Interruption Strategies Research Articles

The Peri-Operative Management of Anticoagulants: Systemic Review of Guidelines

Introduction Venous thromboembolism (VTE) and atrial fibrillation are thrombotic disorders resulting in significant morbidity and mortality, if left untreated. In Canada, 45,000 people, or 1-2 cases per 1000 people, per year will experience an acute VTE, and it is estimated that 200,000 Canadians have atrial fibrillation. The treatment of VTE and atrial fibrillation often includes the use of anticoagulants. Patients on anticoagulation may need interruption of treatment for surgeries and procedures. To evaluate differences in perioperative anticoagulation management strategies we conducted a systematic review of the peri-operative clinical practice guidelines for anticoagulants. Methods A protocol using the Preferred Reporting Items for Systematic review and Meta-analysis Protocols (PRISMA-P) was developed. Relevant primary clinical practice guidelines were identified using MEDLINE, EMBASE, and guideline-specific databases. All guidelines from the preceding 20 years up to January 11, 2019 were screened. Eligible manuscripts were reviewed by two independent reviewers. Data abstraction was independently completed in duplicate for included guidances and categorized according to thrombotic risks and bleeding risks. Guidances on emergency surgeries were not included for the purposes of this review. Information on anticoagulation interruption, bridging regimens, laboratory testing, and reversal strategies were collected. Results Eight guidelines met inclusion criteria and 6 contained sufficient information for peri-operative management of anticoagulants. One guideline focused on patients presenting with bleeding events and restated the same peri-operative guidelines as had been published a year prior by the same group, and was excluded. Another guideline only addressed emergency surgeries and was also excluded from this review. The majority of the guidelines had similar definitions of risk factors for venous and arterial thrombotic events (see table 1). There were no conflicting guidance recommendations identified, but there were differences in the component of peri-operative management addressed by each guideline, ie bridging, reversal agents, laboratory tests. The levels of evidence used to develop recommendations varied between guidelines. All guidelines provided recommendations on warfarin and low molecular weight heparins (LMWH) management and only one guideline provided suggestions for direct oral anticoagulants (DOACs). The findings for perioperative anticoagulation management for patients with atrial fibrillation and VTE are presented in Tables 2 and 3, respectively. For high bleeding risk surgeries, most guidelines cited similar studies resulting in similar recommendations for interruption of warfarin and bridging in high venous and arterial thrombotic risk patients. In high bleeding risk procedures and low thrombotic risk patients, no bridging is recommended. For low bleed risk procedures, regardless of thrombotic risk, guidelines recommended for continuation of anticoagulant therapy. Discussion This systematic review identified 6 guidelines of non-urgent peri-operative management recommendations of primarily warfarin and LMWH in patients with VTE and atrial fibrillation. While no major discrepancies in the guideline suggestions were noted, the scope of data examined (medication management, bridging, blood tests, reversal of agents) differed amongst the various agencies. The guidelines that were most consistent for recommendations of anticoagulant management and bridging tended to be from hematologic societies. The only guideline that addressed perioperative management of DOACs was the 2018 ASH guideline on management of VTE which was against measurement of DOAC levels prior to procedures. The lack of thorough guidance for DOACs is likely due to the year of publication of the guidelines examined and paucity of contributing studies. In terms of reversal agents, all clinical practice guidelines except for the ASH guidelines were prior to specific DOAC reversal agents such as idaracizumab. Future Directions We anticipate that there will be other guidelines developed that address specifically the use of DOACs in the perioperative setting, as well as their reversal agents. Disclosures Shivji: BMS-Pfizer Thrombosis Canada: Other: Fellowship award. Castellucci:BMS: Honoraria; Pfizer: Honoraria; Bayer: Honoraria; LEO Pharma: Honoraria; Sanofi: Honoraria; Aspen: Honoraria; Servier: Honoraria.

Gastric insufflation during cardiopulmonary resuscitation: A study in human cadavers

IntroductionBag-valve-mask ventilation is the first-line ventilation method during cardiopulmonary resuscitation (CPR). Risks include excessive volume delivery and gastric insufflation, the latter increasing the risk of pneumonia. The efficacy of ventilation can also be reduced by airway closure. We hypothesized that continuous chest compression (CC) could limit the risk of gastric insufflation compared to the recommended 30:2 interrupted CC strategy. This experimental study was performed in human “Thiel” cadavers to assess the respective impact of discontinuous vs. continuous chest compressions on gastric insufflation and ventilation during CPR. MethodsThe 30:2 interrupted CC technique was compared to continuous CC in 5 non-intubated cadavers over a 6 min-period. Flow and Airway Pressure were measured at the mask. A percutaneous gastrostomy allowed measuring the cumulative gastric insufflated volume. Two additional cadavers were equipped with esophageal and gastric catheters instead of the gastrostomy. ResultsFor the 7 cadavers studied (4 women) median age of death was 79 [74–84] years.After 6 min of CPR, the cumulative gastric insufflation measured in 5 cadavers was markedly reduced during continuous CC compared to the interrupted CC strategy: (1.0 [0.8–4.1] vs. 5.9 [4.0–5.6] L; p < 0.05) while expired minute ventilation was slightly higher during continuous than interrupted CC (1.9 [1.4–2.8] vs. 1.6 [1.1–2.7] L/min; P < 0.05).In 2 additional cadavers, the progressive rise in baseline gastric pressure was lower during continuous CC than interrupted CC (1 and 2 cmH2O vs. 12 and 5.8 cmH2O). ConclusionContinuous CC significantly reduces the volume of gas insufflated in the stomach compared to the recommended 30:2 interrupted CC strategy. Ventilation actually delivered to the lung is also slightly increased by the strategy.

Individual-based multi-objective optimal structured treatment interruption for HIV infection

In this paper, based on the measurable quantities from an individual patient that has infection to human immunodeficiency virus (HIV) and his/her condition is near to acquired immune deficiency syndrome (AIDS), individual-based multi-objective optimal treatments have been proposed. Firstly, the most effective parameters of the patient in computing Long-term non-progressor (LTNP) equilibrium are derived using global sensitivity analysis (GSA). To accomplish GSA effectively, Latin hypercube sampling (LHS) and partial rank correlation coefficients (PRCC) are utilized to rank each of the parameters based on each state of the 5-dimensional model. Then, these results are used by Dempster–Shafer (D–S) evidence theory (DSET) to rank the most effective parameters comprehensively. Now, these effective identified parameters are estimated using extended Kalman filter (EKF), which its covariance matrices are optimized based on particle swarm optimization (PSO) algorithm. Thus, the proposed methodology gives a calibrated model corresponding to the individual patient. Based on this calibrated model, the LTNP equilibrium related to the individual patient is derived. Using the derived individual-based LTNP equilibrium optimal structured treatment interruption (STI) strategies are extracted by defining suitable multi-objective optimization problem and solving it through using non-dominated sorting genetic algorithm-II (NSGA-II). The results demonstrate that the proposed optimal treatments are able to effectively reach LTNP equilibrium with using the minimum and maximum drug usage of 3.6% and 35.1% of full drug usage treatment. Meanwhile, the different optimal treatments give the decision-makers enough flexibility to choose the suitable treatment based on existing facilities and necessities.

Task Interruption and Control Recovery Strategies After Take-Over Requests Emphasize Need for Measures of Situation Awareness.

Our objective was to determine whether there is a need to go beyond measures of automation deactivation time to understand the transition to manual driving after take-over requests (TORs) using the example of office tasks as nondriving-related tasks (NDRTs). Office tasks are likely NDRTs during automated commutes to/from work. Complex tasks can influence how manual control and visual attention is recovered after TORs. N = 51 participants in a driving simulator performed either one of two office tasks or no task (between subjects). We recorded reaction times in a high-urgency and low-urgency scenario (within subjects) and analyzed task interruption strategies. 90% of the participants who performed an NDRT deactivated the automation after 7 to 8 s. However, 90% of the same drivers looked at the side mirror for the first time only after 11 to 14 s. Drivers with office tasks either interrupted the tasks sequentially or in parallel. Strategies were not adapted to the take-over situation or the task but appeared to be due to individual preferences. Drivers engaged in NDRTs may neglect lower priority subtasks after a TOR, such as mirror checking. Therefore, there is a need to go beyond measures of automation deactivation time to understand the transition to manual driving. Using analyses of attentional dynamics during take-over situations may enhance the safety of future car-driver handover assistance systems. If low driver availability is detected, TORs should only be used as a fallback option if sufficient time and adaptive driver support can be provided.

Perioperative Management of Patients With Atrial Fibrillation Receiving a Direct Oral Anticoagulant

Patients with atrial fibrillation (AF) who use a direct oral anticoagulant (DOAC) and request elective surgery or procedure present a common clinical situation yet perioperative management is uncertain. To investigate the safety of a standardized perioperative DOAC management strategy. The Perioperative Anticoagulation Use for Surgery Evaluation (PAUSE) cohort study conducted at 23 clinical centers in Canada, the United States, and Europe enrolled and screened patients from August 1, 2014, through July 31, 2018. Participants (n = 3007) had AF; were 18 years of age or older; were long-term users of apixaban, dabigatran etexilate, or rivaroxaban; were scheduled for an elective surgery or procedure; and could adhere to the DOAC therapy interruption protocol. A simple standardized perioperative DOAC therapy interruption and resumption strategy based on DOAC pharmacokinetic properties, procedure-associated bleeding risk, and creatinine clearance levels. The DOAC regimens were omitted for 1 day before a low-bleeding-risk procedure and 2 days before a high-bleeding-risk procedure. The DOAC regimens were resumed 1 day after a low-bleeding-risk procedure and 2 to 3 days after a high-bleeding-risk procedure. Follow-up of patients occurred for 30 days after the operation. Major bleeding and arterial thromboembolism (ischemic stroke, systemic embolism, and transient ischemic attack) and the proportion of patients with an undetectable or minimal residual anticoagulant level (<50 ng/mL) at the time of the procedure. The 3007 patients with AF (mean [SD] age of 72.5 [9.39] years; 1988 men [66.1%]) comprised 1257 (41.8%) in the apixaban cohort, 668 (22.2%) in the dabigatran cohort, and 1082 (36.0%) in the rivaroxaban cohort; 1007 patients (33.5%) had a high-bleeding-risk procedure. The 30-day postoperative rate of major bleeding was 1.35% (95% CI, 0%-2.00%) in the apixaban cohort, 0.90% (95% CI, 0%-1.73%) in the dabigatran cohort, and 1.85% (95% CI, 0%-2.65%) in the rivaroxaban cohort. The rate of arterial thromboembolism was 0.16% (95% CI, 0%-0.48%) in the apixaban cohort, 0.60% (95% CI, 0%-1.33%) in the dabigatran cohort, and 0.37% (95% CI, 0%-0.82%) in the rivaroxaban cohort. In patients with a high-bleeding-risk procedure, the rates of major bleeding were 2.96% (95% CI, 0%-4.68%) in the apixaban cohort and 2.95% (95% CI, 0%-4.76%) in the rivaroxaban cohort. In this study, patients with AF who had DOAC therapy interruption for elective surgery or procedure, a perioperative management strategy without heparin bridging or coagulation function testing was associated with low rates of major bleeding and arterial thromboembolism.

Transcriptomic Analysis of Aedes aegypti Innate Immune System in Response to Ingestion of Chikungunya Virus.

Aedes aegypti (L.) is the primary vector of emergent mosquito-borne viruses, including chikungunya, dengue, yellow fever, and Zika viruses. To understand how these viruses interact with their mosquito vectors, an analysis of the innate immune system response was conducted. The innate immune system is a conserved evolutionary defense strategy and is the dominant immune system response found in invertebrates and vertebrates, as well as plants. RNA-sequencing analysis was performed to compare target transcriptomes of two Florida Ae. aegypti strains in response to chikungunya virus infection. We analyzed a strain collected from a field population in Key West, Florida, and a laboratory strain originating from Orlando. A total of 1835 transcripts were significantly expressed at different levels between the two Florida strains of Ae. aegypti. Gene Ontology analysis placed these genes into 12 categories of biological processes, including 856 transcripts (up/down regulated) with more than 1.8-fold (p-adj (p-adjust value) ≤ 0.01). Transcriptomic analysis and q-PCR data indicated that the members of the AaeCECH genes are important for chikungunya infection response in Ae. aegypti. These immune-related enzymes that the chikungunya virus infection induces may inform molecular-based strategies for interruption of arbovirus transmission by mosquitoes.

On Judge’s Trial Discourse in Chinese Courtroom from Goal-Driven Perspective

Abstract Any action has a certain goal, and the judge’s trial discourse is a system of goal with structure and level. Judges usually adopt some discourse strategies to achieve the goal of trial. Based on the court trial corpus collected by us, we find that judges often adopt purposeful discourse strategies to achieve the trial goal and discourse goal, such as question-and-answer strategy, power control strategy, presupposition strategy, repetition strategy and interruption strategy. Strategies actually refer to the means by which to achieve the goal of discourse. Because words are used to express and achieve the goal, the choice of means or strategies depends on the choice of the goal. From this perspective, we can see the relationship between strategy and goal. In a sense, strategy is rhetoric. The purpose of this paper is to study the discourse strategies adopted by judges in Chinese courts from the perspective of the goal principle.

Perioperative Management of DOACs in Vascular Surgery: A Practical Approach.

Approximately 10-15% of patients on DOACs have to interrupt their anticoagulant before an invasive procedure every year. The perioperative management and monitoring of DOACs have proved to be challenging, as differences in patients' status and in the invasiveness of each procedure develop different situations that need a tailored therapeutic approach to each patient's needs. This review aims to summarize current evidence on the perioperative management of DOACs in patients undergoing a vascular surgical procedure focusing with a practical approach on three key clinical questions: (i) can we stop DOAC therapy before the vascular procedure? (ii) is bridging therapy necessary? and (iii) which is the best perioperative strategy for interruption and resumption of the anticoagulant therapy? No specific data exist for the perioperative management of vascular surgery patients on DOACs, as most studies include low number of such patients. Therapeutic strategy on how to handle DOACs perioperatively must be based on their half-life, the bleeding risk of the invasive procedures, and on the thromboembolic risk of the patient. Renal function plays a crucial role in such situations, increasing thromboembolic and bleeding risk. In general, DOACs should be stopped 2 days for high bleed risk, 1 day for low risk and should be resumed 48-72 hrs after high risk, 24 hrs after low-risk procedure. Bridging is almost never needed. Further perioperative research studies on patients undergoing vascular surgery are needed to confirm whether currently accepted therapeutic perioperative strategy is appropriate for these patients.

Incidence of switching to second-line antiretroviral therapy and associated factors in children with HIV: an international cohort collaboration

Estimates of incidence of switching to second-line antiretroviral therapy (ART) among children with HIV are necessary to inform the need for paediatric second-line formulations. We aimed to quantify the cumulative incidence of switching to second-line ART among children in an international cohort collaboration. In this international cohort collaboration study, we pooled individual patient-level data for children younger than 18 years who initiated ART (two or more nucleoside reverse-transcriptase inhibitors [NRTI] plus a non-NRTI [NNRTI] or boosted protease inhibitor) between 1993 and 2015 from 12 observational cohort networks in the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) Global Cohort Collaboration. Patients who were reported to be horizontally infected with HIV and those who were enrolled in trials of treatment monitoring, switching, or interruption strategies were excluded. Switch to second-line ART was defined as change of one or more NRTI plus either change in drug class (NNRTI to protease inhibitor or vice versa) or protease inhibitor change, change from single to dual protease inhibitor, or addition of a new drug class. We used cumulative incidence curves to assess time to switching, and multivariable proportional hazards models to explore patient-level and cohort-level factors associated with switching, with death and loss to follow-up as competing risks. At the data cutoff of Sept 16, 2015, 182 747 children with HIV were included in the CIPHER dataset, of whom 93 351 were eligible, with 83 984 (90·0%) from sub-Saharan Africa. At ART initiation, the median patient age was 3·9 years (IQR 1·6-6·9) and 82 885 (88·8%) patients initiated NNRTI-based and 10 466 (11·2%) initiated protease inhibitor-based regimens. Median duration of follow-up after ART initiation was 26 months (IQR 9-52). 3883 (4·2%) patients switched to second-line ART after a median of 35 months (IQR 20-57) of ART. The cumulative incidence of switching at 3 years was 3·1% (95% CI 3·0-3·2), but this estimate varied widely depending on the cohort monitoring strategy, from 6·8% (6·5-7·2) in settings with routine monitoring of CD4 (CD4% or CD4 count) and viral load to 0·8% (0·6-1·0) in settings with clinical only monitoring. In multivariable analyses, patient-level factors associated with an increased likelihood of switching were male sex, older age at ART initiation, and initial NNRTI-based regimen (p<0·0001). Cohort-level factors that increased the likelihood of switching were higher-income country (p=0·0017) and routine or targeted monitoring of CD4 and viral load (p<0·0001), which was associated with a 166% increase in likelihood of switching compared with CD4 only monitoring (subdistributional hazard ratio 2·66, 95% CI 2·22-3·19). Our global paediatric analysis found wide variations in the incidence of switching to second-line ART across monitoring strategies. These findings suggest the scale-up of viral load monitoring would probably increase demand for paediatric second-line ART formulations. International AIDS Society-CIPHER.

Copper‐Catalyzed [3+2] Cycloaddition and Interrupted Fischer Indolization to Prepare Polycyclic Furo[2,3‐b]indolines from N‐Aryl Isatin Nitrones and Methylenecyclopropanes

AbstractVarious polycyclic furo[2,3‐b]indolines containing a cyclopropane ring have been prepared in moderate yields with high diastereoselectivity from N‐aryl isatin nitrones and methylenecyclopropanes using a copper‐catalyzed [3+2] cycloaddition and subsequent interrupted Fischer indolization strategy under mild reaction conditions. The obtained furo[2,3‐b]indolines were easily converted to piperidinone‐fused furo[2,3‐b]indolines by selective [1,3]‐rearrangement through N−O bond cleavage. Finally, two chiral polycyclic furo[2,3‐b]indolines were obtained by chiral auxiliary control.magnified image

Elite athletes and anticoagulant therapy: an intermittent dosing strategy.

Traditionally, the athlete who requires long-term anticoagulation has been told to forgo participation in contact and collision sports. However, a strategy of short-term interruption of anticoagulant therapy may be designed for some athletes, allowing them return to full athletic activity. A personalized pharmacokinetic/pharmacodynamic study of a direct oral anticoagulant (DOAC) may allow athletic participation when plasma drug concentration is minimal and resumption of treatment after the risk of bleeding sufficiently normalizes. Scientific data and uncertainties regarding this approach, as well as practical challenges in the implementation, will be discussed.

Periprocedural Outcomes of Direct Oral Anticoagulants Versus Warfarin in Nonvalvular Atrial Fibrillation.

Direct oral anticoagulants (DOACs) are surpassing warfarin as the anticoagulant of choice for stroke prevention in nonvalvular atrial fibrillation. DOAC outcomes in elective periprocedural settings have not been well elucidated and remain a source of concern for clinicians. The aim of this meta-analysis was to evaluate the periprocedural safety and efficacy of DOACs versus warfarin in patients with nonvalvular atrial fibrillation. We reviewed the literature for data from phase III randomized controlled trials comparing DOACs with warfarin in the periprocedural period among patients with nonvalvular atrial fibrillation. Substudies from 4 trials (RE-LY [Randomized Evaluation of Long-Term Anticoagulation Therapy], ROCKET AF [Rivaroxaban Once Daily Oral Direct Factor Xa Inhibitor Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation], ARISTOTLE [Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation], and ENGAGE-AF [Effective Anticoagulation With Factor xA Next Generation in Atrial Fibrillation]) were included in the meta-analysis. DOACs as a group and warfarin were compared in terms of the 30-day pooled risk for stroke/systemic embolism, major bleeding, and death, according to whether the study drug was interrupted or not periprocedurally. The overall relative risk (RR) was estimated with a random-effects model. The I2 test was used to assess heterogeneity in RR among the studies. In the uninterrupted anticoagulant strategy, there were no differences in the rates of stroke/systemic embolism (pooled risk, 0.6% [29 events/4519 procedures] versus 1.1% [31/2971]; RR, 0.70; 95% confidence interval [CI], 0.41-1.18) and death (1.4% versus 1.8%; RR, 0.77; 95% CI, 0.53-1.12) between DOACs and warfarin and significantly fewer major bleeding events (2.0% versus 3.3%; RR, 0.62; 95% CI, 0.47-0.82) with DOACs compared to warfarin. Under an interrupted strategy, there was no significant difference between DOACs versus warfarin for stroke/systemic embolism (0.4% [41/9260] versus 0.5% [31/7168]; RR, 0.95; 95% CI, 0.59-1.55), major bleeding (2.1% versus 2.0%; RR, 1.05; 95% CI, 0.85-1.30), and death (0.7% versus 0.6%; RR, 1.24; 95% CI, 0.76-2.04). The studies were homogeneous ( I2=0.0%) for all calculated pooled associations except for the RR of death in the interrupted strategy ( I2=26.3%). The short-term safety and efficacy of DOACs and warfarin are not different in patients with nonvalvular atrial fibrillation periprocedurally. Under an uninterrupted anticoagulation strategy, DOACs are associated with a 38% lower risk of major bleeding compared with warfarin.

화자집중훈련(Speaker Immersion)이 자폐스펙트럼 장애를 가진 유아의 자발적인 맨드(Mand) 및 택트(Tact) 행동 증가에 미치는 영향

The purpose of this study was to examine effects of a Speaker Immersion Procedure on frequency of spontaneous mands and tacts in children with autism spectrum disorders. The study was conducted for 2 girls(4-, 6-year old) and 3 boys (4-, 6-year old) with autism spectrum disorders in a private agency where Early Intensive Behavioral Intervention was provided in a metropolitan city. All of the participants had mands and tact but didn’t show spontaneous mands and tacts. Data were collected in a delayed multiple baseline across participant design. Target behaviors were spontaneous mands and tacts when relevant establishing operations were in place. Intervention was Speaker Immersion during which an intensive mand training was provided with captured or devised establishing operations through a Behavior Chain Interruption Strategies. Relevant establishing operations were manipulated during daily routine such as using bathroom or snack time. The children needed to mand for each step of daily routine in order to complete the routine. For example, the children were required to mand for pulling up pants, using soap, water, paper towel and etc. in order to finish using the bathroom. 6-15 establishing operations were manipulated during one intervention session. During the intervention, the experimenter provided echoic prompts if the children didn’t emit independent mands within 3 to 5 seconds after a relevant establishing operation was in place. The prompted mands were followed immediate reinforcement. Generalizations were tested in other settings such as at a play ground, during art activity or free plays. Spontaneous tacts were also tested to see whether increasing spontaneous mands during daily routine induce increased tacts. The results showed that the intervention procedure were effective in increasing spontaneous and independent mands during training sessions. The results of generalizations and increasing tacts varied across the participants. The results were discussed in terms of the level of verbal capabilities of each participant.

Interrupted reprogramming of alveolar type II cells induces progenitor-like cells that ameliorate pulmonary fibrosis

We describe here an interrupted reprogramming strategy to generate “induced progenitor-like (iPL) cells” from alveolar epithelial type II (AEC-II) cells. A carefully defined period of transient expression of reprogramming factors (Oct4, Sox2, Klf4, and c-Myc (OSKM)) is able to rescue the limited in vitro clonogenic capacity of AEC-II cells, potentially by activation of a bipotential progenitor-like state. Importantly, our results demonstrate that interrupted reprogramming results in controlled expansion of cell numbers yet preservation of the differentiation pathway to the alveolar epithelial lineage. When transplanted to the injured lungs, AEC-II-iPL cells are retained in the lung and ameliorate bleomycin-induced pulmonary fibrosis. Interrupted reprogramming can be used as an alternative approach to produce highly specified functional therapeutic cell populations and may lead to significant advances in regenerative medicine.

Teaching mands for actions to children with autism spectrum disorder using systematic instruction, behavior chain interruption, and a speech-generating device

Q What are the effects of using the behavior chain interruption strategy, with time delay with least-to-most prompting, for teaching mands for actions to three children with autism?Design: Multiple...

Two‐stage load‐scheduling model for the incentive‐based demand response of industrial users considering load aggregators

The demand response (DR) resources provided by modern industrial users tend to be diversified because of the popularisation of renewable energy. In this context, for the problem of satisfaction and uncertainty in the DR, a load-scheduling model considering load aggregators (LAs) is presented. In the multi-level DR scheduling system, the users and aggregator simultaneously participate in the decision; thus, the proposed methodology is a two-stage optimisation process. The first-stage optimisation considers the load interruption strategies of complex industrial processes, where a multi-objective optimisation model is established to coordinate the user benefits and satisfaction. This model is solved by non-dominated sorting genetic algorithm-II (NSGA-II) and the entropy weight double-base point method to obtain the optional interruptible load (IL) contracts for production processes. The second-stage optimisation maximises the economic returns of the LA considering the uncertainty of the resource's response, where chance-constraint programming is applied to solve the problem and select the appropriate IL contract. The effectiveness of the proposed methodology is examined according to the actual industrial production process. The multi-objective coordination effect of production load-scheduling is shown in an example. Finally, the effects of joint resource scheduling and different confidence levels on the profit of the aggregator are analysed.

Intelligent Network DisRuption Analysis (INDRA): A targeted strategy for efficient interruption of hepatitis C transmissions

Hepatitis C virus (HCV) infection is a global public health problem. The implementation of public health interventions (PHI) to control HCV infection could effectively interrupt HCV transmission. PHI targeting high-risk populations, e.g., people who inject drugs (PWID), are most efficient but there is a lack of tools for prioritizing individuals within a high-risk community. Here, we present Intelligent Network DisRuption Analysis (INDRA), a targeted strategy for efficient interruption of hepatitis C transmissions.Using a large HCV transmission network among PWID in Indiana as an example, we compare effectiveness of random and targeted strategies in reducing the rate of HCV transmission in two settings: (1) long-established and (2) rapidly spreading infections (outbreak). Identification of high centrality for the network nodes co-infected with HIV or > 1 HCV subtype indicates that the network structure properly represents the underlying contacts among PWID relevant to the transmission of these infections. Changes in the network's global efficiency (GE) were used as a measure of the PHI effects. In setting 1, simulation experiments showed that a 50% GE reduction can be achieved by removing 11.2 times less nodes using targeted vs random strategies. A greater effect of targeted strategies on GE was consistently observed when networks were simulated: (1) with a varying degree of errors in node sampling and link assignment, and (2) at different levels of transmission reduction at affected nodes. In simulations considering a 10% removal of infected nodes, targeted strategies were ~2.8 times more effective than random in reducing incidence. Peer-education intervention (PEI) was modeled as a probabilistic distribution of actionable knowledge of safe injection practices from the affected node to adjacent nodes in the network. Addition of PEI to the models resulted in a 2–3 times greater reduction in incidence than from direct PHI alone. In setting 2, however, random direct PHI were ~3.2 times more effective in reducing incidence at the simulated conditions. Nevertheless, addition of PEI resulted in a ~1.7-fold greater efficiency of targeted PHI. In conclusion, targeted PHI facilitated by INDRA outperforms random strategies in decreasing circulation of long-established infections. Network-based PEI may amplify effects of PHI on incidence reduction in both settings.

Strategy of transmission interruption of schistosomiasis and its effects in Runzhou District, Zhenjiang City, Jiangsu Province

To evaluate the effects of the strategy of transmission interruption of schistosomiasis in Runzhou District, Zhenjiang City, Jiangsu Province. The comprehensive prevention and control strategy was carried out in RunzhouDistrict, Zhenjiang City, Jiangsu Province. The strategy was relied mainly on the Oncomelania hupensis snail control, extended chemotherapy of schistosomiasis in residents and the health education. The infection rate of schistosomiasis in residents, area with snails, area with snails controlled, and the rates of awareness and correct behavior of schistosomiasis were as evaluation indexes. The area with snails controlled was 7 091.50 hm2 in Runzhou District, Zhenjiang City from 2001 to 2016. The area with snails reduced year by year from 2001 to 2016. There was a negative correlation between the coverage intensity of snail control and the area with snails (r = -0.874, P = 0). There were 1 703 serum positive and 199 fecal positive people of schistosomiasis in the permanent residents from 2001 to 2016. These serum and fecal positive people of schistosomiasis were all treated with praziquantel. The serum positive rate of schistosomiasis in the permanent residents dropped to below 1.0% after 2005. The fecal positive patients were not found in 2004 and later. Totally 189 639 people received the questionnaire survey for the knowledge of schistosomiasis control from 2001 to 2016. The rates of awareness and correct behavior of schistosomiasis were raised in the residents year by year. The goal of the transmission interruption of schistosomiasis came to true in Runzhou District, Zhenjiang City in 2016. The comprehensive prevention and control strategy including mainly the snail control, extended chemotherapy of schistosomiasis and health education could achieve the goal of transmission interruption of schistosomiasis in the areas of marshland along the Yangtze River.

Teaching mands for actions to children with autism spectrum disorder using systematic instruction, behavior chain interruption, and a speech-generating device

Objective: Evaluate the use of procedures to teach three nonvocal children with autism spectrum disorder to use a speech-generating device to mand for actions.Method: A multiple probe across participants design was used to evaluate the effectiveness systematic instruction and the use of a behavior chain interruption.Results: All three participants acquired the target mand. However, generalization to an untrained item only occurred for one participant.Conclusion: Results suggest that mands for actions expressed with a speech-generating device can be taught to children with autism spectrum disorder using systematic instruction and behavior chain interruption strategies.

Teaching Mands to Children with Autism Spectrum Disorder Using Behavior Chain Interruption Strategies: a Systematic Review

We identified and analyzed studies that were aimed at teaching children with autism spectrum disorder (ASD) manding skills using behavior chain interruption strategies. A systematic search of databases, reference lists, and journals identified 15 studies that met the inclusion criteria. Included studies were then summarized in terms of (a) participant characteristics, (b) dependent variables, (c) type of behavior chain interruption strategies used, (d) prompting procedures, (e) communication modality, (f) research design, (g) results, and (h) certainty of evidence. The most commonly used type of behavior chain interruption strategy was the missing item format. All of the studies used systematic prompting and fading procedures, most commonly modeling and time delay. All of the included studies reported gains in targeted communication skills. Results suggest that behavior chain interruption strategies can be effective for teaching manding skills to individuals with ASD. Implications for practitioners and suggestions for future research are discussed.