Facilitating the implementation of clinical technology in healthcare : what role does a national agency play?

Background: Accelerating the implementation of new technology in healthcare is typically complex and multi-faceted. One strategy is to charge a national agency with the responsibility for facilitating implementation. This study examines the role of such an agency in the English National Health Service. In particular, it compares two different facilitation strategies employed by the agency to support the implementation of insulin pump therapy. Methods: The research involved an empirical case study of four healthcare organisations receiving different levels of facilitation from the national agency: two received active hands-on facilitation; one was the intended recipient of a more passive, web-based facilitation strategy; the other implemented the technology without any external facilitation. The primary method of data collection was semi structured qualitative interviews with key individuals involved in implementation. The integrated-PARIHS framework was applied as a conceptual lens to analyse the data. Results: The two sites that received active facilitation from an Implementation Manager in the national agency made positive progress in implementing the technology. In both sites there was a high level of initial receptiveness to implementation. This was similar to a site that had successfully introduced insulin pump therapy without facilitation support from the national agency. By contrast, a site that did not have direct contact with the national agency made little progress with implementation, despite the availability of a web-based implementation resource. Clinicians expressed differences of opinion around the value and effectiveness of the technology and contextual barriers related to funding for implementation persisted. The national agency’s intended roll out strategy using passive web-based facilitation appeared to have little impact. Conclusions: When favourable conditions exist, in terms of agreement around the value of the technology, clinician receptiveness and motivation to change, active facilitation via an external agency can help to structure the implementation process and address contextual barriers. Passive facilitation using web-based implementation resources appears less effective. Moving from initial implementation to wider scale-up presents challenges and is an issue that warrants further attention

A 13C NMR study of Decomposing Logging Residues in an Australian Hoop Pine Plantation

Purpose Residue retention is important for nutrient and water economy in sub-tropical plantation forests. We examined decomposing hoop pine (Araucaria cunninghamii Ait. Ex D. Don) residues – foliage, branches and stem wood – to determine the changes in structural chemistry that occur during decomposition. Materials and methods Residues were incubated in situ using 0.05-m2 microplots. We used solid-state 13C nuclear magnetic resonance (NMR) spectroscopy to determine the structural composition of harvest residues in the first 24 months of decomposition. Results and discussion The spectral data for branch and stem residues were generally similar to one another and showed few changes during decomposition. The lignin content of branch and foliage residues decreased during decomposition. When residues were mixed together during decomposition the O-alkyl fraction of foliage decreased initially then increased up to 24 months, while the alkyl carbon (C) fraction exhibited the opposite pattern. The decomposition of woody hoop pine residues (branch and stem wood) is surprisingly uniform across the major C forms elucidated with 13C NMR, with little evidence of preferential decomposition. When mixed with branch and stem materials, foliage residues showed significant short- and long-term compositional changes. This synergistic effect may be due to the C:N ratio of the treatments and the structure of the microbial decomposer community. Conclusions Twenty-four months of decomposition of hoop pine residues did not result in substantial accumulation of recalcitrant C forms, suggesting that they may not contribute to long-term C sequestration

Inhibition of Poly(ADP-Ribose) polymerase enhances the toxicity of 131I-Metaiodobenzylguanidine/Topotecan combination therapy to cells and xenografts that express the noradrenaline transporter

Targeted radiotherapy using [131I]meta-iodobenzylguanidine ([131I]MIBG) has produced remissions in some neuroblastoma patients. We previously reported that combining [131I]MIBG with the topoisomerase I (Topo-I) inhibitor topotecan induced long-term DNA damage and supra-additive toxicity to NAT-expressing cells and xenografts. This combination treatment is undergoing clinical evaluation. This present study investigated the potential of PARP-1 inhibition, in vitro and in vivo, to further enhance [131I]MIBG/topotecan efficacy

Modeling nonlinear resonance: A modification to the stokes' perturbation expansion

