Adaptive designs in critical care trials: a simulation study.

BACKGROUND: Adaptive clinical trials are growing in popularity as they are more flexible, efficient and ethical than traditional fixed designs. However, notwithstanding their increased use in assessing treatments for COVID-19, their use in critical care trials remains limited. A better understanding of the relative benefits of various adaptive designs may increase their use and interpretation. METHODS: Using two large critical care trials (ADRENAL. CLINICALTRIALS: gov number, NCT01448109. Updated 12-12-2017; NICE-SUGAR. CLINICALTRIALS: gov number, NCT00220987. Updated 01-29-2009), we assessed the performance of three frequentist and two bayesian adaptive approaches. We retrospectively re-analysed the trials with one, two, four, and nine equally spaced interims. Using the original hypotheses, we conducted 10,000 simulations to derive error rates, probabilities of making an early correct and incorrect decision, expected sample size and treatment effect estimates under the null scenario (no treatment effect) and alternative scenario (a positive treatment effect). We used a logistic regression model with 90-day mortality as the outcome and the treatment arm as the covariate. The null hypothesis was tested using a two-sided significance level (α) at 0.05. RESULTS: Across all approaches, increasing the number of interims led to a decreased expected sample size. Under the null scenario, group sequential approaches provided good control of the type-I error rate; however, the type I error rate inflation was an issue for the Bayesian approaches. The Bayesian Predictive Probability and O'Brien-Fleming approaches showed the highest probability of correctly stopping the trials (around 95%). Under the alternative scenario, the Bayesian approaches showed the highest overall probability of correctly stopping the ADRENAL trial for efficacy (around 91%), whereas the Haybittle-Peto approach achieved the greatest power for the NICE-SUGAR trial. Treatment effect estimates became increasingly underestimated as the number of interims increased. CONCLUSIONS: This study confirms the right adaptive design can reach the same conclusion as a fixed design with a much-reduced sample size. The efficiency gain associated with an increased number of interims is highly relevant to late-phase critical care trials with large sample sizes and short follow-up times. Systematically exploring adaptive methods at the trial design stage will aid the choice of the most appropriate method.

Quantum Statistical Enhancement of the Collective Performance of Multiple Bosonic Engines.

We consider an ensemble of indistinguishable quantum machines and show that quantum statistical effects can give rise to a genuine quantum enhancement of the collective thermodynamic performance. When multiple indistinguishable bosonic work resources are coupled to an external system, the internal energy change of the external system exhibits an enhancement arising from permutation symmetry in the ensemble, which is absent when the latter consists of distinguishable work resources.

Collective Effects in Casimir-Polder Forces.

We study cooperative phenomena in the fluctuation-induced forces between a surface and a system of neutral two-level quantum emitters prepared in a coherent collective state, showing that the total Casimir-Polder force on the emitters can be modified via their mutual correlations. Particularly, we find that a one-dimensional chain of emitters prepared in a super- or subradiant state experiences an enhanced or suppressed collective vacuum-induced force, respectively. The collective nature of dispersion forces can be understood as resulting from the interference between the different processes contributing to the surface-modified resonant dipole-dipole interaction. Such cooperative fluctuation forces depend singularly on the surface response at the resonance frequency of the emitters, thus being easily maneuverable. Our results demonstrate the potential of collective phenomena as a new tool to selectively tailor vacuum forces.

Cooperative Effects in Closely Packed Quantum Emitters with Collective Dephasing.

In a closely packed ensemble of quantum emitters, cooperative effects are typically suppressed due to the dephasing induced by the dipole-dipole interactions. Here, we show that by adding sufficiently strong collective dephasing, cooperative effects can be restored. Specifically, we show that the dipole force on a closely packed ensemble of strongly driven two-level quantum emitters, which collectively dephase, is enhanced in comparison to the dipole force on an independent noninteracting ensemble. Our results are relevant to solid-state systems with embedded quantum emitters such as color centers in diamond and superconducting qubits in microwave cavities and waveguides.

The first total synthesis of gobichelin B: a mixed-ligand siderophore of Streptomyces sp. NRRL F-4415.

The first total synthesis of a structurally diverse mixed ligand siderophore, gobichelin B produced by Streptomyces sp. NRRL F-4415, is reported. The systematic assembly of the building blocks to synthesize Gob-B 1st half and Gob-B 2nd half and subsequent coupling of these two fragments followed by global deprotection using Pearlman's catalyst led to the isolation of gobichelin B in excellent yield and purity.

