Clinical characteristics of vulnerable populations hospitalized and diagnosed with COVID-19 in Buenos Aires, Argentina.

There is not in Argentina publications regarding the presentation of patients with COVID-19 requiring hospitalized and emergency care in vulnerable populations (lower incomes and less education tend at greater risk for poor health status and healthcare access), and it has few reports in developing countries. The objective is to determine whether in the care of vulnerable patients, to succeed against COVID-19, multiple public health tools and interventions will be needed to minimize morbidity and mortality. The study is a prospective cohort investigation of patients with lab-confirmed COVID-19, who required to any of the Health Centers response from April 8, 2020, to August 18, 2020. In Buenos Aires Metropolitan Area (AMBA), April 8, 2020 the virus was identified in patients hospitalized in the "Southeast Network" (SN), AMBA. SN covering an area of 661 square kilometers, with 1.8 million inhabitants residing in urban, and rural areas. A total of 14 health centers with different levels of care complexity provide care to patients in the region. The information of each patient with COVID-19 evaluated by SN, was incorporated in an Epidemiological Dashboard. The investigation was designed and reported with consideration of observational studies in epidemiology. We describe the hospitals presentation and care of persons who required SN response and were ultimately diagnosed with COVID-19. From April 8, 2020, to August 18, 2020, were included 1495 patients with lab-confirmed COVID-19 in SN. A total of 58% patients were men, and the mean age (SD) was 48.9 (15.59) years. Eighty one percent patients with pre-existing diseases, most frequent hypertension and diabetes, but hypertension, chronic lung disease, and cardiovascular disease presented higher risk. A total of 13% were hospitalized in Intensive Therapy Unit. The mortality of the cohort was 9.77%. Mortality was higher for patients aged 65 or more (OR 5.09), and for those had some pre-existing disease (OR 2.61). Our observations are consistent with reports demonstrating older persons, and those with comorbidities have the highest risk of mortality related to COVID-19. However, unlike other reports from developed or some developing countries, the mortality in our study is lower. This finding may be related to age of our cohort is younger than other published. Also, the health system was able to respond to the demand.

Agents' beliefs and economic regimes polarization in interacting markets.

In the present paper, a model of a market consisting of real and financial interacting sectors is studied. Agents populating the stock market are assumed to be not able to observe the true underlying fundamental, and their beliefs are biased by either optimism or pessimism. Depending on the relevance they give to beliefs, they select the best performing strategy in an evolutionary perspective. The real side of the economy is described within a multiplier-accelerator framework with a nonlinear, bounded investment function. We study the effect of market integration, in particular, of the financialization of the real market. We show that strongly polarized beliefs in an evolutionary framework can introduce multiplicity of steady states, which, consisting in enhanced or depressed levels of income, reflect and reproduce the optimistic or pessimistic nature of the agents' beliefs. The polarization of these steady states, which coexist with an unbiased steady state, positively depends on that of the beliefs and on their relevance. Moreover, with a mixture of analytical and numerical tools, we show that such static characterization is inherited also at the dynamical level, with possibly complex attractors that are characterized by endogenously fluctuating pessimistic and optimistic prices and levels of national income, with the effect of having several coexisting business cycles. This framework, when stochastic perturbations are included, is able to account for stylized facts commonly observed in real financial markets, such as fat tails and excess volatility in the returns distributions, as well as bubbles and crashes for stock prices.

Adjuvant everolimus in high-risk diffuse large B-cell lymphoma: final results from the PILLAR-2 randomized phase III trial.

