The prevention, detection and management of cancer treatment-induced cardiotoxicity: a meta-review

Background The benefits associated with some cancer treatments do not come without risk. A serious side effect of some common cancer treatments is cardiotoxicity. Increased recognition of the public health implications of cancer treatment-induced cardiotoxicity has resulted in a proliferation of systematic reviews in this field to guide practice. Quality appraisal of these reviews is likely to limit the influence of biased conclusions from systematic reviews that have used poor methodology related to clinical decision-making. The aim of this meta-review is to appraise and synthesise evidence from only high quality systematic reviews focused on the prevention, detection or management of cancer treatment-induced cardiotoxicity. Methods Using Cochrane methodology, we searched databases, citations and hand-searched bibliographies. Two reviewers independently appraised reviews and extracted findings. A total of 18 high quality systematic reviews were subsequently analysed, 67 % (n = 12) of these comprised meta-analyses. Results One systematic review concluded that there is insufficient evidence regarding the utility of cardiac biomarkers for the detection of cardiotoxicity. The following strategies might reduce the risk of cardiotoxicity: 1) The concomitant administration of dexrazoxane with anthracylines; 2) The avoidance of anthracyclines where possible; 3) The continuous administration of anthracyclines (>6 h) rather than bolus dosing; and 4) The administration of anthracycline derivatives such as epirubicin or liposomal-encapsulated doxorubicin instead of doxorubicin. In terms of management, one review focused on medical interventions for treating anthracycline-induced cardiotoxicity during or after treatment of childhood cancer. Neither intervention (enalapril and phosphocreatine) was associated with statistically significant improvement in ejection fraction or mortality. Conclusion This review highlights the lack of high level evidence to guide clinical decision-making with respect to the detection and management of cancer treatment-associated cardiotoxicity. There is more evidence with respect to the prevention of this adverse effect of cancer treatment. This evidence, however, only applies to anthracycline-based chemotherapy in a predominantly adult population. There is no high-level evidence to guide clinical decision-making regarding the prevention, detection or management of radiation-induced cardiotoxicity.

A homogeneous surface-enhanced Raman scattering platform for ultra-trace detection of trinitrotoluene in the environment

A facile and sensitive surface-enhanced Raman scattering substrate was prepared by controlled potentiostatic deposition of a closely packed single layer of gold nanostructures (AuNS) over a flat gold (pAu) platform. The nanometer scale inter-particle distance between the particles resulted in high population of ‘hot spots’ which enormously enhanced the scattered Raman photons. A renewed methodology was followed to precisely quantify the SERS substrate enhancement factor (SSEF) and it was estimated to be (2.2 ± 0.17) × 105. The reproducibility of the SERS signal acquired by the developed substrate was tested by establishing the relative standard deviation (RSD) of 150 repeated measurements from various locations on the substrate surface. A low RSD of 4.37 confirmed the homogeneity of the developed substrate. The sensitivity of pAu/AuNS was proven by determining 100 fM 2,4,6-trinitrotoluene (TNT) comfortably. As a proof of concept on the potential of the new pAu/AuNS substrate in field analysis, TNT in soil and water matrices was selectively detected after forming a Meisenheimer complex with cysteamine.

Rapid detection of TNT in aqueous media by selective label free surface enhanced Raman spectroscopy

We report rapid and ultra-sensitive detection system for 2,4,6-trinitrotoluene (TNT) using unmodified gold nanoparticles and surface-enhanced Raman spectroscopy (SERS). First, Meisenheimer complex has been formed in aqueous solution between TNT and cysteamine in less than 15 min of mixing. The complex formation is confirmed by the development of a pink colour and a new UV–vis absorption band around 520 nm. Second, the developed Meisenheimer complex is spontaneously self-assembled onto unmodified gold nanoparticles through a stable Au–S bond between the cysteamine moiety and the gold surface. The developed mono layer of cysteamine-TNT is then screened by SERS to detect and quantify TNT. Our experimental results demonstrate that the SERS-based assay provide an ultra-sensitive approach for the detection of TNT down to 22.7 ng/L. The unambiguous fingerprint identification of TNT by SERS represents a key advantage for our proposed method. The new method provides high selectivity towards TNT over 2,4 DNT and picric acid. Therefore it satisfies the practical requirements for the rapid screening of TNT in real life samples where the interim 24-h average allowable concentration of TNT in waste water is 0.04 mg/L.