The Stokes' series is a small amplitude perturbation expansion for nonlinear, steadily translating waves of the form u(x - ct). We have developed a modification to the Stokes' perturbation expansion to cope with the type of resonance that occurs when two different wavenumbers have identical phase speeds. Although the nonlinear wave is smooth and bounded at the resonance, the traditional Stokes' expansion fails because of the often-encountered "small denominator" problem. The situation is rectified by adding the resonant harmonic into the expansion at lowest order. The coefficient of the resonant wave is determined at higher order. Near resonance is treated by expanding the dispersion parameter in terms of the amplitude. As an example, we have chosen the Korteweg de Vries equation with an additional fifth degree dispersion term. However, the method is applicable to the amplitude expansions of much more complicated problems, such as the double cnoidal waves of the Korteweg de Vries equation, the problem that motivated this study.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27469/1/0000510.pd

Double cnoidal waves of the Korteweg-de Vries equation: A boundary value approach

Double cnoidal waves of the Korteweg-de Vries equation are studied by direct solution of the nonlinear boundary value problems. These double cnoidal waves, which are the spatially periodic generalization of the well-known double soliton, are exact solutions with two independent phase speeds. The equation is written in terms of two phase variables and expanded in two-dimensional Fourier series. The small-amplitude solution is obtained via the Stokes' perturbation expansion. This solution is numerically extended to larger amplitude by employing a Newton-Kantorovich[+45 degree rule]continuation in amplitude[+45 degree rule] Galerkin algorithm. The crests of the finite amplitude solution closely match the sech2 solitary wave form and the three cases of solitary wave interaction described by Lax are identified for the double cnoidal waves. This simple approach reproduces specific features such as phase shift upon collision, distinction between instantaneous and average phase speeds, and a "paradox of wavenumbers".Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29346/1/0000414.pd

A Review of Transcranial Magnetic Stimulation and Multimodal Neuroimaging to Characterize Post-Stroke Neuroplasticity

Following stroke, the brain undergoes various stages of recovery where the central nervous system can reorganize neural circuitry (neuroplasticity) both spontaneously and with the aid of behavioral rehabilitation and non-invasive brain stimulation. Multiple neuroimaging techniques can characterize common structural and functional stroke-related deficits, and importantly, help predict recovery of function. Diffusion tensor imaging (DTI) typically reveals increased overall diffusivity throughout the brain following stroke, and is capable of indexing the extent of white matter damage. Magnetic resonance spectroscopy (MRS) provides an index of metabolic changes in surviving neural tissue after stroke, serving as a marker of brain function. The neural correlates of altered brain activity after stroke have been demonstrated by abnormal activation of sensorimotor cortices during task performance, and at rest, using functional magnetic resonance imaging (fMRI). Electroencephalography (EEG) has been used to characterize motor dysfunction in terms of increased cortical amplitude in the sensorimotor regions when performing upper limb movement, indicating abnormally increased cognitive effort and planning in individuals with stroke. Transcranial magnetic stimulation (TMS) work reveals changes in ipsilesional and contralesional cortical excitability in the sensorimotor cortices. The severity of motor deficits indexed using TMS has been linked to the magnitude of activity imbalance between the sensorimotor cortices. In this paper, we will provide a narrative review of data from studies utilizing DTI, MRS, fMRI, EEG, and brain stimulation techniques focusing on TMS and its combination with uni- and multimodal neuroimaging methods to assess recovery after stroke. Approaches that delineate the best measures with which to predict or positively alter outcomes will be highlighted

Frontal, Sensorimotor, and Posterior Parietal Regions Are Involved in Dual-Task Walking After Stroke

Background: Walking within the community requires the ability to walk while simultaneously completing other tasks. After a stroke, completing an additional task while walking is significantly impaired, and it is unclear how the functional activity of the brain may impact this. Methods: Twenty individual in the chronic stage post-stroke participated in this study. Functional near-infrared spectroscopy (fNIRS) was used to measure prefrontal, pre-motor, sensorimotor, and posterior parietal cortices during walking and walking while completing secondary verbal tasks of varying difficulty. Changes in brain activity during these tasks were measured and relationships were accessed between brain activation changes and cognitive or motor abilities. Results: Significantly larger activations were found for prefrontal, pre-motor, and posterior parietal cortices during dual-task walking. Increasing dual-task walking challenge did not result in an increase in brain activation in these regions. Higher general cognition related to lower increases in activation during the easier dual-task. With the harder dual-task, a trend was also found for higher activation and less motor impairment. Conclusions: This is the first study to show that executive function, motor preparation/planning, and sensorimotor integration areas are all important for dual-task walking post-stroke. A lack of further brain activation increase with increasing challenge suggests a point at which a trade-off between brain activation and performance occurs. Further research is needed to determine if training would result in further increases in brain activity or improved performance