Background: Patients with diffuse large B-cell lymphoma (DLBCL) with an International Prognostic Index (IPI) ≥3 are at higher risk for relapse after a complete response (CR) to first-line rituximab-based chemotherapy (R-chemo). Everolimus has single-agent activity in lymphoma. PILLAR-2 aimed to improve disease-free survival (DFS) with 1 year of adjuvant everolimus. Patients and methods: Patients with high-risk (IPI ≥3) DLBCL and a positron emission tomography/computed tomography-confirmed CR to first-line R-chemo were randomized to 1 year of everolimus 10 mg/day or placebo. The primary end point was DFS; secondary end points were overall survival, lymphoma-specific survival, and safety. Results: Between August 2009 and December 2013, 742 patients were randomized to everolimus (n = 372) or placebo (n = 370). Median follow-up was 50.4 months (range 24.0-76.9). Overall, 47% of patients were ≥65 years, 50% were male, and 42% had an IPI of 4 or 5. 48% and 67% completed everolimus and placebo, respectively. Primary reasons for everolimus discontinuation versus placebo were adverse events (AEs; 30% versus 12%) and relapsed disease (6% versus 13%). Everolimus did not significantly improve DFS compared with placebo (hazard ratio 0.92; 95% CI 0.69-1.22; P = 0.276). Two-year DFS rate was 77.8% (95% CI 72.7-82.1) with everolimus and 77.0% (95% CI 72.1-81.1) with placebo. Common grade 3/4 AEs with everolimus were neutropenia, stomatitis, and decreased CD4 lymphocytes. Conclusions: Adjuvant everolimus did not improve DFS in patients already in PET/CT-confirmed CR. Future approaches should incorporate targeted agents such as everolimus with R-CHOP rather than as adjuvant therapy after CR has been obtained. ClinicalTrials.gov: NCT00790036.

Real and financial market interactions in a multiplier-accelerator model: Nonlinear dynamics, multistability and stylized facts.

In the present paper, we investigate the dynamics of a model in which the real part of the economy, described within a multiplier-accelerator framework, interacts with a financial market with heterogeneous speculators, in order to study the channels through which the two sectors influence each other. Employing analytical and numerical tools, we investigate stability conditions as well as bifurcations and possible periodic, quasi-periodic, and chaotic dynamics, enlightening how the degree of market interaction, together with the accelerator parameter and the intervention of the fiscal authority, may affect the business cycle and the course of the financial market. In particular, we show that even if the steady state is locally stable, multistability phenomena can occur, with several and complex dynamic structures coexisting with the steady state. Finally, simulations reveal that the proposed model is able to explain several statistical properties and stylized facts observed in real financial markets, including persistent high volatility, fat-tailed return distributions, volatility clustering, and positive autocorrelation of absolute returns.

MEPROCS framework for Craniofacial Superimposition: Validation study.

Craniofacial Superimposition (CFS) involves the process of overlaying a skull with a number of ante-mortem images of an individual and the analysis of their morphological correspondence. The lack of unified working protocols and the absence of commonly accepted standards, led to contradictory consensus regarding its reliability. One of the more important aims of 'New Methodologies and Protocols of Forensic Identification by Craniofacial Superimposition (MEPROCS)' project was to propose a common framework for CFS, what can be considered the first international standard in the field. The framework aimed to serve as a roadmap for avoiding particular assumptions that could bias the process. At the same time, it provides some empirical support to certain practices, technological means, and morphological criteria expected to facilitate the application of the CFS task and to improve its reliability. In order to confirm the utility and potential benefits of the framework use, there is a need to empirically evaluate it in CFS identification scenarios as close as possible to the reality. Thus, the purpose of this study is to validate the CFS framework developed. For that aim 12 participants were asked to report about a variable number of CFS following all the recommendations of the framework. The results are analysed and discussed according to the framework understanding and fulfilment, the participants' performance, and the correlation between expected decisions and those given by the participants. In view of the quantitative results and qualitative examination criteria we can conclude that those who follow the MEPROCS recommendations improve their performance.

[RECONSTRUCTING THE LIFE OF AN UNKNOWN MAN--INTERDISCIPLINARY APPROACH].

