Sexual behaviour in Drosophila is irreversibly programmed during a critical period

AbstractSexual differentiation in Drosophila is controlled by a short cascade of regulatory genes, the expression pattern of which determines all aspects of maleness and femaleness, including complex behaviours displayed by males and females [1–3]. One sex-determining gene is transformer (tra), the activity of which is needed for female development. Flies with a female karyotype (XX) but which are mutant for tra develop and behave as males. In such flies, a female phenotype can be restored by a transgene that carries the female-specific cDNA of tra under the control of a heat-shock promoter. This transgene, called hs[trafem], also transforms XY animals into sterile females [4]. When we raised these XX and XY ‘females’ at 25°C, however, they displayed vigorous male courtship while at the same time, as a result of their female pheromone pattern, they were attractive to males. Intriguingly, their male courtship behaviour was indiscriminately directed towards both females and males. When we forced expression of tra by heat shock, applied during a limited period around puparium formation, male behaviour was abolished and replaced by female behaviour. We conclude that sexual behaviour is irreversibly programmed during a critical period as a result of the activity or inactivity of a single control gene

Cell-autonomous and inductive signals can determine the sex of the germ line of Drosophila by regulating the gene Sxl.

To investigate the mechanism of sex determination in the germ line, we analyzed the fate of XY germ cells in ovaries, and the fate of XX germ cells in testes. In ovaries, germ cells developed according to their X:A ratio, i.e., XX cells underwent oogenesis, XY cells formed spermatocytes. In testes, however, XY and XX germ cells entered the spermatogenic pathway. Thus, to determine their sex, the germ cells of Drosophila have cell-autonomous genetic information, and XX cells respond to inductive signals of the soma. Results obtained with amorphic and constitutive mutations of Sxl show that both the genetic and the somatic signals act through Sxl to achieve sex determination in germ cells

Genetic and developmental analysis of the sex-determining gene ‘double sex' (dsx) of Drosophila melanogaster

Sex determination in Drosophila depends on the ratio of X chromosomes to sets of autosomes (X:A). This chromosomal signal is used to regulate a few control genes whose state of activity selects either the male or the female sexual pathway. We have studied the structure and function of dsx (double sex) which appears to be the last regulatory gene on whose function the sexual pathway eventually depends. We have mutagenized the locus, varied the doses of dominant dsx-mutations and wildtype alleles, and combined different dsx-alleles with recessive mutations in other sex-determining genes, such as ix, tra-2 and tra. The locus dsx harbours two genetic functions, dsxm to implement the male program, dsxf to implement the female program. We found that dsxm and dsxf can mutate independently although most mutations abolish both functions. We conclude that dsxm and dsxf each have their specific domain, but also share a large region of DNA that is essential for both functions. We present evidence that the dominant mutations correspond to a constitutive expression of the male-determining function dsxm, with the simultaneous abolishment of the female-determining function dsxf. This effect can be counteracted by two doses of expressed dsxf so that a female phenotype results. The products of one dose of expressed dsxm and one dose of expressed dsxf in the same cell appear to neutralize each other which leads to a null phenotype. The mutant combinations suggest that the product of dsxf requires the products of ix+, tra-2+ and tra+ to become functiona

User Perceptions of Different Vital Signs Monitor Modalities During High-Fidelity Simulation: Semiquantitative Analysis

