Public attitudes towards novel reproductive technologies: a citizens' jury on mitochondrial donation.

STUDY QUESTION: Does an informed group of citizens endorse the clinical use of mitochondrial donation in a country where this is not currently permitted? SUMMARY ANSWER: After hearing balanced expert evidence and having opportunity for deliberation, a majority (11/14) of participants in a citizens' jury believed that children should be able to be born using mitochondrial donation. WHAT IS KNOWN ALREADY: Research suggests that patients, oocyte donors and health professionals support mitochondrial donation to prevent transmission of mitochondrial disease. Less is known about public acceptability of this novel reproductive technology, especially from evidence using deliberative methods. STUDY DESIGN, SIZE, DURATION: This study comprised a citizens' jury, an established method for determining the views of a well-informed group of community members. The jury had 14 participants, and ran over one and a half days in 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: Jurors were members of the public with no experience of mitochondrial disease. They heard and engaged with relevant evidence and were asked to answer the question: 'Should Australia allow children to be born following mitochondrial donation?' MAIN RESULTS AND THE ROLE OF CHANCE: Eleven jurors decided that Australia should allow children to be born following mitochondrial donation; 7 of whom added conditions such as the need to limit who can access the intervention. Three jurors decided that children should not (or not yet) be born using this intervention. All jurors were particularly interested in the reliability of evidence, licensing/regulatory mechanisms and the rights of children to access information about their oocyte donors. LIMITATIONS, REASONS FOR CAUTION: Jurors' views were well informed and reflected critical deliberation and discussion, but are not intended to be representative of the whole population. WIDER IMPLICATIONS OF THE FINDINGS: When presented with high quality evidence, combined with opportunities to undertake structured deliberation of novel reproductive technologies, members of the public are able to engage in detailed discussions. This is the first study to use an established deliberative method to gauge public views towards mitochondrial donation. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by a University of Sydney Industry and Community Collaboration Seed Award (2017), which was awarded contingent on additional funding from the Mito Foundation. Additional funding was provided by the Mito Foundation. The Foundation was not involved in jury facilitation or deliberation, nor analysis of research data. TRIAL REGISTRATION NUMBER: Not applicable.

Does personalized melanoma genomic risk information trigger conversations about skin cancer prevention and skin examination with family, friends and health professionals?

BACKGROUND: Receiving information about genomic risk of melanoma might trigger conversations about skin cancer prevention and skin examinations. OBJECTIVES: To explore conversations prompted by receiving personalized genomic risk of melanoma with family, friends and health professionals. METHODS: We used a mixed-methods approach. Participants without a personal history and unselected for a family history of melanoma (n = 103, aged 21-69 years, 53% women) completed questionnaires 3 months after receiving a personalized melanoma genomic risk assessment. Semistructured interviews were undertaken with 30 participants in high, average and low genomic risk categories, and data were analysed thematically. RESULTS: From the questionnaires, 74% of participants communicated their genomic risk information with family, and 49% with friends. Communication with a health professional differed by risk level: 41%, 16% and 12% for high, average and low risk, respectively (P = 0·01). Qualitative analysis showed that perceived 'shared risk' and perceived interest of family and friends were motivations for discussing risk or prevention behaviours. The information prompted conversations with family and health professionals about sun protection and skin checks, and general conversations about melanoma risk with friends. Reasons for not discussing with family included existing personal or family health concerns, or existing high levels of sun protection behaviour among family members. CONCLUSIONS: Personalized melanoma genomic risk information can prompt risk-appropriate discussions about skin cancer prevention and skin examinations with family and health professionals. Sharing this information with others might increase its impact on melanoma prevention and skin examination behaviours, and this process could be used to encourage healthy behaviour change within families.

Australians' knowledge and perceptions of direct-to-consumer personal genome testing.

