Determining and updating PET/CT and SPECT/CT diagnostic reference levels : a systematic review

The aim of this systematic review is to investigate the national diagnostic reference level (NDRL) methods for positron emission tomography/computed tomography (PET/CT) and single photon emission tomography/computed tomography (SPECT/CT) procedures. A search strategy was based on the preferred, reporting items for systematic review and meta-analysis (PRISMA). Relevant articles retrieved from Medline, Scopus, Web of Science, Embase, Cinahl, and Google Scholar published up to October 2017. The search yielded 1,057 articles. Fourteen articles were included in the review after a screening process. Relevant information from the selected articles were summarised and analysed. Discrepancies were found between the methodologies utilised to establish and report both PET/CT and SPECT/CT NDRLs, e.g. patient sampling and administered activity. Further research should focus on reporting more NDRLs for hybrid PET/CT and SPECT/CT examinations, and establish a robust NDRL standard for the CT portion associated with PET/CT and SPECT/CT examinations. This review provides updated NDRL reommndations to deliver more comparable international radation doses for administered activity and CT dose across PET/CT and SPECT/CT clinics

Dynamic in-situ sensing of fluid-dispersed 2D materials integrated on microfluidic Si chip

This is the author accepted manuscript. The final version is available from Nature Publishing Group via the DOI in this record.The supplementary videos associated with this article are located in ORE at: https://doi.org/10.24378/exe.1643In this work, we propose a novel approach for wafer-scale integration of 2D materials on CMOS photonics chip utilising methods of synthetic chemistry and microfluidics technology. We have successfully demonstrated that this approach can be used for integration of any fluid-dispersed 2D nano-objects on silicon-on-insulator photonics platform. We demonstrate for the first time that the design of an optofluidic waveguide system can be optimised to enable simultaneous in-situ Raman spectroscopy monitoring of 2D dispersed flakes during the device operation. Moreover, for the first time, we have successfully demonstrated the possibility of label-free 2D flake detection via selective enhancement of the Stokes Raman signal at specific wavelengths. We discovered an ultra-high signal sensitivity to the xyz alignment of 2D flakes within the optofluidic waveguide, which in turn enables precise in-situ alignment detection for the first practicable realisation of 3D photonic microstructure shaping based on 2D-fluid composites and CMOS photonics platform while also representing a useful technological tool for the control of liquid phase deposition of 2D materials.We acknowledge financial support from: The Engineering and Physical Sciences Research Council (EPSRC) of the United Kingdom via the EPSRC Centre for Doctoral Training in Electromagnetic Metamaterials (Grant No. EP/L015331/1) and also via Grant Nos. EP/N035569/1, EP/G036101/1, EP/M002438/1, and EP/M001024/1, Science Foundation Ireland Grant No. 12/IA/1300, the Ministry of Education and Science of the Russian Federation (Grant No. 14.B25.31.0002) and the Royal Society International Exchange Grant 2015/R3. The microfluidic structures were fabricated at Tyndall National Institute under the Science Foundation Ireland NAP368 and NAP94 programs

Ultra-sensitive label-free in-situ detection of dynamically driven self-assembly of 2D nanoplatelets on SOI chip

Fluid dispersed two-dimensional (2D) composite materials with dynamically tunable functional properties have recently emerged as a novel highly promising class of optoelectronic materials, opening up new routes not only for the emerging field of metamaterials but also to chip-scale multifunctional metadevices. However, in-situ monitoring and detection of the dynamic ordering of 2D nanoparticles on chip and during the device operation is still a huge challenge. Here we introduce a novel approach for on-chip, in-situ Raman characterisation of 2D-fluid composite materials incorporated into Si photonics chip. In this work the Raman signal for 2D nanoplatelets is selectively enhanced by Fabry-Perot resonator design of CMOS photonic-compatible microfluidic channels. This has then been extended to demonstrate the first in-situ Raman detection of the dynamics of individual 2D nanoplatelets, within a microfluidic channel. Our work paves the way for the first practicable realisation of 3D photonic microstructure shaping based on 2D-fluid composites and CMOS photonics platform.We acknowledge financial support from: the Engineering and Physical Sciences Research Council (EPSRC) of the United Kingdom via the EPSRC Centre for Doctoral Training in Electromagnetic Metamaterials (Grant No. EP/L015331/1) and also via Grants No. EP/G036101/1, EP/M002438/1, and EP/M001024/1, Science Foundation Ireland Grant No. 12/IA/1300, the Ministry of Education and Science of the Russian Federation (Grant No. 14.B25.31.0002) and the Royal Society International Exchange Grant 2015/R3. The microfluidic structures were fabricated at Tyndall National Institute under the Science Foundation Ireland NAP368 and NAP94 programmes

