Experimental evolution in a warming world - the omics era.

A comprehensive understanding of the genetic mechanisms that shape species responses to thermal variation is essential for more accurate predictions of the impacts of climate change on biodiversity. Experimental evolution with high-throughput resequencing approaches (E&R) is a highly effective tool that has been increasingly employed to elucidate the genetic basis of adaptation. The number of thermal E&R studies is rising, yet there is a dearth of efforts to integrate this new wealth of knowledge. Here we review this literature showing how these studies have contributed to increase our understanding on the genetic basis of thermal adaptation. We identify two major trends: highly polygenic basis of thermal adaptation and general lack of consistency in candidate targets of selection between studies. These findings indicate that the adaptive responses to specific environments are rather independent. A review of the literature reveals several gaps in the existing research. Firstly, there is a paucity of studies done with organisms of diverse taxa. Secondly, there is a need to apply more dynamic and ecologically relevant thermal environments. Thirdly, there is a lack of studies that integrate genomic changes with changes in life-history and behavioural traits. Addressing these issues would allow a more in-depth understanding of the relationship between genotype and phenotype. We highlight key methodological aspects that can address some of the limitations and omissions identified. These include the need for greater standardisation of methodologies and the utilisation of new technologies focusing on the integration of genomic and phenotypic variation in the context of thermal adaptation.

Development of a capillary temperature control system for capillary electrophoresis instruments designed for spaceflight applications.

Capillary temperature control during capillary electrophoresis (CE) separations is key for achieving accurate and reproducible results with a broad array of potential methods. However, the difficulty of enabling typical fluid temperature control loops on portable instruments has meant that active capillary temperature control of in situ CE systems has frequently been overlooked. This work describes construction and test of a solid-state device for capillary temperature control that is suitable for inclusion with in situ instruments, including those designed for space missions. Two test articles were built, a thermal mass model (TMM) and a functional model (FM). The TMM demonstrated that temperature gradients could be limited using the proposed control scheme, and that our thermal modeling of the system can be relied on for future adaptations of physical geometries of the system. The FM demonstrated CE analytical performance while under active temperature control and that the device was compatible with the harsh thermal-vacuum environments that might be encountered during space flight.

A feasibility study using motivational interviewing and a smartphone application to promote physical activity (+Stay-Active) for women with gestational diabetes.

BACKGROUND: Physical activity (PA) interventions have an encouraging role in gestational diabetes mellitus (GDM) management. Digital technologies can potentially be used at scale to support PA. The aim of this study was to assess the feasibility and acceptability of + Stay-Active: a complex intervention which combines motivational interviewing with a smartphone application to promote PA levels in women with GDM. METHODS: This non-randomised feasibility study used a mixed methods approach. Participants were recruited from the GDM antenatal clinic at Oxford University Hospitals. Following baseline assessments (visit 1) including self-reported and device determined PA measurements (wrist worn accelerometer), women participated in an online motivational interview, and then downloaded (visit 2) and used the Stay-Active app (Android or iOS). Women had access to Stay-Active until 36 weeks' gestation, when acceptability and PA levels were reassessed (visit 3). The primary outcome measures were recruitment and retention rates, participant engagement, and acceptability and fidelity of the intervention. Secondary outcome measures included PA levels, app usage, blood glucose and perinatal outcomes. Descriptive statistics were performed for assessments at study visits. Statistics software package Stata 14 and R were used. RESULTS: Over the recruitment period (46 weeks), 114 of 285 women met inclusion criteria and 67 (58%) enrolled in the study. Mean recruitment rate of 1.5 participants/clinic with 2.5 women/clinic meeting inclusion criteria. Fifty-six (83%) received the intervention at visit 2 and 53 (79%) completed the study. Compliance to accelerometer measurement protocols were sufficient in 78% of participants (52/67); wearing the device for more than 10 h on 5 or more days at baseline and 61% (41/67) at 36 weeks. There was high engagement with Stay-Active; 82% (55/67) of participants set goals on Stay-Active. Sustained engagement was evident, participants regularly accessed and logged multiples activities on Stay-Active. The intervention was deemed acceptable; 85% of women rated their care was satisfactory or above, supported by written feedback. CONCLUSIONS: This combined intervention was feasible and accepted. Recruitment rates were lower than expected. However, retention rates remained satisfactory and participant compliance with PA measurements and engagement was a high. Future work will explore the intervention's efficacy to increase PA and impact on clinical outcomes. TRIAL REGISTRATION: The study has received a favourable opinion from South Central-Hampshire B Research Ethics Committee; REC reference: 20/SC/0342. ISRCTN11366562.

