Comparison between sensorial and instrumental measurements for mealiness assessment in apples

Definition and establishment of assessment procedures for mealiness of apple fruits using sensory and instrumental measurements were performed on ‘Boskoop', ‘Cox's Orange Pippin’ and ‘Jonagold’ samples with varying degrees of mealiness. The sensory procedure profiled mealiness as a loss of crispness, hardness, and juiciness, with an increase in the floury sensation in the mouth. High correlations between the sensory descriptors and instrumental parameters was shown through principal component analysis. The instrumental procedures (confined compression of fruit cylinders and acoustic impulse response) gave coefficients of determination for juiciness and crispness of 0.85 and 0.71, respectively. This level of accuracy indicates the possibility of establishin

The effect of discrete vs. continuous-valued ratings on reputation and ranking systems

When users rate objects, a sophisticated algorithm that takes into account ability or reputation may produce a fairer or more accurate aggregation of ratings than the straightforward arithmetic average. Recently a number of authors have proposed different co-determination algorithms where estimates of user and object reputation are refined iteratively together, permitting accurate measures of both to be derived directly from the rating data. However, simulations demonstrating these methods' efficacy assumed a continuum of rating values, consistent with typical physical modelling practice, whereas in most actual rating systems only a limited range of discrete values (such as a 5-star system) is employed. We perform a comparative test of several co-determination algorithms with different scales of discrete ratings and show that this seemingly minor modification in fact has a significant impact on algorithms' performance. Paradoxically, where rating resolution is low, increased noise in users' ratings may even improve the overall performance of the system.Comment: 6 pages, 2 figure

Analysis and modelling of muscles motion during whole body vibration

The aim of the study is to characterize the local muscles motion in individuals undergoing whole body mechanical stimulation. In this study we aim also to evaluate how subject positioning modifies vibration dumping, altering local mechanical stimulus. Vibrations were delivered to subjects by the use of a vibrating platform, while stimulation frequency was increased linearly from 15 to 60Hz. Two different subject postures were here analysed. Platform and muscles motion were monitored using tiny MEMS accelerometers; a contra lateral analysis was also presented. Muscle motion analysis revealed typical displacement trajectories: motion components were found not to be purely sinusoidal neither in phase to each other. Results also revealed a mechanical resonant-like behaviour at some muscles, similar to a second-order system response. Resonance frequencies and dumping factors depended on subject and his positioning. Proper mechanical stimulation can maximize muscle spindle solicitation, which may produce a more effective muscle activation

Refinement of the critical genomic region for congenital hyperinsulinism in the Chromosome 9p deletion syndrome

Version 2; peer review: 3 approved. Available from F1000 Research via the DOI in this recordBackground: Large contiguous gene deletions at the distal end of the short arm of chromosome 9 result in the complex multi-organ condition chromosome 9p deletion syndrome. A range of clinical features can result from these deletions with the most common being facial dysmorphisms and neurological impairment. Congenital hyperinsulinism is a rarely reported feature of the syndrome with the genetic mechanism for the dysregulated insulin secretion being unknown. Methods: We studied the clinical and genetic characteristics of 12 individuals with chromosome 9p deletions who had a history of neonatal hypoglycaemia. Using off-target reads generated from targeted next-generation sequencing of the genes known to cause hyperinsulinaemic hypoglycaemia (n=9), or microarray analysis (n=3), we mapped the minimal shared deleted region on chromosome 9 in this cohort. Targeted sequencing was performed in three patients to search for a recessive mutation unmasked by the deletion. Results: In 10/12 patients with hypoglycaemia, hyperinsulinism was confirmed biochemically. A range of extra-pancreatic features were also reported in these patients consistent with the diagnosis of the Chromosome 9p deletion syndrome. The minimal deleted region was mapped to 7.2 Mb, encompassing 38 protein-coding genes. In silico analysis of these genes highlighted SMARCA2 and RFX3 as potential candidates for the hypoglycaemia. Targeted sequencing performed on three of the patients did not identify a second disease-causing variant within the minimal deleted region. Conclusions: This study identifies 9p deletions as an important cause of hyperinsulinaemic hypoglycaemia and increases the number of cases reported with 9p deletions and hypoglycaemia to 15 making this a more common feature of the syndrome than previously appreciated. Whilst the precise genetic mechanism of the dysregulated insulin secretion could not be determined in these patients, mapping the deletion breakpoints highlighted potential candidate genes for hypoglycaemia within the deleted region.Wellcome TrustRoyal Societ

Fulvestrant is an effective and well-tolerated endocrine therapy for postmenopausal women with advanced breast cancer: results from clinical trials