Phase-dependent Brain Activation of the Frontal and Parietal Regions During Walking After Stroke - An fNIRS Study

Background: Recovery of walking post-stroke is highly variable. Accurately measuring and documenting functional brain activation characteristics during walking can help guide rehabilitation. Previous work in this area has been limited to investigations of frontal brain regions and have not utilized recent technological and analytical advances for more accurate measurements. There were three aims for this study: to characterize the hemodynamic profile during walking post-stroke, to investigate regional changes in brain activation during different phases of walking, and to related brain changes to clinical measures. Methods: Functional near-infrared spectroscopy (fNIRS) along the pre-frontal, premotor, sensorimotor, and posterior parietal cortices was used on twenty individuals greater than six months post-stroke. Individual fNIRS optodes were digitized and used to estimate channel locations on each participant and short separation channels were used to control for extracerebral hemodynamic changes. Participants walked at their comfortable pace several times along a hallway while brain activation was recorded. Exploratory cluster analysis was conducted to determine if there was a link between brain activation and clinical measures. Results: Sustained activation was observed in the pre-frontal cortex with the ipsilesional hemisphere showing greater activation compared to the contralesional side. Sensorimotor cortex was active during the early, acceleration stage of walking only. Posterior parietal cortex showed changes in activation during the later, steady-state stage of walking. Faster gait speeds also related to increased activation in contralesional sensorimotor and posterior parietal cortices. Exploratory analysis clustered participants into two distinct groups based on their brain activation profiles and generally showed that individuals with greater activation tended to have better physical outcomes. Conclusions: These findings can guide future research for obtaining adequate power and determining factors that can be used as effect modifiers to reduce inter-subject variability. Overall, this is the first study to report specific oxygenated and deoxygenated hemoglobin changes in frontal to parietal regions during walking in the stroke population. Our results shed light on the importance of measuring brain activation across the cortex and show the importance of pre-frontal, sensorimotor, and posterior parietal cortices in walking after a stroke

Detection and metabolic investigations of a novel designer steroid: 3-chloro-17α-methyl-5α-androstan-17β-ol

In 2012, seized capsules containing white powder were analyzed to show the presence of unknown steroid-related compounds. Subsequent gas chromatography–mass spectrometry (GC-MS) and nuclear magnetic resonance (NMR) investigations identified a mixture of 3α- and 3β- isomers of the novel compound; 3-chloro-17α-methyl-α-androstan-17β-ol. Synthesis of authentic reference materials followed by comparison of NMR, GC-MS and gas chromatography-tandem mass spectrometry (GC-MS/MS) data confirmed the finding of a new ‘designer’ steroid. Furthermore, in vitro androgen bioassays showed potent activity highlighting the potential for doping using this steroid. Due to the potential toxicity of the halogenated steroid, in vitro metabolic investigations of 3α-chloro-17α-methyl-α-androstan-17β-ol using equine and human S9 liver fractions were performed. For equine, GC-MS/MS analysis identified the diagnostic 3α-chloro-17α-methyl-5α-androstane-16α,17β-diol metabolite. For human, the 17α-methyl-α-androstane-3α,17β-diol metabolite was found. Results from these studies were used to verify the ability of GC-MS/MS precursor-ion scanning techniques to support untargeted detection strategies for designer steroids in anti-doping analyses.Synthesis and in vitro metabolic investigations of 3α/β-chloro-17α-methyl-5α-androstan -17β-ol was suppo rted by the Austr a-lian Research Council Linkage Grant (LP120200444) Strat egies for the detection of designer ster oids in ra cehorses