Drought-adapted leaves are produced even when more water is available in dry tropical forest.

Species in dry environments may adjust their anatomical and physiological behaviors by adopting safer or more efficient strategies. Thus, species distributed across a water availability gradient may possess different phenotypes depending on the specific environmental conditions to which they are subjected. Leaf and vascular tissues are plastic and may vary strongly in response to environmental changes affecting an individual's survival and species distribution. To identify whether and how legumes leaves vary across a water availability gradient in a seasonally dry tropical forest, we quantified leaf construction costs and performed an anatomical study on the leaves of seven legume species. We evaluated seven species, which were divided into three categories of rainfall preference: wet species, which are more abundant in wetter areas; indifferent species, which are more abundant and occur indistinctly under both rainfall conditions; and dry species, which are more abundant in dryer areas. We observed two different patterns based on rainfall preference categories. Contrary to our expectations, wet and indifferent species changed traits in the sense of security when occupying lower rainfall areas, whereas dry species changed some traits when more water was available, such as increasing cuticle and spongy parenchyma thickness, or producing smaller and more numerous stomata. Trischidium molle, the most plastic and wet species, exhibited a similar strategy to the dry species. Our results corroborate the risks to vegetation under future climate change scenarios as stressed species and populations may not endure even more severe conditions.

Directional selection coupled with kin selection favors the establishment of senescence.

BACKGROUND: Conventional wisdom in evolutionary theory considers aging as a non-selected byproduct of natural selection. Based on this, conviction aging was regarded as an inevitable phenomenon. It was also thought that in the wild organisms tend to die from diseases, predation and other accidents before they could reach the time when senescence takes its course. Evidence has accumulated, however, that aging is not inevitable and there are organisms that show negative aging even. Furthermore, old age does play a role in the deaths of many different organisms in the wild also. The hypothesis of programmed aging posits that a limited lifespan can evolve as an adaptation (i.e., positively selected for) in its own right, partly because it can enhance evolvability by eliminating "outdated" genotypes. A major shortcoming of this idea is that non-aging sexual individuals that fail to pay the demographic cost of aging would be able to steal good genes by recombination from aging ones. RESULTS: Here, we show by a spatially explicit, individual-based simulation model that aging can positively be selected for if a sufficient degree of kin selection complements directional selection. Under such conditions, senescence enhances evolvability because the rate of aging and the rate of recombination play complementary roles. The selected aging rate is highest at zero recombination (clonal reproduction). In our model, increasing extrinsic mortality favors evolved aging by making up free space, thereby decreasing competition and increasing drift, even when selection is stabilizing and the level of aging is set by mutation-selection balance. Importantly, higher extrinsic mortality is not a substitute for evolved aging under directional selection either. Reduction of relatedness decreases the evolved level of aging; chance relatedness favors non-aging genotypes. The applicability of our results depends on empirical values of directional and kin selection in the wild. CONCLUSIONS: We found that aging can positively be selected for in a spatially explicit population model when sufficiently strong directional and kin selection prevail, even if reproduction is sexual. The view that there is a conceptual link between giving up clonal reproduction and evolving an aging genotype is supported by computational results.

Submersible Capillary Electrophoresis Analyzer: A Proof-of-Concept Demonstration of an In Situ Instrument for Future Missions to Ocean Worlds.

We report here the first fully automated capillary electrophoresis (CE) system that can be operated underwater. The system performs sample acquisition and analysis by coupling CE to contactless conductivity detection. Using 5 M acetic acid as the background electrolyte (BGE), inorganic cations and amino acids at concentrations as low as 5.2 µM can be separated and identified. This technology could be augmented to include a variety of other detection modes. This system serves as an early prototype for potential future underwater explorers on ocean worlds of the outer solar system such as Europa or Enceladus. This work documents the first step in the development of this general-purpose technology platform.

