•An accurate heuristic solution to the median ranking problem is proposed.•The reference paradigm is the Kemeny–Snell axiomatic framework.•Simulation studies and real data applications are performed ...to evaluate accuracy efficiency of our proposal.
Preference rankings virtually appear in all fields of science (political sciences, behavioral sciences, machine learning, decision making and so on). The well-known social choice problem consists in trying to find a reasonable procedure to use the aggregate preferences or rankings expressed by subjects to reach a collective decision. This turns out to be equivalent to estimate the consensus (central) ranking from data and it is known to be a NP-hard problem. A useful solution has been proposed by Emond and Mason in 2002 through the Branch-and-Bound algorithm (BB) within the Kemeny and Snell axiomatic framework. As a matter of fact, BB is a time demanding procedure when the complexity of the problem becomes untractable, i.e. a large number of objects, with weak and partial rankings, in presence of a low degree of consensus. As an alternative, we propose an accurate heuristic algorithm called FAST that finds at least one of the consensus ranking solutions found by BB saving a lot of computational time. In addition, we show that the building block of FAST is an algorithm called QUICK that finds already one of the BB solutions so that it can be fruitfully considered to speed up even more the overall searching procedure if the number of objects is low. Simulation studies and applications on real data allows to show the accuracy and the computational efficiency of our proposal.
Background: To investigate the effects of the COVID-19 lockdowns on the vasculopathic population. Methods: The Divisions of Vascular Surgery of the southern Italian peninsula joined this multicenter ...retrospective study. Each received a 13-point questionnaire investigating the hospitalization rate of vascular patients in the first 11 months of the COVID-19 pandemic and in the preceding 11 months. Results: 27 out of 29 Centers were enrolled. April-December 2020 (7092 patients) vs. 2019 (9161 patients): post-EVAR surveillance, hospitalization for Rutherford category 3 peripheral arterial disease, and asymptomatic carotid stenosis revascularization significantly decreased (1484 (16.2%) vs. 1014 (14.3%), p = 0.0009; 1401 (15.29%) vs. 959 (13.52%), p = 0.0006; and 1558 (17.01%) vs. 934 (13.17%), p < 0.0001, respectively), while admissions for revascularization or major amputations for chronic limb-threatening ischemia and urgent revascularization for symptomatic carotid stenosis significantly increased (1204 (16.98%) vs. 1245 (13.59%), p < 0.0001; 355 (5.01%) vs. 358 (3.91%), p = 0.0007; and 153 (2.16%) vs. 140 (1.53%), p = 0.0009, respectively). Conclusions: The suspension of elective procedures during the COVID-19 pandemic caused a significant reduction in post-EVAR surveillance, and in the hospitalization of asymptomatic carotid stenosis revascularization and Rutherford 3 peripheral arterial disease. Consequentially, we observed a significant increase in admissions for urgent revascularization for symptomatic carotid stenosis, as well as for revascularization or major amputations for chronic limb-threatening ischemia.
Objective/Background The Dutch Surgical Aneurysm Audit (DSAA) is mandatory for all patients with primary abdominal aortic aneurysms (AAAs) in the Netherlands. The aims are to present the observed ...outcomes of AAA surgery against the predicted outcomes by means of V-POSSUM (Vascular–Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity). Adjusted mortality was calculated by the original and re-estimated V(physiology)-POSSUM for hospital comparisons. Methods All patients operated on from January 2013 to December 2014 were included for analysis. Calibration and discrimination of V-POSSUM and V(p)-POSSUM was analysed. Mortality was benchmarked by means of the original V(p)-POSSUM formula and risk-adjusted by the re-estimated V(p)-POSSUM on the DSAA. Results In total, 5898 patients were included for analysis: 4579 with elective AAA (EAAA) and 1319 with acute abdominal aortic aneurysm (AAAA), acute symptomatic (SAAA; n = 371) or ruptured (RAAA; n = 948). The percentage of endovascular aneurysm repair (EVAR) varied between hospitals but showed no relation to hospital volume (EAAA: p = .12; AAAA: p = .07). EAAA, SAAA, and RAAA mortality was, respectively, 1.9%, 7.5%, and 28.7%. Elective mortality was 0.9% after EVAR and 5.0% after open surgical repair versus 15.6% and 27.4%, respectively, after AAAA. V-POSSUM overestimated mortality in most EAAA risk groups ( p < .01). The discriminative ability of V-POSSUM in EAAA was moderate (C-statistic: .719) and poor for V(p)-POSSUM (C-statistic: .665). V-POSSUM in AAAA repair overestimated in high risk groups, and underestimated in low risk groups ( p < .01). The discriminative ability in AAAA of V-POSSUM was moderate (.713) and of V(p)-POSSUM poor (.688). Risk adjustment by the re-estimated V(p)-POSSUM did not have any effect on hospital variation in EAAA but did in AAAA. Conclusion Mortality in the DSAA was in line with the literature but is not discriminative for hospital comparisons in EAAA. Adjusting for V(p)-POSSUM, revealed no association between hospital volume and treatment or outcome. Risk adjustment for case mix by V(p)-POSSUM in patients with AAAA has been shown to be important.