Fault detection of wind turbine drivetrain utilizing power-speed characteristics

Wind energy, being the fastest growing renewable energy source in the present world, requires a large number of wind turbines to transform wind energy into electricity. One factor driving the cost of this energy is the reliable operation of these turbines. Therefore, it is a growing requirement within the wind farm community, to monitor the operation of the wind turbines on a continuous basis so that a possible fault can be detected ahead of time. As the wind turbine operates in an environment of constantly changing wind speed, it is a challenging task to design a fault detection technique which can accommodate the stochastic operational behavior of the turbines. Addressing this issue, this paper proposes a novel fault detection criterion which is robust against operational uncertainty, as well as having the ability to quantify severity level specifically of the drivetrain abnormality within an operating wind turbine. A benchmark model of wind turbine has been utilized to simulate drivetrain fault condition and effectiveness of the proposed technique has been tested accordingly. From the simulation result it can be concluded that the proposed criterion exhibits consistent performance for drivetrain faults for varying wind speed and has linear relationship with the fault severity level.

From ImageNet to mining: Adapting visual object detection with minimal supervision

This paper presents visual detection and classification of light vehicles and personnel on a mine site.We capitalise on the rapid advances of ConvNet based object recognition but highlight that a naive black box approach results in a significant number of false positives. In particular, the lack of domain specific training data and the unique landscape in a mine site causes a high rate of errors. We exploit the abundance of background-only images to train a k-means classifier to complement the ConvNet. Furthermore, localisation of objects of interest and a reduction in computation is enabled through region proposals. Our system is tested on over 10km of real mine site data and we were able to detect both light vehicles and personnel. We show that the introduction of our background model can reduce the false positive rate by an order of magnitude.

Redefining dermatologists’ role in skin cancer early detection and follow-up care

Early diagnosis of melanoma leads to the best prognosis for patients and may be more likely achieved when those who are at high risk for melanoma undergo regular and systematic monitoring. However, many people rarely or never see a dermatologist. Risk prediction models (recently reviewed by Usher-Smith et al ) could assist to triage people into preventive care appropriate for their risk profile. Most risk prediction models contain measures of phenotype including skin, eye and hair colour as well as genetic mutations. Almost all also contain the number and size of naevi, as well as the presence of naevi with atypical features which are independently associated with melanoma risk. In the absence of formal population-based screening programs for melanoma in most countries worldwide, people with high risk phenotypes may need to consider regular monitoring or self-monitoring of their naevi , especially since the vast majority of melanomas are found by people themselves or their friend and relatives. Another group of patients that will require regular monitoring are patients who have been successfully treated for their first melanoma, whose risk to develop a second melanoma is greatly increased . In a US study of 89,515 melanoma survivors those with a previous diagnosis of melanoma had a 9-fold increased risk of developing subsequent melanoma compared with the general population, equating to a rate of 3.76 per 1000 person-years, while in an Australian study, risk of subsequent melanoma was 6 per 1000 person-years. Regular follow-up is therefore essential for melanoma survivors, especially during the first few years after initial melanoma diagnosis.

Evaluation of object detection proposals under condition variations

Object detection is a fundamental task in many computer vision applications, therefore the importance of evaluating the quality of object detection is well acknowledged in this domain. This process gives insight into the capabilities of methods in handling environmental changes. In this paper, a new method for object detection is introduced that combines the Selective Search and EdgeBoxes. We tested these three methods under environmental variations. Our experiments demonstrate the outperformance of the combination method under illumination and view point variations.

A low-cost attack on branch-based software watermarking schemes

In 2005, Ginger Myles and Hongxia Jin proposed a software watermarking scheme based on converting jump instructions or unconditional branch statements (UBSs) by calls to a fingerprint branch function (FBF) that computes the correct target address of the UBS as a function of the generated fingerprint and integrity check. If the program is tampered with, the fingerprint and integrity checks change and the target address will not be computed correctly. In this paper, we present an attack based on tracking stack pointer modifications to break the scheme and provide implementation details. The key element of the attack is to remove the fingerprint and integrity check generating code from the program after disassociating the target address from the fingerprint and integrity value. Using the debugging tools that give vast control to the attacker to track stack pointer operations, we perform both subtractive and watermark replacement attacks. The major steps in the attack are automated resulting in a fast and low-cost attack.