Temperature adaptation and its impact on the shape of performance curves in Drosophila populations.

Understanding how species adapt to different temperatures is crucial to predict their response to global warming, and thermal performance curves (TPCs) have been employed recurrently to study this topic. Nevertheless, fundamental questions regarding how thermodynamic constraints and evolution interact to shape TPCs in lineages inhabiting different environments remain unanswered. Here, we study Drosophila simulans along a latitudinal gradient spanning 3000 km to test opposing hypotheses based on thermodynamic constrains (hotter-is-better) versus biochemical adaptation (jack-of-all-temperatures) as primary determinants of TPCs variation across populations. We compare thermal responses in metabolic rate and the egg-to-adult survival as descriptors of organismal performance and fitness, respectively, and show that different descriptors of TPCs vary in tandem with mean environmental temperatures, providing strong support to hotter-is-better. Thermodynamic constraints also resulted in a strong negative association between maximum performance and thermal breadth. Lastly, we show that descriptors of TPCs for metabolism and egg-to-adult survival are highly correlated, providing evidence of co-adaptation, and that curves for egg-to-adult survival are systematically narrower and displaced toward lower temperatures. Taken together, our results support the pervasive role of thermodynamics constraining thermal responses in Drosophila populations along a latitudinal gradient, that are only partly compensated by evolutionary adaptation.

A voltage trade study for the design of capillary electrophoresis instruments for spaceflight.

Capillary electrophoresis (CE) systems have undergone extensive development for spaceflight applications. A flight-compatible high voltage power supply and the necessary voltage isolation for other energized components can be large contributors to both the volume and mass of a CE system, especially if typical high voltage levels of 25-30 kV are used. Here, we took advantage of our custom CE hardware to perform a trade study for simultaneous optimization of capillary length, high voltage level, and separation time, without sacrificing method performance. A capillary electrophoresis with capacitively coupled contactless conductivity detection (CE-C4 D) method recently developed by our group to target inorganic cations and amino acids relevant to astrobiology was used as a test case. The results indicate that a 50 cm long capillary with 15 kV applied voltage (half of that used in the original method) can be used to achieve measurement goals while minimizing instrument size.

A hydrodynamic injection approach for capillary electrophoresis using rotor-stator valves.

Sample injection is a critical step in a capillary electrophoresis (CE) analysis. Electrokinetic injection is the simplest approach and is often selected for implementation in portable CE instruments. However, in order to minimize the effect of sample matrix upon the results of a CE analysis, hydrodynamic injection is preferred. Although portable CE instruments with hydrodynamic injection have been reported, injection has always been performed at the grounded end of the capillary. This simplifies fluidic handling but limits coupling with electrochemical detectors and electrospray ionization-mass spectrometry (ESI-MS). We demonstrated previously that injection at the high-voltage (HV) end of the capillary could be performed using an HV-compatible rotary injection valve (fixed-volume injection). However, the mismatch between the bore sizes of the channels on the rotor-stator valve and the separation capillary caused peak tailing and undesired mixing, impairing analytical performance. In this work, we present an HV-compatible hydrodynamic injection approach that overcomes the issues associated with the fixed-volume injection approach reported previously. The performance of the CE instrument was demonstrated by analyzing a mixture of 13 amino acids by CE coupled to laser-induced fluorescence, which showed relative standard deviations for peak area and migration time below 5% and 1%, respectively, for triplicate analysis. Additionally, replicate measurements of a mixture of amino acids, peptides, nucleobases, and nucleosides by CE coupled to electrospray ionization-mass spectrometry (CE-ESI-MS) were performed to evaluate peak tailing, and results were similar to those obtained with a commercial CE-ESI-MS setup.

A gravity-independent single-phase electrode reservoir for capillary electrophoresis applications.