Precursors of osteoclasts seeded on top of a confluent layer of osteoblasts/bone lining cells induced retraction of the latter cells. The (pre)osteoclasts then migrated in the formed cell‐free areas ...and fused to form osteoclast‐like cells. Retraction of the osteoblasts/bone lining cells proved to depend on activity of matrix metalloproteinases, and TGF‐β1 prevented the retraction.
Introduction: It is well known that osteoblasts have a profound effect on (pre)osteoclasts in inducing the formation of bone‐resorbing osteoclasts. Whether, on the other hand, (pre)osteoclasts also modulate osteoblast activity is largely unknown. Because osteoblasts/bone lining cells have to retract from the surface before resorption of bone by osteoclasts, we addressed the question of whether (pre)osteoclasts have the capacity to induce such an activity.
Materials and Methods: Rabbit calvarial osteoblasts/bone lining cells or periosteal fibroblasts were cultured until confluency, after which rabbit peripheral blood mononuclear cells (PBMCs) were seeded on top of them. The co‐cultures were maintained for up to 15 days in the presence or absence of the cytokines transforming growth factor (TGF)‐β1 and TNF‐α and selective inhibitors of matrix metalloproteinases and serine proteinases. The formation of cell‐free areas and the number of TRACP+ multinucleated osteoclast‐like cells were analyzed. In addition, formation of cell‐free areas was analyzed in co‐cultures of osteoblasts with mature osteoclasts.
Results: The seeding of PBMCs on a confluent layer of osteoblasts/bone lining cells resulted in the following sequence of events. (1) A low number of PBMCs strongly attached to osteoblasts. 2) At these sites of contact, the osteoblasts retracted, thus forming cell‐free areas. (3) The PBMCs invaded these areas and attached to the surface of the well, after which they fused and formed multinucleated TRACP+ osteoclast‐like cells. Retraction was only seen if the cells were in direct contact; conditioned media from cultured PBMCs added to osteoblasts had no effect. Mature osteoclasts seeded on osteoblasts similarly induced retraction, but this retraction occurred at a much faster rate (within 2 days) than the retraction effectuated by the osteoclast precursors (after 8 days in co‐culture). Inhibition of matrix metalloproteinase activity, but not of serine proteinases, strongly reduced retraction of the osteoblasts, thus indicating that this type of cell movement depends on the activity of matrix metalloproteinases. A similar inhibitory effect was found with TGF‐β1. TNF‐α had no effect on osteoblast retraction but enhanced the formation of multinucleated osteoclast‐like cells. Addition of PBMCs to confluent layers of periosteal fibroblasts resulted in similar phenomena as observed in co‐cultures with osteoblasts. However, the cell‐free areas proved to be significantly smaller, and the number of multinucleated cells formed within cell‐free areas was three to four times lower.
Conclusion: Our results indicate that osteoclast precursors and mature osteoclasts have the capacity to modulate the activity of osteoblasts and that, yet unknown, membrane‐bound signaling molecules are essential in inducing retraction of osteoblasts and the subsequent formation of cell‐free areas.
Dutch national guidelines on the diagnosis and treatment of gastric cancer recommend the use of perioperative chemotherapy in patients with resectable gastric cancer. However, adjuvant chemotherapy ...is often not administered. The aim of this study was to evaluate hospital variation on the probability to receive adjuvant chemotherapy and to identify associated factors with special attention to postoperative complications.
