Multi-criteria analysis in transport project evaluation: an institutional approach

We demonstrate that multi-criteria analysis (MCA), though initially developed in the operations research field, can be usefully applied within the context of the stakeholder-driven or institutional approach to transport project evaluation. We first compare the features of the institutional and neoclassical approaches to economic evaluation. We then identify a number of conditions to be fulfilled for the institutional approach to result in a social optimum that is neutral from a distributional perspective. Such an optimum may not have been intentionally pursued, but may eventually arise as a by-product of the actions of self-interested, individual stakeholder groups. We illustrate the relevance of our approach through a number of recent case studies. Policy makers can use our findings as an input for designing formal decision-making processes, geared towards including stakeholder objectives in transport project evaluation

Sentinel-1 detects firn aquifers in the Greenland ice sheet

Firn aquifers in Greenland store liquid water within the upper ice sheet and impact the hydrological system. Their location and area have been estimated with airborne radar sounder surveys (Operation IceBridge, OIB). However, the OIB coverage is limited to narrow flight lines, offering an incomplete view. Here, we show the ability of satellite radar measurements from Sentinel-1 to map firn aquifers across all of Greenland at 1 km(2) resolution. The detection of aquifers relies on a delay in the freezing of meltwater within the firn above the water table, causing a distinctive pattern in the radar backscatter. The Sentinel-1 aquifer locations are in very good agreement with those detected along the OIB flight lines (Cohen's kappa = 0.84). The total aquifer area is estimated at 54,800 km(2). With continuity of Sentinel-1 ensured until 2030, our study lays a foundation for monitoring the future response of firn aquifers to climate change

A first-in-human, randomized, controlled, subject- and reviewer-blinded multicenter study of Actamax™ Adhesion Barrier

Purpose: Post-surgical adhesions remain a significant concern following abdominopelvic surgery. This study was to assess safety, manageability and explore preliminary efficacy of applying a degradable hydrogel adhesion barrier to areas of surgical trauma following gynecologic laparoscopic abdominopelvic surgery. Methods: This first-in-human, prospective, randomized, multicenter, subject- and reviewer-blinded clinical study was conducted in 78 premenopausal women (18–46 years) wishing to maintain fertility and undergoing gynecologic laparoscopic abdominopelvic surgery with planned clinically indicated second-look laparoscopy (SLL) at 4–12 weeks. The first two patients of each surgeon received hydrogel, up to 30 mL sprayed over all sites of surgical trauma, and were assessed for safety and application only (n = 12). Subsequent subjects (n = 66) were randomized 1:1 to receive either hydrogel (Treatment, n = 35) or not (Control, n = 31); 63 completed the SLL. Results: No adverse event was assessed as serious, or possibly device related. None was severe or fatal. Adverse events were reported for 17 treated subjects (17/47, 36.2%) and 13 Controls (13/31, 41.9%). For 95.7% of treated subjects, surgeons found the device “easy” or “very easy” to use; in 54.5%, some residual material was evident at SLL. For 63 randomized subjects who completed the SLL, adjusted between-group difference in the change from baseline adhesion score demonstrated a 41.4% reduction for Treatment compared with Controls (p = 0.017), with a 49.5% reduction (p = 0.008) among myomectomy subjects (n = 34). Conclusion: Spray application of a degradable hydrogel adhesion barrier during gynecologic laparoscopic abdominopelvic surgery was performed easily and safely, without evidence of clinically significant adverse outcomes. Data suggest the hydrogel was effective in reducing postoperative adhesion development, particularly following myomectomy

334phealth related quality of life in women with hr her2 advanced or metastatic breast cancer treated in real world settings in italy and germany

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Structure-activity relationship study of the plant-derived decapeptide OSIP108 inhibiting Candida albicans biofilm formation

We performed a structure-activity relationship study of the antibiofilm plant-derived decapeptide OSIP108. Introduction of positively charged amino acids R, H, and K resulted in an up-to-5-fold-increased antibiofilm activity against Candida albicans compared to native OSIP108, whereas replacement of R9 resulted in complete abolishment of its antibiofilm activity. By combining the most promising amino acid substitutions, we found that the double-substituted OSIP108 analogue Q6R/G7K had an 8-fold-increased antibiofilm activity

Stimulation of superoxide production increases fungicidal action of miconazole against Candida albicans biofilms