Capillary electrophoresis (CE) holds great promise as an in situ analytical technique for a variety of applications. However, typical instrumentation operates with open reservoirs (e.g., vials) to accommodate reagents and samples, which is problematic for automated instruments designed for space or underwater applications that may be operated in various orientations. Microgravity conditions add an additional challenge due to the unpredictable position of the headspace (air layer above the liquid) in any two-phase reservoir. One potential solution for these applications is to use a headspace-free, flow-through reservoir design that is sealed and connected to the necessary reagents and samples. Here, we demonstrate a flow-through high-voltage (HV) reservoir for CE that is compatible with automated in situ exploration needs, and which can be electrically isolated from its source fluidics (in order to prevent unwanted leakage current). We also demonstrate how the overall system can be rationally designed based on the operational parameters for CE to prevent electrolysis products generated at the electrode from entering the capillary and interfering with the CE separation. A reservoir was demonstrated with a 19 mm long, 1.8 mm inner diameter channel connecting the separation capillary and the HV electrode. Tests of these reservoirs integrated into a CE system show reproducible CE system operation with a variety of background electrolytes at voltages up to 25 kV. Rotation of the reservoirs, and the system, showed that their performance was independent of the direction of the gravity vector.

Evolution of linkage and genome expansion in protocells: The origin of chromosomes.

Chromosomes are likely to have assembled from unlinked genes in early evolution. Genetic linkage reduces the assortment load and intragenomic conflict in reproducing protocell models to the extent that chromosomes can go to fixation even if chromosomes suffer from a replicative disadvantage, relative to unlinked genes, proportional to their length. Here we numerically show that chromosomes spread within protocells even if recurrent deleterious mutations affecting replicating genes (as ribozymes) are considered. Dosage effect selects for optimal genomic composition within protocells that carries over to the genic composition of emerging chromosomes. Lacking an accurate segregation mechanism, protocells continue to benefit from the stochastic corrector principle (group selection of early replicators), but now at the chromosome level. A remarkable feature of this process is the appearance of multigene families (in optimal genic proportions) on chromosomes. An added benefit of chromosome formation is an increase in the selectively maintainable genome size (number of different genes), primarily due to the marked reduction of the assortment load. The establishment of chromosomes is under strong positive selection in protocells harboring unlinked genes. The error threshold of replication is raised to higher genome size by linkage due to the fact that deleterious mutations affecting protocells metabolism (hence fitness) show antagonistic (diminishing return) epistasis. This result strengthens the established benefit conferred by chromosomes on protocells allowing for the fixation of highly specific and efficient enzymes.

Using a novel ambulatory monitoring system to support patient safety on an acute infectious disease ward during an unfolding pandemic.

AIM: To gain staff feedback on the implementation and impact of a novel ambulatory monitoring system to support coronavirus patient management on an isolation ward. DESIGN: Qualitative service evaluation. METHODS: Semi-structured interviews were conducted with 15 multidisciplinary isolation ward staff in the United Kingdom between July 2020 and May 2021. Interviews were audio-recorded, transcribed and analysed using thematic analysis. FINDINGS: Adopting Innovation to Assist Patient Safety was identified as the overriding theme. Three interlinked sub-themes represent facets of how the system supported patient safety. Patient Selection was developed throughout the pandemic, as clinical staff became more confident in choosing which patients would benefit most. Trust In the System described how nurses coped with discrepancies between the ambulatory system and ward observation machines. Finally, Resource Management examined how, once trust was built, staff perceived the ambulatory system assisted with caseload management. This supported efficient personal protective equipment resource use by reducing the number of isolation room entries. Despite these reported benefits, face-to-face contact was still highly valued, despite the risk of coronavirus exposure. CONCLUSION: Hospital wards should consider using ambulatory monitoring systems to support caseload management and patient safety. Patients in isolation rooms or at high risk of deterioration may particularly benefit from this additional monitoring. However, these systems should be seen as an adjunct to nursing care, not a replacement. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Nurses valued ambulatory monitoring as a means of ensuring the safety of patients at risk of deterioration and prioritizing their workload. IMPACT: The findings of this research will be useful to all those developing or considering implementation of ambulatory monitoring systems in hospital wards. REPORTING METHOD: This manuscript follows the Consolidated criteria for Reporting Qualitative Research (COREQ) guidelines with inclusion of relevant SQUIRE guidelines for reporting quality improvement. PATIENT OR PUBLIC CONTRIBUTION: No Patient or Public Contribution.

Long-Term Blood Pressure Control After Hypertensive Pregnancy Following Physician-Optimized Self-Management: The POP-HT Randomized Clinical Trial.

