From sick kids to SicKids!

This report outlines the varied activities undertaken by SicKids in Cambodia up to and including the April 2017 visit by Dr Joan Livesley and Professor Andrew Rowland. Both the November 2016 and April 2017 visits were part-funded by a Humanitarian Grant from the British Medical Association. SicKids is a children’s health charity currently working in the North West of England and Cambodia. It believes every child deserves the right to grow up healthy, and safe from abuse, exploitation and trafficking. The charity raises funds and work on projects to support children and young people

Novel targeted siRNA-loaded hybrid nanoparticles: preparation, characterization and in vitro evaluation.

BACKGROUND: siRNAs have a high potential for silencing critical molecular pathways that are pathogenic. Nevertheless, their clinical application has been limited by a lack of effective and safe nanotechnology-based delivery system that allows a controlled and safe transfection to cytosol of targeted cells without the associated adverse effects. Our group recently reported a very effective and safe hybrid nanoparticle delivery system composing human IgG and poloxamer-188 for siRNA delivery to cancer cells. However, these nanoparticles need to be optimized in terms of particle size, loading capacity and encapsulation efficiency. In the present study, we explored the effects of certain production parameters on particle size, loading capacity and encapsulation efficiency. Further, to make these nanoparticles more specific in their delivery of siRNA, we conjugated anti-NTSR1-mAb to the surface of these nanoparticles to target NTSR1-overexpressing cancer cells. The mechanism of siRNA release from these antiNTSR1-mAb functionalized nanoparticles was also elucidated. RESULTS: It was demonstrated that the concentration of human IgG in the starting nanoprecipitation medium and the rotation speed of the magnetic stirrer influenced the encapsulation efficiency, loading capacity and the size of the nanoparticles produced. We also successfully transformed these nanoparticles into actively targeted nanoparticles by functionalizing with anti-NTSR1-mAb to specifically target NTSR1-overexpressing cancer cells, hence able to avoid undesired accumulation in normal cells. The mechanism of siRNA release from these nanoparticles was elucidated to be by Fickian diffusion. Using flow cytometry and fluorescence microscopy, we were able to confirm the active involvement of NTSR1 in the uptake of these anti-NTSR1-mAb functionalized hybrid nanoparticles by lung adenocarcinoma cells. CONCLUSIONS: This hybrid nanoparticle delivery system can be used as a platform technology for intracellular delivery of siRNAs to NTSR1-overexpressing tumor cells

Original Contribution RELATIONSHIP BETWEEN SOME BODY MEASUREMENTS AND LIVE WEIGHT IN ADULT MUSCOVY DUCKS USING PATH ANALYSIS

ABSTRACT Weight and body dimensions (body length (BL), chest circumference (CC), thigh length (TL), shank length (SL) and neck length (NL) were studied using 215 fifteen weeks male and female Nigerian indigenous Muscovy ducks by path analysis. The result showed that the correlation coefficient between live weight and body dimensions on the other hand were 0.89, .94, .87, .88 and .75 (male) and .29, .59, .41, .37, -.10 (female) for BL, CC, TL, SL and NL respectively. The direct effect of chest circumference was higher in both male and female (0.616, .571) with the neck length having the least and negative direct effects on weight for both sexes. Indirect effect of body length through chest circumference was also the highest .chest circumference is the most influential variable and can be included in the model in estimating live weight of both male and female Muscovy duck at 15 weeks of age

Recent Arctic amplification and extreme mid-latitude weather

This is the author accepted manuscript. The final version is available from Nature via the DOI in this record.The Arctic region has warmed more than twice as fast as the global average — a phenomenon known as Arctic amplification. The rapid Arctic warming has contributed to dramatic melting of Arctic sea ice and spring snow cover, at a pace greater than that simulated by climate models. These profound changes to the Arctic system have coincided with a period of ostensibly more frequent extreme weather events across the Northern Hemisphere mid-latitudes, including severe winters. The possibility of a link between Arctic change and mid-latitude weather has spurred research activities that reveal three potential dynamical pathways linking Arctic amplification to mid-latitude weather: changes in storm tracks, the jet stream, and planetary waves and their associated energy propagation. Through changes in these key atmospheric features, it is possible, in principle, for sea ice and snow cover to jointly influence mid-latitude weather. However, because of incomplete knowledge of how high-latitude climate change influences these phenomena, combined with sparse and short data records, and imperfect models, large uncertainties regarding the magnitude of such an influence remain. We conclude that improved process understanding, sustained and additional Arctic observations, and better coordinated modelling studies will be needed to advance our understanding of the influences on mid-latitude weather and extreme events

The expression of TRMT2A, a novel cell cycle regulated protein, identifies a subset of breast cancer patients with HER2 over-expression that are at an increased risk of recurrence

