Sandy Clarke

ROBUSTNESS OF MULTIPLE TESTING PROCEDURES AGAINST DEPENDENCE

An important aspect of multiple hypothesis testing is controlling the significance level, or the level of Type I error. When the test statistics are not independent it can be particularly challenging to deal with this problem, without resorting to very conservative procedures. In this paper we show that, in the context of contemporary multiple testing problems, where the number of tests is often very large, the difficulties caused by dependence are less serious than in classical cases. This is particularly true when the null distributions of test statistics are relatively light-tailed, for example, when they can be based on Normal or Students t approximations. There, if the test statistics can fairly be viewed as being generated by a linear process, an analysis founded on the incorrect assumption of independence is asymptotically correct as the number of hypotheses diverges. In particular, the point process representing the null distribution of the indices at which statistically significant test results occur is approximately Poisson, just as in the case of independence. The Poisson process also has the same mean as in the independence case, and of course exhibits no clustering of false discoveries. However, this result can fail if the null distributions are particularly heavy-tailed. There clusters of statistically significant results can occur, even when the null hypothesis is correct. We give an intuitive explanation for these disparate properties in light- and heavy-tailed cases, and provide rigorous theory underpinning the intuition.

Epigenetic Changes in Response to Tai Chi Practice: A Pilot Investigation of DNA Methylation Marks

Tai chi exercise has been shown to improve physiological and psychosocial functions, well-being, quality of life, and disease conditions. The biological mechanisms by which tai chi exerts its holistic effects remain unknown. We investigated whether tai chi practice results in positive epigenetic changes at the molecular level. Design. The DNA methylation profiles of sixty CpG-dinucleotide marks in female tai chi practitioners (N = 237; 45–88 years old) who have been practising tai chi for three or more years were compared with those of age-matched control females (N = 263) who have never practised tai chi. Results. Six CpG marks originating from three different chromosomes reveal a significant difference (P < 0.05) between the two cohorts. Four marks show losses while two marks show gains in DNA methylation with age in the controls. In the tai chi cohort all six marks demonstrate significant slowing (by 5–70%) of the age-related methylation losses or gains observed in the controls, suggesting that tai chi practice may be associated with measurable beneficial epigenetic changes. Conclusions. The results implicate the potential use of DNA methylation as an epigenetic biomarker to better understand the biological mechanisms and the health and therapeutic efficacies of tai chi.

Interatrial septum motion but not Doppler assessment predicts elevated pulmonary capillary wedge pressure in patients undergoing cardiac surgery.

Background:Left atrial pressure and its surrogate, pulmonary capillary wedge pressure (PCWP), are important for determining diastolic function. The role of transthoracic echocardiography (TTE) in assessing diastolic function is well established in awake subjects. The objective was to assess the accuracy of predicting PCWP by TTE and transesophageal echocardiography (TEE) during coronary artery surgery. Methods:In 27 adult patients undergoing on-pump coronary artery surgery, simultaneous echocardiographic and hemodynamic measurements were obtained immediately before anesthesia (TTE), after anesthesia and mechanical ventilation (TTE and TEE), during conduit harvest (TEE), and after separation from cardiopulmonary bypass (TEE). Results:Twenty patients had an ejection fraction (EF) of 0.5 or greater. With the exception of E/e′ and S/D ratios, echocardiographic values changed over the echocardiographic studies. In patients with low EF, E velocity, deceleration time, pulmonary vein D, S/D, and E/e′ ratios correlated well with PCWP before anesthesia. After induction of anesthesia using TTE or TEE, correlations were poor. In normal EF patients, correlations were poor for both TEE and TTE at all five stages. The sensitivity and specificity of echocardiographic values were not high enough to predict raised PCWP except for a fixed curve pattern of interatrial septum (area under the curve 0.89 for PCWP ≥17, and 0.98 for ≥18 mmHg) and S/D less than 1 (area under the curve 0.74 for PCWP ≥17, and 0.78 for ≥18 mmHg). Conclusion:Doppler assessment of PCWP was neither sensitive nor specific enough to be clinically useful in anesthetized patients with mechanical ventilation. The fixed curve pattern of the interatrial septum was the best predictor of raised PCWP.

Falls by individuals with chronic obstructive pulmonary disease: a preliminary 12-month prospective cohort study.

