Public willingness to participate in population DNA screening in Australia.

BACKGROUND: Population-based DNA screening for medically actionable conditions has the potential to improve public health by enabling early detection, treatment and/or prevention; however, public attitudes and willingness to participate in DNA screening have not been well investigated. METHODS: We presented a scenario to members of the Australian public, randomly selected from the electoral roll via the Australian Survey of Societal Attitudes, describing an adult population DNA screening programme currently under development, to detect risk of medically actionable cancers and heart disease. We asked questions regarding willingness to participate and pay, preferred delivery methods and concerns. RESULTS: We received 1060 completed questionnaires (response rate 23%, mean age 58 years). The vast majority (>92%) expressed willingness to undertake DNA screening. When asked about the optimal age of screening, most (56%) favoured early adulthood (aged 18-40 years) rather than at birth or childhood. Many respondents would prefer samples and data be kept for re-screening (36%) or research use (43%); some preferred samples to be destroyed (21%). Issues that decrease likelihood of participation included privacy (75%) and insurance (86%) implications. CONCLUSION: Our study demonstrates public willingness to participate in population DNA screening in Australia, and identifies barriers to participation, to be addressed in the design of screening programmes. Results are informing the development of a pilot national DNA screening programme.

Combined population genomic screening for three high-risk conditions in Australia: a modelling study.

Background: No previous health-economic evaluation has assessed the impact and cost-effectiveness of offering combined adult population genomic screening for mutliple high-risk conditions in a national public healthcare system. Methods: This modeling study assessed the impact of offering combined genomic screening for hereditary breast and ovarian cancer, Lynch syndrome and familial hypercholesterolaemia to all young adults in Australia, compared with the current practice of clinical criteria-based testing for each condition separately. The intervention of genomic screening, assumed as an up-front single cost in the first annual model cycle, would detect pathogenic variants in seven high-risk genes. The simulated population was 18-40 year-olds (8,324,242 individuals), modelling per-sample test costs ranging AU$100-$1200 (base-case AU$200) from the year 2023 onwards with testing uptake of 50%. Interventions for identified high-risk variant carriers follow current Australian guidelines, modelling imperfect uptake and adherence. Outcome measures were morbidity and mortality due to cancer (breast, ovarian, colorectal and endometrial) and coronary heart disease (CHD) over a lifetime horizon, from healthcare-system and societal perspectives. Outcomes included quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER), discounted 5% annually (with 3% discounting in scenario analysis). Findings: Over the population lifetime (to age 80 years), the model estimated that genomic screening per-100,000 individuals would lead to 747 QALYs gained by preventing 63 cancers, 31 CHD cases and 97 deaths. In the total model population, this would translate to 31,094 QALYs gained by preventing 2612 cancers, 542 non-fatal CHD events and 4047 total deaths. At AU$200 per-test, genomic screening would require an investment of AU$832 million for screening of 50% of the population. Our findings suggest that this intervention would be cost-effective from a healthcare-system perspective, yielding an ICER of AU$23,926 (∼£12,050/€14,110/US$15,345) per QALY gained over the status quo. In scenario analysis with 3% discounting, an ICER of AU$4758/QALY was obtained. Sensitivity analysis for the base case indicated that combined genomic screening would be cost-effective under 70% of simulations, cost-saving under 25% and not cost-effective under 5%. Threshold analysis showed that genomic screening would be cost-effective under the AU$50,000/QALY willingness-to-pay threshold at per-test costs up to AU$325 (∼£164/€192/US$208). Interpretation: Our findings suggest that offering combined genomic screening for high-risk conditions to young adults would be cost-effective in the Australian public healthcare system, at currently realistic testing costs. Other matters, including psychosocial impacts, ethical and societal issues, and implementation challenges, also need consideration. Funding: Australian Government, Department of Health, Medical Research Future Fund, Genomics Health Futures Mission (APP2009024). National Heart Foundation Future Leader Fellowship (102604).

Micropatterning for the control of surface cavitation: visualization through high-speed imaging.

For the first time, we apply a high-speed imaging technique to record the activity of acoustically driven cavitation bubbles (86 kHz) on micropatterned surfaces with hydrophobic and hydrophilic stripes. The width of the hydrophobic stripes lies between 3.5 and 115 µm. This work provides the first direct visualization of the preferential location of bubbles on the hydrophobic areas of the patterns. The results confirm our previous prediction that surface cavitation strongly depends on the surface energy of the irradiated substrate. The observations show a remarkable effect of the stripe width on the size, movement, growth, splitting, and multiplying of the bubbles. The high-speed imaging also reveals that there is a minimal width of the hydrophobic stripes that allows bubble attraction and formation. Our observations are supported by a theoretical approach based on the forces acting on the bubbles.

Sonoluminescence quenching and cavitation bubble temperature measurements in an ionic liquid.

A comparison between the temperatures within imploding acoustic cavitation bubbles and the extent of sonoluminescence (SL) quenching by C(1)-C(5) aliphatic alcohols in 1-ethyl-3-methylimidazolium ethylsulfate ([EMIM][EtSO(4)], a well known imidazolium based room temperature ionic liquid (RTIL)), has been made at an ultrasound frequency of 213 kHz. The temperatures obtained ranged from 3500 ± 200K, in neat [EMIM][EtSO(4)], to about 3200 ± 200K in RTIL-alcohol containing solutions. It was also found that the SL intensity decreased with increasing concentration (up to 1M) of the alcohols to a greater extent compared with the relative changes to the bubble temperatures. Both the extent of the reduction in the bubble temperatures and the SL quenching were much smaller than those obtained in comparable aqueous solutions containing aliphatic alcohols. Possible reasons for the differences in the observed trends between water/alcohol and [EMIM][EtSO(4)]/alcohol systems under sonication at 213 kHz are discussed.

