Influencia algorítmica e inmutabilidad de los Smart Contacts: ¿cómo impactan estas tecnologías en la asimetría contractual?

En el presente trabajo nos proponenos analizar el impacto de dos tecnologías de la Cuarta Revolución Industrial en el Derecho de los Contratos, con un marcado enfoque en los sujetos vulnerables del contrato. La primera de ellas es la “inteligencia artificial” que tiene un rol preponderante al momento de la formación, celebración y análisis del contrato. Aquí nos preguntamos cómo impactan los algoritmos en la toma de decisiones, para lo cual, haremos un paso por las neurociencias. La segunda tecnología a abordar, es la denominada blockchain que se emplea en los Smart Contracts (contratos inteligentes). El eje del análisis radicará en una de sus más destacadas características: la inmutabilidad

Recent extension driven by mantle upwelling beneath the Admiralty Mountains (East Antarctica)

Northern Victoria Land is located at the boundary between an extended, presumably hot, region (West Antarctic Rift System) and the thick, possibly cold, East Antarctic craton. The style and timing of Tertiary deformation along with relationships with the magmatic activity are still unclear, and contrasting models have been proposed. We performed structural and morphotectonic analyses at the NE termination of northern Victoria Land in the Admiralty Mountains area, where the relationship between topography, tectonics, and magmatism is expected to be well pronounced. We found evidence of two subsequent episodes of faulting, occurring concurrently with the Neogene McMurdo volcanism. The first episode is associated with dextral transtension, and it is overprinted by extensional tectonics during the emplacement of large shield alkaline volcanoes. Upper mantle seismic tomography shows that the extensional regime is limited to regions overlying a low-velocity anomaly. We interpret this anomaly to be of thermal origin, and have tested the role of largescale upwelling on lithosphere deformation in the area. The results of this integrated analysis suggest that the morphotectonic setting of the region and the magmatism is likely the result of upwelling flow at the boundary between the cold cratonic and the hot stretched province (WARS), at work until recent time in this portion of the northern Victoria Land

Enamel interproximal reduction during treatment with clear aligners: digital planning versus OrthoCAD analysis

Background The aim of the study was to compare the amount of interproximal enamel reduction (IPR) provided on ClinCheck software with the amount of IPR carried out by the orthodontist during treatment with clear aligners. Methods 30 subjects (14 males, 16 females; mean age of 24.53 +/- 13.41 years) randomly recruited from the Invisalign account of the Department of Orthodontics at the University of Rome "Tor Vergata" from November 2018 to October 2019, were collected according to the following inclusion criteria: mild to moderate dento-alveolar discrepancy (1.5-6.5 mm); Class I canine and molar relationship; full permanent dentition (excluding third molars); both arches treated only using Comprehensive Package by Invisalign system; treatment plan including IPR. Pre- (T0) and post-treatment (T1) digital models (.stl files), created from an iTero scan, were collected from all selected patients. The OrthoCAD digital software was used to measure tooth mesiodistal width in upper and lower arches before (T0) and at the end of treatment (T1) before any refinement. The widest mesio-distal diameter was measured for each tooth excluding molars by "Diagnostic" OrthoCAD tool. The total amount of IPR performed during treatment was obtained comparing the sum of mesio-distal widths of all measured teeth at T0 and T1. Significant T1-T0 differences were tested with dependent sample t-test (P < 0.05). Results In the upper arch, IPR was digitally planned on average for 0.62 mm while in the lower arch was on average for 1.92 mm. As for the amount of enamel actually removed after IPR performing, it was on average 0.62 mm in the maxillary arch. In the mandibular arch, the mean of IPR carried out was 1.93 mm. The difference between planned IPR and performed IPR is described: this difference was on average 0.00 mm in the upper arch and 0.01 in the lower arch. Conclusions The amount of enamel removed in vivo corresponded with the amount of IPR planned by the Orthodontist using ClinCheck software

Assessing depleted uranium (DU) contamination of soil, plants and earthworms at UK weapons testing sites

Depleted uranium (DU) weapons testing programmes have been conducted at two locations within the UK. An investigation was therefore carried out to assess the extent of any environmental contamination arising from these test programmes using both alpha spectrometry and mass spectrometry techniques. Uranium isotopic signatures indicative of DU contamination were observed in soil, plant and earthworm samples collected in the immediate vicinity of test firing points and targets, but contamination was found to be localised to these areas. The paper demonstrates the superiority of the 235U:238U ratio over the 234U:238U ratio for identifying and quantifying DU contamination in environmental samples and also describes the respective circumstances under which alpha spectrometry or mass spectrometry may be the more appropriate analytical tool

