Background independent action for double field theory

Double field theory describes a massless subsector of closed string theory with both momentum and winding excitations. The gauge algebra is governed by the Courant bracket in certain subsectors of this double field theory. We construct the associated nonlinear background-independent action that is T-duality invariant and realizes the Courant gauge algebra. The action is the sum of a standard action for gravity, antisymmetric tensor, and dilaton fields written with ordinary derivatives, a similar action for dual fields with dual derivatives, and a mixed term that is needed for gauge invariance.Comment: 45 pages, v2: minor corrections, refs. added, to appear in JHE

Droplet-based millifluidic synthesis of a proton-conducting sulfonate metal–organic framework

Metal–organic frameworks (MOFs) have emerged as promising candidate materials for proton exchange membranes (PEMs), due to the control of proton transport enabled by functional groups and the structural order within the MOFs. In this work, we report a millifluidic approach for the synthesis of a MOF incorporating both sulfonate and amine groups, termed Cu-SAT, which exhibits a high proton conductivity. The fouling-free multiphase flow reactor synthesis was operated for more than 5 h with no reduction in yield or change in the particle size distribution, demonstrating a sustained space–time yield up to 131.7 kg m−3 day−1 with consistent particle quality. Reaction yield and particle size were controllably tuned by the adjustment of reaction parameters, such as residence/reaction time, temperature, and reagent concentration. The reaction yields from the flow reactor were 10–20% higher than those of corresponding batch syntheses, indicating improved mass and heat transfer in flow. A systematic exploration of synthetic parameters using a factorial design of experiments approach revealed the key correlations between the process parameters and yields and particle size distributions. The proton conductivity of the synthesized Cu-SAT MOF was evaluated in a mixed matrix membrane model PEM with polyvinylpyrrolidone and polyvinylidene fluoride polymers, exhibiting a promising composite conductivity of 1.34 ± 0.05 mS cm−1 at 353 K and 95% relative humidity (RH)

Survival and health economic outcomes in heart failure diagnosed at hospital admission versus community settings: a propensity-matched analysis

BACKGROUND AND AIMS: Most patients with heart failure (HF) are diagnosed following a hospital admission. The clinical and health economic impacts of index HF diagnosis made on admission to hospital versus community settings are not known. METHODS: We used the North West London Discover database to examine 34 208 patients receiving an index diagnosis of HF between January 2015 and December 2020. A propensity score-matched (PSM) cohort was identified to adjust for differences in socioeconomic status, cardiovascular risk and pre-diagnosis health resource utilisation cost. Outcomes were stratified by two pathways to index HF diagnosis: a 'hospital pathway' was defined by diagnosis following hospital admission; and a 'community pathway' by diagnosis via a general practitioner or outpatient services. The primary clinical and health economic endpoints were all-cause mortality and cost-consequence differential, respectively. RESULTS: The diagnosis of HF was via hospital pathway in 68% (23 273) of patients. The PSM cohort included 17 174 patients (8582 per group) and was matched across all selected confounders (p>0.05). The ratio of deaths per person-months at 24 months comparing community versus hospital diagnosis was 0.780 (95% CI 0.722 to 0.841, p<0.0001). By 72 months, the ratio of deaths was 0.960 (0.905 to 1.020, p=0.18). Diagnosis via hospital pathway incurred an overall extra longitudinal cost of £2485 per patient. CONCLUSIONS: Index diagnosis of HF through hospital admission continues to dominate and is associated with a significantly greater short-term risk of mortality and substantially increased long-term costs than if first diagnosed in the community. This study highlights the potential for community diagnosis-early, before symptoms necessitate hospitalisation-to improve both clinical and health economic outcomes

Maternal Condition Does Not Influence Birth Sex Ratios in Anubis Baboons (Papio anubis)

Trivers and Willard predicted that when parental condition has differential effects on the fitness of male and female offspring, parents who are in good condition will bias investment toward the sex that benefits most from additional investment. Efforts to test predictions derived from Trivers and Willard's model have had mixed results, perhaps because most studies have relied on proxy measures of parental condition, such as dominance rank. Here, we examine the effects of female baboons condition on birth sex ratios and post-natal investment, based on visual assessments of maternal body condition. We find that local environmental conditions have significant effects on female condition, but maternal condition at conception has no consistent relationship with birth sex ratios. Mothers who are in poorer condition at the time of conception resume cycling significantly later than females who are in better condition, but the sex of their infants has no effect on the time to resumption of cycling. Thus, our findings provide strong evidence that maternal condition influences females' ability to reproduce, but females do not facultatively adjust the sex ratio of their offspring in relation to their dominance rank or current condition

Smartphone-based remote monitoring in heart failure with reduced ejection fraction: retrospective cohort study of secondary care use and costs