Importance: Pregnancy hypertension results in adverse cardiac remodeling and higher incidence of hypertension and cardiovascular diseases in later life. Objective: To evaluate whether an intervention designed to achieve better blood pressure control in the postnatal period is associated with lower blood pressure than usual outpatient care during the first 9 months postpartum. Design, Setting, and Participants: Randomized, open-label, blinded, end point trial set in a single hospital in the UK. Eligible participants were aged 18 years or older, following pregnancy complicated by preeclampsia or gestational hypertension, requiring antihypertensive medication postnatally when discharged. The first enrollment occurred on February 21, 2020, and the last follow-up, November 2, 2021. The follow-up period was approximately 9 months. Interventions: Participants were randomly assigned 1:1 to self-monitoring along with physician-optimized antihypertensive titration or usual postnatal care. Main Outcomes and Measures: The primary outcome was 24-hour mean diastolic blood pressure at 9 months postpartum, adjusted for baseline postnatal blood pressure. Results: Two hundred twenty participants were randomly assigned to either the intervention group (n = 112) or the control group (n = 108). The mean (SD) age of participants was 32.6 (5.0) years, 40% had gestational hypertension, and 60% had preeclampsia. Two hundred participants (91%) were included in the primary analysis. The 24-hour mean (SD) diastolic blood pressure, measured at 249 (16) days postpartum, was 5.8 mm Hg lower in the intervention group (71.2 [5.6] mm Hg) than in the control group (76.6 [5.7] mm Hg). The between-group difference was -5.80 mm Hg (95% CI, -7.40 to -4.20; P < .001). Similarly, the 24-hour mean (SD) systolic blood pressure was 6.5 mm Hg lower in the intervention group (114.0 [7.7] mm Hg) than in the control group (120.3 [9.1] mm Hg). The between-group difference was -6.51 mm Hg (95% CI, -8.80 to -4.22; P < .001). Conclusions and Relevance: In this single-center trial, self-monitoring and physician-guided titration of antihypertensive medications was associated with lower blood pressure during the first 9 months postpartum than usual postnatal outpatient care in the UK. Trial Registration: ClinicalTrials.gov Identifier: NCT04273854.

Past history shapes evolution of reproductive success in a global warming scenario.

Adaptive evolution is critical for animal populations to thrive in the fast-changing natural environments. Ectotherms are particularly vulnerable to global warming and, although their limited coping ability has been suggested, few real-time evolution experiments have directly accessed their evolutionary potential. Here, we report a long-term experimental evolution study addressing the evolution of Drosophila thermal reaction norms, after ∼30 generations under different dynamic thermal regimes: fluctuating (daily variation between 15 and 21 °C) or warming (daily fluctuation with increases in both thermal mean and variance across generations). We analyzed the evolutionary dynamics of Drosophila subobscura populations as a function of the thermally variable environments in which they evolved and their distinct background. Our results showed clear differences between the historically differentiated populations: high latitude D. subobscura populations responded to selection, improving their reproductive success at higher temperatures whereas their low latitude counterparts did not. This suggests population variation in the amount of genetic variation available for thermal adaptation, an aspect that needs to be considered to allow for better predictions of future climate change responses. Our results highlight the complex nature of thermal responses in face of environmental heterogeneity and emphasize the importance of considering inter-population variation in thermal evolution studies.

Screen-Printed Technologies Combined with Flow Analysis Techniques: Moving from Benchtop to Everywhere.

Screen-printed electrodes (SPEs) coupled with flow systems have been reported in recent decades for an ever-growing number of applications in modern electroanalysis, aiming for portable methodologies. The information acquired through this combination can be attractive for future users with basic knowledge, especially due to the increased measurement throughput, reduction in reagent consumption and minimal waste generation. The trends and possibilities of this set rely on the synergistic behavior that maximizes both SPE and flow analyses characteristics, allowing mass production and automation. This overview addresses an in-depth update about the scope of samples, target analytes, and analytical throughput (injections per hour, limits of detection, linear range, etc.) obtained by coupling injection techniques (FIA, SIA, and BIA) with SPE-based electrochemical detection.