The remains of a tomb were discovered below the foundations of the Roman church of "Majka Bozja Gorska" in Lobor in 2002. It was a vaulted tomb carved from a single stone. The narthex of ancient Christian and pre-roman churches often served as the resting place of religious, secular and noble dignitaries, who were credited for founding the church at the time. By anthropological methods, the age, gender, height, pathological changes, tendon and ligament hinges and degree of development were able to be analysed. The stable isotopes of Carbon-13, Nitrogen-15 and Oxygen-18 were analysed and expressed as ��-values according to the PDB standard. Dental analysis showed a build-up of tartar on the buccal side, with 5 teeth missing from the dentition post-mortem and a partial lowering and accretion of the alveolar walls of the 2nd molar space secondary to tooth loss. The remains of the person from grave 107 show that the person was approximately 30-35 years of age, confirmed by microscopical analysis of the bone samples. Almost all of the cranial sutures were exposed with the exception of the saggital suture which was closed at the S3 position, while the transverse palatal suture was in the initial stages of closure on the lateral sides. Analysis of the iliac bone showed visible changes on the bone. The surface had retained its youthful appearance however with a microporous and pronounced granular structure and only a slight apical and marginal activity. The transverse striations are still apparent, but no longer along the entirety of the bone surface. Anthropometric analysis according to cranial cavity indexes, showed a cranium or relatively large volume (aristencephalic in type), long, narrow and medium in height. The index values were used in facial reconstruction. Analysis of the development of tendon and ligament hinges of the preserved anatomical elements, gave further information about the morphology and physical activity of the person. The hinge sites of the brachial and antebrachial muscles showed a significant development and these enthesopathies would be consistent with a strenuous physical activity, especially at the biceps tendon and shoulder girdle, portraying an anterior elevation, cubital flexion, pronation, circumduction and fixation. It can be said that the person predominantly used the left arm. The developed muscle hinges, show common pronatory and supinatory movements and presume a routine swinging motion of an object above the head or in front of the person. The left tibia was suggestive of the height and male gender of the person. According to Pearson's regression formula, for the length of the brachium, radius and tibia, it can be reasoned that the person was approximately 169 cm tall. The upper third of the L3 vertebra shows a Schmorl's hernia which can be secondary to strong anteroposterior and lateral flexion of the spine. On the supero-lateral surface of the left patella, there is a Messeri sign, suggestive of a long and repeated flexion of the knee (kneeling). The molars of the lower and especially upper jaw show signs of paradontosis and a slight abrasion of the first degree according to Gustafson. The secondary dentin can be seen on the incisors, canines and molars. The bone impression of the left temporal bone, was oval in shape and measured 12x9 mm. It was probably and old, healed wound, possibly consequential to a fall or strike from a sharp object. The left tibia, showed a treated but still active periostitis. Analysis of the stable isotopes (C, N, O) shows an increased consumption of vegetables, common to a moderately warm and dry climate (millet). The person had access to water of a good quality, possibly from a well and did not eat fish or drink wine. We do not know whether the person from grave 107 was a member of the clergy or nobility, but was most likely a member of the social elite.

Study on the performance of different craniofacial superimposition approaches (II): Best practices proposal.

Craniofacial superimposition, although existing for one century, is still a controversial technique within the scientific community. Objective and unbiased validation studies over a significant number of cases are required to establish a more solid picture on the reliability. However, there is lack of protocols and standards in the application of the technique leading to contradictory information concerning reliability. Instead of following a uniform methodology, every expert tends to apply his own approach to the problem, based on the available technology and deep knowledge on human craniofacial anatomy, soft tissues, and their relationships. The aim of this study was to assess the reliability of different craniofacial superimposition methodologies and the corresponding technical approaches to this type of identification. With all the data generated, some of the most representative experts in craniofacial identification joined in a discussion intended to identify and agree on the most important issues that have to be considered to properly employ the craniofacial superimposition technique. As a consequence, the consortium has produced the current manuscript, which can be considered the first standard in the field; including good and bad practices, sources of error and uncertainties, technological requirements and desirable features, and finally a common scale for the craniofacial matching evaluation. Such a document is intended to be part of a more complete framework for craniofacial superimposition, to be developed during the FP7-founded project MEPROCS, which will favour and standardize its proper application.

Histologic transformation in marginal zone lymphomas†.

