Non-invasive brain stimulation techniques for chronic pain (Review)

Background: This is an updated version of the original Cochrane Review published in 2010, Issue 9, and last updated in 2014, Issue 4. Non-invasive brain stimulation techniques aim to induce an electrical stimulation of the brain in an attempt to reduce chronic pain by directly altering brain activity. They include repetitive transcranial magnetic stimulation (rTMS), cranial electrotherapy stimulation (CES), transcranial direct current stimulation (tDCS), transcranial random noise stimulation (tRNS) and reduced impedance non-invasive cortical electrostimulation (RINCE). Objectives: To evaluate the efficacy of non-invasive cortical stimulation techniques in the treatment of chronic pain. Search methods: For this update we searched CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, LILACS and clinical trials registers from July 2013 to October 2017. Selection criteria: Randomised and quasi-randomised studies of rTMS, CES, tDCS, RINCE and tRNS if they employed a sham stimulation control group, recruited patients over the age of 18 years with pain of three months’ duration or more, and measured pain as an outcome. Outcomes of interest were pain intensity measured using visual analogue scales or numerical rating scales, disability, quality of life and adverse events. Data collection and analysis: Two review authors independently extracted and verified data. Where possible we entered data into meta-analyses, excluding studies judged as high risk of bias. We used the GRADE system to assess the quality of evidence for core comparisons, and created three ’Summary of findings’ tables. Main results: We included an additional 38 trials (involving 1225 randomised participants) in this update, making a total of 94 trials in the review (involving 2983 randomised participants). This update included a total of 42 rTMS studies, 11 CES, 36 tDCS, two RINCE and two tRNS. One study evaluated both rTMS and tDCS. We judged only four studies as low risk of bias across all key criteria. Using the GRADE criteria we judged the quality of evidence for each outcome, and for all comparisons as low or very low; in large part this was due to issues of blinding and of precision. rTMS: Meta-analysis of rTMS studies versus sham for pain intensity at short-term follow-up (0 to \u3c 1 week postintervention), (27 studies, involving 655 participants), demonstrated a small effect with heterogeneity (standardised mean difference (SMD) -0.22, 95% confidence interval (CI) -0.29 to -0.16, low-quality evidence). This equates to a 7% (95% CI 5% to 9%) reduction in pain, or a 0.40 (95% CI 0.53 to 0.32) point reduction on a 0 to 10 pain intensity scale, which does not meet the minimum clinically important difference threshold of 15% or greater. Pre-specified subgroup analyses did not find a difference between low-frequency stimulation (low-quality evidence) and rTMS applied to the prefrontal cortex compared to sham for reducing pain intensity at short-term follow-up (very low-quality evidence). High-frequency stimulation of the motor cortex in single-dose studies was associated with a small short-term reduction in pain intensity at short-term follow-up (low-quality evidence, pooled n = 249, SMD -0.38 95% CI -0.49 to -0.27). This equates to a 12% (95% CI 9% to 16%) reduction in pain, or a 0.77 (95% CI 0.55 to 0.99) point change on a 0 to 10 pain intensity scale, which does not achieve the minimum clinically important difference threshold of 15% or greater. The results from multiple-dose studies were heterogeneous and there was no evidence of an effect in this subgroup (very low-quality evidence). We did not find evidence that rTMS improved disability. Meta-analysis of studies of rTMS versus sham for quality of life (measured using the Fibromyalgia Impact Questionnaire (FIQ) at short-term follow-up demonstrated a positive effect (MD -10.80 95% CI -15.04 to -6.55, low-quality evidence). CES: For CES (five studies, 270 participants) we found no evidence of a difference between active stimulation and sham (SMD -0.24, 95% CI -0.48 to 0.01, low-quality evidence) for pain intensity. We found no evidence relating to the effectiveness of CES on disability. One study (36 participants) of CES versus sham for quality of life (measured using the FIQ) at short-term follow-up demonstrated a positive effect (MD -25.05 95% CI -37.82 to -12.28, very low-quality evidence). tDCS: Analysis of tDCS studies (27 studies, 747 participants) showed heterogeneity and a difference between active and sham stimulation (SMD -0.43 95% CI -0.63 to -0.22, very low-quality evidence) for pain intensity. This equates to a reduction of 0.82 (95% CI 0.42 to 1.2) points, or a percentage change of 17% (95% CI 9% to 25%) of the control group outcome. This point estimate meets our threshold for a minimum clinically important difference, though the lower confidence interval is substantially below that threshold. We found evidence of small study bias in the tDCS analyses. We did not find evidence that tDCS improved disability. Meta-analysis of studies of tDCS versus sham for quality of life (measured using different scales across studies) at short-term follow-up demonstrated a positive effect (SMD 0.66 95% CI 0.21 to 1.11, low-quality evidence). Adverse events: All forms of non-invasive brain stimulation and sham stimulation appear to be frequently associated with minor or transient side effects and there were two reported incidences of seizure, both related to the active rTMS intervention in the included studies. However many studies did not adequately report adverse events. Authors’ conclusions: There is very low-quality evidence that single doses of high-frequency rTMS of the motor cortex and tDCS may have short-term effects on chronic pain and quality of life but multiple sources of bias exist that may have influenced the observed effects. We did not find evidence that low-frequency rTMS, rTMS applied to the dorsolateral prefrontal cortex and CES are effective for reducing pain intensity in chronic pain. The broad conclusions of this review have not changed substantially for this update. There remains a need for substantially larger, rigorously designed studies, particularly of longer courses of stimulation. Future evidence may substantially impact upon the presented results