Despite evidence of an increased fall risk in people with chronic obstructive pulmonary disease (COPD), there is a paucity of prospective fall data in this population. This preliminary study aimed to prospectively examine the prevalence rate, incidence rate and associated risk factors for falls in a sample of community‐dwelling people with COPD over 1 year.

Satisfaction is not substantially affected by quality of recovery: different constructs or are we lost in statistics?

Satisfaction has been used as a surrogate measure of quality of recovery for many years, principally because it is easy to perform, and is a widely-used feedback tool throughout society. Consider how often people press the ‘like’ button on various social media platforms! However, the constructs around satisfaction may be very different to the constructs around quality of recovery. This is not to say that satisfaction is not a patient-centered outcome, but rather that it is a different outcome from other quality of recovery domains. Berning and colleagues investigated the relationship between quality of recovery measured using the QoR-15 scale [1], and compared it with a custom composite satisfaction scale [1]. They concluded that quality of recovery only has a marginal supplementary effect on patient satisfaction. This is a slightly counterintuitive finding, as others have found aspects of quality of recovery such as pain and nausea to influence patient satisfaction [2, 3]. Nonetheless, the article raises the important question of whether patient satisfaction is an adequate measure to assess other quality of recovery outcomes. Although their conclusion pitches this question in the alternative view – that quality of recovery is not an important metric to determine patient satisfaction, outcomes reflecting the quality of recovery, are becoming important in determining whether patients receive value for their surgery. Initiatives such as Enhanced Recovery After Surgery, Peri-operative Medicine, and the Peri-operative Surgical Home are designed to improve the surgical journey, of which the quality of recovery of the patients is an important component. When assessing their finding that there is no meaningful association between quality of recovery and satisfaction, we need to consider three questions. Firstly, are the constructs of satisfaction and quality of recovery very different and therefore a lack of association is predictable? Secondly, have they used appropriate tools to support their broad conclusion? Thirdly, could their methods of analysis be unsuitable to answer the research question?

Pregnant women maintain body temperatures within safe limits during moderate-intensity aqua-aerobic classes conducted in pools heated up to 33 degrees Celsius: an observational study

QUESTION What is the body temperature response of healthy pregnant women exercising at moderate intensity in an aqua-aerobics class where the water temperature is in the range of 28 to 33 degrees Celsius, as typically found in community swimming pools? DESIGN An observational study. PARTICIPANTS One hundred and nine women in the second and third trimester of pregnancy who were enrolled in a standardised aqua-aerobics class. OUTCOME MEASURES Tympanic temperature was measured at rest pre-immersion (T1), after 35minutes of moderate-intensity aqua-aerobic exercise (T2), after a further 10minutes of light exercise while still in the water (T3) and finally on departure from the facility (T4). The range of water temperatures in seven indoor community pools was 28.8 to 33.4 degrees Celsius. RESULTS Body temperature increased by a mean of 0.16 degrees Celsius (SD 0.35, p<0.001) at T2, was maintained at this level at T3 and had returned to pre-immersion resting values at T4. Regression analysis demonstrated that the temperature response was not related to the water temperature (T2 r = -0.01, p = 0.9; T3 r = -0.02, p=0.9; T4 r=0.03, p=0.8). Analysis of variance demonstrated no difference in body temperature response between participants when grouped in the cooler, medium and warmer water temperatures (T2 F=0.94, p=0.40; T3 F=0.93, p=0.40; T4 F=0.70, p=0.50). CONCLUSIONS Healthy pregnant women maintain body temperatures within safe limits during moderate-intensity aqua-aerobic exercise conducted in pools heated up to 33 degrees Celsius. The study provides evidence to inform guidelines for safe water temperatures for aqua-aerobic exercise during pregnancy.