Background: Patient safety during anesthesia is crucially dependent on the monitoring of vital signs. However, the values obtained must also be perceived and correctly classified by the attending care providers. To facilitate these processes, we developed Visual-Patient-avatar, an animated virtual model of the monitored patient, which innovatively presents numerical and waveform data following user-centered design principles. After a high-fidelity simulation study, we analyzed the participants' perceptions of 3 different monitor modalities, including this newly introduced technique. Objective: The aim of this study was to collect and evaluate participants' opinions and experiences regarding 3 different monitor modalities, which are Visual-Patient-avatar, Split Screen (avatar and Conventional monitor alongside each other), and Conventional monitor after using them during simulated critical anesthetic events. Methods: This study was a researcher-initiated, single-center, semiquantitative study. We asked 92 care providers right after finishing 3 simulated emergency scenarios about their positive and negative opinions concerning the different monitor modalities. We processed the field notes obtained and derived the main categories and corresponding subthemes following qualitative research methods. Results: We gained a total of 307 statements. Through a context-based analysis, we identified the 3 main categories of "Visual-Patient-avatar," "Split Screen," and "Conventional monitor" and divided them into 11 positive and negative subthemes. We achieved substantial interrater reliability in assigning the statements to 1 of the topics. Most of the statements concerned the design and usability features of the avatar or the Split Screen mode. Conclusions: This study semiquantitatively reviewed the clinical applicability of the Visual-Patient-avatar technique in a high-fidelity simulation study and revealed the strengths and limitations of the avatar only and Split Screen modality. In addition to valuable suggestions for improving the design, the requirement for training prior to clinical implementation was emphasized. The responses to the Split Screen suggest that this symbiotic modality generates better situation awareness in combination with numerical data and accurate curves. As a subsequent development step, a real-life introduction study is planned, where we will test the avatar in Split Screen mode under actual clinical conditions. Keywords: avatar; patient monitoring; semiquantitative research; simulation study; situation awareness; user-centered design; visual-patient-avata

Improving Visual-Patient-Avatar Design Prior to Its Clinical Release: A Mixed Qualitative and Quantitative Study

Visual-Patient-avatar, an avatar-based visualisation of patient monitoring, is a newly developed technology aiming to promote situation awareness through user-centred design. Before the technology’s introduction into clinical practice, the initial design used to validate the concept had to undergo thorough examination and adjustments where necessary. This mixed qualitative and quantitative study, consisting of three different study parts, aimed to create a design with high user acceptance regarding perceived professionalism and potential for identification while maintaining its original functionality. The first qualitative part was based on structured interviews and explored anaesthesia personnel’s first impressions regarding the original design. Recurrent topics were identified using inductive coding, participants’ interpretations of the vital sign visualisations analysed and design modifications derived. The second study part consisted of a redesign process, in which the visualisations were adapted according to the results of the first part. In a third, quantitative study part, participants rated Likert scales about Visual-Patient-avatar’s appearance and interpreted displayed vital signs in a computer-based survey. The first, qualitative study part included 51 structured interviews. Twenty-eight of 51 (55%) participants mentioned the appearance of Visual-Patient-avatar. In 23 of 51 (45%) interviews, 26 statements about the general impression were identified with a balanced count of positive (14 of 26) and negative (12 of 26) comments. The analysis of vital sign visualisations showed deficits in several vital sign visualisations, especially central venous pressure. These findings were incorporated into part two, the redesign of Visual-Patient-avatar. In the subsequent quantitative analysis of study for part three, 20 of 30 (67%) new participants agreed that the avatar looks professional enough for medical use. Finally, the participants identified 73% (435 of 600 cases) of all vital sign visualisations intuitively correctly without prior instruction. This study succeeded in improving the original design with good user acceptance and a reasonable degree of intuitiveness of the new, revised design. Furthermore, the study identified aspects relevant for the release of Visual-Patient-avatar, such as the requirement for providing at least some training, despite the design’s intuitiveness. The results of this study will guide further research and improvement of the technology. The study provides a link between Visual-Patient-avatar as a scientific concept and as an actual product from a cognitive engineering point of view, and may serve as an example of methods to study the designs of technologies in similar contexts

Faster Time to Treatment Decision of Viscoelastic Coagulation Test Results through Improved Perception with the Animated Visual Clot: A Multicenter Comparative Eye-Tracking Study