BACKGROUND: As direct-to-consumer personal genome testing (DTC-PGT) is increasingly available in Australia, knowledge of Australians' perceptions and attitudes towards this technology is needed in order to assess the (potential) impact it might have on the Australian public and healthcare system. AIMS: To explore the knowledge and perceptions of DTC-PGT in an Australian sample. METHODS: An online survey asking about knowledge and perceptions of DTC-PGT, undertaken between October 2011 and April 2012, of 270 Australian residents. Results were analysed using SAS. RESULTS: Our study found limited consumer knowledge of, and interest in, pursuing DTC-PGT in Australia. Ninety-three per cent of respondents correctly identified DTC-PGT as available to consumers directly, but only 40% correctly identified its availability in Australia. When asked about the content and value of the information DTC-PGT provides, the majority of respondents indentified that DTC-PGT could provide information about one's health and/or ancestry (82% and 74%). Additionally, respondents indicated they believed this information to be equally important as non-genetic information about one's ancestry and health. CONCLUSION: While a minority of respondents expressed an intention to pursue DTC-PGT (27%), the majority of respondents, irrespective of whether they wished to pursue it or not, believed that genetic information was as important as non-genetic information in regards to their health and their ancestry. The value ascribed to genetic information suggests that genetics plays a role in people's lives, and that further qualitative research could explore the ways in which people might use and understand the genetic information provided by DTC-PGT.

Is informed choice in prenatal testing universally valued? A population-based survey in Europe and Asia.

OBJECTIVE: Informed choice has become an integral part of healthcare provision. We investigated the extent to which informed choice in the context of prenatal testing is universally valued. DESIGN: The value attached to parental choice in prenatal testing and the perceived importance of significant others' views when making test decisions were assessed in a cross-sectional, descriptive study. SAMPLE AND SETTING: Male and female participants from general population samples in six countries: the UK (n = 210), the Netherlands (n = 197), Italy (n = 200), Greece (n = 200), China (n = 200) and India (n = 199). METHODS: The questionnaires assessed values attached to parental involvement and the perceived importance of the views of significant others when making prenatal test decisions. MAIN OUTCOME MEASURES: Attitudes towards parental choice and attitudes towards the importance of others' views were analysed by age, gender and education using Chi-squared tests, Analysis of Variances and multiple logistic regression. RESULTS: The majority of respondents from Northern European countries believed that undergoing prenatal tests should reflect parental choice. Conversely, only a minority of respondents from Southern European and Asian countries advocated parental choice, with most expressing the belief that all pregnant women should have the procedure. The perceived importance of significant others' views when making test decisions also varied across countries: those in favour of parental choice perceived others' views as less important in the test decision. A preference for prenatal testing decisions to reflect an informed choice was predicted by (i) country and (ii) the perceived importance of significant others' views. Education, age and gender did not predict decisions. CONCLUSION: The implications of these findings for policy and practice depend upon whether placing a low value on parental choice, but a high value on the others' views regarding prenatal testing is considered an informed choice. Further research is needed to determine whether cultural variation in values remains significant in a multicultural society.

Comparison of midazolam with thiopentone for outpatient anaesthesia.

The water soluble benzodiazepine, midazolam, was compared with thiopentone as an intravenous induction agent in unpremedicated patients undergoing cystoscopy as out-patients. Induction time was longer with midazolam, though subsequent transition to halothane inhalation anaesthesia was smooth and uneventful. Both drugs had similar effects on the cardiovascular and respiratory systems and were without local irritation following intravenous injection. Recovery was more prolonged with midazolam, tests of memory and unaided mobility showing greater impairment one hour after anaesthesia. Notwithstanding a slower and less predictable onset of unconsciousness and somewhat slower recovery phase, midazolam provides a safe alternative to thiopentone as an induction agent suited to minor surgical procedures.

Dr GD Monteith: an unobtrusive Wellington surgeon who became coroner, provincial surgeon and hospital superintendent.