Aural toilet (ear cleaning) for chronic suppurative otitis media

BACKGROUND: Chronic suppurative otitis media (CSOM), sometimes referred to as chronic otitis media (COM), is a chronic inflammation and often polymicrobial infection (involving more than one micro-organism) of the middle ear and mastoid cavity, characterised by ear discharge (otorrhoea) through a perforated tympanic membrane. The predominant symptoms of CSOM are ear discharge and hearing loss. Aural toileting is a term describing a number of processes for manually cleaning the ear. Techniques used may include dry mopping (with cotton wool or tissue paper), suction clearance (typically under a microscope) or irrigation (using manual or automated syringing). Dry mopping may be effective in removing mucopurulent discharge. Compared to irrigation or microsuction it is less effective in removing epithelial debris or thick pus. Aural toileting can be used alone or in addition to other treatments for CSOM, such as antibiotics or topical antiseptics. OBJECTIVES: To assess the effects of aural toilet procedures for people with CSOM. SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL via the Cochrane Register of Studies); Ovid MEDLINE; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 16 March 2020. SELECTION CRITERIA: We included randomised controlled trials (RCTs) with at least a one-week follow-up involving people (adults and children) who had chronic ear discharge of unknown cause or CSOM, where the ear discharge had continued for more than two weeks. We included any aural toileting method as the intervention, at any frequency and for any duration. The comparisons were aural toileting compared with a) placebo or no intervention, and b) any other aural toileting method. We analysed trials in which background treatments were used in both arms (e.g. topical antiseptics or topical antibiotics) separately. DATA COLLECTION AND ANALYSIS: We used the standard Cochrane methodological procedures. We used GRADE to assess the certainty of the evidence for each outcome. Our primary outcomes were: resolution of ear discharge or 'dry ear' (whether otoscopically confirmed or not), measured at between one week and up to two weeks, two weeks to up to four weeks, and after four weeks; health-related quality of life using a validated instrument; and ear pain (otalgia) or discomfort or local irritation. Secondary outcomes were hearing, serious complications, and the adverse events of ear bleeding and dizziness/vertigo/balance problems. MAIN RESULTS: We included three studies with a total of 431 participants (465 ears), reporting on two comparisons. Two studies included only children with CSOM in the community (351 participants) and the other study (80 participants) included children and adults with chronic ear discharge for at least six weeks. None of the included studies reported the outcomes of health-related quality of life, ear pain or the adverse event of ear bleeding. Daily aural toileting (dry mopping) versus no treatment Two studies (351 children; 370 ears) compared daily dry mopping with no treatment. Neither study presented results for resolution of ear discharge at between one and up to two weeks or between two to four weeks. For resolution of ear discharge after four weeks, one study reported the results per person. We are very uncertain whether there is a difference at 16 weeks (risk ratio (RR) 1.01, 95% confidence interval (CI) 0.60 to 1.72; 1 study; 217 participants) because the certainty of the evidence is very low. No results were reported for the adverse events of dizziness, vertigo or balance problems. Only one study reported serious complications, but it was not clear which group these patients were from, or whether the complications occurred pre- or post-treatment. One study reported hearing, but the results were presented by treatment outcome rather than by treatment group so it is not possible to determine whether there is a difference between the two groups. Daily aural toileting versus single aural toileting on top of topical ciprofloxacin One study (80 participants; 95 ears) compared daily aural toileting (suction) with administration of topical antibiotic (ciprofloxacin) ear drops in a clinic, to a single aural toileting (suction) episode followed by daily self-administered topical antibiotic drops, in participants of all ages. We are unsure whether there is a difference in resolution of ear discharge at between one and up to two weeks (RR 1.09, 95% CI 0.91 to 1.30; 1 study; 80 participants) because the certainty of the evidence is very low. There were no results reported for resolution of ear discharge at between two to four weeks. The results for resolution of ear discharge after four weeks were presented by ear, not person, and could not be adjusted to by person. One patient in the group with single aural toileting and self administration of topical antibiotic ear drops reported the adverse event of dizziness, which the authors attributed to the use of cold topical ciprofloxacin. It is very uncertain whether there is a difference between the groups (RR 0.33, 95% CI 0.01 to 7.95; 1 study; 80 participants, very low-certainty). No results were reported for the other adverse events of vertigo or balance problems, or for serious complications. The authors only reported qualitatively that there was no difference between the two groups in hearing results (very low-certainty). AUTHORS' CONCLUSIONS: We are very uncertain whether or not treatment with aural toileting is effective in resolving ear discharge in people with CSOM, due to a lack of data and the poor quality of the available evidence. We also remain uncertain about other outcomes, including adverse events, as these were not well reported. Similarly, we are very uncertain whether daily suction clearance, followed by antibiotic ear drops administered at a clinic, is better than a single episode of suction clearance followed by self-administration of topical antibiotic ear drops