As the interpretation of viscoelastic coagulation test results remains challenging, we created Visual Clot, an animated blood clot aiming to facilitate raw rotational thromboelastometry (ROTEM) parameters. This study investigated anesthesia personnel's cognitive processing in managing simulated bleeding scenarios using eye-tracking technology. This multicenter, international, computer-based study across five large, central European hospitals included 35 participants with minimal to no prior experience interpreting viscoelastic test results. Using eye-tracking technology and an iPad tagged with quick response codes, we defined the time to treatment decision and the time on screen surface in seconds of correctly solved scenarios as our outcomes. The median time to treatment decision was 52 s for Visual Clot and 205 s for ROTEM (p < 0.0001). The probability of solving the scenario correctly was more than 8 times higher when using Visual Clot than when using ROTEM (Hazard ratio [HR] 8.54, 95% CI from 6.5 to 11.21; p < 0.0001). Out of 194 correctly answered scenarios of participants with the eye-tracker, 154 (79.4%) were solved with Visual Clot and 40 (20.6%) with ROTEM. Participants spent on average 30 s less looking at the screen surface with Visual Clot compared to ROTEM (Coefficient -30.74 s, 95% CI from -39.27 to -22.27; p < 0.0001). For a comparison of the two modalities in terms of information transfer, we calculated the percentage of time on the screen surface of the overall time to treatment decision, which with Visual Clot was 14 percentage points shorter than with ROTEM (Coefficient -14.55, 95% CI from -20.05 to -9.12; p < 0.0001). Visual Clot seems to improve perception and detection of coagulopathies and leads to earlier initiation of the appropriate treatment. In a high-pressure working environment such as the operating and the resuscitation room, correct and timely decisions regarding bleeding management may have a relevant impact on patients' outcomes. Keywords: Visual Clot; avatar; blood coagulation; eye-tracking; point-of-care; rotational thromboelastometry; viscoelastic test; visual perception

Improved Task Performance, Low Workload, and User-Centered Design in Medical Diagnostic Equipment Enhance Decision Confidence of Anesthesia Providers: A Meta-Analysis and a Multicenter Online Survey

Decision confidence-the subjective belief to have made the right decision-is central in planning actions in a complex environment such as the medical field. It is unclear by which factors it is influenced. We analyzed a pooled data set of eight studies and performed a multicenter online survey assessing anesthesiologists' opinions on decision confidence. By applying mixed models and using multiple imputation to determine the effect of missing values from the dataset on the results, we investigated how task performance, perceived workload, the utilization of user-centered medical diagnostic devices, job, work experience, and gender affected decision confidence. The odds of being confident increased with better task performance (OR: 1.27, 95% CI: 0.94 to 1.7; p = 0.12; after multiple imputation OR: 3.19, 95% CI: 2.29 to 4.45; p < 0.001) and when user-centered medical devices were used (OR: 5.01, 95% CI: 3.67 to 6.85; p < 0.001; after multiple imputation OR: 3.58, 95% CI: 2.65 to 4.85; p < 0.001). The odds of being confident decreased with higher perceived workload (OR: 0.94, 95% CI: 0.93 to 0.95; p < 0.001; after multiple imputation, OR: 0.94, 95% CI: 0.93 to 0.95; p < 0.001). Other factors, such as gender, job, or professional experience, did not affect decision confidence. Most anesthesiologists who participated in the online survey agreed that task performance (25 of 30; 83%), perceived workload (24 of 30; 80%), work experience (28 of 30; 93%), and job (21 of 30; 70%) influence decision confidence. Improved task performance, lower perceived workload, and user-centered design in medical equipment enhanced the decision confidence of anesthesia providers. Keywords: diagnostic; diagnostic confidence; gender; online survey; over-confidence; self-assessment; under-confidence; user-centered design; workloa

Improved Task Performance, Low Workload, and User-Centered Design in Medical Diagnostic Equipment Enhance Decision Confidence of Anesthesia Providers: A Meta-Analysis and a Multicenter Online Survey