The first general surgical operation performed on an etherised patient in New Zealand took place early on the afternoon of Monday, 27 September 1847, at the recently opened Wellington Colonial Hospital. The surgeon Dr JP Fitzgerald, M.D. was assisted by Dr GD Monteith and the ether was administered by JH Marriott Esq. Whereas the biographies of Dr Fitzgerald and James Manrriott have been well documented nationally, little has been recorded concerning Dr Monteith. The following article has been compiled in an attempt to prevent the life and contributions of Dr Monteith from slipping into oblivion.

The contribution of newspapers and their advertisements to the history of colonial anaesthesia.

The first news to reach New Zealand about the beneficial effects of inhalation of ether during surgical operations arrived in Wellington on Sunday July 4 1847. This was 283 days after the first successful demonstration in Boston. The mail services that brought this news and the original source of this news are described. After this news had reached Wellington, it then took another 84 days before the first successful trial of the agent took place in the recently opened Wellington Colonial Hospital. This period of eighty-four days compares unfavourably with those for Sydney and Cape Town. The reasons for this delay are discussed and using information available in the local Sydney and Wellington newspapers, the delay is shown to have been due to the unavailability of supplies of the necessary chemical reagents.

All here are agog with the chloroform.

Two letters written by James Y. Simpson are included among a bound collection of 25 of his pamphlets held in the Gordon Craig Collection of the Library of the Royal Australasian College of Surgeons. Both letters are written in pamphlets relating to Simpson's championing of chloroform. The first letter is written in a proof copy of a pamphlet titled Notice of a new anaesthetic agent as a substitute for Sulphuric ether in Surgery and Midwifery. This very rare pamphlet was posted to Dr Fleetwood Churchill, a Dublin obstetrician, on 13 November 1847, 9 days after the 'dining room experiment' in Simpson' s home, when the anaesthetic properties of chloroform were dramatically demonstrated. The second letter is written 10 months later and is also addressed to Dr Fleetwood Churchill. The content of both letters is discussed, as is also the rarity of the proof copies of the first printed document describing the use of chloroform.

New Zealand's first general anaesthetic.

The administration of New Zealand's first general anaesthetic took place at the Colonial Gaol, Wellington, on the morning of Monday, September 27th, 1847. The agent used was sulphuric ether which was administered by Mr. Marriot, the manufacturer of the Herapath-type inhaler used on this occasion. The operation, a dental extraction, was performed by the Colonial Surgeon, Dr. J. P. Fitzgerald.

The effectiveness and duration of preoperative antacid therapy.

The administration of 10 ml of magnesium trisilicate mixture to premedicated patients, maintains the pH of gastric contents below pH 2-5 during subsequent general anaesthesia. This effect was sustained for over seven hours--the longest anaesthetic time studied. No antacid supplementation is required to offer protection from acid aspiration during emergence and initial recovery from general anaesthesia.

A visual monitor for piped oxygen supply systems to anaesthetic machines.

A pressure sensitive recording device for monitoring piped oxygen systems supplying anaesthetic machines is described. The monitor displays a colour change and is powered by pressure of oxygen from the piped oxygen supply line.

Pre-operative neutralization of gastric acidity.

The incidence of Mendelson's syndrome in the four major Auckland hospitals is reviewed. The frequency of this condition was reduced following the pre-operative administration of magnesium trisilicate mixture in two hospitals. A trial was conducted in a third hospital and this showed that a 52 per cent incidence of highly acid gastric juice (pH less than 2.5) in patients prepared for elective surgery was reduced by administration of magnesium trisilicate mixture at the time of premedication. When the magnesium trisilicate mixture was given within the 30 minutes prior to induction of anaesthesia, the number of patients with highly acid gastric content fell to one per cent.

Investigations using logistic regression models on the effect of the LMA on morphine induced vomiting after tonsillectomy.