We performed a whole-transcriptome analysis of miconazole-treated Candida albicans biofilms, using RNA-sequencing. Our aim was to identify molecular pathways employed by biofilm cells of this pathogen to resist action of the commonly used antifungal miconazole. As expected, genes involved in sterol biosynthesis and genes encoding drug efflux pumps were highly induced in biofilm cells upon miconazole treatment. Other processes were affected as well, including the electron transport chain (ETC), of which eight components were transcriptionally downregulated. Within a diverse set of 17 inhibitors/inducers of the transcriptionally affected pathways, the ETC inhibitors acted most synergistically with miconazole against C. albicans biofilm cells. Synergy was not observed for planktonically growing C. albicans cultures or when biofilms were treated in oxygen-deprived conditions, pointing to a biofilm-specific oxygen-dependent tolerance mechanism. In line, a correlation between miconazole's fungicidal action against C. albicans biofilm cells and the levels of superoxide radicals was observed, and confirmed both genetically and pharmacologically using a triple superoxide dismutase mutant and a superoxide dismutase inhibitor N-N'-diethyldithiocarbamate, respectively. Consequently, ETC inhibitors that result in mitochondrial dysfunction and affect production of reactive oxygen species can increase miconazole's fungicidal activity against C. albicans biofilm cells

Apoptosis-inducing antifungal peptides and proteins

Abstract Despite the availability of various classes of antimycotics, the treatment of patients with systemic fungal infections is challenging. Therefore the development of new antifungals is urgently required. Promising new antifungal candidates are antimicrobial peptides. In the present review, we provide an overview of antifungal peptides isolated from plants, insects, amphibians and mammals that induce apoptosis. Their antifungal spectrum, mode of action and toxicity are discussed in more detail

Traumatic avulsion of the trochanter minor in a 15-year-old boy: an uncommon injury.

A 15-year-old boy was seen at the emergency department with severe groin pain following an acute soccer injury. The pain irradiated towards the knee region. He was unable to move his right leg, and unable to stand on it. Physical examination revealed an extremely tender groin. Hip function was difficult to assess due to the severe pain. Hip and pelvis radiographs demonstrated a 1.3 cm large bone fragment detached and displaced superiorly relative to the trochanter minor (Fig. A). MR images revealed the retracted bone fragment (arrow) with the iliopsoas tendon (arrowheads) attached to it (Fig. B, C ). The tendon, bone fragment and trochanter minor were surrounded by a hyperintense fluid collection. Ultrasound also revealed the bone fragment with the attached tendon, although the relationship to the deeper trochanter minor was difficult to appreciate on ultrasound ). Recovery was uneventful. The patient was seen back after 9 weeks and clinical symptoms had complete subsided with entirely normal hip testing

Caenorhabditis elegans as an alternative in vivo model to determine oral uptake, nanotoxicity, and efficacy of melatonin-loaded lipid-core nanocapsules on paraquat damage

Caenorhabditis elegans is an alternative in vivo model that is being successfully used to assess the pharmacological and toxic effects of drugs. The exponential growth of nanotechnology requires the use of alternative in vivo models to assess the toxic effects of theses nanomaterials. The use of polymeric nanocapsules has shown promising results for drug delivery. Moreover, these formulations have not been used in cases of intoxication, such as in treatment of paraquat (PQ) poisoning. Thus, the use of drugs with properties improved by nanotechnology is a promising approach to overcome the toxic effects of PQ. This research aimed to evaluate the absorption of rhodamine B-labeled melatonin (Mel)-loaded lipid-core nanocapsules (LNC) by C. elegans, the application of this model in nanotoxicology, and the protection of Mel-LNC against PQ damage. The formulations were prepared by self-assembly and characterized by particle sizing, zeta potential, drug content, and encapsulation efficiency. The results demonstrated that the formulations had narrow size distributions. Rhodamine B-labeled Mel-LNC were orally absorbed and distributed in the worms. The toxicity assessment of LNC showed a lethal dose 50% near the highest dose tested, indicating low toxicity of the nanocapsules. Moreover, pretreatment with Mel-LNC significantly increased the survival rate, reduced the reactive oxygen species, and maintained the development in C. elegans exposed to PQ compared to those worms that were either untreated or pretreated with free Mel. These results demonstrated for the first time the uptake and distribution of Mel-LNC by a nematode, and indicate that while LNC is not toxic, Mel-LNC prevents the effects of PQ poisoning. Thus, C. elegans may be an interesting alternative model to test the nanocapsules toxicity and efficacy