<b><i>Topoisomerase 1</i></b> Promoter Variants and Benefit from Irinotecan in Metastatic Colorectal Cancer Patients

Objective: Topoisomerase 1 (topo-1) is an important target for the treatment of metastatic colorectal cancer (CRC). The aim of the present study was to evaluate the correlation between topo-1 single-nucleotide polymorphisms (SNPs) and clinical outcome in metastatic CRC (mCRC) patients. Methods: With the use of specific software (PROMO 3.0), we performed an in silico analysis of topo-1 promoter SNPs; the rs6072249 and rs34282819 SNPs were included in the study. DNA was extracted from 105 mCRC patients treated with FOLFIRI ± bevacizumab in the first line. SNP genotyping was performed by real-time PCR. Genotypes were correlated with clinical parameters (objective response rate, progression-free survival, and overall survival). Results: No single genotype was significantly associated with clinical variables. The G allelic variant of rs6072249 topo-1 SNP is responsible for GC factor and X-box-binding protein transcription factor binding. The same allelic variant showed a nonsignificant trend toward a shorter progression-free survival (GG, 7.5 months; other genotypes, 9.3 months; HR 1.823, 95% CI 0.8904-3.734; p = 0.1). Conclusion: Further analyses are needed to confirm that the topo-1 SNP rs6072249 and transcription factor interaction could be a part of tools to predict clinical outcome in mCRC patients treated with irinotecan-based regimens

Dental anomalies : prevalence and associations between them in a large sample of non-orthodontic subjects, a cross-sectional study

Background: To analyze the prevalence and associations between dental anomalies detectable on panoramic radiographs in a sample of non-orthodontic growing subjects. Methods: For this cross-sectional study, digital panoramic radiographs of 5005 subjects were initially screened from a single radiographic center in Rome. Inclusion criteria were: subjects who were aged 8–12 years, Caucasian, and had good diagnostic quality radiographs. Syndromic subjects, those with craniofacial malformation, or orthodontic patients were excluded and this led to a sample of 4706 subjects [mean (SD) age = 9.6 (1.2) years, 2366 males and 2340 females]. Sample was subsequently divided into four subgroups (8, 9, 10, and 11–12 year-old groups). Two operators examined panoramic radiographs to observe the presence of common dental anomalies. The prevalence and associations between dental anomalies were also investigated. Results: The overall prevalence of dental anomalies was 20.9%. Approximately, 17.9% showed only one anomaly, 2.7% two anomalies, while only 0.3% had more than two anomalies. The most frequent anomalies were the displacement of maxillary canine (7.5%), hypodontia (7.1%), impacted teeth (3.9%), tooth ankylosis (2.8%), and tooth transposition (1.4%). The lower right second premolar was the most frequent missing teeth; 3.7% had only one tooth agenesis, and 0.08% had six or more missing tooth (Oligodontia). Mesiodens was the most common type of supernumerary tooth (0.66%). Two subjects had taurodontic tooth (0.04%). Tooth transpositions and displacement of maxillary canine were seen in 1.4 and 7.5%, retrospectively (approximately 69 and 58% were in the 8 and 9 year-old groups, retrospectively). Significant associations were detected between the different dental anomalies (P < .05). Conclusions: The results of our study revealed significant associations among different dental anomalies and provide further evidences to support common etiological factors

Posttransplant lymphoproliferative disorders in neuronal xenotransplanted macaques

Posttransplant lymphoproliferative disorders (PTLDs) are a heterogeneous group of lymphoid proliferations that occur in the setting of depressed T-cell function due to immunosuppressive therapy used following solid organ transplantation, hematopoietic stem cell transplantation, and also xenotransplantation. In the present study, 28 immunosuppressed parkinsonian Macaca fascicularis were intracerebrally injected with wild-type or CTLA4-Ig transgenic porcine xenografts to identify a suitable strategy to enable long-term cell survival, maturation, and differentiation. Nine of 28 (32%) immunosuppressed primates developed masses compatible with PTLD, located mainly in the gastrointestinal tract and/or nasal cavity. The masses were classified as monomorphic PTLD according to the World Health Organization classification. Immunohistochemistry and polymerase chain reaction (PCR) analyses revealed that the PTLDs were associated with macaca lymphocryptovirus as confirmed by double-labeling immunohistochemistry for CD20 and Epstein-Barr nuclear antigen 2 (EBNA-2), where the viral protein was located within the CD20+ neoplastic B cells. In sera from 3 distinct phases of the experimental life of the primates, testing by quantitative PCR revealed a progression of the viral load that paralleled the PTLD progression and no evidence of zoonotic transmission of porcine lymphotropic herpesvirus through xenoneuronal grafts. These data suggest that monitoring the variation of macaca lymphocryptovirus DNA in primates could be used as a possible early diagnostic tool for PTLD progression, allowing preemptive treatment such as immunosuppression therapy reduction

Can we improve the treatment of congestion in heart failure?

