Scoliosis imaging : an analysis of radiation risk in the CT scan projection radiograph and a comparison with projection radiography and EOS

Introduction: Scoliosis is defined as a deformity of the spine with lateral curvature in the coronal plane. It requires regular X-ray imaging to monitor the progress of the disorder, therefore scoliotic patients are frequently exposed to radiation. It is important to lower the risk from these exposures for young patients. The aim of this work is to compare organ dose (OD) values resulting from Scan Projection Radiograph (SPR) mode in CT against projection radiography and EOS® imaging system when assessing scoliosis. Methods: A dosimetry phantom was used to represent a 10-year old child. Thermoluminescent dosimetry detectors were used for measuring OD. The phantom was imaged with CT in SPR mode using 27 imaging parameters; projection radiography and EOS machines using local scoliosis imaging procedures. Imaging was performed in anteroposterior, posteroanterior and lateral projections. Results: 17 protocols delivered significantly lower radiation dose than projection radiography (p <0.05). OD values from the CT SPR imaging protocols and projection radiography were statistically significant higher than the results from EOS. No statistically significant differences in OD were observed between 10 imaging protocols and those from projection radiography and EOS imaging protocols (p >0.05). Conclusion: EOS has the lowest dose. Where this technology is not available we suggest there is a potential for OD reduction in scoliosis imaging using CT SPR compared to projection radiography. Further work is required to investigate image quality in relation to the measurement of Cobb angle with CT SPR

Development and validation of a bespoke phantom to test accuracy of Cobb angle measurements

Introduction: Adolescent idiopathic scoliosis (AIS) is a spinal deformity that causes the spine to bend laterally. Patients with AIS undergo frequent X-ray examinations to monitor the progression of the disorder by through the measurement of the Cobb angle. Frequent exposure of adolescents poses the risk of radiation-induced cancer. The aim of this research was to design and build a bespoke phantom representing a 10-year-old child with AIS to allow optimisation of imaging protocols for AIS assessment through the accuracy of Cobb angle measurements. Method: Poly-methyl methacrylate (PMMA) and plaster of Paris (PoP) were used to represent human soft tissue and bone tissue, respectively, to construct a phantom exhibiting a 15olateral curve of the spine. The phantom was validated by comparing the Hounsfield unit (HU)of its vertebrae with that of human and sheep. Additionally, comparisons of signal-to-noise ratio (SNR) to those from a commercially available phantom. An assessment of the accuracy of the radiographic assessment of the Cobb angle measurement was performed. Results: The HU of the PoP vertebrae was 628 (SD= 56), human vertebrae was 598 (SD= 79) and sheep vertebra was 605 (SD= 83). The SNR values of the two phantoms correlated strongly (r = 0.93 (p = 0.00)). The measured scoliosis angle was 14 degrees. Conclusion:The phantom has physical characteristics (in terms of spinal deformity) and radiological characteristics (in terms of HU and SNR values) of the spine of a 10-year-old child with AIS. This phantom has utility for the optimisation of x-ray imaging techniques in 10 year old children. Implications for practice: A phantom to investigate new x-ray imaging techniques and technology in the assessment of scoliosis and to optimise currently used protocols

The accuracy of Cobb angle measurement on CT scan projection radiograph images

Introduction: Adolescent idiopathic scoliosis (AIS) is a spinal deformity that can affect young children. It requires frequent exposure to X-rays to monitor the deformity, which can lead to the development of radiation-induced cancer later in life. The aim of this study is to test the accuracy of using scan projection radiography (SPR) in computed tomography (CT) scans for AIS assessment. This scanning mode delivers low radiation compared with conventional radiography. Method: A bespoke phantom with a 14°scoliotic spine was scanned in CT SPR mode using 18 imaging acquisitions. These images were visually evaluated against set criteria to determine their suitability for Cobb angle measurements Those deemed of insufficient quality were excluded from the study (n=8, excluded). Cobb angle measurements were then performed on the remaining images (n=10, included) by 13 observers. Results: On average, the difference between the measured Cobb angle andthe known angle was –2.75°(SD 1.46°). The agreement between the observers was good (p = 0.861, 95% CI 0.70-0.95)and comparable to similar studies on other imaging modalities which are used for Cobb angle estimation. Conclusion: CT SPR images can be usedfor AIS assessment with the 5°margin of error that is clinically acceptable. Implications for practice: The outcome is promising for patients and health providers because it provides an opportunity to reduce patient dose, achieve clinically acceptable Cobb angle measurements whilst using existing (CT) technology that is available in most hospital