Quantum Performance of Thermal Machines over Many Cycles.

The performance of quantum heat engines is generally based on the analysis of a single cycle. We challenge this approach by showing that the total work performed by a quantum engine need not be proportional to the number of cycles. Furthermore, optimizing the engine over multiple cycles leads to the identification of scenarios with a quantum enhancement. We demonstrate our findings with a quantum Otto engine based on a two-level system as the working substance that supplies power to an external oscillator.

Cardiometabolic disease in South Asians: A global health concern in an expanding population.

Cardiovascular disease (CVD) is one of the main causes of mortality and morbidity worldwide. As an emerging population, South Asians (SAs) bear a disproportionately high burden of CVD relative to underlying classical risk factors, partly attributable to a greater prevalence of insulin resistance and diabetes and distinct genetic and epigenetic influences. While the phenotypic distinctions between SAs and other ethnicities in CVD risk are becoming increasingly clear, the biology of these conditions remains an area of active investigation, with emerging studies involving metabolism, genetic variation and epigenetic modifiers (e.g., extracellular RNA). In this review, we describe the current literature on prevalence, prognosis and CVD risk in SAs, and provide a landscape of translational research in this field toward ameliorating CVD risk in SAs.

Incidence of Prosthetic Complications associated with Implant-borne Prosthesis in a Sleep Disorder Center.

BACKGROUND: Obstructive sleep apnea (OSA) is one of the common prevalent conditions present worldwide. The process of abnormal habits related to clenching and grinding of teeth is referred to as bruxism and is characterized under the heading of parafunctional activity of the masticatory system. Osseointegrated dental implants represent advancements in the field of odontology. Despite its high success rate, failure and complications are often associated with dental implant treatment due to a number of factors. Hence, we aimed for the present study to assess the incidence of prosthetic complications in patients rehabilitated with implant-borne prosthesis in a sleep disorder unit. MATERIALS AND METHODS: The present study included the assessment of all the patients who underwent prosthetic rehabilitation by dental implants. An experienced registered prosthodontist was given duty for examination of all the cases from the record file data. Prosthetic complications in the patients were identified using photographs, radiographs, and all other relevant data of the patients obtained from the record files. All types of complications and other factors were recorded separately and analyzed. RESULTS: While correlating the prosthetic complications in OSA patients grouped based on number of dental implants, nonsignificant results were obtained. Significant correlation was observed while comparing the prosthetic complications divided based on type of prosthesis. Fracture of the porcelain was observed in four and eight cases respectively, of screwed and cemented dental implant cases. CONCLUSION: Some amount of significant correlation existed between the incidences of prosthetic complications and OSA. CLINICAL SIGNIFICANCE: Proper history of the patients undergoing dental implant procedures should be taken to avoid failure.

Backaction-driven transport of Bloch oscillating atoms in ring cavities.

We predict that an atomic Bose-Einstein condensate strongly coupled to an intracavity optical lattice can undergo resonant tunneling and directed transport when a constant and uniform bias force is applied. The bias force induces Bloch oscillations, causing amplitude and phase modulation of the lattice which resonantly modifies the site-to-site tunneling. For the right choice of parameters a net atomic current is generated. The transport velocity can be oriented oppositely to the bias force, with its amplitude and direction controlled by the detuning between the pump laser and the cavity. The transport can also be enhanced through imbalanced pumping of the two counterpropagating running wave cavity modes. Our results add to the cold atoms quantum simulation toolbox, with implications for quantum sensing and metrology.

N-(6-Chloro-1-methyl-1H-imidazo[4,5-c]pyridin-4-yl)benzene-sulfonamide.

The asymmetric unit of the title compound, C13H11ClN4O2S, contains two mol-ecules (A and B), in which the dihedral angles between the 1H-imidazo[4,5-c]pyridine system and terminal phenyl ring are 80.83 (10) and 62.34 (1)°. In the crystal, A-B dimers are linked by pairs of N-H⋯N hydrogen bonds, which generate R (2) 2(10) loops. The dimers are linked by C-H⋯O and C-H⋯Cl inter-actions, generating a three-dimensional network. Aromatic π-π stacking inter-actions [shortest centroid-centroid distance = 3.5211 (12) Å] are also observed.