BACKGROUND: Histologic transformation (HT) is a poorly understood event in patients with marginal zone lymphoma (MZL). The aim of this study was to analyze incidence and risk factors for HT in a large series of MZL patients. PATIENTS AND METHODS: The studied cohort included 340 MZL patients diagnosed and treated between 1995 and 2012: 157 extranodal MZLs [mucosa-associated lymphoid tissue (MALT) lymphoma, 46%], 85 splenic MZLs (SMZLs, 25%) and 37 nodal MZLs (NMZLs, 11%). Sixty-one patients (18%) had bone marrow infiltration at presentation, with or without detectable involvement of peripheral blood, but without other involved sites; they were considered clonal B-cell lymphocytosis of marginal zone origin (CBL-MZ). RESULTS: With a median follow-up of 4.8 years, the median overall survival and progression-free survival of the whole population were 14.5 and 5 years, respectively. HT was observed in 13 cases [3.8%, 95% confidence interval (95% CI) 2%-6.5%]. Elevated lactate dehydrogenase (LDH) at diagnosis was associated with the risk of HT (P = 0.019). HT occurred in 5% of SMZLs, 4% of MALT lymphomas, 3% of NMZLs and 3% of CBL-MZ (P = 0.974). The risk of HT was 5% (95% CI 3-9%) at 5 and 10 years after diagnosis and 10% (95% CI 5%-20%) at 12 years. At the time of HT, most patients had high LDH and B symptoms. At a median follow-up of 12 months after HT, 4 of 13 patients died, all for lymphoma-related causes, with a 2-year post-transformation survival rate of 57% (95% CI 13%-86%). CONCLUSIONS: In this large retrospective series, the risk of HT across all MZL types appeared lower than the one reported for follicular lymphoma.

Life expectancy of young adults with follicular lymphoma.

BACKGROUND: This study was aimed at investigating the clinical features and outcomes of follicular lymphoma (FL) patients younger than 40 years, which have not been extensively investigated yet. PATIENTS AND METHODS: One hundred and fifty-five patients younger than 40 years were retrospectively studied from a series of 1002 FL patients diagnosed in four different European Oncology Centres (Barcelona, Spain; Bellinzona, Switzerland; London, UK; Novara, Italy) from 1985 to 2010. RESULTS: Patients younger than 40 had a lower incidence of elevated LDH, high beta2-microglobulin, and a high-risk Follicular Lymphoma International Prognostic Index (FLIPI) score, whereas bone marrow involvement and bulky and disseminated lymphadenopathy were more frequent. At a median follow-up of 10 years, younger patients, in comparison with those older than 40, had significantly better overall (OS), cause-specific survival (CSS), and progression-free survival (PFS), with 10-year OS rate of 81% versus 51% (P < 0.0001), 10-year CSS rate of 82% versus 60% (P < 0.0001), and 10-year PFS of 39% versus 24% (P = 0.0098). However, there were no significant CSS and PFS differences in comparison with the patients aged 40-60. In multivariate analysis, having the lymphoma diagnosed in the last two decades and a favourable FLIPI score were associated with a significantly longer PFS and CSS in younger patients, whereas only FLIPI retained statistical significance for OS. CONCLUSIONS: In our series, FL patients younger than 40 have a median OS of 24 years and their outcome seems to be improving over time. However, they still have a significantly shorter life expectancy than that of an age-matched general healthy population.

Study on the performance of different craniofacial superimposition approaches (I).

As part of the scientific tasks coordinated throughout The 'New Methodologies and Protocols of Forensic Identification by Craniofacial Superimposition (MEPROCS)' project, the current study aims to analyse the performance of a diverse set of CFS methodologies and the corresponding technical approaches when dealing with a common dataset of real-world cases. Thus, a multiple-lab study on craniofacial superimposition has been carried out for the first time. In particular, 26 participants from 17 different institutions in 13 countries were asked to deal with 14 identification scenarios, some of them involving the comparison of multiple candidates and unknown skulls. In total, 60 craniofacial superimposition problems divided in two set of females and males. Each participant follow her/his own methodology and employed her/his particular technological means. For each single case they were asked to report the final identification decision (either positive or negative) along with the rationale supporting the decision and at least one image illustrating the overlay/superimposition outcome. This study is expected to provide important insights to better understand the most convenient characteristics of every method included in this study.

Ground truth data generation for skull-face overlay.

Objective and unbiased validation studies over a significant number of cases are required to get a more solid picture on craniofacial superimposition reliability. It will not be possible to compare the performance of existing and upcoming methods for craniofacial superimposition without a common forensic database available for the research community. Skull-face overlay is a key task within craniofacial superimposition that has a direct influence on the subsequent task devoted to evaluate the skull-face relationships. In this work, we present the procedure to create for the first time such a dataset. We have also created a database with 19 skull-face overlay cases for which we are trying to overcome legal issues that allow us to make it public. The quantitative analysis made in the segmentation and registration stages, together with the visual assessment of the 19 face-to-face overlays, allows us to conclude that the results can be considered as a gold standard. With such a ground truth dataset, a new horizon is opened for the development of new automatic methods whose performance could be now objectively measured and compared against previous and future proposals. Additionally, other uses are expected to be explored to better understand the visual evaluation process of craniofacial relationships in craniofacial identification. It could be very useful also as a starting point for further studies on the prediction of the resulting facial morphology after corrective or reconstructive interventionism in maxillofacial surgery.