Characterization of acoustic cavitation bubbles in different sound fields.

Various fundamental properties of acoustic cavitation bubbles have been investigated in single- and dual-frequency sound fields. It was found that the relative extent of bubble coalescence in the dual-frequency field correlated strongly with the synergistic enhancement of the sonochemical reaction rates. Both the relative extent of coalescence and the sonochemical synergy observed were enhanced through the addition of coalescence-inhibiting solutes. This was attributed to greater nucleation in the dual-frequency mode compared with the single-frequency modes, producing a very localized and high-density bubble field. The acoustic bubble size, compared with that measured at 355 kHz alone, was found to increase upon the application of synchronous 20 kHz pulses but was reduced dramatically when the low frequency was applied as a continuous wave. This trend is consistent with previous reports indicating that the bubble density and cavitation activity are relatively higher in the pulsed system and that the continuous wave application exerts a strong cancellation effect. The changes in bubble density and coalescence rates are proposed to govern the acoustic bubble size. The bubble lifetime was found to be longer in the dual-frequency field (>0.30 ms; >6 low-frequency oscillations, >100 high-frequency oscillations) compared with both single-frequency fields (0.26 ms and 5 oscillations for the low frequency; 0.22 ms and 75 oscillations for the high frequency). The confluence of a longer bubble lifetime and more asymmetric collapse conditions, the latter inferred from a more pronounced sodium atom emission in the sonoluminescence spectrum, resulted in a lower bubble collapse temperature measured in the dual-frequency system.

Acoustic bubble sizes, coalescence, and sonochemical activity in aqueous electrolyte solutions saturated with different gases.

Acoustic bubble sizes, coalescence behavior, and sonochemical activity have been investigated in water in the presence of various electrolyte additives (KCl, HCl, and NaNO(3)) and saturating gases-helium, air, and argon. A strong correlation was identified between the bubble radius and the dissolved gas concentration in the cavitation medium. The extent of bubble coalescence for each gas was also studied in different electrolyte solutions. A causal relationship between coalescence and bubble size was inferred. Importantly, the effects of the different electrolytes could be completely attributed to their "salting out" effect on the dissolved gas, providing valuable insight into the contentious issue of ion-specific coalescence inhibition. Extrapolation of the bubble size data to conditions where bubble coalescence is minimal, i.e., zero gas concentration and zero ultrasound exposure time, yielded a bubble radius of 1.5 +/- 0.5 microm at an acoustic frequency of 515 kHz. In addition, the effects of electrolyte concentration and gas type on sonochemical activity were investigated. Sonochemical yields were increased by up to 1 order of magnitude at high electrolyte concentrations. This has been attributed to reduced gas and vapor content in the bubble core prior to collapse and a lower clustering density.

Cavitation activation by dual-frequency ultrasound and shock waves.

High-speed photographic observations of cavitation occurring under a low-frequency (21 kHz) sonotrode tip in the presence of an additional, high-frequency (355 kHz) ultrasound source have been made in water and in dilute aqueous solute solutions. Acoustic emission spectra were measured to support the visual observations. It was seen that a nucleating effect of the high-frequency action on cavitation at the low-frequency sonotrode was highly power dependent, with cavitation being homogenous at low acoustic power and highly localised at high acoustic power. The presence of solutes was found to significantly affect the cavitation structures and the bubble fragmentation process. Both the fundamental high-frequency acoustic emission peak and the higher order low-frequency harmonics were significantly intensified in the dual-frequency mode in the presence of these solutes. Additionally, the application of a high-voltage induced acoustic shock-wave to two different ultrasound fields was investigated in water and surfactant solutions.

Effect of power and frequency on bubble-size distributions in acoustic cavitation.

Acoustic bubble-size distributions have been determined using a pulsed ultrasound method at different ultrasound powers and frequencies. It was observed that the mean bubble size increased with increasing acoustic power and decreased with increasing ultrasound frequency. It was also recognized that the mean size of bubbles emitting sonoluminescence was greater than those producing sonochemiluminescence indicating that the two processes take place in different populations of cavitation bubbles in the system.

Experimental and theoretical investigations on sonoluminescence under dual frequency conditions.

The multibubble sonoluminescence (MBSL) intensities from water exposed to the simultaneous ultrasonic irradiation from 20 kHz (fixed at 6.3 W) and 355 kHz (variable power) ultrasound sources have been compared to the MBSL from the individual ultrasound sources under the same power conditions. A synergistic enhancement of the sonoluminescence (SL) signal, >30-fold, at low powers (4.6 W) of the higher frequency was observed. At a higher acoustic power level (15.8 W) the dual frequency operation produced a decrease in the SL signal. These results are in agreement with previously reported data [P. Ciuti, N.V. Dezhkunov, A. Francescutto, F. Calligaris, F. Sturman, Ultrasonics Sonochem. 10 (2003) 337; N.V. Dezhkunov, J. Eng. Phys. Therm. 76 (2003) 142] under similar experimental conditions. Numerical single bubble (SB) dynamics calculations have been used to help interpret the experimental results. It is suggested that the observed effects are caused by a combination of changes to the peak collapse temperature of individual bubbles as well as to changes in the active bubble population.