<p>Abstract</p> <p>Background</p> <p>Over-expression of <it>HER2 </it>in a subset of breast cancers (<it>HER2</it>+) is associated with high histological grade and aggressive clinical course. Despite these distinctive features, the differences in response of <it>HER2</it>+ patients to both adjuvant cytotoxic chemotherapy and targeted therapy (e.g. trastuzumab) suggests that unrecognized biologic and clinical diversity is confounding treatment strategies. Furthermore, the small but established risk of cardiac morbidity with trastuzumab therapy compels efforts towards the identification of biomarkers that might help stratify patients.</p> <p>Methods</p> <p>A single institution tissue array cohort assembled at the Clearview Cancer Institute of Huntsville (CCIH) was screened by immunohistochemistry staining using a large number of novel and commercially available antibodies to identify those with a univariate association with clinical outcome in <it>HER2</it>+ patients. Staining with antibody directed at TRMT2A was found to be strongly associated with outcome in <it>HER2</it>+ patients. This association with outcome was tested in two independent validation cohorts; an existing staining dataset derived from tissue assembled at the Cleveland Clinic Foundation (CCF), and in a new retrospective study performed by staining archived paraffin blocks available at the Roswell Park Cancer Institute (RPCI).</p> <p>Results</p> <p>TRMT2A staining showed a strong correlation with likelihood of recurrence at five years in 67 <it>HER2</it>+ patients from the CCIH discovery cohort (HR 7.0; 95% CI 2.4 to 20.1, p < 0.0004). This association with outcome was confirmed using 75 <it>HER2</it>+ patients from the CCF cohort (HR 3.6; 95% CI 1.3 to 10.2, p < 0.02) and 64 patients from the RPCI cohort (HR 3.4; 95% CI 1.3-8.9, p < 0.02). In bivariable analysis the association with outcome was independent of grade, tumor size, nodal status and the administration of conventional adjuvant chemotherapy in the CCIH and RPCI cohorts.</p> <p>Conclusions</p> <p>Studies from three independent single institution cohorts support TRMT2A protein expression as a biomarker of increased risk of recurrence in <it>HER2+ </it>breast cancer patients. These results suggest that TRMT2A expression should be further studied in the clinical trial setting to explore its predictive power for response to adjuvant cytotoxic chemotherapy in combination with <it>HER2 </it>targeted therapy.</p

Extending the functionality of a symbolic computational dynamic solver by using a novel term-tracking method

Symbolic computational dynamic solvers are currently under development in order to provide new and powerful tools for modelling nonlinear dynamical systems. Such solvers consist of two parts; the core solver, which comprises an approximate analytical method based on perturbation, averaging, or harmonic balance, and a specialised term-tracker. A term-tracking approach has been introduced to provide a powerful new feature into computational approximate analytical solutions by highlighting the many mathematical connections that exist, but which are invariably lost through processing, between the physical model of the system, the solution procedure itself, and the final result which is usually expressed in equation form. This is achieved by a highly robust process of term-tracking, recording, and identification of all the symbolic mathematical information within the problem. In this paper, the novel source and evolution encoding method is introduced for the first time and an implementation in Mathematica is described through the development of a specialised algorithm

Awareness of HPV and cervical cancer prevention among Cameroonian healthcare workers

<p>Abstract</p> <p>Background</p> <p>Cervical cancer, although largely preventable, remains the most common cause of cancer mortality among women in low-resource countries.</p> <p>The objective of this study was to assess knowledge and awareness of cervical cancer prevention among Cameroonian healthcare workers.</p> <p>Methods</p> <p>A cross-sectional self-administered questionnaire in 5 parts with 46 items regarding cervical cancer etiology and prevention was addressed to healthcare workers in six hospitals of Yaoundé, Cameroon. The investigators enlisted heads of nursing and midwifery to distribute questionnaires to their staff, recruited doctors individually, in hospitals and during conferences and distributed questionnaires to students in Yaoundé University Hospital and Medical School. Eight hundred and fifty questionnaires were distributed, 401 collected. Data were analyzed with SPSS version 16.0. Chi-square tests were used and P-values < 0.05 were considered significant.</p> <p>Results</p> <p>Mean age of respondents was 38 years (range 20-71 years). Most participants were aware that cervical cancer is a major public health concern (86%), were able to identify the most important etiological factors (58%) and believed that screening may prevent cervical cancer (90%) and may be performed by Pap test (84%). However, less than half considered VIA or HPV tests screening tests (38 and 47%, respectively). Knowledge about cancer etiology and screening was lowest among nurse/midwives.</p> <p>Conclusion</p> <p>Knowledge of cervical cancer and prevention by screening showed several gaps and important misconceptions regarding screening methods.</p> <p>Creating awareness among healthcare workers on risk factors and current methods for cervical cancer screening is a necessary step towards implementing effective prevention programs.</p