A validation of the Oswestry Spinal Risk Index

Purpose The purpose of this study was to validate the Oswestry Spinal Risk Index (OSRI) in an external population. The OSRI predicts survival in patients with metastatic spinal cord compression (MSCC). Methods We analysed the data of 100 patients undergoing surgical intervention for MSCC at a tertiary spinal unit and recorded the primary tumour pathology and Karnofsky performance status to calculate the OSRI. Logistic regression models and survival plots were applied to the data in accordance with the original paper. Results Lower OSRI scores predicted longer survival. The OSRI score predicted survival accurately in 74% of cases (p = 0.004). Conclusions Our study has found that the OSRI is a significant predictor of survival at levels similar to those of the original authors and is a useful and simple tool in aiding complex decision making in patients presenting with MSC

Regulation of the tumour suppressor PDCD4 by miR-499 and miR-21 in oropharyngeal cancers

© 2016 Zhang et al. Background: The rates of oropharyngeal cancers such as tonsil cancers are increasing. The tumour suppressor protein Programmed Cell Death Protein 4 (PDCD4) has been implicated in the development of various human cancers and small RNAs such as microRNAs (miRNAs) can regulate its expression. However the exact regulation of PDCD4 by multiple miRNAs in oropharyngeal squamous cell carcinoma (SCC) is not well understood. Results: Using two independent oropharyngeal SCC cohorts with a focus on the tonsillar region, we identified a miRNA profile differentiating SCC tissue from normal. Both miR-21 and miR-499 were highly expressed in tonsil SCC tissues displaying a loss of PDCD4. Interestingly, expression of the miRNA machinery, Dicer1, Drosha, DDX5 (Dead Box Helicase 5) and DGCR8 (DiGeorge Syndrome Critical Region Gene 8) were all elevated by greater than 2 fold in the tonsil SCC tissue. The 3'UTR of PDCD4 contains three binding-sites for miR-499 and one for miR-21. Using a wild-type and truncated 3'UTR of PDCD4, we demonstrated that the initial suppression of PDCD4 was mediated by miR-21 whilst sustained suppression was mediated by miR-499. Moreover the single miR-21 site was able to elicit the same magnitude of suppression as the three miR-499 sites. Conclusion: This study describes the regulation of PDCD4 specifically in tonsil SCC by miR-499 and miR-21 and has documented the loss of PDCD4 in tonsil SCCs. These findings highlight the complex interplay between miRNAs and tumour suppressor gene regulation and suggest that PDCD4 loss may be an important step in tonsillar carcinogenesis

Two loop electroweak corrections to Bˉ→Xsγ\bar B\rightarrow X_s\gamma and Bs0→μ+μ−B_s^0\rightarrow \mu^+\mu^- in the B-LSSM

The rare decays $\bar B\rightarrow X_s\gamma$ and $B_s^0\rightarrow \mu^+\mu^-$ are important to research new physics beyond standard model. In this work, we investigate two loop electroweak corrections to $\bar B\rightarrow X_s\gamma$ and $B_s^0\rightarrow \mu^+\mu^-$ in the minimal supersymmetric extension of the SM with local $B-L$ gauge symmetry (B-LSSM), under a minimal flavor violating assumption for the soft breaking terms. In this framework, new particles and new definition of squarks can affect the theoretical predictions of these two processes, with respect to the MSSM. Considering the constraints from updated experimental data, the numerical results show that the B-LSSM can fit the experimental data for the branching ratios of $\bar B\rightarrow X_s\gamma$ and $B_s^0\rightarrow \mu^+\mu^-$. The results of the rare decays also further constrain the parameter space of the B-LSSM.Comment: 33 pages, 9 figures, Published in EPJ

Aetiology and management of malnutrition in HIV-positive children

Worldwide, more than 3 million children are infected with HIV and, without treatment, mortality among these children is extremely high. Both acute and chronic malnutrition are major problems for HIV-positive children living in resource-limited settings. Malnutrition on a background of HIV represents a separate clinical entity, with unique medical and social aetiological factors. Children with HIV have a higher daily calorie requirement than HIV-negative peers and also a higher requirement for micronutrients; furthermore, coinfection and chronic diarrhoea due to HIV enteropathy play a major role in HIV-associated malnutrition. Contributory factors include late presentation to medical services, unavailability of antiretroviral therapy, other issues surrounding healthcare provision and food insecurity in HIV-positive households. Treatment protocols for malnutrition have been greatly improved, yet there remains a discrepancy in mortality between HIV-positive and HIV-negative children. In this review, the aetiology, prevention and treatment of malnutrition in HIV-positive children are examined, with particular focus on resource-limited settings where this problem is most prevalent. © 2014 BMJ Publishing Group Ltd & Royal College of Paediatrics and Child Health

Candidate-gene based GWAS identifies reproducible DNA markers for metabolic pyrethroid resistance from standing genetic variation in East African Anopheles gambiae.

Metabolic resistance to pyrethroid insecticides is widespread in Anopheles mosquitoes and is a major threat to malaria control. DNA markers would aid predictive monitoring of resistance, but few mutations have been discovered outside of insecticide-targeted genes. Isofemale family pools from a wild Ugandan Anopheles gambiae population, from an area where operational pyrethroid failure is suspected, were genotyped using a candidate-gene enriched SNP array. Resistance-associated SNPs were detected in three genes from detoxification superfamilies, in addition to the insecticide target site (the Voltage Gated Sodium Channel gene, Vgsc). The putative associations were confirmed for two of the marker SNPs, in the P450 Cyp4j5 and the esterase Coeae1d by reproducible association with pyrethroid resistance in multiple field collections from Uganda and Kenya, and together with the Vgsc-1014S (kdr) mutation these SNPs explained around 20% of variation in resistance. Moreover, the >20 Mb 2La inversion also showed evidence of association with resistance as did environmental humidity. Sequencing of Cyp4j5 and Coeae1d detected no resistance-linked loss of diversity, suggesting selection from standing variation. Our study provides novel, regionally-validated DNA assays for resistance to the most important insecticide class, and establishes both 2La karyotype variation and humidity as common factors impacting the resistance phenotype

Ultra-broadband frequency generation in a cavity confined Raman medium

Throughout the past few decades, science has progressed towards the ability to probe many extremely fast processes and a large amount of research has been aimed at the area of few-femtosecond pulse generation. This thesis describes the generation of coherent broadband radiation through two-colour pumping of molecular hydrogen confined to a unidirectional ring cavity, and the subsequent synthesis of high peak power and few-femtosecond pulses. A set of normalised semi-classical field equations are derived in Bloch form describing the process of ultra-broadband multi-frequency Raman generation or UMRG, and a 3-wave gain suppression analysis is derived from a subset of the plane wave UMRG field equations which describes gain suppression within the ring cavity in terms of both medium and cavity parameters. The gain suppression analysis is further generalised to include finite levels of linear two-photon frequency detuning of the pump beams. Simulations of the plane wave ultra-broadband multi-frequency Raman (UMRG) equations show that a broad frequency spectrum of mutually coherent sideband can be generated. The inverse Fourier transform of spectra generated in this way yields a train of high power near Fourier limited pulses in the time domain which can range from a few-femtoseconds in duration to tens of attoseconds with repetition rates equal to the Raman transition frequency. Pulses synthesised in this way are limited only by the level of medium dispersion, the reflection bandwidth of the chosen coupling mirror and the chosen Raman medium. Simulations of the transverse UMRG equations within the ring cavity geometry have shown ring cavity enhanced UMRG to be resilient to transverse effects such as finite beam width, beam diffraction and the transverse beam separation of the applied pump beams