All patients who received neoadjuvant chemotherapy and underwent an elective surgical resection for stage IB-IVa (M0) gastric adenocarcinoma between 2011 and 2015 were identified from a national database (Dutch Upper GI Cancer Audit). A multivariable linear mixed model was used to evaluate case-mix adjusted hospital variation and to identify factors associated with adjuvant therapy.
Of all surgically treated gastric cancer patients who received neoadjuvant chemotherapy (n = 882), 68% received adjuvant chemo(radio)therapy. After adjusting for case-mix and random variation, a large hospital variation in the administration rates for adjuvant was observed (OR range 0.31–7.1). In multivariable analysis, weight loss, a poor health status and failure of neoadjuvant chemotherapy completion were strongly associated with an increased likelihood of adjuvant therapy omission. Patients with severe postoperative complications had a threefold increased likelihood of adjuvant therapy omission (OR 3.07 95% CI 2.04–4.65).
Despite national guidelines, considerable hospital variation was observed in the probability of receiving adjuvant chemo(radio)therapy. Postoperative complications were strongly associated with adjuvant chemo(radio)therapy omission, underlining the need to further reduce perioperative morbidity in gastric cancer surgery.
Abstract
Background
Increased use of endovascular aneurysm repair (EVAR) and reduced open surgical repair (OSR), has decreased postoperative mortality after elective repair of abdominal aortic ...aneurysms (AAAs). The choice between EVAR or OSR depends on aneurysm anatomy, and the experience and preference of the vascular surgeon, and therefore differs between hospitals. The aim of this study was to investigate the current mortality risk difference (RD) between EVAR and OSR, and the effect of hospital preference for EVAR on overall mortality.
Methods
Primary elective infrarenal or juxtarenal aneurysm repairs registered in the Dutch Surgical Aneurysm Audit (2013–2017) were analysed. First, mortality in hospitals with a higher preference for EVAR (high-EVAR group) was compared with that in hospitals with a lower EVAR preference (low-EVAR group), divided by the median percentage of EVAR. Second, the mortality RD between EVAR and OSR was determined by unadjusted and adjusted linear regression and propensity-score (PS) analysis and then by instrumental-variable (IV) analysis, adjusting for unobserved confounders; percentage EVAR by hospital was used as the IV.
Results
A total of 11 997 patients were included. The median hospital rate of EVAR was 76.6 per cent. The overall mortality RD between high- and low-EVAR hospitals was 0.1 (95 per cent −0.5 to 0.4) per cent. The OSR mortality rate was significantly higher among high-EVAR hospitals than low-EVAR hospitals: 7.3 versus 4.0 per cent (RD 3.3 (1.4 to 5.3) per cent). The EVAR mortality rate was also higher in high-EVAR hospitals: 0.9 versus 0.7 per cent (RD 0.2 (−0.0 to 0.6) per cent). The RD following unadjusted, adjusted, and PS analysis was 4.2 (3.7 to 4.8), 4.4 (3.8 to 5.0), and 4.7 (4.1 to 5.3) per cent in favour of EVAR over OSR. However, the RD after IV analysis was not significant: 1.3 (−0.9 to 3.6) per cent.
Conclusion
Even though EVAR has a lower mortality rate than OSR, the overall effect is offset by the high mortality rate after OSR in hospitals with a strong focus on EVAR.
Abstract The aim of this study was to evaluate the suitability of tissue-engineered mucosa (TEM) as a model for studying the acute effects of ionizing radiation (IR) on the oral mucosa. TEM and ...native non-keratinizing oral mucosa (NNOM) were exposed to a single dose of 16.5 Gy and harvested at 1, 6, 24, 48, and 72 h post-irradiation. DNA damage induced by IR was determined using p53 binding protein 1 (53BP1), and DNA repair was determined using Rad51. Various components of the epithelial layer, basement membrane, and underlying connective tissue were analyzed using immunohistochemistry. The expression of cytokines interleukin-1β (IL-1β) and transforming growth factor beta 1 (TGF-β1) was analyzed using an enzyme-linked immunosorbent assay. The expression of DNA damage protein 53BP1 and repair protein Rad51 were increased post-irradiation. The expression of keratin 19, vimentin, collage type IV, desmoglein 3, and integrins α6 and β4 was altered post-irradiation. Proliferation significantly decreased at 24, 48, and 72 h post-irradiation in both NNOM and TEM. IR increased the secretion of IL-1β, whereas TGF-β1 secretion was not altered. All observed IR-induced alterations in TEM were also observed in NNOM. Based on the similar response of TEM and NNOM to IR we consider our TEM construct a suitable model to quantify the acute biological effects of IR.