Effectiveness of in-office blood pressure measurement by eye care practitioners in early detection and management of hypertension

AIM To investigate the number of hypertensive patients, the optometrist is able to identify by routinely taking blood pressure (BP) measurements for patients in "at -risk" groups, and to sample patients' opinions regarding in -office BP measurement. Many of the optometrists in Saudi Arabia practice in optical stores. These stores are wide spread, easily accessible and seldom need appointments. The expanding role of the optometrist as a primary health care provider (PHCP) and the increasing global prevalence of hypertension, highlight the need for an integrated approach towards detecting and monitoring hypertension. METHODS Automated BP measurements were made twice (during the same session) at five selected optometry practices using a validated BP monitor (Omron M6) to assess the number of patients with high BP (HBP) - in at -risk groups -visiting the eye clinic routinely. Prior to data collection, practitioners underwent a two-day training workshop by a cardiologist on hypertension and how to obtain accurate BP readings. A protocol for BP measurement was distributed and retained in all participating clinics. The general attitude towards cardiovascular health of 480 patients aged 37.2 (依12.4)y and their opinion towards in-office BP measurement was assessed using a self -administered questionnaire. RESULTS A response rate of 83.6% was obtained for the survey. Ninety -three of the 443 patients (21.0% ) tested for BP in this study had HBP. Of these, (62 subjects) 67.7% were unaware of their HBP status. Thirty of the 105 subjects (28.6%) who had previously been diagnosed with HBP, still had HBP at the time of this study, and only 22 (73.3%) of these patients were on medication. Also, only 25% of the diagnosed hypertensive patients owned a BP monitor. CONCLUSION Taking BP measurements in optometry practices, we were able to identify one previously undiagnosed patient with HBP for every 8 adults tested. We also identified 30 of 105 previously diagnosed patients whose BP was poorly controlled, twenty-two of whom were on medication. The patients who participated in this study were positively disposed toward the routine measurement of BP by optometrists.

Microscopy for the detection, identification and quantification of malaria parasites on stained thick and thin blood films in research settings

Summary This manual was developed to guide a move towards common standards for undertaking and reporting research microscopy for malaria parasite detection, identification and quantification. It contains procedures based on agreed quality assurance standards for research malaria microscopy defined at a consultation of: TDR, the Special Programme for Research and Training in Tropical Diseases; the Worldwide Antimalarial Resistance Network (WWARN), United Kingdom; the Foundation for Innovative New Diagnostics (FIND), Switzerland; the Centers for Disease Control and Prevention (CDC), USA; the Kenya Medical Research Institute (KEMRI) and later expanded to include Amref Health Africa (Kenya); the Eijkman-Oxford Clinical Research Unit (EOCRU), Indonesia; Institut Pasteur du Cambodge (IPC); Institut de recherche pour le Développement (IRD), Senegal; the Global Good and Intellectual Ventures Laboratory (GG-IVL), USA; the Mahidol-Oxford Tropical Medicine Research Unit (MORU), Thailand; Queensland University of Technology (QUT), Australia, and the Shoklo Malaria Research Unit (SMRU), Thailand. These collaborating institutions commit to adhering to these standards in published research studies. It is hoped that they will form a solid basis for the wider adoption of standardized reference microscopy protocols for malaria research.

Reproducible and label-free biosensor for the selective extraction and rapid detection of proteins in biological fluids