C4 -consumers in southern Europe: the case of Friuli V.G. (NE-Italy) during early and central Middle Ages.

Isotope variations were studied in necropolises of the early (6th to 7th century CE) and central (10th to 11th century CE) medieval period located in Fruili-Venezia Giulia (Northeastern Italy). The two periods each shortly followed two great barbarian invasions that changed the politics and economy of Italy: the arrivals of Langobards in 578 CE and the Hungarian incursions from the end of the 9th to the first half of the 10th century. These events had a tragic effect on the economy of Friuli-Venezia Giulia: severe depopulation and the partial abandonment of the countryside with fall of agricultural production.

Epigenomic alterations define lethal CIMP-positive ependymomas of infancy.

Ependymomas are common childhood brain tumours that occur throughout the nervous system, but are most common in the paediatric hindbrain. Current standard therapy comprises surgery and radiation, but not cytotoxic chemotherapy as it does not further increase survival. Whole-genome and whole-exome sequencing of 47 hindbrain ependymomas reveals an extremely low mutation rate, and zero significant recurrent somatic single nucleotide variants. Although devoid of recurrent single nucleotide variants and focal copy number aberrations, poor-prognosis hindbrain ependymomas exhibit a CpG island methylator phenotype. Transcriptional silencing driven by CpG methylation converges exclusively on targets of the Polycomb repressive complex 2 which represses expression of differentiation genes through trimethylation of H3K27. CpG island methylator phenotype-positive hindbrain ependymomas are responsive to clinical drugs that target either DNA or H3K27 methylation both in vitro and in vivo. We conclude that epigenetic modifiers are the first rational therapeutic candidates for this deadly malignancy, which is epigenetically deregulated but genetically bland.

Early-stage diffuse large B cell lymphoma of the head and neck: clinico-biological characterization and 18 year follow-up of 488 patients (IELSG 23 study).

It is known that extranodal head and neck diffuse large B cell lymphomas (eHN-DLBCL) can affect various anatomical structures what is not well-known, however, is whether they differ in terms of clinical presentation and outcome. Clinical data of the multi-institutional series, the largest of its kind as yet, has been analysed with the aim of answering these open questions and providing long-term follow-up information. Data from 488 patients affected by stage I/II eHN-DLBCL was collected: 300 of the Waldeyer's Ring (WR), 38 of the parotid and salivary glands (PSG), 48 of the thyroid gland (TG), 53 of the nasal cavity and paranasal sinuses (NPS), 24 of the palate and oral cavity (POC) and 25 with more than one involved site. Different eHN-DLBCL arising have distinct characteristics at presentation. The intermediate high risk-modified IPI was 67 % in TG, 44 % in WR, 38 % in PSG and POC and 20 % in MS. The worst 5-year survival rate had TG-DLBCL (61 %) due to the 61 % of patients with a mIPI >1. The addition of radiotherapy (cRT) to remitters did not translate into a survival advantage (5-year disease-free survival of 67 % in the cRT group vs. 70 % in the other). Three of four central nervous system recurrences occurred in NPS-DLBCL. Survival of HN-DLBCL was inferior to nodal DLBCL. This study showed that eHN-DLBCL remitters have an inferior survival when compared to nodal DLBCL, and that the addition of cRT does not provide a survival advantage. Since the standard of care nowadays is chemo-immunotherapy, survival of these patients might have been improved.

Large genomic aberrations detected by SNP array are independent prognosticators of a shorter time to first treatment in chronic lymphocytic leukemia patients with normal FISH.

