Failure analysis of a steel motorcycle kickstand

Copyright @ 2009 Springer US.A fractured steel motorcycle kickstand was metallurgically investigated using a range of failure analysis tools [visual examination, energy dispersive X-ray (EDX) analysis, electron microprobe analysis (EPMA), scanning electron microscopy (SEM), fractography, optical microscopy, hardness testing and non-destructive testing (NDT)]. The steel kickstand’s composition, its microstructure, electron fractographs, and mechanical test results have been critically interpreted. Some evidence of wear damage, in the failed kickstand, was observed. The microstructural and fractographic analyses showed pre-existing micro-cracks which were believed to have grown to result in ductile failure followed by acceleration of corrosion. Recommendations have been made to avoid the failure of the motorcycle kickstand

Relearning the lesson – amelanotic malignant melanoma: a case report

Although not as common as the other melanomas, amelanotic melanoma often evades diagnosis by masquerading as other pathology. A high index of suspicion is therefore required for early and appropriate intervention. We present a patient who was diagnosed and managed as having paronychia of the middle finger while in actual fact he had a subungual amelanotic melanoma. By the time of his referral to the orthopaedic team it had progressed to an advanced stage. Our case underlies the importance of early recognition and referral of this rare but malignant lesion by primary care physicians

Second best toll and capacity optimisation in network: solution algorithm and policy implications

This paper looks at the first and second-best jointly optimal toll and road capacity investment problems from both policy and technical oriented perspectives. On the technical side, the paper investigates the applicability of the constraint cutting algorithm for solving the second-best problem under elastic demand which is formulated as a bilevel programming problem. The approach is shown to perform well despite several problems encountered by our previous work in Shepherd and Sumalee (2004). The paper then applies the algorithm to a small sized network to investigate the policy implications of the first and second-best cases. This policy analysis demonstrates that the joint first best structure is to invest in the most direct routes while reducing capacities elsewhere. Whilst unrealistic this acts as a useful benchmark. The results also show that certain second best policies can achieve a high proportion of the first best benefits while in general generating a revenue surplus. We also show that unless costs of capacity are known to be low then second best tolls will be affected and so should be analysed in conjunction with investments in the network

Medical graduates’ preparedness to practice: A comparison of undergraduate medical school training

Background: There is evidence that newly qualified doctors do not feel prepared to start work. This study examined views of first year Foundation doctors (F1s) regarding how prepared they felt by their undergraduate medical education for skills required during the first Foundation training year in relation to their type of training. Method: One-hundred and eighty two F1s completed a questionnaire during their first rotation of Foundation training. Analysis was conducted by type of medical school training: Problem-Based Learning (PBL), Traditional or Reformed. Results: F1s from medical schools with a PBL curriculum felt better prepared for tasks associated with communication and team working, and paperwork than graduates from the other medical school types; but the majority of F1s from all three groups felt well prepared for most areas of practice. Less than half of graduates in all three groups felt well prepared to deal with a patient with neurological/visual problems; write referral letters; understand drug interactions; manage pain; and cope with uncertainty. F1s also indicated that lack of induction or support on starting work was affecting their ability to work in some areas. Conclusions: Whilst F1s from medical schools with a PBL curriculum did feel better prepared in multiple areas compared to graduates from the other medical school types, specific areas of unpreparedness related to undergraduate and postgraduate medical training were identified across all F1s. These areas need attention to ensure F1s are optimally prepared for starting work

Spatial contrast sensitivity in adolescents with autism spectrum disorders

Adolescents with autism spectrum disorders (ASD) and typically developing (TD) controls underwent a rigorous psychophysical assessment that measured contrast sensitivity to seven spatial frequencies (0.5-20 cycles/degree). A contrast sensitivity function (CSF) was then fitted for each participant, from which four measures were obtained: visual acuity, peak spatial frequency, peak contrast sensitivity, and contrast sensitivity at a low spatial frequency. There were no group differences on any of the four CSF measures, indicating no differential spatial frequency processing in ASD. Although it has been suggested that detail-oriented visual perception in individuals with ASD may be a result of differential sensitivities to low versus high spatial frequencies, the current study finds no evidence to support this hypothesis

