This paper deals with a new flexible job-shop scheduling problem in which the objective function to be minimised is the sum of the earliness and tardiness costs of the jobs and the costs of the ...operations required to perform the jobs, the latter depending on the machine and the time interval in which they are performed (as happens in many countries with the costs of electric power or those of manpower). We formalise the problem with a mathematical model and we propose a heuristic procedure that is based primarily on constructing a multistage graph and finding in it the shortest path from the source to the sink. We also describe the generation of the data-set used in an extensive computational experiment and expose and analyse the obtained results.
Purpose of the review
Intracranial atherosclerotic disease is a complex stroke etiology with numerous challenges in its management. We present an update on the latest therapeutic research on this ...disease and the potential role of surgical interventions.
Recent findings
Despite improvements in medical therapy, intracranial atherosclerosis presents one of the highest stroke recurrences even with the best contemporary medical management. Interventions such as direct bypass, angioplasty, and stenting have failed to demonstrate superiority to medical management in well-conducted randomized clinical trials. New avenues of research are focusing on alternative interventions such as submaximal angioplasty and indirect bypass.
Summary
Patients with intracranial atherosclerosis should undergo intensive medical management. Angioplasty and stenting should be avoided in this population outside of well-designed clinical trials. Surgical strategies are promising but have not been tested in pivotal studies. There is an urgent need for randomized controlled clinical trials to evaluate surgical interventions like indirect bypass in patients with intracranial atherosclerosis. There is a need for early and intermediate development clinical trials for other interventions such as angioplasty without stenting or new stenting techniques.
BackgroundEndovascular reperfusion techniques are a promising intervention for acute ischemic stroke (AIS). Prior studies have identified markers of initial injury (arrival NIH stroke scale (NIHSS) ...or infarct volume) as predictive of outcome after these procedures. We sought to define the role of collateral flow at the time of presentation in determining the extent of initial ischemic injury and its influence on final outcome.MethodsDemographic, clinical, laboratory, and radiographic data were prospectively collected on a consecutive cohort of patients who received endovascular therapy for acute cerebral ischemia at a single tertiary referral center from September 2004 to August 2010.ResultsHigher collateral grade as assessed by the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) grading scheme on angiography at the time of presentation was associated with improved reperfusion rates after endovascular intervention, decreased post-procedural hemorrhage, smaller infarcts on presentation and discharge, as well as improved neurological function on arrival to the hospital, discharge, and 90 days later. Patients matched by vessel occlusion, age, and time of onset demonstrated smaller strokes on presentation and better functional and radiographic outcome if found to have superior collateral flow. In multivariate analysis, lower collateral grade independently predicted higher NIHSS on arrival.ConclusionsImproved collateral flow in patients with AIS undergoing endovascular therapy was associated with improved radiographic and clinical outcomes. Independent of age, vessel occlusion and time, in patients with comparable ischemic burdens, changes in collateral grade alone led to significant differences in initial stroke severity as well as ultimate clinical outcome.
Purpose
Lingual thyroid glands are rare embryologic variants of undescended tissue centered in the base of the tongue. Despite notable size, many lingual thyroids can be asymptomatic, though ...intervention is warranted for progressive or emergent symptoms. We report a rare manifestation of a hemorrhagic lingual thyroid addressed with both interventional radiology and robotic techniques.
Methods
A previously asymptomatic 41-year old female presented to the emergency department with massive hematemesis after significant binge drinking and vomiting. Emergent intubation was performed and gastroenterology workup ruled out Mallory–Weiss tears or ruptured esophageal varices. Fiberoptic laryngoscopy and imaging revealed a bleeding tongue base mass concerning for malignancy.
Results
Aberrant feeding vessels with identifiable blush were embolized by Neurointerventional Radiology and the patient underwent tracheostomy for airway protection. Lingual thyroid was confirmed by biopsy and the mass was definitively resected via transoral robotic surgery. The patient had no further bleeding events and was decannulated uneventfully.
Conclusions
Lingual thyroid glands can present with life-threatening hematemesis and obstruction that may masquerade as entities of vascular or neoplastic origin. Management encompasses multidisciplinary diagnostic confirmation, airway protection, and minimally invasive resection that minimizes functional morbidity.
Background
Intracranial atherosclerotic disease (ICAD) is one of the most challenging stroke etiologies, with frequent recurrences despite optimized medical management. ...Encephaloduroarteriosynangiosis (EDAS) is an indirect revascularization method that produces extra-cranial collaterals to intracranial vessels. We present the results of a phase-II trial of EDAS in intracranial atherosclerotic disease patients.
Aims
To evaluate the feasibility, safety, and preliminary efficacy of EDAS in intracranial atherosclerotic disease patients.