1-(6-Chloro-1-methyl-1H-imidazo[4,5-c]pyridin-4-yl)-3-(2-chloro-phen-yl)urea.

In the title compound, C14H11Cl2N5O, the plane of the 1H-imidazo[4,5-c]pyridine ring system [r.m.s. deviation = 0.087 (19) Å] makes a dihedral angle of 4.87 (10)° with the terminal phenyl ring. An intra-molecular N-H⋯N hydrogen bond stabilizes the mol-ecular conformation. In the crystal, N-H⋯O hydrogen bonds link the mol-ecules into inversion dimers. These dimers are connected by π-π inter-actions between imidazole rings [shortest centroid-centroid distance = 3.4443 (14) Å].

Controlling work output and coherence in finite-time quantum Otto engines through monitoring.

We examine the role of diagnostic quantum measurements on the work statistics of a finite-time quantum Otto heat engine operated in the steady state. We consider three pointer-based measurement schemes that differ in the number of system-pointer interactions and pointer measurements. We show that the coherence of the working substance and the work output of the engine can be controlled by tuning the monitoring measurements. Moreover, for a working substance consisting of a two-level system we show that while all three schemes reproduce the predictions of the cycle without any monitoring for the average work in the limit of infinitely weak measurement, only two of the schemes can reproduce the two-point projective measurement results in the limit of strong measurement.

Hybrid optimization algorithm for enhanced performance and security of counter-flow shell and tube heat exchangers.

A shell and tube heat exchanger (STHE) for heat recovery applications was studied to discover the intricacies of its optimization. To optimize performance, a hybrid optimization methodology was developed by combining the Neural Fitting Tool (NFTool), Particle Swarm Optimization (PSO), and Grey Relational Analysis (GRE). STHE heat exchangers were analyzed systematically using the Taguchi method to analyze the critical elements related to a particular response. To clarify the complex relationship between the heat exchanger efficiency and operational parameters, grey relational grades (GRGs) are first computed. A forecast of the grey relation coefficients was then conducted using NFTool to provide more insight into the complex dynamics. An optimized parameter with a grey coefficient was created after applying PSO analysis, resulting in a higher grey coefficient and improved performance of the heat exchanger. A major and far-reaching application of this study was based on heat recovery. A detailed comparison was conducted between the estimated values and the experimental results as a result of the hybrid optimization algorithm. In the current study, the results demonstrate that the proposed counter-flow shell and tube strategy is effective for optimizing performance.

Performance optimization for an optimal operating condition for a shell and heat exchanger using a multi-objective genetic algorithm approach.

In this study, shell and heat exchangers are optimized using an integrated optimization framework. In this research, A structured Design of Experiments (DOE) comprising 16 trials was first conducted to systematically determine the essential parameters, including mass flow rates (mh, mc), temperatures (T1, t1, T2, t2), and heat transfer coefficients (€, TR, U). By identifying the first four principal components, PCA was able to determine 87.7% of the variance, thereby reducing the dimensionality of the problem. Performance-related aspects of the system are the focus of this approach. Key outcomes (€, TR, U) were predicted by 99% R-squared using the RSM models. Multiple factors, such as the mass flow rate and inlet temperature, were considered during the design process. The maximizing efficiency, thermal resistance, and utility were achieved by considering these factors. By using genetic algorithms, Pareto front solutions that meet the requirements of decision-makers can be found. The combination of the shell and tube heat exchangers produced better results than expected. Engineering and designers can gain practical insight into the mass flow rate, temperature, and key responses (€, TR, U) if they quantify improvements in these factors. Despite the importance of this study, it has several potential limitations, including specific experimental conditions and the need to validate it in other situations as well. Future research could investigate other factors that influence system performance. A holistic optimization framework can improve the design and engineering of heat exchangers in the future. As a result of the study, a foundation for innovative advancements in the field has been laid with tangible improvements. The study exceeded expectations by optimizing shell and heat exchanger systems using an integrated approach, thereby contributing significantly to the advancement of the field.

Optimising essential oil yields and quality from Pimenta dioica (L.) merr. Leaf: impact of NaCl concentrations, pH media and sequential separation of essential oil components during hydrodistillation.