Thermal tolerance in Drosophila: Repercussions for distribution, community coexistence and responses to climate change.

Here we combined controlled experiments and field surveys to determine if estimates of heat tolerance predict distributional ranges and phenology of different Drosophila species in southern South America. We contrasted thermal death time curves, which consider both magnitude and duration of the challenge to estimate heat tolerance, against the thermal range where populations are viable based on field surveys in an 8-year longitudinal study. We observed a strong correspondence of the physiological limits, the thermal niche for population growth, and the geographic ranges across studied species, which suggests that the thermal biology of different species provides a common currency to understand how species will respond to warming temperatures both at a local level and throughout their distribution range. Our approach represents a novel analytical toolbox to anticipate how natural communities of ectothermic organisms will respond to global warming.

Dynamics of nonstructural carbohydrates in a deciduous woody species from tropical dry forests under recurrent water deficit.

In tropical dry forests, both the dry and the short rainy seasons have become increasingly irregular. This study replicated these conditions to investigate the effects of two water deficit cycles on Cenostigma microphyllum seedlings. Impacts were assessed by measuring growth traits, water relations, gas exchange, and dynamics of nonstructural carbohydrate (NSC) content in the whole plant under greenhouse conditions in potted plants. In the first water deficit cycle, the leaf relative water content (RWC) was maintained at the expense of a rapid drop in gas exchange. Furthermore, there was a slight accumulation of NSC, mainly soluble sugars (SS) in the stem wood and roots, to the detriment of height and stem diameter growth. In the second cycle, the leaf RWC remained 40% higher than the lowest level measured in the first water deficit, and CO2 assimilation remained twice as long in previously stressed plants. The SS content of the stems and roots was strongly correlated with the predawn leaf RWC. No strong reduction was observed in the bark stock even with the gradual increase of SS in the wood. Our data suggest that under recurrent water deficit prior to leaf drop, CO2 assimilation is maintained, with the highest possible leaf RWC, under reduced stomatal conductance. This assists in SS transport to wood and root, which is no longer used to support the growth of the aboveground parts.

Dehydration response in Stylosanthes scabra: Transcriptional, biochemical, and physiological modulations.

Stylosanthes scabra, popularly known as stylo, is native to the Brazilian Caatinga semiarid region and stands out as a drought-tolerant shrub forage crop. This work provides information about the plant response during the first 48 h of water deficit, followed by a rehydration treatment. Besides root transcriptomics data, 13 physiological or biochemical parameters were scrutinized. Additionally, RNA-Seq annotated transcripts not associated with the "Viridiplantae" clade were taxonomically categorized. It was found that S. scabra quickly perceives and recovers from the oscillations of the imposed water regime. Physiologically, mechanisms that minimize evapotranspiration or protect the photosynthetic apparatus stood out. Biochemically, it was found that the root tissue invests in synthesizing compounds that can act as osmolytes (proline and sugars), emphasizing the importance of osmoregulation to water deficit acclimation. Consistently, transcriptome and qPCR analyses showed that a set of enriched biological processes with upregulated (UR) transcripts were involved in protective functions against reactive oxygen species or encoding enzymes of important metabolic pathways, which might contribute to S. scabra response to water deficit. Additionally, several UR kinases and transcription factors were identified. Finally, in an innovative approach, some naturally occurring microbial groups (such as Schizosaccharomyces, Bradyrhizobium, etc.) were identified in the S. scabra roots. This study reveals insights into the physiological, biochemical, and molecular mechanisms underlying the S. scabra response to water deficit and provides candidate genes that may be useful in developing drought-tolerant crop varieties through biotechnological applications.

The Use of Wearable Pulse Oximeters in the Prompt Detection of Hypoxemia and During Movement: Diagnostic Accuracy Study.

