A biogenic amine and a neuropeptide act identically: tyramine signals through calcium in drosophila tubule stellate cells

Insect osmoregulation is subject to highly sophisticated endocrine control. In Drosophila, both Drosophila kinin and tyramine act on the Malpighian (renal) tubule stellate cell to activate chloride shunt conductance, and so increase the fluid production rate. Drosophila kinin is known to act through intracellular calcium, but the mode of action of tyramine is not known. Here, we used a transgenically encoded GFP::apoaequorin translational fusion, targeted to either principal or stellate cells under GAL4/UAS control, to demonstrate that tyramine indeed acts to raise calcium in stellate, but not principal cells. Furthermore, the EC(50) tyramine concentration for half-maximal activation of the intracellular calcium signal is the same as that calculated from previously published data on tyramine-induced increase in chloride flux. In addition, tyramine signalling to calcium is markedly reduced in mutants of NorpA (a phospholipase C) and itpr, the inositol trisphosphate receptor gene, which we have previously shown to be necessary for Drosophila kinin signalling. Therefore, tyramine and Drosophila kinin signals converge on phospholipase C, and thence on intracellular calcium; and both act to increase chloride shunt conductance by signalling through itpr. To test this model, we co-applied tyramine and Drosophila kinin, and showed that the calcium signals were neither additive nor synergistic. The two signalling pathways thus represent parallel, independent mechanisms for distinct tissues (nervous and epithelial) to control the same aspect of renal function

Rescaling quality of life values from discrete choice experiments for use as QALYs: a cautionary tale

Background: Researchers are increasingly investigating the potential for ordinal tasks such as ranking and discrete choice experiments to estimate QALY health state values. However, the assumptions of random utility theory, which underpin the statistical models used to provide these estimates, have received insufficient attention. In particular, the assumptions made about the decisions between living states and the death state are not satisfied, at least for some people. Estimated values are likely to be incorrectly anchored with respect to death (zero) in such circumstances. Methods: Data from the Investigating Choice Experiments for the preferences of older people CAPability instrument (ICECAP) valuation exercise were analysed. The values (previously anchored to the worst possible state) were rescaled using an ordinal model proposed previously to estimate QALY-like values. Bootstrapping was conducted to vary artificially the proportion of people who conformed to the conventional random utility model underpinning the analyses. Results: Only 26% of respondents conformed unequivocally to the assumptions of conventional random utility theory. At least 14% of respondents unequivocally violated the assumptions. Varying the relative proportions of conforming respondents in sensitivity analyses led to large changes in the estimated QALY values, particularly for lower-valued states. As a result these values could be either positive (considered to be better than death) or negative (considered to be worse than death). Conclusion: Use of a statistical model such as conditional (multinomial) regression to anchor quality of life values from ordinal data to death is inappropriate in the presence of respondents who do not conform to the assumptions of conventional random utility theory. This is clearest when estimating values for that group of respondents observed in valuation samples who refuse to consider any living state to be worse than death: in such circumstances the model cannot be estimated. Only a valuation task requiring respondents to make choices in which both length and quality of life vary can produce estimates that properly reflect the preferences of all respondents

Bedside rationing by general practitioners: A postal survey in the Danish public healthcare system

<p>Abstract</p> <p>Background</p> <p>It is ethically controversial whether medical doctors are morally permitted to ration the care of their patients at the bedside. To explore whether general practitioners in fact do ration in this manner we conducted a study within primary care in the Danish public healthcare system. The purpose of the study was to measure the extent to which general practitioners (GPs) would be willing to factor in cost-quality trade-offs when prescribing medicine, and to discover whether, and if so to what extent, they believe that patients should be informed about this.</p> <p>Methods</p> <p>Postal survey of 600 randomly selected Danish GPs, of which 330 responded to the questionnaire. The Statistical Package for the Social Sciences (SPSS, version 14.0) was used to produce general descriptive statistics. Significance was calculated with the McNemar and the chi-square test. The main outcome measures of the study were twofold: an assessment of the proportion of GPs who, in a mainly hypothetical setting, would consider cost-quality trade-offs relevant to their clinical decision-making given their economic impact on the healthcare system; and a measure of the extent to which they would disclose this information to patients.</p> <p>Results</p> <p>In the hypothetical setting 95% of GPs considered cost-quality trade-offs relevant to their clinical decision-making given the economic impact of such trade-offs on the healthcare system. In all 90% stated that this consideration had been relevant in clinical decision-making within the last month. In the hypothetical setting 55% would inform their patients that they considered a cost-quality trade-off relevant to their clinical decisions given the economic impact of such trade-offs on the healthcare system. The most common reason (68%) given for not wanting to inform patients about this matter was the belief that the information would not prove useful to patients. In the hypothetical setting cost-quality trade-offs were considered relevant significantly more often in connection with concerns about costs to the patient (86%) than they were in connection with concerns about costs to the healthcare system (55%; p < 0.001).</p> <p>Conclusion</p> <p>Although readiness to consider cost-quality trade-offs relevant to clinical decisions is prevalent among GPs in Denmark, only half of GPs would disclose to patients that they consider this relevant to their clinical decision-making. The results of this study raise two important ethical problems. First, under Danish law physicians are required to inform patients about all equal treatments. The fact that only a few GPs would inform their patients about all of the relevant treatments therefore seems to contravene Danish law. Second, it is ethically controversial that physicians act as economic gatekeepers.</p