Methods
ERSIAS was a prospective objective-performance-criterion trial of EDAS plus intensive medical management (IMM) in intracranial atherosclerotic disease (ICAD) patients failing medical treatment. Primary endpoint was any stroke/death within 30-days post-surgery or stroke in the territory of the qualifying artery beyond 30 days. The primary analysis compared event rates through one year with an objective-performance-criterion based on a 10% reduction from the 20% rate in the intensive medical management arm of the stenting versus aggressive medical management for preventing recurrent stroke in intracranial stenosis trial (SAMMPRIS) in patients with poor collaterals. Event rates through two years were compared with propensity-score-matched (PSM) medically treated patients from SAMMPRIS and the carotid occlusion surgery study (COSS).
Results
During a median follow-up of 24.5 months, 5 (9.6%) of 52 patients had a primary endpoint event. The primary endpoint rate at one year met the threshold for nonfutility and advancement to phase III (<10%). In the sensitivity analysis, primary endpoint event rate at two years was lower than in PSM controls, 9.6% versus 21.2% (p < 0.07). Overall, 86% of EDAS-plus-intensive medical management patients were functionally independent at last follow-up and 89% demonstrated neovascularization. There were two (3.8%) surgical complications and no intracranial hemorrhages.
Conclusion
ERSIAS phase II provides evidence of safety and strong signals of efficacy of EDAS-plus-intensive medical management, supporting advancement to a seamless phase-IIb/III trial.
Clinical Trial Registration
URL: https://www.clinicaltrials.gov.NCT01819597.
We analyzed the impact of detailed anatomic characteristics on the results of endovascular coil embolization for anterior communicating artery (AcoA) aneurysms and developed a predictive model ...estimating the probability of successful endovascular treatment.
One hundred eighty-one AcoA aneurysms were treated with endovascular coil embolization between August 1991 and November 2005. Morphological characteristics that were analyzed included direction of the dome, location of the neck, association with hypoplasia or aplasia of AcoA complex vessels, sac, and neck size. Immediate clinical and anatomic results, long-term morbidity/mortality, recanalization rate, and delayed aneurysm thrombosis were analyzed. ORs were calculated for each anatomic and clinical result and logistic regression was used in formulating a predictive model.
There were 115 females and 66 males. Age range was 9 to 86 years (mean 57). Factors significantly associated with complete embolization included small aneurysms (<10 mm), small neck (<4 mm), and anterior dome orientation. Factors significantly associated with aneurysm recanalization after long-term follow-up included aneurysm domes >10 mm, neck location on the AcoA, posterior dome orientation, and incomplete original embolization. Globally, the majority of patients remained neurologically intact or unchanged after the procedure (92.8%). Mortality was significantly influenced by the preoperative condition of the patient. The predictive model successfully represented the likely outcomes based on morphological features.
AcoA aneurysm coil embolization can be safely performed with acceptable rates of morbidity. Dome and neck orientation, sack and neck size, sac-to-neck ratio, and associated anomalies should be considered to accurately assess the probability of successful treatment for AcoA aneurysms.
Background
The objective of this study is to characterize the relationship between ICP and EEG
Methods
Simultaneous ICP and EEG data were obtained from burst-suppressed patients and segmented by EEG ...bursts. Segments were categorized as increasing/decreasing and peak/valley to investigate relationship between ICP changes and EEG burst duration. A generalized ICP response was obtained by averaging all segments time-aligned at burst onsets. A vasodilatation index (VDI) was derived from the ICP pulse waveform and calculated on a sliding interval to investigate cerebrovascular changes post-burst.
Results
Data from two patients contained 309 bursts. 246 ICP segments initially increased, of which 154 peaked. 63 ICP segments decreased, and zero reached a valley. The change in ICP (0.54 ± 0.85 mmHg) was significantly correlated with the burst duration (
p
< 0.001). Characterization of the ICP segments showed a peak at 8.1 s and a return to baseline at 14.7 s. The VDI for increasing segments was significantly elevated (median 0.56, IQR 0.31,
p
< 0.001) and correlated with burst duration (
p
< 0.001).
Conclusions
Changes in the ICP and pulse waveform shape after EEG burst suggest that these signals can be related within the context of neurovascular coupling.
Significance
Existence of a physiological relationship between ICP and EEG may allow the study of neurovascular coupling in acute brain injury patients.
OBJECTIVE
To determine whether skeletal muscle‐derived stem cells (MDSCs) convert into smooth muscle cells (SMCs) both in vitro and in vivo, and in so doing ameliorate the erectile dysfunction (ED) ...of aged rats, and whether endogenous stem cells are present in the rat corpora cavernosa.
