Stochastic surgery selection and sequencing under dynamic emergency break-ins

Anticipating the impact of urgent emergency arrivals on operating room schedules remains methodologically and computationally challenging. This paper investigates a model for surgery scheduling, in which both surgery durations and emergency patient arrivals are stochastic. When an emergency patient arrives he enters the first available room. Given the sets of surgeries available to each operating room for that day, as well as the distributions of the main stochastic variables, we aim to find the per-room surgery sequences that minimise a joint objective, which includes over- and under-utilisation, the amount of cancelled patients, as well as the risk that emergencies suffer an excessively long waiting time. We show that a detailed analysis of emergency break-ins and their disruption of the schedule leads to a lower total cost compared to less sophisticated models. We also map the trade-off between the threshold for excessive waiting time, and the set of other objectives. Finally, an efficient heuristic is proposed to accurately estimate the value of a solution with significantly less computational effort.Anticipating the impact of urgent emergency arrivals on operating room schedules remains methodologically and computationally challenging. This paper investigates a model for surgery scheduling, in which both surgery durations and emergency patient arrivals are stochastic. When an emergency patient arrives he enters the first available room. Given the sets of surgeries available to each operating room for that day, as well as the distributions of the main stochastic variables, we aim to find the per-room surgery sequences that minimise a joint objective, which includes over- and under-utilisation, the amount of cancelled patients, as well as the risk that emergencies suffer an excessively long waiting time. We show that a detailed analysis of emergency break-ins and their disruption of the schedule leads to a lower total cost compared to less sophisticated models. We also map the trade-off between the threshold for excessive waiting time, and the set of other objectives. Finally, an efficient heuristic is proposed to accurately estimate the value of a solution with significantly less computational effort.A

Optimized expression of the Starmerella bombicola lactone esterase in Pichia pastoris through temperature adaptation, codon-optimization and co-expression with HAC1

The Starmerella bombicola lactone esterase (SBLE) is a novel enzyme that, in vivo, catalyzes the intramolecular esterification (lactonization) of acidic sophorolipids in an aqueous environment. In fact, this is an unusual reaction given the unfavorable conditions for dehydration. This characteristic strongly contributes to the potential of SBLE to become a 'green' tool in industrial applications. Indeed, lactonization occurs normally in organic solvents, an application for which microbial lipases are increasingly used as biocatalysts. Previously, we described the production of recombinant SBLE (rSBLE) in Pichia pastoris (syn. Komagataella phaffii). However, expression was not optimal to delve deeper into the enzyme's potential for industrial application. In the current study, we explored codon-optimization of the SBLE gene and we optimized the rSBLE expression protocol. Temperature reduction had the biggest impact followed by codon-optimization and co-expression of the HAC1 transcription factor. Combining these approaches, we achieved a 32-fold improvement of the yield during rSBLE production (from 0.75 mg/l to 24 mg/L culture) accompanied with a strong reduction of contaminants after affinity purification

Asymmetric speed modulation of a rotary blood pump affects ventricular unloading

OBJECTIVES Rotary blood pumps (RBPs) running at a constant speed are routinely used for the mechanical support of the heart in various clinical applications, from short-term use in heart-lung machines to long-term support of a failing heart. Their operating range is delineated by suction and regurgitation events, leaving limited control on the cardiac workload. This study investigates whether different ratios of systolic/diastolic support are advantageous over a constant-speed operation. METHODS In order to effectively control the load on the heart, this study aimed at developing a pulsatile control algorithm for rotary pumps to investigate the impact of pump speed modulation during systole and diastole on the left ventricle unloading. The CentriMagTM RBP with a modified controller was implanted in four sheep via a left thoracotomy and cannulated from the ventricular apex to the descending aorta. To modulate the pump speed synchronized with the heartbeat, custom-made real-time software detected the QRS complex of the electrocardiogram and controlled the pump speed during systole and diastole. Four different speed modulations with the same average speed but different systolic and diastolic speeds were compared with the baseline and the constant speed support. Left ventricular (LV) pressure and volume, coronary flow and pump flow were analysed to examine the influence of the pump speed modulation. RESULTS Pulsatile setting reduces the cardiac workload to 64% of the baseline and 72% of the constant speed value. Maximum unloading is obtained with the highest speed during diastole and high-pulse amplitude. End-diastolic volume in the pulsatile modes varied from 85 to 94% of the baseline and 96 to 107% of the constant speed value. Consequently, the mechanical load on the heart can be adjusted to provide assuagement, which may lead to myocardial recovery. The higher pump speed during systole results in an increase in the pulse pressure up to 140% compared with the constant speed. CONCLUSIONS The present study is an initial step to more accurate speed modulation of RBPs to optimize the cardiac load control. To develop future control algorithms, the concept of high speed during diastole having a maximal unloading effect on the LV and high speed during systole increasing the pulse pressure is worth considerin