Investigation of forelimb hoof wall strains and hoof shape in unshod horses exercised on a treadmill at various speeds and gaits

OBJECTIVE To investigate forelimb hoof wall strains and shape changes in unshod horses undergoing regular moderate exercise on a treadmill at selected speeds and gaits. ANIMALS 6 horses of various body types. PROCEDURES Each horse was exercised on a treadmill (walking, trotting, and cantering, with or without galloping at 12.5 m/s) 3 times a week for 4 consecutive weeks; duration of each exercise session ranged from 10 to 14 minutes. During the 4-week period, the proximal hoof circumference (PHC) and toe angle (TA) of each forelimb hoof were measured weekly with a flexible measuring tape and a hoof gauge, respectively. Forelimb hoof wall strains were measured bilaterally at the toe and each quarter (3 strain gauges) immediately before the first and after the last exercise session. RESULTS Strain measurements revealed a consistent pattern of deformation of the hoof wall in both forelimbs at all gaits; strains increased during the stance phase of the stride. Strain values were dependent on site and gait. Compared with initial findings, mean TA increased significantly, whereas mean PHC did not, after the 4-week exercise period. A relationship between TA changes and hoof wall strains could not be established. CONCLUSIONS AND CLINICAL RELEVANCE In unshod horses, forelimb hoof wall strains were affected by site and gait, but not by discrete changes in TA; PHC did not change in response to moderate regular exercise. The pattern of hoof loading was consistent despite significant changes in TA.

Speech intelligibility benefits of frequency-lowering algorithms in adult hearing aid users: a systematic review and meta-analysis

Abstract Objective: This systematic review evaluated the effectiveness of two frequency-lowering schemes, non-linear frequency compression and frequency transposition, at improving speech intelligibility for adult hearing-impaired populations. Design: A systematic search of 10 electronic databases was carried out using pre-defined inclusion criteria. Accepted articles were then critically appraised using the Effective Public Health Practice Project (EPHPP) Critical Appraisal Tool. Outcome results were further synthesised where possible using random effects meta-analysis to provide overall combined estimates of the treatment differences along with 95% confidence intervals. Study sample: A total of 20 articles were accepted for final review. Results: Overall, study quality was of moderate strength. Meta-analysis found a statistically significant benefit in favour of frequency-lowering for consonant recognition testing in quiet across 145 participants with both algorithms providing comparable gains. Equivalent results were found between frequency-lowering and conventional processing on all other speech measures. Conclusions: Based on the available data, frequency-lowering does seem to provide some improvement in an individual’s speech intelligibility dependant on the stimulus type, although the benefits were modest. This improvement was not seen across all measures, however those who do not benefit from the technology will also not be harmed by trialling it.

Hearing the evidence: using archaeological data to analyse the long-term impacts of dugong (Dugong dogon) hunting on Mabuyag, Torres Strait, over the past 1000 years

Abstract Dugong hunting by Torres Strait Islanders has a long history dating back at least 4000 years. Dugongs are highly susceptible to over-predation, due to slow development and low fecundity/reproductive rates. While attempts to model catch sustainability using recent survey and catch data have caused conservation concern, lack of historical data prevents reliable statements on the sustainability of past dugong hunting practices. In the absence of historical data, archaeological data in the form of dugong bones provide a unique and valuable data archive to examine long-term hunting sustainability in terms of changes in prey body size. Dimensional measurements of 229 ear bones (periotic bones) were used as a proxy for dugong size, to examine whether or not human hunting activity might have caused changes in dugong body size over time. Three archaeological sites of the Mabuyag Islands of the Goemulgal people of central western Torres Strait were selected for comparison – a village midden (Goemu) and two ceremonial dugong bone mounds (Dabangay Bone Mound and Moegi Sibuy), which span 1000 years up to c.1900 AD. Statistical analysis revealed periotic bone size from the three sites is remarkably similar. Despite their high susceptibility to over-hunting, our archaeological results do not provide evidence for over-predation of dugongs by the Goemulgal in the past.

Factors influencing audiologists’ perception of moral climate in the workplace

Abstract Objective: The purpose of this study was to assess audiologists’ perceptions of ethics and moral climate in the workplace. Design: The Ethics Environmental Questionnaire (EEQ) was sent out to all audiologists registered with the professional body Audiology Australia. Participants were also invited to undertake a semi-structured interview. Study sample: A total of 301 audiologists completed the questionnaire. Eight of these participants also agreed to complete the interview. Results: The overall mean on the EEQ was approximately equivalent to that of a positive ethical environment, with the exception of those working in adult rehabilitation settings who scored significantly poorer. Scores were significantly associated with state and age. Qualitative analysis from the interviews found that sales pressure from employers was the dominant cause for concern amongst the group. Conclusions: For those working in adult rehabilitation, moral distress is most likely to occur as the result of conflicting goals between the organisation and the audiologist. There is a need to regulate the practice at an organisational as well as individual level to ensure the focus remains on ethical practice.