MATERIALS AND METHODS
MDSCs were obtained from mouse muscle, and shown by immunocytochemistry for α‐smooth muscle actin (αSMA) to originate in vitro in myofibroblasts and SMCs, discriminating SMCs by calponin 1 expression. In vivo these MDSCs, labelled with 4′,6‐diamidino‐2‐phenylindole, were implanted into the corpora cavernosa of young adult (5‐month old) and aged (20‐month old) rats for 2 and 4 weeks. Histological changes were assessed by immunohistochemistry and quantitative Western blot. Functional changes were determined by electrical field stimulation (EFS) of the cavernosal nerve.
RESULTS
The exogenous cells replicated and converted into SMCs, as shown in corporal tissue sections by confocal immunofluorescence microscopy for proliferating cell nuclear antigen (PCNA), αSMA, and smoothelin, and also by Western blot for αSMA and PCNA. MDSC differentiation was confirmed by the activation of the αSMA promoter‐linked β‐galactosidase in transfected cells, both in vitro and after implantation in the corpora. Putative endogenous stem cells were shown in corporal tissue sections and Western blots by detecting CD34 and a possible Sca1 variant. EFS showed that implanted MDSCs raised in aged rats the maximal intracavernosal pressure/mean arterial pressure levels above (2 weeks) or up to (4 weeks) those of young adult rats.
CONCLUSIONS
MDSCs implanted into the corpora cavernosa of aged rats converted into SMCs and corrected ED, and endogenous cells expressing stem cell markers were also found in untreated tissue. This suggests that exogenous stem cell implantation and/or endogenous stem cell modulation might be viable therapeutic approaches for ageing‐related ED.
Remote ischemic preconditioning (RIPC) is a form of endogenous neuroprotection induced by transient, subcritical ischemia in a distant tissue. RIPC effects on cerebral hemodynamics and metabolism ...have not been explored in humans. This study evaluates hemodynamic and metabolic changes induced by RIPC in patients with aneurysmal subarachnoid hemorrhage (SAH).
Patients underwent three or four RIPC sessions 2-12 days following SAH. Continuous vitals, intracranial pressure (ICP), and transcranial Doppler (TCD) data were collected. Brain microdialysis metabolic changes were monitored. ICP and TCD morphological clustering and analysis of intracranial pulse (MOCAIP) metrics were compared to positive and negative control groups for cerebral vasodilation.
Seven ICP and six TCD recordings from four patients demonstrated an increase in mean ICP (8-14.57 mmHg, p < 0.05). There was a reduction in middle cerebral artery (MCA) mean velocities (111-87 cm/s, p = 0.039). ICP and TCD MOCAIP metrics demonstrated variances consistent with vasodilation that returned to baseline following the RIPC. Over the duration of the RIPC, microdialysis showed reduction in the lactate/pyruvate (L/P) ratio (42.37-33.77, p = 0.005) and glycerol (174.04-126 μg/l, p < 0.005), which persisted for 25-54 h after the last RIPC.
This study demonstrated cerebrovascular effects induced by RIPC consistent with transient vasodilation. Cerebral metabolic effects suggest protection from ischemia and cell membrane preservation lasting up to 2 days following RIPC.
Remote ischemic conditioning (RIC) is a powerful innate response to transient subcritical ischemia that protects against severe ischemic insults at distant sites. We have previously shown the safety ...and feasibility of limb RIC in aneurysmal subarachnoid hemorrhage (aSAH) patients, along with changes in neurovascular and cerebral metabolism. In this study, we aim to detect the potential effect of an established lower-limb conditioning protocol on clinical outcomes of aSAH patients. Neurologic outcome (modified Rankin Scale (mRS)) of patients enrolled in a prospective trial (RIPC-SAH) was measured. A matching algorithm was applied to identify control patients with aSAH from an institutional departmental database. RIC patients underwent four lower-limb conditioning sessions, consisting of four 5-min cycles per session over nonconsecutive days. Good functional outcome was defined as mRS of 0 to 2. The study population consisted of 21 RIC patients and 61 matched controls. There was no significant intergroup difference in age, gender, aneurysm location, clipping vs coiling, Fisher grades, Hunt and Hess grades, or vasospasm. RIC was independently associated with good outcome (OR 5.17; 95 % confidence interval (CI) 1.21–25.02). RIC also showed a trend toward lower incidence of stroke (28.6 vs. 47.5 %) and death (4.8 vs. 19.7 %). Lower-limb RIC following aSAH appears to have a positive effect in the functional outcomes of patients with aSAH. While this effect is consistent with prior preclinical studies, future trials are necessary to conclusively evaluate the effects of RIC for aSAH.
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