The study examined the effects of herb drying, salt concentration, pH, and sampling approach on essential oil yield and composition in Pimenta dioica (L.) Merr. Fresh samples yielded higher essential oil (EO) (1.25%) than shade-dried ones. Increasing NaCl concentration correlated with higher EO yields, while a basic pH favoured superior yields. Gas Chromatography identified Eugenol and ß-myrcene as primary constituents. Eugenol content peaked at 10% NaCl (56.429%) and was lowest at pH 4 (42.850%). ß-myrcene content was highest at pH 4 (31.476%). Hydro distillation with systematic sampling evaluated the effects of 14 fractions in different time frames. Phenylpropanoids (mainly eugenol) and acyclic monoterpene (mainly ß-myrcene) dominated all fractions, with cyclic monoterpene (mainly limonene) enriched in the first four fractions. Fractions 10 to 14 showed significant increases in eugenol compared to the control. These findings provide insights for meeting market demands, enhancing the commercial potential of P. dioica EO.

Organization of the Fugu rubripes Hox clusters: evidence for continuing evolution of vertebrate Hox complexes.

The clustered organization of Hox genes provides a powerful opportunity to examine gene gain and loss in evolution because physical linkage is a key diagnostic feature which allows homology to be established unambiguously. Furthermore, Hox genes play a key role in determination of axial and appendicular skeletal morphology and may be a key component of the evolution of diverse metazoan body forms. Despite suggestions that changes in Hox gene number played a role in evolution of metazoan body plans, there has been a general lack of evidence for such variation amongst gnathostomes (or indeed any vertebrate) and it has therefore been widely assumed that differential regulation may be the key element in all vertebrate Hox evolution. We have studied the Hox gene clusters of a teleost fish, Fugu rubripes, to test the possibility that Hox organization may have varied since the origin of jawed vertebrates. We have identified four Hox complexes in Fugu and found an unprecedented degree of variation when compared with tetrapod clusters. Our data show that: Fugu clusters are widely variant with respect to length; at least nine genes have been lost; there is a new group-2 paralogue; and pseudo-gene remnants of group-1 and group-3 paralogues were found in the Hoxc complex, when compared with the present mammalian clusters. We show that gene loss after duplication of the prototypical vertebrate Hox clusters is a key feature of both tetrapod and fish evolution.

Prospective memory in the ICU: the effect of visual cues on task execution in a representative simulation.

Despite the potential dangers of clinical tasks being forgotten, few researchers have investigated prospective memory (PM) - the ability to remember to execute future tasks - in health-care contexts. Visual cues help people remember to execute intentions at the appropriate moment. Using an intensive care unit simulator, we investigated whether nurses' memory for future tasks improves when visual cues are present, and how nurses manage PM demands. Twenty-four nurses participated in a 40-minute scenario simulating the start of a morning shift. The scenario included eight PM tasks. The presence or absence of a visually conspicuous cue for each task was manipulated. The presence of a visual cue improved recall compared to no cue (64% vs. 50%, p = 0.03 one-tailed, η(p)(2) = 0.15). Nurses used deliberate reminders to manage their PM demands. PM in critical care might be supported by increasing the visibility of cues related to tasks. PRACTITIONER SUMMARY: Nurses must remember to execute multiple future tasks to ensure patient safety. We investigated the effect of visual cues on nurses' ability to remember future tasks. Experimental manipulation of cues in a representative intensive care unit simulation indicated that visual cues increase the likelihood that future tasks are executed.

2-Oxo-2-(2-oxo-2H-chromen-3-yl)ethyl di-ethyl-dithio-carbamate.

In the title compound, C16H17NO3S2, the dihedral angles between the O/C/C/S group and the 2H-chromene ring system and the thio-carbamate group are 14.46 (9) and 83.30 (9)°, respectively. The bond-angle sum at the N atom is 360.0°. One of the methyl C atoms lies above the thio-carbamate plane and one lies below it [deviations = 1.264 (3) and -1.147 (3) Å, respectively]. In the crystal, inversion dimers linked by pairs of C-H⋯O hydrogen bonds generate R 2 (2)(10) loops. Weak aromatic π-π stacking inter-actions [shortest centroid-centroid distance = 3.8138 (11) Å] are also observed.

(2E)-1-(5-Bromothiophen-2-yl)-3-(4-chloro-phen-yl)prop-2-en-1-one.

In the title compound, C13H8BrClOS, the thio-phene and phenyl rings are inclined by 40.69 (11)° to each other. The crystal structure is characterized by C-H⋯π inter-actions, which link the mol-ecules into broad layers parallel to (100). Short Br⋯Cl contacts [3.698 (1) Å] link these layers along [100].