Antibiotics versus topical antiseptics for chronic suppurative otitis media

Background Chronic suppurative otitis media (CSOM), sometimes referred to as chronic otitis media (COM), is a chronic inflammation and infection of the middle ear and mastoid cavity, characterised by ear discharge (otorrhoea) through a perforated tympanic membrane. The predominant symptoms of CSOM are ear discharge and hearing loss. Antibiotics and antiseptics kill or inhibit the micro‐organisms that may be responsible for the infection. Antibiotics can be applied topically or administered systemically via the oral or injection route. Antiseptics are always directly applied to the ear (topically). Objectives To assess the effectiveness of antibiotics versus antiseptics for people with chronic suppurative otitis media (CSOM). Search methods The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL; 2019, Issue 4, via the Cochrane Register of Studies); Ovid MEDLINE; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 1 April 2019. Selection criteria We included randomised controlled trials (RCTs) with at least a one‐week follow‐up involving patients (adults and children) who had chronic ear discharge of unknown cause or CSOM, where ear discharge had continued for more than two weeks. The intervention was any single, or combination of, antibiotic agent, whether applied topically (without steroids) or systemically. The comparison was any single, or combination of, topical antiseptic agent, applied as ear drops, powders or irrigations, or as part of an aural toileting procedure. Two comparisons were topical antiseptics compared to: a) topical antibiotics or b) systemic antibiotics. Within each comparison we separated where both groups of patients had received topical antibiotic a) alone or with aural toilet and b) on top of background treatment (such as systemic antibiotics). Data collection and analysis We used the standard Cochrane methodological procedures. We used GRADE to assess the certainty of the evidence for each outcome. Our primary outcomes were: resolution of ear discharge or 'dry ear' (whether otoscopically confirmed or not), measured at between one week and up to two weeks, two weeks to up to four weeks, and after four weeks; health‐related quality of life using a validated instrument; and ear pain (otalgia) or discomfort or local irritation. Secondary outcomes included hearing, serious complications and ototoxicity measured in several ways. Main results We identified seven studies (935 participants) across four comparisons with antibiotics compared against acetic acid, aluminium acetate, boric acid and povidone‐iodine. None of the included studies reported the outcomes of quality of life or serious complications. A. Topical antiseptic (acetic acid) versus topical antibiotics (quinolones or aminoglycosides) It is very uncertain if there is a difference in resolution of ear discharge with acetic acid compared with aminoglycosides at one to two weeks (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.72 to 1.08; 1 study; 100 participants; very low‐certainty evidence). No study reported results for ear discharge after four weeks. It was very uncertain if there was more ear pain, discomfort or local irritation with acetic acid or topical antibiotics due to the low numbers of participants reporting events (RR 0.16, 95% CI 0.02 to 1.34; 2 RCTs; 189 participants; very low‐certainty evidence). No differences between groups were reported narratively for hearing (quinolones) or suspected ototoxicity (aminoglycosides) (very low‐certainty evidence). B. Topical antiseptic (aluminium acetate) versus topical antibiotics No results for the one study comparing topical antibiotics with aluminium acetate could be used in the review. C. Topical antiseptic (boric acid) versus topical antibiotics (quinolones) One study reported more participants with resolution of ear discharge when using topical antibiotics (quinolones) compared with boric acid ear drops at between one to two weeks (risk ratio (RR) 1.86, 95% confidence interval (CI) 1.48 to 2.35; 1 study; 411 participants; moderate‐certainty evidence). This means that one additional person will have resolution of ear discharge for every four people receiving topical antibiotics (compared with boric acid) at two weeks. No study reported results for ear discharge after four weeks. There was a bigger improvement in hearing in the topical antibiotic group compared to the topical antiseptic group (mean difference (MD) 2.79 decibels (dB), 95% CI 0.48 to 5.10; 1 study; 390 participants; low‐certainty evidence) but this difference may not be clinically significant. There may be more ear pain, discomfort or irritation with boric acid compared with quinolones (RR 0.56, 95% CI 0.32 to 0.98; 2 studies; 510 participants; low‐certainty evidence). Suspected ototoxicity was not reported. D. Topical antiseptic (povidone‐iodine) versus topical antibiotics (quinolones) It is uncertain if there is a difference between quinolones and povidone‐iodine with respect to resolution of ear discharge at one to two weeks (RR 1.02, 95% CI 0.82 to 1.26; 1 RCT, 39 participants; very low‐certainty evidence). The study reported qualitatively that there were no differences between the groups for hearing and no patients developed ototoxic effects (very low‐certainty evidence). No results for resolution of ear discharge beyond four weeks, or ear pain, discomfort or irritation, were reported. E. Topical antiseptic (acetic acid) + aural toileting versus topical + systemic antibiotics (quinolones) One study reported that participants receiving topical and oral antibiotics had less resolution of ear discharge compared with acetic acid ear drops and aural toileting (suction clearance every two days) at one month (RR 0.69, 95% CI 0.53 to 0.90; 100 participants). The study did not report results for resolution of ear discharge at between one to two weeks, ear pain, discomfort or irritation, hearing or suspected ototoxicity. Authors' conclusions Treatment of CSOM with topical antibiotics (quinolones) probably results in an increase in resolution of ear discharge compared with boric acid at up to two weeks. There was limited evidence for the efficacy of other topical antibiotics or topical antiseptics and so we are unable to draw conclusions. Adverse events were not well reported

