with SCI

Blaming Active Volcanoes or Active Volcanic Blame? Volcanic Crisis Communication and Blame Management in the Cameroon

This chapter examines the key role of blame management and avoidance in crisis communication with particular reference to developing countries and areas that frequently experience volcanic episodes and disasters. In these contexts, the chapter explores a key paradox prevalent within crisis communication and blame management concepts that has been rarely tested in empirical terms (see De Vries 2004; Brändström 2016a). In particular, the chapter examines, what it calls, the ‘paradox of frequency’ where frequency of disasters leads to twin dispositions for crisis framed as either: (i) policy failure (active about volcanic blame on others), where issues of blame for internal incompetency takes centre stage, and blame management becomes a focus of disaster managers, and/or: (ii) as event failure (in this case, the blaming of lack of external capacity on active volcanoes and thereby the blame avoidance of disaster managers). Put simply, the authors investigate whether perceptions of frequency itself is a major determinant shaping the existence, operation, and even perceived success of crisis communication in developing regions, and countries experiencing regular disaster episodes. The authors argue frequency is important in shaping the behaviour of disaster managers and rather ironically as part of crisis communication can shape expectations of community resilience and (non)-compliance. In order to explore the implications of the ‘paradox of frequency’ further, the chapter examines the case of the Cameroon, where volcanic activity and events have been regular, paying particular attention to the major disasters in 1986 (Lake Nyos Disaster - LND) and 1999 (Mount Cameroon volcanic eruption - MCE)