Randomised controlled trial of oxygen therapy and high-flow nasal therapy in African children with pneumonia.

PURPOSE: The life-saving role of oxygen therapy in African children with severe pneumonia is not yet established. METHODS: The open-label fractional-factorial COAST trial randomised eligible Ugandan and Kenyan children aged > 28 days with severe pneumonia and severe hypoxaemia stratum (SpO2  3 h receipt of oxygen were excluded. The primary endpoint was 48 h mortality; secondary endpoints included mortality or neurocognitive sequelae at 28 days. RESULTS: The trial was stopped early after enrolling 1852/4200 children, including 388 in the severe hypoxaemia stratum (median 7 months; median SpO2 75%) randomised to HFNT (n = 194) or LFO (n = 194) and 1454 in the hypoxaemia stratum (median 9 months; median SpO2 88%) randomised to HFNT (n = 363) vs LFO (n = 364) vs permissive hypoxaemia (n = 727). Per-protocol 15% of patients in the permissive hypoxaemia group received oxygen (when SpO2 < 80%). In the severe hypoxaemia stratum, 48-h mortality was 9.3% for HFNT vs. 13.4% for LFO groups. In the hypoxaemia stratum, 48-h mortality was 1.1% for HFNT vs. 2.5% LFO and 1.4% for permissive hypoxaemia. In the hypoxaemia stratum, adjusted odds ratio for 48-h mortality in liberal vs permissive comparison was 1.16 (0.49-2.74; p = 0.73); HFNT vs LFO comparison was 0.60 (0.33-1.06; p = 0.08). Strata-specific 28 day mortality rates were, respectively: 18.6, 23.4 and 3.3, 4.1, 3.9%. Neurocognitive sequelae were rare. CONCLUSIONS: Respiratory support with HFNT showing potential benefit should prompt further trials

"Half plate of rice to a male casual sexual partner, full plate belongs to the husband": Findings from a qualitative study on sexual behaviour in relation to HIV and AIDS in northern Tanzania

A thorough understanding of the contexts of sexual behaviour of the people who are vulnerable to HIV infection is an important component in the battle against AIDS epidemic. We conducted a qualitative study to investigate perceptions, attitudes and practices of sexually active people in three districts of northern Tanzania with the view of collecting data to inform the formulation of appropriate complementary interventions against HIV and AIDS in the study communities. We conducted 96 semi-structured interviews and 48 focus group discussions with sexually active participants (18-60 years of age) who were selected purposively in two fishing and one non-fishing communities. The study revealed a number of socio-economic and cultural factors which act as structural drivers of HIV epidemic. Mobility and migration were mentioned to be associated with the risk of HIV acquisition and transmission. Sexual promiscuous behaviour was common in all study communities. Chomolea, (a quick transactional sex) was reported to exist in fishing communities, whereas extramarital sex in the bush was reported in non-fishing community which was predominantly Christian and polygamous. Traditional practices such as Kusomboka (death cleansing through unprotected sex) was reported to exist. Other risky sexual behaviour and traditional practices together with their socio-economic and cultural contexts are presented in details and discussed. Knowledge of condom was low as some people mistook them for balloons to play with and as decorations for their living rooms. Acute scarcity of condoms in some remote areas such as vizingani (fishing islands) push some people to make their own condoms locally known as kondomu za pepsi using polythene bags. HIV prevention efforts can succeed by addressing sexual behaviour and its socio-economic and cultural contexts. More innovative, interdisciplinary and productive structural approaches to HIV prevention need to be developed in close collaboration with affected communities and be closely related to policy-making and implementation; to go beyond the limited success of traditional behavioural and biomedical interventions to particularly address the underlying social and structural drivers of HIV risk and vulnerability in the study communities

The relationship between cadence, pedalling technique and gross efficiency in cycling

