Assessing the number of users who are excluded by domestic heating controls

This is the pre-print version of the Article. This Article is also referred to as: "Assessing the 'Design Exclusion' of Heating Controls at a Low-Cost, Low-Carbon Housing Development". - Copyright @ 2011 Taylor & FrancisSpace heating accounts for almost 60% of the energy delivered to housing which in turn accounts for nearly 27% of the total UK's carbon emissions. This study was conducted to investigate the influence of heating control design on the degree of ‘user exclusion’. This was calculated using the Design Exclusion Calculator, developed by the Engineering Design Centre at the University of Cambridge. To elucidate the capability requirements of the system, a detailed hierarchical task analysis was produced, due to the complexity of the overall task. The Exclusion Calculation found that the current design placed excessive demands upon the capabilities of at least 9.5% of the UK population over 16 years old, particularly in terms of ‘vision’, ‘thinking’ and ‘dexterity’ requirements. This increased to 20.7% for users over 60 years old. The method does not account for the level of numeracy and literacy and so the true exclusion may be higher. Usability testing was conducted to help validate the results which indicated that 66% of users at a low-carbon housing development could not programme their controls as desired. Therefore, more detailed analysis of the cognitive demands placed upon the users is required to understand where problems within the programming process occur. Further research focusing on this cognitive interaction will work towards a solution that may allow users to behave easily in a more sustainable manner

An assessment of orofacial clefts in Tanzania

<p>Abstract</p> <p>Background</p> <p>Clefts of the lip (CL), the palate (CP), or both (CLP) are the most common orofacial congenital malformations found among live births, accounting for 65% of all head and neck anomalies. The frequency and pattern of orofacial clefts in different parts of the world and among different human groups varies widely. Generally, populations of Asian or Native American origin have the highest prevalence, while Caucasian populations show intermediate prevalence and African populations the lowest. To date, little is known regarding the epidemiology and pattern of orofacial clefts in Tanzania.</p> <p>Methods</p> <p>A retrospective descriptive study was conducted at Bugando Medical Centre to identify all children with orofacial clefts that attended or were treated during a period of five years. Cleft lip and/or palate records were obtained from patient files in the Hospital's Departments of Surgery, Paediatrics and medical records. Age at presentation, sex, region of origin, type and laterality of the cleft were recorded. In addition, presence of associated congenital anomalies or syndromes was recorded.</p> <p>Results</p> <p>A total of 240 orofacial cleft cases were seen during this period. Isolated cleft lip was the most common cleft type followed closely by cleft lip and palate (CLP). This is a departure from the pattern of clefting reported for Caucasian and Asian populations, where CLP or isolated cleft palate is the most common type. The distribution of clefts by side showed a statistically significant preponderance of the left side (43.7%) (χ²= 92.4, p < 0.001), followed by the right (28.8%) and bilateral sides (18.3%). Patients with isolated cleft palate presented at very early age (mean age 1.00 years, SE 0.56). Associated congenital anomalies were observed in 2.8% of all patients with orofacial clefts, and included neural tube defects, Talipes and persistent ductus arteriosus.</p> <p>Conclusions</p> <p>Unilateral orofacial clefts were significantly more common than bilateral clefts; with the left side being the most common affected side. Most of the other findings did not show marked differences with orofacial cleft distributions in other African populations.</p

The influence of phenobarbital and butylated hydroxytoluene on the ploidy rate in rat hepatocarcinogenesis

The effect of the 'promoters' phenobarbital (PB) and butylated hydroxytoluene (BHT) on the ploidy changes during hepatocarcinogenesis in rats was compared in a densitometric analysis of Feulgen-stained nuclei on paraffin-embedded tissue slices. The triphasic Gerlans protocol for liver-cancer induction was applied. Initiation with a single dose of diethylnitrosamine (DEN), and selection with 2-acetylamino-fluorene (2-AAF) combined with a proliferative stimulus (CCl4 administration), was followed by a treatment with PB or BHT for periods up to 22 weeks. Control animals received no treatment after the initiation and selection procedure. Despite intra- and inter-individual variations, an increase in the amount of 2N nuclei is found in the putative preneoplastic lesions of animals that received initiation and selection (I-S) and 3 weeks basal diet (BD). When the diet is supplemented with PB (after I-S), the increase of diploid nuclei starts earlier. At the time carcinoma arise (22 weeks PB treatment) a decrease in the frequency of 2N nuclei is found. BHT-treated animals which develop no carcinoma within the considered timespan, show a clear increased amount of 2N nuclei in the precancerous lesions only after 14 weeks treatment. It seems that there is a positive correlation between the outgrowth of putative preneoplastic foci and nodules in rat liver and an increase of diploid nuclei in these lesions. PB, as promoter used after initiation and selection, speeds up the development of carcinoma in rat liver, and therefore also the shift to diploidization in these rats starts earlier in comparison with I-S-treated rats. Although BHT does not promote liver carcinogenesis, an increase of diploid nuclei is also observed here during lesion formation. It may, therefore, be concluded that the phenomenon of diploidization is closely linked to and probably necessary for preneoplastic development, but that it is not an absolute indicator for neoplastic transformation