BACKGROUND: Despite effective therapies, the economic burden of heart failure with reduced ejection fraction (HFrEF) is driven by frequent hospitalizations. Treatment optimization and admission avoidance rely on frequent symptom reviews and monitoring of vital signs. Remote monitoring (RM) aims to prevent admissions by facilitating early intervention, but the impact of noninvasive, smartphone-based RM of vital signs on secondary health care use and costs in the months after a new diagnosis of HFrEF is unknown. OBJECTIVE: The purpose of this study is to conduct a secondary care health use and health-economic evaluation for patients with HFrEF using smartphone-based noninvasive RM and compare it with matched controls receiving usual care without RM. METHODS: We conducted a retrospective study of 2 cohorts of newly diagnosed HFrEF patients, matched 1:1 for demographics, socioeconomic status, comorbidities, and HFrEF severity. They are (1) the RM group, with patients using the RM platform for >3 months and (2) the control group, with patients referred before RM was available who received usual heart failure care without RM. Emergency department (ED) attendance, hospital admissions, outpatient use, and the associated costs of this secondary care activity were extracted from the Discover data set for a 3-month period after diagnosis. Platform costs were added for the RM group. Secondary health care use and costs were analyzed using Kaplan-Meier event analysis and Cox proportional hazards modeling. RESULTS: A total of 146 patients (mean age 63 years; 42/146, 29% female) were included (73 in each group). The groups were well-matched for all baseline characteristics except hypertension (P=.03). RM was associated with a lower hazard of ED attendance (hazard ratio [HR] 0.43; P=.02) and unplanned admissions (HR 0.26; P=.02). There were no differences in elective admissions (HR 1.03, P=.96) or outpatient use (HR 1.40; P=.18) between the 2 groups. These differences were sustained by a univariate model controlling for hypertension. Over a 3-month period, secondary health care costs were approximately 4-fold lower in the RM group than the control group, despite the additional cost of RM itself (mean cost per patient GBP £465, US $581 vs GBP £1850, US$2313, respectively; P=.04). CONCLUSIONS: This retrospective cohort study shows that smartphone-based RM of vital signs is feasible for HFrEF. This type of RM was associated with an approximately 2-fold reduction in ED attendance and a 4-fold reduction in emergency admissions over just 3 months after a new diagnosis with HFrEF. Costs were significantly lower in the RM group without increasing outpatient demand. This type of RM could be adjunctive to standard care to reduce admissions, enabling other resources to help patients unable to use RM

Assessment of the incorporation of CNV surveillance into gene panel next-generation sequencing testing for inherited retinal diseases.

BACKGROUND: Diagnostic use of gene panel next-generation sequencing (NGS) techniques is commonplace for individuals with inherited retinal dystrophies (IRDs), a highly genetically heterogeneous group of disorders. However, these techniques have often failed to capture the complete spectrum of genomic variation causing IRD, including CNVs. This study assessed the applicability of introducing CNV surveillance into first-tier diagnostic gene panel NGS services for IRD. METHODS: Three read-depth algorithms were applied to gene panel NGS data sets for 550 referred individuals, and informatics strategies used for quality assurance and CNV filtering. CNV events were confirmed and reported to referring clinicians through an accredited diagnostic laboratory. RESULTS: We confirmed the presence of 33 deletions and 11 duplications, determining these findings to contribute to the confirmed or provisional molecular diagnosis of IRD for 25 individuals. We show that at least 7% of individuals referred for diagnostic testing for IRD have a CNV within genes relevant to their clinical diagnosis, and determined a positive predictive value of 79% for the employed CNV filtering techniques. CONCLUSION: Incorporation of CNV analysis increases diagnostic yield of gene panel NGS diagnostic tests for IRD, increases clarity in diagnostic reporting and expands the spectrum of known disease-causing mutations

Hybridization in parasites: consequences for adaptive evolution, pathogenesis and public health in a changing world

[No abstract available

Red Queen Dynamics with Non-Standard Fitness Interactions

Antagonistic coevolution between hosts and parasites can involve rapid fluctuations of genotype frequencies that are known as Red Queen dynamics. Under such dynamics, recombination in the hosts may be advantageous because genetic shuffling can quickly produce disproportionately fit offspring (the Red Queen hypothesis). Previous models investigating these dynamics have assumed rather simple models of genetic interactions between hosts and parasites. Here, we assess the robustness of earlier theoretical predictions about the Red Queen with respect to the underlying host-parasite interactions. To this end, we created large numbers of random interaction matrices, analysed the resulting dynamics through simulation, and ascertained whether recombination was favoured or disfavoured. We observed Red Queen dynamics in many of our simulations provided the interaction matrices exhibited sufficient ‘antagonicity’. In agreement with previous studies, strong selection on either hosts or parasites favours selection for increased recombination. However, fast changes in the sign of linkage disequilibrium or epistasis were only infrequently observed and do not appear to be a necessary condition for the Red Queen hypothesis to work. Indeed, recombination was often favoured even though the linkage disequilibrium remained of constant sign throughout the simulations. We conclude that Red Queen-type dynamics involving persistent fluctuations in host and parasite genotype frequencies appear to not be an artefact of specific assumptions about host-parasite fitness interactions, but emerge readily with the general interactions studied here. Our results also indicate that although recombination is often favoured, some of the factors previously thought to be important in this process such as linkage disequilibrium fluctuations need to be reassessed when fitness interactions between hosts and parasites are complex

ADC Nonlinearity Correction for the Majorana Demonstrator

Imperfections in analog-to-digital conversion (ADC) cannot be ignored when signal digitization requirements demand both wide dynamic range and high resolution, as is the case for the Majorana Demonstrator 76Ge neutrinoless double-beta decay search. Enabling the experiment's high-resolution spectral analysis and efficient pulse shape discrimination required careful measurement and correction of ADC nonlinearities. A simple measurement protocol was developed that did not require sophisticated equipment or lengthy data-taking campaigns. A slope-dependent hysteresis was observed and characterized. A correction applied to digitized waveforms prior to signal processing reduced the differential and integral nonlinearities by an order of magnitude, eliminating these as dominant contributions to the systematic energy uncertainty at the double-beta decay Q value