Erythropoietin (EPO), a glycoprotein hormone of ∼34 kDa, is an important hematopoietic growth factor, mainly produced in the kidney and controls the number of red blood cells circulating in the blood stream. Sensitive and rapid recombinant human EPO (rHuEPO) detection tools that improve on the current laborious EPO detection techniques are in high demand for both clinical and sports industry. A sensitive aptamer-functionalized biosensor (aptasensor) has been developed by controlled growth of gold nanostructures (AuNS) over a gold substrate (pAu/AuNS). The aptasensor selectively binds to rHuEPO and, therefore, was used to extract and detect the drug from horse plasma by surface enhanced Raman spectroscopy (SERS). Due to the nanogap separation between the nanostructures, the high population and distribution of hot spots on the pAu/AuNS substrate surface, strong signal enhancement was acquired. By using wide area illumination (WAI) setting for the Raman detection, a low RSD of 4.92% over 150 SERS measurements was achieved. The significant reproducibility of the new biosensor addresses the serious problem of SERS signal inconsistency that hampers the use of the technique in the field. The WAI setting is compatible with handheld Raman devices. Therefore, the new aptasensor can be used for the selective extraction of rHuEPO from biological fluids and subsequently screened with handheld Raman spectrometer for SERS based in-field protein detection.

Complete-linkage clustering for voice activity detection in audio and visual speech

We propose a novel technique for conducting robust voice activity detection (VAD) in high-noise recordings. We use Gaussian mixture modeling (GMM) to train two generic models; speech and non-speech. We then score smaller segments of a given (unseen) recording against each of these GMMs to obtain two respective likelihood scores for each segment. These scores are used to compute a dissimilarity measure between pairs of segments and to carry out complete-linkage clustering of the segments into speech and non-speech clusters. We compare the accuracy of our method against state-of-the-art and standardised VAD techniques to demonstrate an absolute improvement of 15% in half-total error rate (HTER) over the best performing baseline system and across the QUT-NOISE-TIMIT database. We then apply our approach to the Audio-Visual Database of American English (AVDBAE) to demonstrate the performance of our algorithm in using visual, audio-visual or a proposed fusion of these features.

Stroke: A brain attack!

Brain cells control everything we do - from speaking to walking to breathing. The brain needs a steady supply of blood and oxygen to function properly. Without this vital steady supply of blood, brain cells don't get enough nutrients and oxygen to do their job, and a stroke or 'brain attack' occurs. The human brain is divided into regions that control various motor (movement) and sensory (the senses) functions. Damage from stroke to a specific region may affect the functions it controls. This causes symptoms such as paralysis (loss of movement), difficulty speaking, or loss of coordination. The left side of the brain controls motor and sensory functions on the right side of the body. The left side is also responsible for scientific functions, understanding written and spoken language, number skills and reasoning. The right side of the brain controls motor and sensory functions on the left side of the body. It also controls artistic functions, such as music, art awareness, and insight. If an artery inside the brain or leading to the brain becomes temporarily blocked, the flow of blood to an area of the brain slows or stops. The lack of blood can cause temporary symptoms such as weakness, numbness, problems with speech, dizziness, or loss of vision.

Building a "brain attack" team to administer thrombolytic therapy for acute ischemic stroke

Before tissue plasminogen activator (tPA) was licensed for use in Canada, in February 1999, the Calgary Regional Stroke Program spearheaded the development and organization of local resources to use thrombolytic therapy in patients who had experienced acute ischemic stroke. In 1996 special permission was obtained from the Calgary Regional Health Authority to use intravenously administered tPA for acute ischemic stroke, and ethical and scientific review boards approved the protocols. After 3 years our efforts have resulted in improved patient outcomes, shorter times from symptom onset to treatment and acceptable adverse event rates. Areas for continued improvement include the door-to-needle time and broader education of the public about the symptoms of acute ischemic stroke.

The attack of the clones: Patent law and stem cell research

This article considers the integral role played by patent law in respect of stem cell research. It highlights concerns about commercialization, access to essential medicines and bioethics. The article maintains that there is a fundamental ambiguity in the Patents Act 1990 (Cth) as to whether stem cell research is patentable subject matter. There is a need to revise the legislation in light of the establishment of the National Stem Cell Centre and the passing of the Research Involving Embryos Act 2002 (Cth). The article raises concerns about the strong patent protection secured by the Wisconsin Alumni Research Foundation and Geron Corporation in respect of stem cell research in the United States. It contends that a number of legal reforms could safeguard access to stem cell lines, and resulting drugs and therapies. Finally, this article explores how ethical concerns are addressed within the framework of the European Biotechnology Directive. It examines the decision of the European Patent Office in relation to the so-called Edinburgh patent, and the inquiry of the European Group on Ethics in Science and New Technologies into The Ethical Aspects of Patenting Involving Human Stem Cells.