Alcohol consumption and lifetime change in cognitive ability:a gene × environment interaction study

Studies of the effect of alcohol consumption on cognitive ability are often confounded. One approach to avoid confounding is the Mendelian randomization design. Here, we used such a design to test the hypothesis that a genetic score for alcohol processing capacity moderates the association between alcohol consumption and lifetime change in cognitive ability. Members of the Lothian Birth Cohort 1936 completed the same test of intelligence at age 11 and 70 years. They were assessed for recent alcohol consumption in later life and genotyped for a set of four single-nucleotide polymorphisms in three alcohol dehydrogenase genes. These variants were unrelated to late-life cognition or to socioeconomic status. We found a significant gene × alcohol consumption interaction on lifetime cognitive change (p = 0.007). Individuals with higher genetic ability to process alcohol showed relative improvements in cognitive ability with more consumption, whereas those with low processing capacity showed a negative relationship between cognitive change and alcohol consumption with more consumption. The effect of alcohol consumption on cognitive change may thus depend on genetic differences in the ability to metabolize alcohol

Oxaliplatin-dacarbazine combination chemotherapy for the treatment of advanced soft tissue sarcoma of the limbs

<p>Abstract</p> <p>Background</p> <p>This study was designed to explore the feasibility, safety, and outcomes of pre-operative oxaliplatin-dacarbazine combination therapy for the treatment of advanced soft tissue sarcoma (STS) of the limb.</p> <p>Patients and Methods</p> <p>Between November 2005 and November 2008, 31 patients with advanced limb STS classified with stage IV STS were randomly assigned into experimental or control groups, and both were given 2 cycles of chemotherapy before undergoing surgery. The regimen for the experimental group was oxaliplatin (120 mg/m², d₁) in combination with dacarbazine (175 mg/m², d₁₃), while that for the control group was a standard vincristine, epirubicin, cyclophosphamide therapy. Operations were carried out four weeks after the second chemotherapy cycle, followed by another 24 more chemotherapy cycles of the previous regimen.</p> <p>Results</p> <p>Following preoperative chemotherapy, the experimental group exhibited a significant improvement in tumor regression compared to controls. Both regimens were well-tolerated, and no significant differences in adverse reactions were noted. At a median follow-up of 24 months, 28 patients were still alive and had normal limb function. The progression free survival rate of the experimental group was significantly higher than that of the control group (10/15 vs. 4/16, <it>p </it>< 0.05).</p> <p>Conclusion</p> <p>Oxaliplatin- dacarbazine neoadjuvant/adjuvant chemotherapy improved the prognosis of patients with advanced limb STS in comparison with vincristine, epirubicin, cyclophosphamide combination therapy.</p

Effect of carnitine on muscular glutamate uptake and intramuscular glutathione in malignant diseases

Abnormally low intramuscular glutamate and glutathione (GSH) levels and/or a decreased muscular uptake of glutamate by the skeletal muscle tissue have previously been found in malignant diseases and simian immunodeficiency virus (SIV) infection and may contribute to the development of cachexia. We tested the hypothesis that an impaired mitochondrial energy metabolism may compromise the Na+-dependent glutamate transport. A randomized double-blind clinical trial was designed to study the effects of L -carnitine, i.e. an agent known to enhance mitochondrial integrity and function, on the glutamate transport and plasma glutamate level of cancer patients. The effect of carnitine on the intramuscular glutamate and GSH levels was examined in complementary experiments with tumour-bearing mice. In the mice, L -carnitine treatment ameliorated indeed the tumour-induced decrease in muscular glutamate and GSH levels and the increase in plasma glutamate levels. The carnitine-treated group in the randomized clinical study showed also a significant decrease in the plasma glutamate levels but only a moderate and statistically not significant increase in the relative glutamate uptake in the lower extremities. Further studies may be warranted to determine the effect of L -carnitine on the intramuscular GSH levels in cancer patients. © 2000 Cancer Research Campaig

A multi-gene signature predicts outcome in patients with pancreatic ductal adenocarcinoma.

© 2014 Haider et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Improved usage of the repertoires of pancreatic ductal adenocarcinoma (PDAC) profiles is crucially needed to guide the development of predictive and prognostic tools that could inform the selection of treatment options