Technique and energy saving are two variables often considered as important for performance in cycling and related to each other. Theoretically, excellent pedalling technique should give high gross efficiency (GE). The purpose of the present study was to examine the relationship between pedalling technique and GE. 10 well-trained cyclists were measured for GE, force effectiveness (FE) and dead centre size (DC) at a work rate corresponding to ~75% of VO2max during level and inclined cycling, seat adjusted forward and backward, at three different cadences around their own freely chosen cadence (FCC) on an ergometer. Within subjects, FE, DC and GE decreased as cadence increased (p < 0.001). A strong relationship between FE and GE was found, which was to great extent explained by FCC. The relationship between cadence and both FE and GE, within and between subjects, was very similar, irrespective of FCC. There was no difference between level and inclined cycling position. The seat adjustments did not affect FE, DC and GE or the relationship between them. Energy expenditure is strongly coupled to cadence, but force effectiveness, as a measure for pedalling technique, is not likely the cause of this relationship. FE, DC and GE are not affected by body orientation or seat adjustments, indicating that these parameters and the relationship between them are robust to coordinative challenges within a range of cadence, body orientation and seat position that is used in regular cycling

The use of discrete choice experiments to inform health workforce policy: a systematic review.

BACKGROUND: Discrete choice experiments have become a popular study design to study the labour market preferences of health workers. Discrete choice experiments in health, however, have been criticised for lagging behind best practice and there are specific methodological considerations for those focused on job choices. We performed a systematic review of the application of discrete choice experiments to inform health workforce policy. METHODS: We searched for discrete choice experiments that examined the labour market preferences of health workers, including doctors, nurses, allied health professionals, mid-level and community health workers. We searched Medline, Embase, Global Health, other databases and grey literature repositories with no limits on date or language and contacted 44 experts. Features of choice task and experimental design, conduct and analysis of included studies were assessed against best practice. An assessment of validity was undertaken for all studies, with a comparison of results from those with low risk of bias and a similar objective and context. RESULTS: Twenty-seven studies were included, with over half set in low- and middle-income countries. There were more studies published in the last four years than the previous ten years. Doctors or medical students were the most studied cadre. Studies frequently pooled results from heterogeneous subgroups or extrapolated these results to the general population. Only one third of studies included an opt-out option, despite all health workers having the option to exit the labour market. Just five studies combined results with cost data to assess the cost effectiveness of various policy options. Comparison of results from similar studies broadly showed the importance of bonus payments and postgraduate training opportunities and the unpopularity of time commitments for the uptake of rural posts. CONCLUSIONS: This is the first systematic review of discrete choice experiments in human resources for health. We identified specific issues relating to this application of which practitioners should be aware to ensure robust results. In particular, there is a need for more defined target populations and increased synthesis with cost data. Research on a wider range of health workers and the generalisability of results would be welcome to better inform policy

Can social dancing prevent falls in older adults? a protocol of the Dance, Aging, Cognition,Economics (DAnCE) fall prevention randomised controlled trial

Background:&nbsp; Falls are one of the most common health problems among older people and pose a major economic burden on health care systems. Exercise is an accepted stand-alone fall prevention strategy particularly if it is balance training or regular participation in Tai chi. Dance shares the &lsquo;holistic&rsquo; approach of practices such as Tai chi. It is a complex sensorimotor rhythmic activity integrating multiple physical, cognitive and social elements. Small-scale randomised controlled trials have indicated that diverse dance styles can improve measures of balance and mobility in older people, but none of these studies has examined the effect of dance on falls or cognition. This study aims to determine whether participation in social dancing: i) reduces the number of falls; and ii) improves cognitive functions associated with fall risk in older people. Methods/design: A single-blind, cluster randomised controlled trial of 12 months duration will be conducted. Approximately 450 participants will be recruited from 24 self-care retirement villages that house at least 60 residents each in Sydney, Australia. Village residents without cognitive impairment and obtain medical clearance will be eligible. After comprehensive baseline measurements including physiological and cognitive tests and self-completed questionnaires, villages will be randomised to intervention sites (ballroom or folk dance) or to a wait-listed control using a computer randomisation method that minimises imbalances between villages based on two baseline fall risk measures. Main outcome measures are falls, prospectively measured, and the Trail Making cognitive function test. Cost-effectiveness and cost-utility analyses will be performed. Discussion: This study offers a novel approach to balance training for older people. As a community-based approach to fall prevention, dance offers older people an opportunity for greater social engagement, thereby making a major contribution to healthy ageing. Providing diversity in exercise programs targeting seniors recognises the heterogeneity of multicultural populations and may further increase the number of taking part in exercise

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic