Magneto: A Step-Wise Approach to Exploit Vulnerabilities in Dependent Libraries via LLM-Empowered Directed Fuzzing

Introduction: Expert guidelines recommend a stepwise approach (lifestyle modification followed by addition of metformin in those not meeting goals) in high-risk people to delay progression to diabetes. However, there is scant evidence on the cost-effectiveness of implementing stepwise diabetes prevention. We estimated the 3-year within trial cost-effectiveness of a stepwise diabetes prevention approach in the Diabetes Community Lifestyle Improvement Program (D-CLIP) study in Chennai, India. Hypothesis: We assessed the cost-effectiveness of a stepwise diabetes prevention approach in India. Methods: The D-CLIP study was a randomized, controlled, translation trial in 578 overweight/obese Asian Indian adults with isolated impaired glucose tolerance (IGT) and/or isolated impaired fasting glucose (IFG), comparing a 6-month lifestyle modification curriculum and stepwise addition of metformin vs. standard lifestyle advice. We assessed direct medical costs including costs to deliver the intervention, general health care utilization, and direct non-medical costs. We also calculated costs for screening which included identifying and recruiting eligible individuals with IGT and/or IFG. Health effects were measured as absolute reductions in cumulative diabetes risk and in quality adjusted life years (QALYs) gained. Generalized linear regressions models adjusted for age, sex and baseline levels were fitted to estimate incremental costs and health effects. Bootstrapping was applied to describe the uncertainty around incremental cost-effectiveness ratios (ICER). Results: Over 3 years, the intervention resulted in incremental direct medical costs of 211 USD; incremental direct non-medical costs of 34 USD, an absolute diabetes risk reduction of 10.2%, and incremental QALYs gained of 0.098 per person. The absolute diabetes risk reduction in people with IFG was 6.4%, with IGT was 9% and with both IFG and IGT was 8.1%. ICERs from a multi-payer perspective (including the screening costs) averaged 4,275 USD per diabetes case prevented/delayed. That figure was 5,220 USD in people with IFG, 2,627 USD with IGT and 3,312 USD with both IFG and IGT. ICERs from a multi-payer perspective (including the screening costs) averaged 4,472 USD per QALY gained. That figure was 4,589 USD in people with IFG, 4,270 USD with IGT and 4,335 USD with both IFG and IGT. ICERs from a societal perspective were slightly higher. In the sensitivity analysis, with the scenario of a 50% increase/decrease in screening and intervention costs, from a multi-payer perspective, the average of ICERs varied 1,907 to 6,420 USD per diabetes case prevented, from 1,995 to 6,715 USD per QALY gained. Conclusions: In conclusion, a stepwise approach for diabetes prevention is likely to be cost-effective over a three-year time horizon.

A stepwise multidisciplinary approach to determine the date and provenance of historical wooden objects

A new era of atrial fibrillation (AF) treatment began in 1997–1998 with the discovery that triggers within the pulmonary veins initiate AF and reports that elimination of these triggers is successful in treating AF in its paroxysmal form.1–3 However, in patients with persistent AF, the success rate of exclusive pulmonary vein isolation is substantially lower.4,5 To improve the outcome of persistent AF ablation, different ablation strategies have been explored, but to date the optimal strategy has not been defined. Although some groups argue that limited ablation, including pulmonary vein isolation and, if present, ablation of nonpulmonary vein triggers, is sufficient for persistent AF ablation, other groups, including ours, favor more extensive, substrate-based ablation in addition to pulmonary vein isolation. In this review, we will discuss the rationale for a substrate-based ablation strategy to treat persistent AF and show why elimination of triggers is not sufficient in most patients with persistent AF. Response by Roten et al on p 1232 In a simple model, an electric impulse in AF can form because of abnormalities in impulse generation (triggers) or can result from abnormal impulse propagation (reentry). By a strict definition, a trigger is a focal source of new impulse generation. The mechanism by which a new impulse can form is either abnormal automaticity or triggered activity. Trigger-ablation protocols target these sources of new impulse generation. Abnormal impulse propagation, on the other hand, depends on altered substrate properties causing nonuniform or slowed conduction. This in turn causes multiple forms of wave reentry thought to be responsible for AF perpetuation: random reentry (multiple wavelets), macro- and microreentry, or functional reentry (rotors). Substrate-based ablation strategies aim to abate abnormal impulse propagation and interrupt any form of atrial reentry. Triggers of paroxysmal AF are mainly located in the pulmonary …

Purpose:This work describes a stepwise surgical approach to draining choroidal detachments and 2 cases for which this approach was used.Methods:The first step involves insertion of an anterior chamber maintainer and a nonvalved 23- or 25-gauge trocar cannula at the highest peak of hemorrhagic choroidal detachment (as determined using B-scan ultrasonography), 6 to 8 mm from and angled 20° to 30° toward the limbus. The second step involves removal of the trocar to expose the sclerotomy. Alternatively, the second step can be insertion of a second trocar. The third step involves the creation of a small focal peritomy around the preexisting sclerotomy and enlargement of the preexisting sclerotomy into a radial sclerotomy. Progression between steps only occurs if prior steps did not provide adequate drainage.Results:Two cases of appositional hemorrhagic choroidal detachments in hypotonic eyes were successfully resolved by this stepwise approach. In case 1, a choroidal detachment developed after a corneal ulcer perforation. The hemorrhagic choroidal detachment in case 1 was resolved with steps 1 and 2, and an unnecessary scleral cutdown was avoided. In case 2, a choroidal detachment developed after a trabeculectomy. The detachment in case 2 required progression to step 3, extension of the trocar insertion site into a radial sclerotomy.Conclusions:This stepwise approach should be considered to reduce excessive manipulation of the globe and conjunctiva in hemorrhagic and serous choroidal detachments that warrant surgical intervention.

Acute chest pain—a stepwise approach, the challenge of the correct clinical diagnosis

Current delivery tools were not designed for left bundle branch area pacing (LBBAP). Challenges using these tools include lack of reach into the right ventricle and poor support for the lead to penetrate the interventricular septum. Concerns using stylet-driven leads (SDL) for LBBAP have been previously highlighted. Knowledge and the technical know-how of using SDL for LBBAP need to be evaluated in a fair and consistent manner. A stepwise approach is devised for use of Agilis HisProTM steerable catheter with Tendril STS Model 2088TC lead for LBBAP and evaluated for safety and reproducibility. Consecutive patients undergoing LBBAP using the stepwise approach with Agilis HisProTM steerable catheter were analyzed. The safety, efficacy and reproducibility of the technique were evaluated. The lead parameters were analyzed in the immediate (1 day) and short-term period (3-6 months) post implantation. LBBAP was attempted in 41 patients using the stepwise approach of which 37 (90.7%) were successful. The lead parameters were stable in the immediate and short-term post implantation in all our patients. There was no significant difference between the group of patients with multiple repositioning of the lead compared to those successful at the 1st attempt. There were no acute or short-term lead and procedural complications. A stepwise and systematic approach using the Agilis HisProTM steerable catheter and proper handling of the Tendril STS Model 2088TC stylet-driven lead is an important part of the armamentarium to deliver LBBAP in a practical, effective and reproducible manner.

A Stepwise Approach to Locating the Antrum During Gastric Ultrasound

Considering the lack of evidence, we evaluated the impact on cardiovascular outcome of the systematic introduction in our institution of a personalized strike early and strong (SES) approach for lipid-lowering therapy (LLT) in patients admitted for acute myocardial infarction (MI). We retrospectively analysed data from 500 consecutive patients hospitalized across three periods: Period A (N=198, January-June 2019), when the low-density lipoprotein cholesterol (LDL-C) goal was <70mg/dL and a stepwise LLT approach was recommended; Period B (N=180, January-June 2021), when the LDL-C goal was <55mg/dL and a stepwise approach was recommended; Period C (N=122, January-June 2023), when the LDL-C goal was <55mg/dL and our SES protocol was implemented. Primary endpoints were achievement of the LDL-C goal during follow-up and 1-year incidence of major adverse cardiovascular events (MACE). Compared to the other periods, in Period C, there was a higher use of potent statins, alone or in combination with ezetimibe, and of proprotein convertase subtilisin/kexin type 9 inhibitor inhibitors at discharge. This translated into higher achievement of the LDL-C goal (83%vs. 55% in Period A and 43% in Period B; P<0.001) and reduced incidence of MACE (3%vs. 12% and 11%; P=0.026). MACE rates were lowest in patients with early and sustained LDL-C <55mg/dL and in those achieving both LDL-C <55mg/dL and≥50% LDL-C reduction. The systematic introduction of a personalized, SES strategy for LLT in patients with acute MI led to greater achievement of LDL-C goal and lower risk of MACE at 1 year vs. the stepwise approach.

The intramural site of origin is a major cause of ablation failure of ventricular arrhythmias, and the optimal strategy is unclear. This study investigated the efficacy of a stepwise ablation approach for intramural outflow tract (OT) premature ventricular complexes (PVCs) guided by mapping of the septal coronary venous system. Consecutive patients with OT PVCs were included, in whom an intramural origin was confirmed by demonstration of earliest activation in a septal coronary vein. Radiofrequency ablation was performed from the closest endocardial site in the left ventricular OT or right ventricular OT independent of the local activation time. If there was no suppression by endocardial ablation, then retrograde transvenous ethanol infusion with a single- or double-balloon technique was performed, targeting the earliest septal coronary vein. If venous anatomy was not suitable for ethanol ablation or if this failed, then bipolar ablation was performed. Sixty patients (age 61±12 years; 78% men) were included. The mean QRS duration of the PVC was 150.8±17.6 ms with a maximum deflection index of 0.51±0.11, and the most common ECG pattern was a left bundle branch block with inferior axis and V3 transition (63%), followed by a right bundle branch block with inferior axis and no transition (27%). Earliest ventricular activation (28.6±11.2 ms before QRS) was recorded in the left ventricular annular vein in 15 cases and a septal perforator vein in 45 cases. Acute PVC suppression at the end of the procedure was achieved in all cases. In 87% of cases (n=52), endocardial ablation from the endocardial left ventricular OT, right ventricular OT, or both was successful in eliminating the PVC. In the remaining 8 patients, the PVC was eliminated with ethanol infusion (n=7) and bipolar ablation (n=1). Complications included one case of pericardial effusion related to venous mapping. During follow-up (17±24 months), the PVC burden was reduced from 28±12% to 2.3±4.7%, and long-term success (≥80% burden reduction) was 88%. Most intramural OT PVCs can be successfully eliminated with endocardial ablation adjacent to the earliest intramural activation site. A high success rate is achieved when following a stepwise approach, with bailout ablation strategies required in a minority of cases.

Traditionally, three ports are used in laparoscopic appendicectomy. However to reduce surgical incision and cost, it is feasible to remove the appendix using fewer ports. In this study, we compared the efficacy of stepwise and standard approach in laparoscopic appendicectomies in children. Between August 2008 and September 2010, 378 children with appendicitis were allotted to either the stepwise or standard laparoscopy group depending on the operating surgeon's preference. In the former group, an operating telescope was inserted first. The number of ports used was based on the pathology (stepwise approach). In the latter group, three ports were inserted in all patients (standard approach). The two groups were similar. In the stepwise group, we performed 95 single port (utilising a scope with an instrument channel), 37 two ports and 13 three ports appendicectomies. In the stepwise group, operating time was shorter (not yet statistically significant) and it reduced the port numbers by more than 50%. The stepwise approach provides an evidence-based management of appendicitis with comparable outcomes. This procedure further reduces incision trauma, operating times and the cost of operation. However, the reduction of post-operative analgesic requirement needs further study.

A stepwise approach towards diagnostic workup in dementia using online cognitive tools

A 25-week gestation infant experienced chest infection complicated by septic shock and tension pneumothorax. Despite multiple drains, it was impossible to reinflate the lung, thus suggesting a bronchopleural fistula. Multidisciplinary...

None.

A stepwise approach for right anterior minithoracotomy aortic valve replacement (RAT-AVR), without sutureless valves, special instruments, or preoperative imaging, was developed. We report our experience with this widely applicable, simplified approach. Patients with a history of previous chest surgery, documented PVD, severe COPD, LVOT size <2.0 cm, and root size <2.8 cm were excluded. Chest CT was not mandatory. The stepwise surgical approach consists of 1) tolerability of single-lung ventilation; 2) 5-cm long incision on third right anterior ICS; 3) small pericardial opening to localize the aortic valve annular plane by digital palpation; 4) shingling of the correct rib to create a box field; 5) optimizing exposure with stay sutures; 6) femoral or central cannulation with right superior pulmonary vein venting and usual antegrade cardioplegia; 7) performing a standard AVR without adjunct instruments; and 8) reconstructing 1 costochondral cartilage. Fifty-five patients were operated. The mean age was 68.5 years (SD 10.4); 29.1% were female. Median STS PROM was 1.18 (0.4 to 6.6). Pump and cross-clamp times were 104.8 minutes (SD 27.9) and 73.2 minutes (SD 22.8), respectively. There was no need for a knot pusher. There was 1 conversion, 1 reopening for bleeding, and 1 pacemaker insertion. No patient had a stroke, MI, or death at 30 days. The median LOS was 6 days (3 to 19). RAT-AVR can be applicable and performed safely in a wide range of patients by adopting a simple, stepwise approach with intraoperative assessment, without the need for special imaging, instrumentation, or advanced training.

This paper explores a stepwise learning approach based on a system’s decomposition into functional subsystems. Two case studies are examined: a visually guided robot that learns to track a maneuvering object, and a robot that learns to use the information from a force sensor in order to put a peg into a hole. These two applications show the features and advantages of the proposed approach: i) the subsystems naturally arise as functional components of the hardware and software; ii) these subsystems are building blocks of the robot behavior and can be combined in several ways for performing various tasks; iii) this decomposition makes it easier to check the performances and detect the cause of a malfunction; iv) only those subsystems for which a satisfactory solution is not available need to be learned; v) the strategy proposed for coordinating the optimization of all subsystems ensures an improvement at the task-level; vi) the overall system’s behavior is significantly improved by the stepwise learning approach.