Rainfall and sentinel chicken seroconversions predict human cases of Murray Valley encephalitis in the north of Western Australia

Background Murray Valley encephalitis virus (MVEV) is a flavivirus that occurs in Australia and New Guinea. While clinical cases are uncommon, MVEV can cause severe encephalitis with high mortality. Sentinel chicken surveillance is used at many sites around Australia to provide an early warning system for risk of human infection in areas that have low population density and geographical remoteness. MVEV in Western Australia occurs in areas of low population density and geographical remoteness, resulting in logistical challenges with surveillance systems and few human cases. While epidemiological data has suggested an association between rainfall and MVEV activity in outbreak years, it has not been quantified, and the association between rainfall and sporadic cases is less clear. In this study we analysed 22 years of sentinel chicken and human case data from Western Australia in order to evaluate the effectiveness of sentinel chicken surveillance for MVEV and assess the association between rainfall and MVEV activity. Methods Sentinel chicken seroconversion, human case and rainfall data from the Kimberley and Pilbara regions of Western Australia from 1990 to 2011 were analysed using negative binomial regression. Sentinel chicken seroconversion and human cases were used as dependent variables in the model. The model was then tested against sentinel chicken and rainfall data from 2012 and 2013.Results Sentinel chicken seroconversion preceded all human cases except two in March 1993. Rainfall in the prior three months was significantly associated with both sentinel chicken seroconversion and human cases across the regions of interest. Sentinel chicken seroconversion was also predictive of human cases in the models. The model predicted sentinel chicken seroconversion in the Kimberley but not in the Pilbara, where seroconversions early in 2012 were not predicted. The latter may be due to localised MVEV activity in isolated foci at dams, which do not reflect broader virus activity in the region. Conclusions We showed that rainfall and sentinel chickens provide a useful early warning of MVEV risk to humans across endemic and epidemic areas, and that a combination of the two indicators improves the ability to assess MVEV risk and inform risk management measures

Autophagy in healthy aging and disease

Autophagy is a fundamental cellular process that eliminates molecules and subcellular elements, including nucleic acids, proteins, lipids and organelles, via lysosome-mediated degradation to promote homeostasis, differentiation, development and survival. While autophagy is intimately linked to health, the intricate relationship among autophagy, aging and disease remains unclear. This Review examines several emerging features of autophagy and postulates how they may be linked to aging as well as to the development and progression of disease. In addition, we discuss current preclinical evidence arguing for the use of autophagy modulators as suppressors of age-related pathologies such as neurodegenerative diseases. Finally, we highlight key questions and propose novel research avenues that will likely reveal new links between autophagy and the hallmarks of aging. Understanding the precise interplay between autophagy and the risk of age-related pathologies across organisms will eventually facilitate the development of clinical applications that promote long-term health

Study design and baseline characteristics of patients on dialysis in the ASCEND-D trial

BACKGROUND: The Anemia Studies in chronic kidney disease (CKD): Erythropoiesis via a Novel prolyl hydroxylase inhibitor (PHI) Daprodustat-Dialysis (ASCEND-D) trial will test the hypothesis that daprodustat is non-inferior to comparator epoetin alfa or darbepoetin alfa for two co-primary endpoints: haemoglobin efficacy and cardiovascular safety. METHODS: We report the trial design, key demographic, clinical, and laboratory findings, and baseline therapies of 2964 patients randomised in the open-label (sponsor-blinded) active-controlled, parallel-group, randomised ASCEND-D clinical trial. We also compare baseline characteristics of ASCEND-D patients with patients who are on dialysis (CKD G5D) enrolled in other large cardiovascular outcome trials (CVOTs) and in the most relevant registries. RESULTS: The median age of patients was 58 years, 43% were female; 67% were white and 16% were black. The median haemoglobin at baseline was 10.4 g/dL. Among randomised patients, 89% were receiving haemodialysis and 11% peritoneal dialysis. Among key co-morbidities, 42% reported a history of diabetes mellitus, and 45% a history of cardiovascular disease. Median blood pressure was 134/74 mmHg. The median weekly dose of epoetin was 5751 units. Intravenous and oral iron use was noted in 64% and 11% of patients, respectively. Baseline demographics were similar to patients with CKD G5D enrolled in other CVOTs and renal patient registries. CONCLUSION: ASCEND-D will evaluate the efficacy and safety of daprodustat compared with epoetin alfa or darbepoetin alfa in the treatment of patients with anaemia with CKD G5D