UNcommon EGFR mutations: International Case series on efficacy of Osimertinib in Real-life practice in first-liNe setting (UNICORN) [1206P]

BACKGROUND : About 10% of EGFR mutations (EGFRmut) are ‘uncommon mutations’ (ucEGFRmut), correlating with lower response to 1st & 2nd generation EGFR inhibitors (EGFRi) compared to common mutations. Osimertinib is a 3rd generation EGFRi, active against common EGFRmut. Efficacy data of osimertinib in ucEGFRmut are scarce. We aimed to collect real-world data of the usage of osimertinib as the 1st EGFRi for ucEGFRmut. [...

UNcommon EGFR mutations: International Case series on efficacy of osimertinib in Real-life practice in first liNe setting (UNICORN).

BACKGROUND About 10% of EGFR mutations (EGFRmut) are 'uncommon mutations' (ucEGFRmut). We aimed to collect real-world data about osimertinib for ucEGFRmut patients. METHODS This is a multi-center, retrospective study of ucEGFRmut (exon 20 insertions excluded) metastatic NSCLC osimertinib-treated as first EGFR inhibitor. RECIST and RANO-BM brain objective response rate (ORR) were evaluated by investigators. mPFS, mOS and mDOR were calculated from osimertinib initiation. Mutations found at resistance were collected. RESULTS 60 patients included (22 centres, 9 countries): median age - 64 years, 75% females, 83% Caucasian. The largest subgroups were G719X (30%), L861Q (20%) and de novo T790M (15%). ORR was 61%, mPFS 9.5 months (m), mDOR 17.4m, mOS 24.5m. Regarding patients with no concurrent common mutations or T790M (group A, n=44), ORR was 60%, mPFS 8.6 months, mDOR 11 months. For G719X ORR was 47%, mPFS 8.8m and mDOR 9.1m. For L861Q ORR was 80%, mPFS 16m and mDOR 16m. For de novo T790M ORR was 44%, mPFS 12.7m, mDOR 46.2m. Compound EGFRmut including common mutations had better outcome compared to only ucEGFRmut. For 13 patients with a RANO-BM evaluable brain metastases, brain ORR was 46%. For 14 patients, rebiopsy was analysed: 4 patients - additional EGFR mutation (C797S, D585Y, E709K), 3 - new TP53 mutation, 1 - c-Met amplification, 1 - PIK3CA mutation and 1 - neuroendocrine transformation. CONCLUSIONS Osimertinib demonstrated activity in ucEGFRmut with high rate of disease control systemically and intracranially. Several resistance mechanisms were identified. This report comprises, to the best of our knowledge, the largest dataset of its kind

Fetal polymorphisms at the ABCB1-transporter gene locus are associated with susceptibility to non-syndromic oral cleft malformations

ATP-binding cassette (ABC) proteins in the placenta regulate fetal exposure to xenobiotics. We hypothesized that functional polymorphisms in ABC genes influence risk for non-syndromic oral clefts (NSOC). Both family-based and case–control studies were undertaken to evaluate the association of nine potentially functional single-nucleotide polymorphisms within four ABC genes with risk of NSOC. Peripheral blood DNA from a total of 150 NSOC case-parent trios from Singapore and Taiwan were genotyped, as was cord blood DNA from 189 normal Chinese neonates used as controls. In trios, significant association was observed between the ABCB1 single-nucleotide polymorphisms and NSOC (P<0.05). Only ABCB1 rs1128503 retained significant association after Bonferroni correction (odds ratio (OR)=2.04; 95% confidence interval (CI)=1.42–2.98), while rs2032582 and rs1045642 showed nominal significance. Association with rs1128503 was replicated in a case–control analysis comparing NSOC probands with controls (OR=1.58; 95% CI=1.12–2.23). A comparison between the mothers of probands and controls showed no evidence of association, suggesting NSOC risk is determined by fetal and not maternal ABCB1 genotype. The two studies produced a combined OR of 1.79 (95% CI=1.38–2.30). The T-allele at rs1128503 was associated with higher risk. This study thus provides evidence that potentially functional polymorphisms in fetal ABCB1 modulate risk for NSOC, presumably through suboptimal exclusion of xenobiotics at the fetal–maternal interface