INTRODUCTION: Dyspnoea and peripheral oedema, caused by fluid redistribution to the lungs and/or by fluid overload, are the main causes of hospitalization in patients with heart failure and are associated with poor outcomes. Treatment of fluid overload should relieve symptoms and have a neutral or favorable effect on outcomes. AREAS COVERED: We first consider the results obtained with furosemide administration, which is still the mainstay of treatment of congestion in patients with heart failure. We then discuss important shortcomings of furosemide treatment, including the development of resistance and side effects (electrolyte abnormalities, neurohormonal activation, worsening renal function), as well as the relationship of furosemide - and its doses - with patient prognosis. Finally, the results obtained with potential alternatives to furosemide treatment, including different modalities of loop diuretic administration, combined diuretic therapy, dopamine, inotropic agents, ultrafiltration, natriuretic peptides, vasopressin and adenosine antagonists, are discussed. EXPERT OPINION: Relief of congestion is a major objective of heart failure treatment but therapy remains based on the administration of furosemide, an agent that is often not effective and is associated with poor outcomes. The results of the few controlled studies aimed at the assessment of new treatments to overcome resistance to furosemide and/or to protect the kidney from its untoward effects have been mostly neutral. Better treatment of congestion in heart failure remains a major unmet need

REDUCED CARDIOTOXICITY AND INCREASED CYTOTOXICITY IN A NOVEL ANTHRACYCLINE ANALOG, 4'-AMINO-3'-HYDROXY-DOXORUBICIN

The acute and chronic cardiotoxicity and cytotoxicity of the novel doxorubicin (DXR) derivative 4'-amino-3'-hydroxy-DXR were compared with those of 4'-deoxy-DXR and DXR. In the acute cardiotoxicity study, the ECG and hemodynamic changes recorded in anesthetized rats that had been treated i.v. with 10 mg/kg 4'-amino-3'-hydroxy-DXR or 8.6 mg/kg 4'-deoxy-DXR were significantly less severe than those caused by 13 mg/kg DXR. In the chronic cardiotoxicity study, rats received 3 weekly i.v. injections of 3 mg/kg DXR, 3 mg/kg 4'-amino-3'-hydroxy-DXR, or 2 mg/kg 4'-deoxy-DXR during the first 14 days of the study and were observed for an additional 35-day period. DXR induced severe cardiomyopathy that was characterized by ECG changes in vivo (S-alpha-T-segment widening and T-wave flattening) and by impairment of the contractile responses (F(max), +/- dF/dt(max)) to adrenaline of hearts isolated from treated animals. 4'-Deoxy-DXR caused a progressive enlargement of the S-alpha-T segment in vivo and a significant impairment of the - dF/dt(max) value in vitro, which were less severe than those produced by DXR. The least cardiotoxic drug was 4'-amino-3'-hydroxy-DXR, which induced minor ECG changes without causing significant alterations in the contractile responses of isolated hearts to adrenaline. On the basis of the drug concentration required to inhibit 50% of the colony formation (IC50) of cell lines in vitro, 4'-amino-3'-hydroxy-DXR was less active than 4'-deoxy-DXR but at least twice as active as DXR against human cancer and murine transformed cell lines. These data indicate that 4'-amino-3'-hydroxy-DXR is significantly less cardiotoxic and more cytotoxic than DXR

Refining sorafenib therapy: lessons from clinical practice

Understanding the best use of sorafenib is essential in order to maximize clinical benefit in hepatocellular carcinoma. Based on Phase III and noninterventional study data, as well as our extensive experience, we discuss dose modification in order to manage adverse events, disease response evaluation and how to maximize treatment benefit. Sorafenib should be initiated at the approved dose (400 mg twice daily) and reduced/interrupted as appropriate in order to manage adverse events. Dose modification should be considered before discontinuation. Appropriate tumor response assessment is critical. Focusing on radiologic response may result in premature sorafenib discontinuation; symptomatic progression should also be considered. If second-line therapies or trials are unavailable, continuing sorafenib beyond radiologic progression may provide a clinical benefit. Our recommendations enable the maximization of treatment duration, and hence clinical benefit, for patients