Fulvestrant (‘Faslodex’) is a new type of endocrine treatment – an oestrogen receptor (ER) antagonist that downregulates the ER and has no agonist effects. Early efficacy data from phase I/II trials have demonstrated fulvestrant to be effective and well tolerated. Two randomised phase III trials have compared the efficacy of fulvestrant and the aromatase inhibitor, anastrozole, in postmenopausal women with advanced breast cancer progressing on prior endocrine therapy. Fulvestrant (intramuscular injection 250 mg month−1) was found to be at least as effective as anastrozole (orally 1 mg day−1) for time to progression (5.5 vs 4.1 months, respectively (hazard ratio (HR): 0.95; 95.14% confidence interval (CI), 0.82–1.10; P=0.48)) and objective response 19.2 vs 16.5%, respectively; treatment difference 2.75%; 95.14% CI, −2.27 to 9.05%; P=0.31). More recently, fulvestrant has also been shown to be noninferior to anastrozole in terms of overall survival, with median time to death being 26.4 months in fulvestrant-treated patients and 24.2 months in those treated with anastrozole (HR: 0.97; 95% CI, 0.78–1.21; P=0.82). In a further randomised phase III trial, fulvestrant was compared with tamoxifen as first-line therapy for advanced disease in postmenopausal women. In the overall population, efficacy differences favoured tamoxifen and noninferiority of fulvestrant could not be ruled out. In the prospectively defined subset of patients with ER-positive and/or progesterone receptor-positive disease, there was no statistically significant difference between fulvestrant and tamoxifen. This paper reviews the efficacy and tolerability results from these trials

Elongation differences between the sub-tendons of gastrocnemius medialis and lateralis during plantarflexion in different frontal plane position of the foot

© 2019 Background: Gastrocnemius medialis (GM) and lateralis (GL) act at the ankle complex in the sagittal and frontal planes and there is evidence that their actions can be somewhat uncoupled from each other. Some independence of GM and GL from each other could be advantageous, e.g. to stabilise the ankle complex in unstable walking conditions. Given the compartmentalised structure of the Achilles tendon, the sub-tendons of GM and GL may exhibit different elongation during plantarflexion contractions, particularly with the foot in different frontal plane positions. Research Questions: • Is elongation within a sub-tendon affected by frontal plane foot position? • Does elongation between the two sub-tendons differ? • Are elongation differences between the sub-tendons affected by frontal plane foot position? Methods: Sub-tendon elongation was determined from 18 participants during ramped isometric plantarflexion contractions to 70% of their maximum voluntary contraction (MVC) level with the foot in neutral, inversion and eversion. One-dimensional statistical parametric mapping was applied to determine elongation differences. Results: Elongation within a sub-tendon did not differ in the three foot positions. Elongation was similar between both sub-tendons at very low contraction levels, but GM sub-tendon elongation exceeded GL sub-tendon displacement significantly from 30% MVC. The elongation differences between the sub-tendons were not affected by foot position. Significance: Greater GM sub-tendon elongation is likely caused by the greater force production capability of GM but may also indicate that the sub-tendons of GM and GL have different mechanical properties, which is currently unknown. Elongation differences were contraction level dependent suggesting that contributions of GM and GL to plantarflexion torque may also be contraction level dependent

An Amish founder variant consolidates disruption of CEP55 as a cause of hydranencephaly and renal dysplasia

This is the author accepted manuscript. The final version is available from Springer Nature via the DOI in this record.The centrosomal protein 55 kDa (CEP55 (OMIM 610000)) plays a fundamental role in cell cycle regulation and cytokinesis. However, the precise role of CEP55 in human embryonic growth and development is yet to be fully defined. Here we identified a novel homozygous founder frameshift variant in CEP55, present at low frequency in the Amish community, in two siblings presenting with a lethal foetal disorder. The features of the condition are reminiscent of a Meckel-like syndrome comprising of Potter sequence, hydranencephaly, and cystic dysplastic kidneys. These findings, considered alongside two recent studies of single families reporting loss of function candidate variants in CEP55, confirm disruption of CEP55 function as a cause of this clinical spectrum and enable us to delineate the cardinal clinical features of this disorder, providing important new insights into early human development.Medical Research CouncilNewlife Foundation for disabled childre

Comparing the Epidermal Growth Factor Interaction with Four Different Cell Lines: Intriguing Effects Imply Strong Dependency of Cellular Context

The interaction of the epidermal growth factor (EGF) with its receptor (EGFR) is known to be complex, and the common over-expression of EGF receptor family members in a multitude of tumors makes it important to decipher this interaction and the following signaling pathways. We have investigated the affinity and kinetics of 125I-EGF binding to EGFR in four human tumor cell lines, each using four culturing conditions, in real time by use of LigandTracer®

Fulvestrant and the sequential endocrine cascade for advanced breast cancer

Following relapse on endocrine therapy for advanced, hormone receptor-positive breast cancer, it is common for patients to experience responses to alternative endocrine agents. Fulvestrant (‘Faslodex’) is a new type of endocrine treatment – an oestrogen receptor (ER) antagonist with no agonist effects. Fulvestrant downregulates cellular levels of the ER resulting in decreased expression of the progesterone receptor. This unique mode of action means that it is important that fulvestrant is placed optimally within the sequence of endocrine therapies to ensure that patients gain maximum benefit. Fulvestrant has shown efficacy when used after progression on tamoxifen or anastrozole in postmenopausal women with advanced breast cancer. After progression on fulvestrant, subsequent endocrine treatments can produce responses in many patients, demonstrating that fulvestrant does not lead to crossresistance with other endocrine therapies. Responses to fulvestrant have also been observed in patients heavily pretreated with prior endocrine therapy. Fulvestrant is a versatile endocrine agent that may be integrated into the therapeutic sequence prior to, or subsequent to, other hormonal therapies, and represents a valuable additional antioestrogen for the treatment of postmenopausal women with advanced breast cancer