BACKGROUND: Commercially available wearable (ambulatory) pulse oximeters have been recommended as a method for managing patients at risk of physiological deterioration, such as active patients with COVID-19 disease receiving care in hospital isolation rooms; however, their reliability in usual hospital settings is not known. OBJECTIVE: We report the performance of wearable pulse oximeters in a simulated clinical setting when challenged by motion and low levels of arterial blood oxygen saturation (SaO2). METHODS: The performance of 1 wrist-worn (Wavelet) and 3 finger-worn (CheckMe O2+, AP-20, and WristOx2 3150) wearable, wireless transmission-mode pulse oximeters was evaluated. For this, 7 motion tasks were performed: at rest, sit-to-stand, tapping, rubbing, drinking, turning pages, and using a tablet. Hypoxia exposure followed, in which inspired gases were adjusted to achieve decreasing SaO2 levels at 100%, 95%, 90%, 87%, 85%, 83%, and 80%. Peripheral oxygen saturation (SpO2) estimates were compared with simultaneous SaO2 samples to calculate the root-mean-square error (RMSE). The area under the receiver operating characteristic curve was used to analyze the detection of hypoxemia (ie, SaO2<90%). RESULTS: SpO2 estimates matching 215 SaO2 samples in both study phases, from 33 participants, were analyzed. Tapping, rubbing, turning pages, and using a tablet degraded SpO2 estimation (RMSE>4% for at least 1 device). All finger-worn pulse oximeters detected hypoxemia, with an overall sensitivity of ≥0.87 and specificity of ≥0.80, comparable to that of the Philips MX450 pulse oximeter. CONCLUSIONS: The SpO2 accuracy of wearable finger-worn pulse oximeters was within that required by the International Organization for Standardization guidelines. Performance was degraded by motion, but all pulse oximeters could detect hypoxemia. Our findings support the use of wearable, wireless transmission-mode pulse oximeters to detect the onset of clinical deterioration in hospital settings. TRIAL REGISTRATION: ISRCTN Registry 61535692; http://www.isrctn.com/ISRCTN61535692. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2019-034404.

Effect of Self-monitoring of Blood Pressure on Blood Pressure Control in Pregnant Individuals With Chronic or Gestational Hypertension: The BUMP 2 Randomized Clinical Trial.

Importance: Inadequate management of elevated blood pressure is a significant contributing factor to maternal deaths. The role of blood pressure self-monitoring in pregnancy in improving clinical outcomes for the pregnant individual and infant is unclear. Objective: To evaluate the effect of blood pressure self-monitoring, compared with usual care alone, on blood pressure control and other related maternal and infant outcomes, in individuals with pregnancy hypertension. Design, Setting, and Participants: Unblinded, randomized clinical trial that recruited between November 2018 and September 2019 in 15 hospital maternity units in England. Individuals with chronic hypertension (enrolled up to 37 weeks' gestation) or with gestational hypertension (enrolled between 20 and 37 weeks' gestation). Final follow-up was in May 2020. Interventions: Participants were randomized to either blood pressure self-monitoring using a validated monitor and a secure telemonitoring system in addition to usual care (n = 430) or to usual care alone (n = 420). Usual care comprised blood pressure measured by health care professionals at regular antenatal clinics. Main Outcomes and Measures: The primary maternal outcome was the difference in mean systolic blood pressure recorded by health care professionals between randomization and birth. Results: Among 454 participants with chronic hypertension (mean age, 36 years; mean gestation at entry, 20 weeks) and 396 with gestational hypertension (mean age, 34 years; mean gestation at entry, 33 weeks) who were randomized, primary outcome data were available from 444 (97.8%) and 377 (95.2%), respectively. In the chronic hypertension cohort, there was no statistically significant difference in mean systolic blood pressure for the self-monitoring groups vs the usual care group (133.8 mm Hg vs 133.6 mm Hg, respectively; adjusted mean difference, 0.03 mm Hg [95% CI, -1.73 to 1.79]). In the gestational hypertension cohort, there was also no significant difference in mean systolic blood pressure (137.6 mm Hg compared with 137.2 mm Hg; adjusted mean difference, -0.03 mm Hg [95% CI, -2.29 to 2.24]). There were 8 serious adverse events in the self-monitoring group (4 in each cohort) and 3 in the usual care group (2 in the chronic hypertension cohort and 1 in the gestational hypertension cohort). Conclusions and Relevance: Among pregnant individuals with chronic or gestational hypertension, blood pressure self-monitoring with telemonitoring, compared with usual care, did not lead to significantly improved clinic-based blood pressure control. Trial Registration: ClinicalTrials.gov Identifier: NCT03334149.