The functional relationship between transglutaminase 2 and transforming growth factor β1 in the regulation of angiogenesis and endothelial-mesenchymal transition

The importance of transglutaminase 2 (TG2) in angiogenesis has been highlighted in recent studies, but other roles of this multi-functional enzyme in endothelial cell (EC) function still remains to be fully elucidated. We previously showed that the extracellular TG2 is involved in maintaining tubule formation in ECs by a mechanism involving matrix-bound vascular endothelial growth factor (VEGF) signalling. Here, by using the ECs and fibroblast co-culture and ECs 3D culture models, we demonstrate a further role for TG2 in both endothelial tubule formation and in tubule loss, which involves its role in the regulation of transforming growth factor β1 (TGFβ1) and Smad signalling. We demonstrate that inhibition of tubule formation by TG2 inhibitors can be restored by add-back of exogenous TGFβ1 at pg/ml levels and show that TG2 -/- mouse ECs are unable to form tubules in 3D culture and display negligible Smad signalling compared to wild-type cells. Loss of tubule formation in the TG2 -/- ECs can be reconstituted by transduction with TG2. We demonstrate that extracellular TG2 also has an important role in TGFβ1-induced transition of ECs into myofibroblast-like cells (endothelial-mesenchymal transition), resulting in loss of EC tubules and tubule formation. Our data also indicate that TG2 may have a role in regulating TGFβ signalling through entrapment of active TGFβ1 into the extracellular matrix. In conclusion, our work demonstrates that TG2 has multi-functional roles in ECs where its ability to fine-tune of TGFβ1 signalling means it can be involved in both endothelial tubule formation and tubule rarefaction

Future climate effects on suitability for growth of oil palms in Malaysia and Indonesia

The production of palm oil (PO) is highly profitable. The economies of the principal producers, Malaysia and Indonesia, and others, benefit considerably. Climate change (CC) will most likely have an impact on the distribution of oil palms (OP) (Elaeis guineensis). Here we present modelled CC projections with respect to the suitability of growing OP, in Malaysia and Indonesia. A process-oriented niche model of OP was developed using CLIMEX to estimate its potential distribution under current and future climate scenarios. Two Global Climate Models (GCMs), CSIRO-Mk3.0 and MIROC-H, were used to explore the impacts of CC under the A1B and A2 scenarios for 2030, 2070 and 2100. Decreases in climatic suitability for OP in the region were gradual by 2030 but became more pronounced by 2100. These projections imply that OP growth will be affected severely by CC, with obvious implications to the economies of (a) Indonesia and Malaysia and (b) the PO industry, but with potential benefits towards reducing CC. A possible remedial action is to concentrate research on development of new varieties of OP that are less vulnerable to CC.The Portuguese-based authors thank the FCT Strategic Project of UID/BIO/04469/2013 unit, the project RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER-027462) and the Project "BioEnv - Biotechnology and Bioengineering for a sustainable world", REF. NORTE-07-0124-FEDER-000048, co-funded by the Programa Operacional Regional do Norte (ON.2 - O Novo Norte), QREN, FEDER

The role of the helper lipid on the DNA transfection efficiency of lipopolyplex formulations.

Multifunctional, lipopolyplex formulations comprising a mixture of cationic liposomes and cationic, receptor-targeting peptides have potential use in gene therapy applications. Lipopolyplex formulations described here are typically far more efficient transfection agents than binary lipoplex or polyplex formulations. It has been shown previously that the peptide component mediates both DNA packaging and targeting of the nanoparticle while in this report we investigate the contribution of the lipid component. We hypothesised that the lipid components synergise with the peptides in the transfection process by promoting endosomal escape after lipid bilayer fusion. Lipopolyplexes were prepared with cationic liposomes comprising DOTAP with either neutral lipid DOPE or DOPC. DOPE promotes fusogenic, inverted hexagonal lipid structures while DOPC promotes more stable laminar structures. Lipopolyplexes containing DOPE showed substantially higher transfection efficiency than those formulated with DOPC, both in vitro and in vivo. DOPE-containing lipopolyplexes showed rapid endosomal trafficking and nuclear accumulation of DNA while DOPC-containing formulations remained within the late endo-lysosomal compartments. These findings are consistent with previous finding for the role of DOPE in lipoplexes and support the hypothesis regarding the function of the lipid components in lipopolyplexes. These findings will help to inform future lipopolyplex design, strategies and clinical development processes