ESR Statement on the Validation of Imaging Biomarkers

Medical imaging capable of generating imaging biomarkers, specifically radiology and nuclear medicine image acquisition and analysis processes, differs from frequently used comparators like blood or urine biomarkers. This difference arises from the sample acquisition methodology. While different analysis methodologies and equipment provide slightly different results in any analytical domain, unlike blood or urine analysis where the samples are obtained by simple extraction or excretion, in radiology the acquisition of the sample is heterogeneous by design, since complex equipment from different vendors is used. Therefore, with this additional degree of freedom in medical imaging, there is still risk of persistent heterogeneity of image quality through time, due to different technological implementations across vendors and protocols used in different centres. Quantitative imaging biomarkers have yet to demonstrate an impact on clinical practice due to this lack of comprehensive standardisation in terms of technical aspects of image acquisition, analysis algorithms, processes and clinical validation. The aim is establishing a standard methodology based on metrology for the validation of image acquisition and analysis methods used in the extraction of biomarkers and radiomics data. The appropriate implementation of the guidelines herein proposed by radiology departments, research institutes and industry will allow for a significant reduction in inter-vendor & inter-centre variability in imaging biomarkers and determine the measurement error obtained, enabling them to be used in imaging-based criteria for diagnosis, prognosis or treatment response, ultimately improving clinical workflows and patient care. The validation of developed analytical methods must be based on a technical performance validation and clinical validation

Different conformations and packing motifs in the crystal structures of four thiophene--carbohydrazide--pyridine derivatives

Peer reviewedPublisher PD

High biological productivity in the central Arabian Sea during the summer monsoon driven by Ekman pumping and lateral advection

Open oceans are generally oligotrophic and support less biological production. Results from the central Arabian Sea show that it may be an exception to this. We provide the observational evidence of fairly high biological production (up to 1700 mg C m-2 d-1) in the central Arabian Sea, along 64oE, during the summer monsoons of 1995 and 1996. The reasons for the observed high biological production, comparable to that from the traditionally well-known Somali upwelling region, were examined in light of the physical forcing and prevailing chemical fields. In the northern part of the central Arabian Sea, north of the axis of the Findlater Jet, upward Ekman pumping and entrainment driven by basin-wide winds along with advection of upwelled waters from the coastal region of Arabia supply nutrients to the upper layers. In the southern part, production is supported by nutrients advected from the Somali upwelling regio

Mapping of land use and geomorphology in the APAPORE project area by LANDSAT satellite data, volume 1

The results of a land use and geomorphological mapping of the so-called Projeto APAPORE area, at Mato Grosso do Sul State are presented. The study was carried out using multispectral scanner (MSS) and return beam vidicon LANDSAT images (channels 5 and 7 for the MSS) at the scale of 1:250,000 from 1980 through visual interpretation. The results indicate that pastureland is the most widespead class and that the agricultural areas re concentrated in the north of the area under study. The area covered with cerradao (arboreous savanna type) has a great areal extention, thus permitting the advance of the agricultural frontier. The geomorphological mapping can be useful to regional planning of future land use within the studied area

Use of neoadjuvant chemotherapy prior to radical hysterectomy in cervical cancer: monitoring tumour shrinkage and molecular profile on magnetic resonance and assessment of 3-year outcome