YKL-40 tissue expression and plasma levels in patients with ovarian cancer

<p>Abstract</p> <p>Background</p> <p>YKL-40 (chitinase-3-like-1) is a member of "mammalian chitinase-like proteins". The protein is expressed in many types of cancer cells and the highest plasma YKL-40 levels have been found in patients with metastatic disease, short recurrence/progression-free intervals, and short overall survival. The aim of the study was to determine the expression of YKL-40 in tumor tissue and plasma in patients with borderline ovarian tumor or epithelial ovarian cancer (OC), and investigate prognostic value of this marker.</p> <p>Methods</p> <p>YKL-40 protein expression was determined by immunohistochemistry in tissue arrays from 181 borderline tumors and 473 OC. Plasma YKL-40 was determined by ELISA in preoperative samples from 19 patients with borderline tumor and 76 OC patients.</p> <p>Results</p> <p>YKL-40 protein expression was found in cancer cells, tumor associated macrophages, neutrophils and mast cells. The tumor cell expression was higher in OC than in borderline tumors (p = 0.001), and associated with FIGO stage (p < 0.0001) and histological subtype (p = 0.0009). Positive YKL-40 expression (≥ 5% staining) was not associated with reduced survival. Plasma YKL-40 was also higher in patients with OC than in patients with borderline tumors (p < 0.0001), and it was positively correlated to serum CA-125 (p < 0.0001) and FIGO stage (p = 0.0001). Univariate Cox analysis of plasma YKL-40 showed association with overall survival (p < 0.0001). Multivariate Cox analysis, including plasma YKL-40, serum CA125, FIGO stage, age and radicality after primary surgery as variables, showed that elevated plasma YKL-40 was associated with a shorter survival (HR = 2.13, 95% CI: 1.40–3.25, p = 0.0004).</p> <p>Conclusion</p> <p>YKL-40 in OC tissue and plasma are related to stage and histology, but only plasma YKL-40 is a prognostic biomarker in patients with OC.</p

The ASCEND-ND trial: Study design and participant characteristics

BACKGROUND: Anaemia is common in chronic kidney disease (CKD), and assessment of the risks and benefits of new therapies is important. METHODS: The Anaemia Study in CKD: Erythropoiesis via a Novel prolyl hydroxylase inhibitor Daprodustat-Non-Dialysis (ASCEND-ND) trial includes adult patients with CKD Stages 3-5, not using erythropoiesis-stimulating agents (ESAs) with screening haemoglobin (Hb) 8-10 g/dL, or receiving ESAs with screening Hb of 8-12 g/dL. Participants were randomised to daprodustat or darbepoetin alfa (1:1) in an open- label trial (steering committee- and sponsor-blinded), with blinded endpoint assessment. The co-primary endpoints are mean change in Hb between baseline and evaluation period (average over Weeks 28 to 52) and time to first adjudicated major adverse cardiovascular (CV) event. Baseline characteristics were compared with those of participants in similar anaemia trials. RESULTS: Overall, 3872 patients were randomised from 39 countries (median age 67 years, 56% female; 56% White, 27% Asian, and 10% Black). Median baseline Hb was 9.9 g/dL, blood pressure was 135/74 mmHg and eGFR was 18 mL/min/1.73 m2. Among randomised patients, 53% were ESA non-users, 57% had diabetes and 37% had a history of CV disease. At baseline, 61% of participants were using renin- angiotensin system blockers, 55% were taking statin and 49% oral iron. Baseline demographics were similar to those in other large non-dialysis anaemia trials. CONCLUSION: ASCEND-ND will define the efficacy and safety of daprodustat compared with darbepoetin alfa in the treatment of patients with anaemia associated with CKD not on dialysis