The effect of intraoperative airway management on postoperative vomiting after tonsillectomy is unknown. Logistic regression was used in a retrospective study to investigate the effect of the laryngeal mask airway (LMA) on a morphine dose-vomiting response curve. Charts were reviewed in 351 children in whom the airway was managed with either a LMA (n=177) or a tracheal tube (n=174). A mean perioperative morphine dose of 0.10 mg.kg(-1) (SD 0.09) was used in 248 children and a further 103 children were given no opioid. One hundred and eighteen of these 248 children vomited (47.6%) compared to 14 of 103 children given no morphine (13.6%). The probability of vomiting was related to morphine dose using logistic regression with both a linear and an E(max) model. Both the calibration (Hosmer-Lemishow goodness of fit chi-squared test lambda(2), P=0.81) and discrimination (area under the receiver operating characteristic plot, AUC ROC=0.67) of the E(max) model were better than the linear model (lambda(2), P=0.49; AUC ROC=0.64). Pharmacodynamic parameter estimates for the Emax model were P(0) (the baseline probability of vomiting) 0.139, P(max) (the maximal probability of vomiting due to morphine) 0.96, ED(50) (morphine dose that induces an effect equivalent to 50% of the logit P(max)) 0.09 mg.kg-1. The probability of vomiting was 50% after morphine 0.125 mg.kg-1. The use of the LMA had no effect on this dose-response curve. A covariate analysis investigating propofol for induction or isoflurane for the intraoperative maintenance of anaesthesia, however, showed that both drugs shifted the curve to the right. The probability of vomiting was 50% after morphine 0.17 mg.kg(-1) and 0.21 mg.kg(-1) for the isoflurane and propofol use curves, respectively. The concomitant use of propofol and isoflurane, but not the use of the LMA, decreases the probability of vomiting due to morphine.

Gene structure and sequence analysis of mouse centromere proteins A and C.

We have determined the genomic structure and organization of the mouse Cenpa and Cenpc genes. CENPA is a member of the histone H3-like proteins and is thought to replace histone H3 in centromeric nucleosomes. CENPC is a DNA-binding protein that is located at the inner kinetochore plate of active mammalian centromeres. The Cenpa cDNA encodes a 134-amino-acid product that is 70% identical and 84% similar to its human homolog. The mouse Cenpa gene is approximately 8 kb in length and contains five exons. Sequence analysis of the 5' DNA sequence of the gene revealed two consensus CAAT boxes, a putative TFIID-binding site, an Sp1-binding domain, and two cell cycle regulatory motifs, but no consensus TATA element. The mouse Cenpc gene spans 60 kb and contains 19 exons that range in size from 44 to 602 bp. Sequence analysis of the C+G-rich promoter region showed the presence of known promoter elements, including a CpG island, a CAAT box, and several GC boxes, but the absence of a consensus TATA element.

Early disruption of centromeric chromatin organization in centromere protein A (Cenpa) null mice.

Centromere protein A (Cenpa for mouse, CENP-A for other species) is a histone H3-like protein that is thought to be involved in the nucleosomal packaging of centromeric DNA. Using gene targeting, we have disrupted the mouse Cenpa gene and demonstrated that the gene is essential. Heterozygous mice are healthy and fertile whereas null mutants fail to survive beyond 6.5 days postconception. Affected embryos show severe mitotic problems, including micronuclei and macronuclei formation, nuclear bridging and blebbing, and chromatin fragmentation and hypercondensation. Immunofluorescence analysis of interphase cells at day 5.5 reveals complete Cenpa depletion, diffuse Cenpb foci, absence of discrete Cenpc signal on centromeres, and dispersion of Cenpb and Cenpc throughout the nucleus. These results suggest that Cenpa is essential for kinetochore targeting of Cenpc and plays an early role in organizing centromeric chromatin at interphase. The evidence is consistent with the proposal of a critical epigenetic function for CENP-A in marking a chromosomal region for centromere formation.

Chromosomal localization of mouse Cenpa gene.

Using a previously isolated mouse centromere protein A (Cenpa) probe, we have localized the gene to the proximal region of mouse Chromosome 5, between the known Il6 and Yes1 loci near [Adra2C-D5H4S43-Hdh]. Comparison of this localization with that of human CENPA, which maps to chromosome 2, is consistent with the presence of a new region of conserved synteny between the two species.