Development and validation of a patient reported outcome measure for health-related quality of life for locally recurrent rectal cancer: a multicentre, three-phase, mixed-methods, cohort study

Background Locally recurrent rectal cancer (LRRC) occurs in 5–10% of patients following previous treatment of rectal cancer. It has a significant impact on patients’ overall health-related quality of life (HrQoL). Major advances in surgical treatments have led to improved survival outcomes. However, due to the lack of disease-specific, validated patient-reported outcome measure (PROM), HrQoL, is variably assessed. The aim of this study is to develop a disease-specific, psychometrically robust, and validated PROM for use in LRRC. Methods A multicentre, three phase, mixed-methods, observational study was performed across five centres in the UK and Australia. Adult patients (>18 years old) with an existing or previously treated LRRC within the last 2 years were eligible to participate. Patients completed the proposed LRRC-QoL, EORTC QLQ-CR29, and FACT-C questionnaires. Scale structure was analysed using multi-trait scaling analysis and exploratory factor analysis, reliability was assessed using Cronbach's and the intra-class coefficient, convergent validity was assessed using Pearson's correlation, and known-groups comparison was assessed using the student t-test or ANOVA. Findings Between 01/03/2015 and 31/12/2019, 117 patients with a diagnosis of LRRC were recruited. The final scale structure of the LRRC-QoL consisted of nine multi-item scales (healthcare services, psychological impact, pain, urostomy-related symptoms, lower limb symptoms, stoma, sexual function, sexual interest, and urinary symptoms) and three single items. Cronbach's Alpha and Intraclass correlation values of >0.7 across the majority of scales supported overall reliability. Convergent validity was demonstrated between LRRC-QoL Pain Scale and FACT-C Physical Well Being scale (r = 0.528, p < 0.001), LRRC-QoL Psychological Impact scale with EORTC QLQ CR29 Body Image (r = 0.680, p < 0.001) and the FACT-C Emotional Well Being scale (r = 0.326, p < 0.001), and LRRC-QoL Urinary Symptoms scale with EORTC QLQ-CR29 Urinary Frequency scale (r = 0.310, p < 0.001). Known-groups validity was demonstrated for gender, disease location, treatment intent, and re-recurrent disease. Interpretation The LRRC-QoL has demonstrated robust psychometric properties and can be used in clinical and academic practice. Funding None

Homologous and heterologous desensitization of guanylyl cyclase-B signaling in GH3 somatolactotropes

The guanylyl cyclases, GC-A and GC-B, are selective receptors for atrial and C-type natriuretic peptides (ANP and CNP, respectively). In the anterior pituitary, CNP and GC-B are major regulators of cGMP production in gonadotropes and yet mouse models of disrupted CNP and GC-B indicate a potential role in growth hormone secretion. In the current study, we investigate the molecular and pharmacological properties of the CNP/GC-B system in somatotrope lineage cells. Primary rat pituitary and GH3 somatolactotropes expressed functional GC-A and GC-B receptors that had similar EC50 properties in terms of cGMP production. Interestingly, GC-B signaling underwent rapid homologous desensitization in a protein phosphatase 2A (PP2A)-dependent manner. Chronic exposure to either CNP or ANP caused a significant down-regulation of both GC-A- and GC-B-dependent cGMP accumulation in a ligand-specific manner. However, this down-regulation was not accompanied by alterations in the sub-cellular localization of these receptors. Heterologous desensitization of GC-B signaling occurred in GH3 cells following exposure to either sphingosine-1-phosphate or thyrotrophin-releasing hormone (TRH). This heterologous desensitization was protein kinase C (PKC)-dependent, as pre-treatment with GF109203X prevented the effect of TRH on CNP/GC-B signaling. Collectively, these data indicate common and distinct properties of particulate guanylyl cyclase receptors in somatotropes and reveal that independent mechanisms of homologous and heterologous desensitization occur involving either PP2A or PKC. Guanylyl cyclase receptors thus represent potential novel therapeutic targets for treating growth-hormone-associated disorders