Atlantic cod (Gadus morhua) hemoglobin genes: multiplicity and polymorphism

Background: Hemoglobin (Hb) polymorphism, assessed by protein gel electrophoresis, has been used almost exclusively to characterize the genetic structure of Atlantic cod (Gadus morhua) populations and to establish correlations with phenotypic traits such as Hb oxygen binding capacity, temperature tolerance and growth characteristics. The genetic system used to explain the results of gel electrophoresis entails the presence of one polymorphic locus with two major alleles (HbI-1; HbI-2). However, vertebrates have more than one gene encoding Hbs and recent studies have reported that more than one Hb gene is present in Atlantic cod. These observations prompted us to re-evaluate the number of Hb genes expressed in Atlantic cod, and to perform an in depth search for polymorphisms that might produce relevant phenotypes for breeding programs. Results: Analysis of Expressed Sequence Tags (ESTs) led to the identification of nine distinct Hb transcripts; four corresponding to the α Hb gene family and five to the β Hb gene family. To gain insights about the Hb genes encoding these transcripts, genomic sequence data was generated from heterozygous (HbI-1/2) parents and fifteen progeny; five of each HbI type, i.e., HbI-1/1, HbI-1/2 and HbI-2/2. β Hb genes displayed more polymorphism than α Hb genes. Two major allele types (β1A and β1B) that differ by two linked non-synonymous substitutions (Met55Val and Lys62Ala) were found in the β1 Hb gene, and the distribution of these β1A and β1B alleles among individuals was congruent with that of the HbI-1 and HbI-2 alleles determined by protein gel electrophoresis. RT-PCR and Q-PCR analysis of the nine Hb genes indicates that all genes are expressed in adult fish, but their level of expression varies greatly; higher expression of almost all Hb genes was found in individuals displaying the HbI-2/2 electrophoretic type. Conclusion: This study indicates that more Hb genes are present and expressed in adult Atlantic cod than previously documented. Our finding that nine Hb genes are expressed simultaneously in adult fish suggests that Atlantic cod, similarly to fish such as rainbow trout, carp, and goldfish, might be able to respond to environmental challenges such as chronic hypoxia or long-term changes in temperature by altering the level of expression of these genes. In this context, the role of the non-conservative substitution Lys62Ala found in the β1 Hb gene, which appears to explain the occurrence of the HbI-1 and HbI-2 alleles described by gel electrophoresis, and which was found to be present in other fish such as eel, emerald rockcod, rainbow trout and moray, requires further investigation

The most plausible explanation of the cyclical period changes in close binaries: the case of the RS CVn-type binary WW Dra

We searched the orbital period changes in 182 EA-type (including the 101 Algol systems used by \cite{hal89}), 43 EB-type and 53 EW-type binaries with known both the mass ratio and the spectral type of their secondary components. We reproduced and improved the same diagram as Hall's (1989) according to the new collected data. Our plots do not support the conclusion derived by \cite{hal89} that all cases of cyclical period changes are restricted to binaries having the secondary component with spectral types later than F5. The presence of period changes also among stars with secondary component of early type indicates that the magnetic activity is one cause, but not the only one, for the period variation. It is discovered that cyclic period changes, likely due to the presence of a third body are more frequent in EW-type binaries among close binaries. Therefore, the most plausible explanation of the cyclical period changes is the LTTE via the presence of a third body. By using the century-long historical record of the times of light minimum, we analyzed the cyclical period change in the Algol binary WW Dra. It is found that the orbital period of the binary shows a $\sim112.2 \textbf{\textrm{yr}}$ cyclic variation with an amplitude of $\sim0.1977\textbf{\textrm{days}}$. The cyclic oscillation can be attributed to the LTTE via a third body with a mass no less than $6.43 M_{\odot}$. However, no spectral lines of the third body were discovered indicating that it may be a candidate black hole. The third body is orbiting the binary at a distance shorter than 14.4 AU and it may play an important role in the evolution of this system.Comment: 9 pages, 5 figures, published by MNRA