Decision confidence-the subjective belief to have made the right decision-is central in planning actions in a complex environment such as the medical field. It is unclear by which factors it is influenced. We analyzed a pooled data set of eight studies and performed a multicenter online survey assessing anesthesiologists' opinions on decision confidence. By applying mixed models and using multiple imputation to determine the effect of missing values from the dataset on the results, we investigated how task performance, perceived workload, the utilization of user-centered medical diagnostic devices, job, work experience, and gender affected decision confidence. The odds of being confident increased with better task performance (OR: 1.27, 95% CI: 0.94 to 1.7; p = 0.12; after multiple imputation OR: 3.19, 95% CI: 2.29 to 4.45; p < 0.001) and when user-centered medical devices were used (OR: 5.01, 95% CI: 3.67 to 6.85; p < 0.001; after multiple imputation OR: 3.58, 95% CI: 2.65 to 4.85; p < 0.001). The odds of being confident decreased with higher perceived workload (OR: 0.94, 95% CI: 0.93 to 0.95; p < 0.001; after multiple imputation, OR: 0.94, 95% CI: 0.93 to 0.95; p < 0.001). Other factors, such as gender, job, or professional experience, did not affect decision confidence. Most anesthesiologists who participated in the online survey agreed that task performance (25 of 30; 83%), perceived workload (24 of 30; 80%), work experience (28 of 30; 93%), and job (21 of 30; 70%) influence decision confidence. Improved task performance, lower perceived workload, and user-centered design in medical equipment enhanced the decision confidence of anesthesia providers. Keywords: diagnostic; diagnostic confidence; gender; online survey; over-confidence; self-assessment; under-confidence; user-centered design; workloa

Visual Attention of Anesthesia Providers in Simulated Anesthesia Emergencies Using Conventional Number-Based and Avatar-Based Patient Monitoring: Prospective Eye-Tracking Study

Background: Inadequate situational awareness accounts for two-thirds of preventable complications in anesthesia. An essential tool for situational awareness in the perioperative setting is the patient monitor. However, the conventional monitor has several weaknesses. Avatar-based patient monitoring may address these shortcomings and promote situation awareness, a prerequisite for good decision making. Objective: The spatial distribution of visual attention is a fundamental process for achieving adequate situation awareness and thus a potential quantifiable surrogate for situation awareness. Moreover, measuring visual attention with a head-mounted eye-tracker may provide insights into usage and acceptance of the new avatar-based patient monitoring modality. Methods: This prospective eye-tracking study compared anesthesia providers' visual attention on conventional and avatar-based patient monitors during simulated critical anesthesia events. We defined visual attention, measured as fixation count and dwell time, as our primary outcome. We correlated visual attention with the potential confounders: performance in managing simulated critical anesthesia events (task performance), work experience, and profession. We used mixed linear models to analyze the results. Results: Fifty-two teams performed 156 simulations. After a manual quality check of the eye-tracking footage, we excluded 57 simulations due to technical problems and quality issues. Participants had a median of 198 (IQR 92.5-317.5) fixations on the patient monitor with a median dwell time of 30.2 (IQR 14.9-51.3) seconds. We found no significant difference in participants' visual attention when using avatar-based patient monitoring or conventional patient monitoring. However, we found that with each percentage point of better task performance, the number of fixations decreased by about 1.39 (coefficient -1.39; 95% CI -2.44 to -0.34; P=.02), and the dwell time diminished by 0.23 seconds (coefficient -0.23; 95% CI: -0.4 to -0.06; P=.01). Conclusions: Using eye tracking, we found no significant difference in visual attention when anesthesia providers used avatar-based monitoring or conventional patient monitoring in simulated critical anesthesia events. However, we identified visual attention in conjunction with task performance as a surrogate for situational awareness. Keywords: Anesthesia; avatar based model; eye-tracking technology; patient monitoring; patient simulation; perioperative; simulated anesthesia; situation awareness; task performance; visual attention