The Diest Formation : a review of insights from the last decades

Research conducted since the 1960s on the upper Miocene Diest Formation in NE Belgium is reviewed and integrated. Their lithology unites the deposits of the glauconiferous Diest Sand in one formation, though biozones and internal sedimentary structures strongly suggest the formation may agglomerate the deposits of two separate, successive sedimentary cycles. The lowermost cycle is thought to have deposited the "Hageland Diest sand" during the early or middle Tortonian. It contains the Diest Sand in the main outcrop area in Hageland, Zuiderkempen and central Limburg, and probably also the Deurne Member near the city of Antwerpen. It furthermore includes the lower part of the Dessel Member in the central Kempen and in the Belgian part of the Roer Valley Graben (RVG). The Hageland Diest cycle represents the infill of a large tidal inlet tributary to the southern North Sea bight, then situated over the southern Netherlands and the Lower Rhine embayment. The Hageland Diest sand has the composition of a marine deposit, yet the confined area of occurrence and the presence of tens of metres deep incisions at the base, set it apart. The confinement of the embayment, strong tides and a steady supply of coastal-marine sand arc invoked as the main driving forces that resulted in the distinctive geometry and internal architecture of the unit. The upper cycle is associated with the "Kempen Diest sand", which is found in the subsurface of the RVG and the Noorderkempen. It has a late Tortonian to earliest Messinian age with progressively younger ages occurring to the NW. It encompasses the upper part of the Dessel Member and the overlying, coarser Diest Sand, and correlates to most or all of the thickly developed Diessen Formation in The Netherlands. It is the deposit of a prograding marine delta, containing both marine components and continental components fed by the palaeo-Meuse/Rhine river mouths. Accommodation space kept increasing during deposition, due to subsidence of the deposition area, especially inside the RVG but also in the Noorderkempen. Although there is a fair consensus on the above, many concrete points about the geometry and depositional history of the Diest Formation and even a definitive decision on its single or dual character remain to be sorted out. In addition, this review excludes the Flemish Hills sand and the Gruitrode Member from the Diest Formation

Mediation analysis of time-to-event endpoints accounting for repeatedly measured mediators subject to time-varying confounding.

In this article, we will present statistical methods to assess to what extent the effect of a randomised treatment (versus control) on a time-to-event endpoint might be explained by the effect of treatment on a mediator of interest, a variable that is measured longitudinally at planned visits throughout the trial. In particular, we will show how to identify and infer the path-specific effect of treatment on the event time via the repeatedly measured mediator levels. The considered proposal addresses complications due to patients dying before the mediator is assessed, due to the mediator being repeatedly measured, and due to posttreatment confounding of the effect of the mediator by other mediators. We illustrate the method by an application to data from the LEADER cardiovascular outcomes trial

Asymmetric speed modulation of a rotary blood pump affects ventricular unloading

Rotary blood pumps (RBPs) running at a constant speed are routinely used for the mechanical support of the heart in various clinical applications, from short-term use in heart-lung machines to long-term support of a failing heart. Their operating range is delineated by suction and regurgitation events, leaving limited control on the cardiac workload. This study investigates whether different ratios of systolic/diastolic support are advantageous over a constant-speed operation

Outcome in patients perceived as receiving excessive care across different ethical climates : a prospective study in 68 intensive care units in Europe and the USA

Whether the quality of the ethical climate in the intensive care unit (ICU) improves the identification of patients receiving excessive care and affects patient outcomes is unknown. In this prospective observational study, perceptions of excessive care (PECs) by clinicians working in 68 ICUs in Europe and the USA were collected daily during a 28-day period. The quality of the ethical climate in the ICUs was assessed via a validated questionnaire. We compared the combined endpoint (death, not at home or poor quality of life at 1 year) of patients with PECs and the time from PECs until written treatment-limitation decisions (TLDs) and death across the four climates defined via cluster analysis. Of the 4747 eligible clinicians, 2992 (63%) evaluated the ethical climate in their ICU. Of the 321 and 623 patients not admitted for monitoring only in ICUs with a good (n = 12, 18%) and poor (n = 24, 35%) climate, 36 (11%) and 74 (12%), respectively were identified with PECs by at least two clinicians. Of the 35 and 71 identified patients with an available combined endpoint, 100% (95% CI 90.0-1.00) and 85.9% (75.4-92.0) (P = 0.02) attained that endpoint. The risk of death (HR 1.88, 95% CI 1.20-2.92) or receiving a written TLD (HR 2.32, CI 1.11-4.85) in patients with PECs by at least two clinicians was higher in ICUs with a good climate than in those with a poor one. The differences between ICUs with an average climate, with (n = 12, 18%) or without (n = 20, 29%) nursing involvement at the end of life, and ICUs with a poor climate were less obvious but still in favour of the former. Enhancing the quality of the ethical climate in the ICU may improve both the identification of patients receiving excessive care and the decision-making process at the end of life

Simulation of dilated heart failure with continuous flow circulatory support

Lumped parameter models have been employed for decades to simulate important hemodynamic couplings between a left ventricular assist device (LVAD) and the native circulation. However, these studies seldom consider the pathological descending limb of the Frank-Starling response of the overloaded ventricle. This study introduces a dilated heart failure model featuring a unimodal end systolic pressure-volume relationship (ESPVR) to address this critical shortcoming. The resulting hemodynamic response to mechanical circulatory support are illustrated through numerical simulations of a rotodynamic, continuous flow ventricular assist device (cfVAD) coupled to systemic and pulmonary circulations with baroreflex control. The model further incorporated septal interaction to capture the influence of left ventricular (LV) unloading on right ventricular function. Four heart failure conditions were simulated (LV and bi-ventricular failure with/ without pulmonary hypertension) in addition to normal baseline. Several metrics of LV function, including cardiac output and stroke work, exhibited a unimodal response whereby initial unloading improved function, and further unloading depleted preload reserve thereby reducing ventricular output. The concept of extremal loading was introduced to reflect the loading condition in which the intrinsic LV stroke work is maximized. Simulation of bi-ventricular failure with pulmonary hypertension revealed inadequacy of LV support alone. These simulations motivate the implementation of an extremum tracking feedback controller to potentially optimize ventricular recovery. © 2014 Wang et al