Use of neoadjuvant chemotherapy prior to radical hysterectomy in cervical cancer: monitoring tumour shrinkage and molecular profile on magnetic resonance and assessment of 3-year outcome The objective of this study is to assess tumour response to neoadjuvant chemotherapy prior to radical hysterectomy in cervical cancer using magnetic resonance (MR) to monitor tumour volume and changes in molecular profile and to compare the survival to that of a control group. Eligibility included Stage Ib-IIb previously untreated cervical tumours >10 cm(3). Neoadjuvant chemotherapy in 22 patients ( methotrexate 300 mg m(-2) (with folinic acid rescue), bleomycin 30 mg m(-2), cisplatin 60 mg m(-2)) was repeated twice weekly for three courses and followed by radical hysterectomy. Post-operative radiotherapy was given in 14 cases. A total of 23 patients treated either with radical surgery or chemoradiotherapy over the same time period comprised the nonrandomised control group. MR scans before and after neoadjuvant chemotherapy and in the control group documented tumour volume on imaging and metabolites on in vivo spectroscopy. Changes were compared using a paired t-test. Survival was calculated using the Kaplan-Meier method. There were no significant differences between the neoadjuvant chemotherapy and control groups in age ( mean, s.d. 43.3 +/- 10, 44.7 +/- 8.5 years, respectively, P = 0.63) or tumour volume (medians, quartiles 35.8, 17.8, 57.7 cm(3) vs 23.0, 15.0, 37.0 cm(3), respectively, P = 0.068). The reduction in tumour volume post-chemotherapy (median, quartiles 7.5, 3.0, 19.0 cm(3)) was significant ( P = 0.002). The reduction in - CH2 triglyceride approached significance ( P = 0.05), but other metabolites were unchanged. The 3-year survival in the chemotherapy group (49.1%) was not significantly different from the control group (46%, P = 0.94). There is a significant reduction in tumour volume and - CH2 triglyceride levels after neoadjuvant chemotherapy, but there is no survival advantage

Interferometric imaging with the 32 element Murchison Wide-field Array

The Murchison Wide-field Array (MWA) is a low frequency radio telescope, currently under construction, intended to search for the spectral signature of the epoch of re-ionisation (EOR) and to probe the structure of the solar corona. Sited in Western Australia, the full MWA will comprise 8192 dipoles grouped into 512 tiles, and be capable of imaging the sky south of 40 degree declination, from 80 MHz to 300 MHz with an instantaneous field of view that is tens of degrees wide and a resolution of a few arcminutes. A 32-station prototype of the MWA has been recently commissioned and a set of observations taken that exercise the whole acquisition and processing pipeline. We present Stokes I, Q, and U images from two ~4 hour integrations of a field 20 degrees wide centered on Pictoris A. These images demonstrate the capacity and stability of a real-time calibration and imaging technique employing the weighted addition of warped snapshots to counter extreme wide field imaging distortions.Comment: Accepted for publication in PASP. This is the draft before journal typesetting corrections and proofs so does contain formatting and journal style errors, also has with lower quality figures for space requirement

A new layout optimization technique for interferometric arrays, applied to the MWA

Antenna layout is an important design consideration for radio interferometers because it determines the quality of the snapshot point spread function (PSF, or array beam). This is particularly true for experiments targeting the 21 cm Epoch of Reionization signal as the quality of the foreground subtraction depends directly on the spatial dynamic range and thus the smoothness of the baseline distribution. Nearly all sites have constraints on where antennas can be placed---even at the remote Australian location of the MWA (Murchison Widefield Array) there are rock outcrops, flood zones, heritages areas, emergency runways and trees. These exclusion areas can introduce spatial structure into the baseline distribution that enhance the PSF sidelobes and reduce the angular dynamic range. In this paper we present a new method of constrained antenna placement that reduces the spatial structure in the baseline distribution. This method not only outperforms random placement algorithms that avoid exclusion zones, but surprisingly outperforms random placement algorithms without constraints to provide what we believe are the smoothest constrained baseline distributions developed to date. We use our new algorithm to determine antenna placements for the originally planned MWA, and present the antenna locations, baseline distribution, and snapshot PSF for this array choice.Comment: 12 pages, 6 figures, 1 table. Accepted for publication in MNRA

Correlations in Nuclear Arrhenius-Type Plots

Arrhenius-type plots for multifragmentation process, defined as the transverse energy dependence of the single-fragment emission-probability, -ln(p_{b}) vs 1/sqrt(E_{t}), have been studied by examining the relationship of the parameters p_{b} and E_{t} to the intermediate-mass fragment multiplicity . The linearity of these plots reflects the correlation of the fragment multiplicity with the transverse energy. These plots may not provide thermal scaling information about fragment production as previously suggested.Comment: 12 pages, Latex, 3 Postscript figures include

The Murchison Widefield Array: the Square Kilometre Array Precursor at low radio frequencies

The Murchison Widefield Array (MWA) is one of three Square Kilometre Array Precursor telescopes and is located at the Murchison Radio-astronomy Observatory in the Murchison Shire of the mid-west of Western Australia, a location chosen for its extremely low levels of radio frequency interference. The MWA operates at low radio frequencies, 80-300 MHz, with a processed bandwidth of 30.72 MHz for both linear polarisations, and consists of 128 aperture arrays (known as tiles) distributed over a ~3 km diameter area. Novel hybrid hardware/software correlation and a real-time imaging and calibration systems comprise the MWA signal processing backend. In this paper the as-built MWA is described both at a system and sub-system level, the expected performance of the array is presented, and the science goals of the instrument are summarised.Comment: Submitted to PASA. 11 figures, 2 table