BACKGROUND: Genomic complexity can predict the clinical course of patients affected by chronic lymphocytic leukemia (CLL) with a normal FISH. However, large studies are still lacking. Here, we analyzed a large series of CLL patients and also carried out the so far largest comparison of FISH versus single-nucleotide polymorphism (SNP) array in this disease. PATIENTS AND METHODS: SNP-array data were derived from a previously reported dataset. RESULTS: Seventy-seven of 329 CLL patients (23%) presented with a normal FISH. At least one large (>5 Mb) genomic aberration was detected by SNP array in 17 of 77 patients (22%); this finding significantly affected TTT. There was no correlation with the presence of TP53 mutations. In multivariate analysis, including age, Binet stage, IGHV genes mutational status and large genomic lesion, the latter three factors emerged as independent prognosticators. The concordance between FISH and SNP array varied between 84 and 97%, depending on the specific genomic locus investigated. CONCLUSIONS: SNP array detected additional large genomic aberrations not covered by the standard FISH panel predicting the outcome of CLL patients.

Clinical activity of bortezomib in relapsed/refractory MALT lymphomas: results of a phase II study of the International Extranodal Lymphoma Study Group (IELSG).

BACKGROUND: The nuclear factor-kappa B activation in mucosa-associated lymphoid tissue (MALT) lymphoma pathogenesis provided the rationale for the evaluation of bortezomib in this malignancy. PATIENTS AND METHODS: Thirty-two patients with relapsed/refractory MALT lymphoma were enrolled. Thirty-one patients received bortezomib 1.3 mg/m(2) i.v., on days 1, 4, 8, and 11, for up to six 21-day cycles. RESULTS: Median age was 63 years (range, 37-82 years). Median number of prior therapies was 2 (range, 1-4). Nine patients had Ann Arbor stage I, 7 patients had stage II, and 16 patients had stage IV. Primary lymphoma localization was the stomach in 14 patients; multiple extranodal sites were present in 10 patients. Among the 29 patients assessable for response, the overall response rate was 48% [95% confidence interval (CI) 29% to 67%], with 9 complete and 5 partial responses. Nine patients experienced stable disease and six had disease progression during therapy. The most relevant adverse events were fatigue, thrombocytopenia, neutropenia, and peripheral neuropathy. After a median follow-up of 24 months, the median duration of response was not reached yet. Five deaths were reported, in two patients due to disease progression. CONCLUSION: Bortezomib is active in relapsed MALT lymphomas. Further investigations to identify optimal bortezomib dose, schedule, and combination regimens are needed since the frequent detection of dose-limiting peripheral neuropathy.

Clinical and molecular determinants of survival in pancreatic cancer patients treated with second-line chemotherapy: results of an Italian/Swiss multicenter survey.

BACKGROUND: Increased knowledge about the treatment of pancreatic cancer has influenced the management of locally advanced and metastatic disease. Nonetheless, prognosis remains dismal (24%, 1-year survival). The impact on overall survival (OS) of second-line therapy has not been clarified and the use of platinum salts and/or fluoropyrimidines is hotly debated. It is the hope that future treatment can be tailored to predict chemosensitivity in order to improve outcomes in patients with locally advanced and metastatic pancreatic cancer. Since DNA-damaging agents could be one therapeutic option, a retrospective multicenter study was performed to evaluate the efficacy of salvage treatment with the hypothesis that levels of the DNA repair gene excision repair cross complementing 1 (ERCC1) could influence OS. PATIENTS AND METHODS: In a population of 160 patients treated with fluoropyrimidine-based second-line chemotherapy, expression levels of ERCC1 were determined by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). In 108 patients with locally advanced and metastatic pancreatic cancer treated with either fluoropyrimidines and platinum salts (group A=58) or fluoropyrimidines alone (group B=50), ERCC1 levels were correlated with OS, time to progression and response to chemotherapy. RESULTS: Median survival was significantly higher in group A with low ERCC1 levels [11.9 versus 9.9 months; p ≤ 0.05] (median follow-up 24 months). Moreover in the same group, a trend towards longer time to progression was observed. No differences in OS were observed when ERCC1 was studied (low versus high) in patients not treated with platinum salts. On multivariate analysis of pretreatment prognostic factors, ERCC1 emerged as an independent predictive factor for OS. CONCLUSION: The results of this study indicate that ERCC1 may predict survival in pancreatic cancer patients treated by platinum and fluoropyrimidine as second-line chemotherapy.