Bone resorption by osteoclasts depends on the activity of various proteolytic enzymes, in particular those belonging to the group of cysteine proteinases. Next to these enzymes, tartrate-resistant ...acid phosphatase (TRAP) is considered to participate in this process. TRAP is synthesized as an inactive proenzyme, and in vitro studies have shown its activation by cysteine proteinases. In the present study, the possible involvement of the latter enzyme class in the in vivo modulation of TRAP was investigated using mice deficient for cathepsin K and/or L and in bones that express a high (long bone) or low (calvaria) level of cysteine proteinase activity. The results demonstrated, in mice lacking cathepsin K but not in those deficient for cathepsin L, significantly higher levels of TRAP activity in long bone. This higher activity was due to a higher number of osteoclasts. Next, we found considerable differences in TRAP activity between calvarial and long bones. Calvarial bones contained a 25-fold higher level of activity than long bones. This difference was seen in all mice, irrespective of genotype. Osteoclasts isolated from the two types of bone revealed that calvarial osteoclasts expressed higher enzyme activity as well as a higher level of mRNA for the enzyme. Analysis of TRAP-deficient mice revealed higher levels of nondigested bone matrix components in and around calvarial osteoclasts than in long bone osteoclasts. Finally, inhibition of cysteine proteinase activity by specific inhibitors resulted in increased TRAP activity. Our data suggest that neither cathepsin K nor L is essential in activating TRAP. The findings also point to functional differences between osteoclasts from different bone sites in terms of participation of TRAP in degradation of bone matrix. We propose that the higher level of TRAP activity in calvarial osteoclasts compared to that in long bone cells may partially compensate for the lower cysteine proteinase activity found in calvarial osteoclasts and TRAP may contribute to the degradation of noncollagenous proteins during the digestion of this type of bone.
A census of 83 Infralittoral Prograding Wedges (IPWs) was carried out in the Central-Eastern Tyrrhenian Sea, to learn more about their morpho-bathymetric variability and test their reliability as ...environmental indicators of current sea level. With this aim, a database recording for each wedge the main morphometric indices, the effective fetch and the significant height of the storm waves– here used as proxies for sea state forcing to which they are exposed- and the ground elevation in the backshore - here used as a numerical descriptor of coastal morphology and energy of the relief- was realized (Campania Region IPWs Database).
The statistical analysis on the entire IPWs dataset explored the relationship between the environmental and morphometric variables while the Principal Component Analysis grouped the variables into two clusters, governed by sea state forcing and energy of relief in the backshore, respectively. The multi-regression analysis highlighted a significant correlation of IPWs depth with effective fetch and extreme significant wave height and a moderate correlation with the ground elevation in the backshore. The outcomes that emerged from the observational law on present-day IPWs were then applied to relict IPWs, currently lying on the continental shelf and at the shelf margin, with the aim of establishing their original depth of formation. This procedure aims to solve the non-trivial issue, namely that concerning the reliability of paleo-IPWs as proxies for past sea levels. Thus, a simplified equation based only on the use of geographical variables is proposed here to roughly establish the original depth (with errors of few metres) of paleo-IPWs, whose geographical exposure is known and the effective fetch computable. Although the applicability of this method suffers from spatial and temporal restrictions, due to the girth of the original dataset, it provides a first analytical procedure for gauging the original depth of formation of paleo-IPWs which, over the last decade, have been increasingly used as environmental indicators of past sea levels. This study highlights the relationship between the depth of these sedimentary coastal bodies and sea storm wave climate at a regional scale and provides clues for the use of their past counterparts as morphological proxies of past sea level stands. Further developments of this study would use a wider dataset so as to extend the observational law on present-day IPWs to a Mediterranean scale and strengthen the applicability of the method to a spatially broader set of paleo-IPWs.
•Morpho-bathymetric variability of present-day IPWs in the Central-Eastern Tyrrhenian Sea.•Observational law between rollover point depth versus sea storm waves at a regional scale.•Multiregression analysis among morphometric indices of IPWs, storm waves climate, and backshore height.•Numerical model to derive the original formation depth of paleo-IPWs in the Tyrrhenian Sea, based on observational laws.•Clues to the use of paleo-IPWs as proxies of paleo-sea levels.
PDF
