Convex Learning of Multiple Tasks and their Structure

Reducing the amount of human supervision is a key problem in machine learning and a natural approach is that of exploiting the relations (structure) among different tasks. This is the idea at the core of multi-task learning. In this context a fundamental question is how to incorporate the tasks structure in the learning problem.We tackle this question by studying a general computational framework that allows to encode a-priori knowledge of the tasks structure in the form of a convex penalty; in this setting a variety of previously proposed methods can be recovered as special cases, including linear and non-linear approaches. Within this framework, we show that tasks and their structure can be efficiently learned considering a convex optimization problem that can be approached by means of block coordinate methods such as alternating minimization and for which we prove convergence to the global minimum.Comment: 26 pages, 1 figure, 2 table

Centric relation—A biological perspective of a technical concept

Background: Few terms and concepts have been so extensively debated in dentistry as the words 'centric relation' (CR). Debates involve its biological, diagnostic and therapeutic usefulness. Methods: A review of the literature on the current concepts on CR as a diagnostic or therapeutic aid in dentistry was provided. Clinical trials assessing the superiority of one CR recording method over the others to identify patients with temporomandibular disorders (diagnostic use) or to manage patients with prosthodontic or orthodontic needs (therapeutic use) were tentatively included. Results: Due to the absence of literature addressing either of the above targets, a comprehensive overview was provided. The diagnostic use of CR as a reference position to identify the correct position of the temporomandibular joint condyle within the glenoid fossa is not supported and lacks anatomical support. From a therapeutic standpoint, the use of CR can be pragmatically useful in prosthodontics as a maxillo-mandibular reference position when occlusal re-organization is warranted and/or when the position of maximum intercuspation is no longer available. Conclusions: The derived occlusal goals from a diagnostic misuse of CR are generally the result of circular reasoning, that is a technique is based on the recording of a certain condylar position that is believed to be 'ideal' and the treatment is considered successful when such position is shown by the specific instrument that was manufactured for that purpose. The term 'Centric Relation' might be replaced with the term 'Maxillo-Mandibular Utility Position'

Convex learning of multiple tasks and their structure

Reducing the amount of human supervision is a key problem in machine learning and a natural approach is that of exploiting the relations (structure) among different tasks. This is the idea at the core of multi-task learning. In this context a fundamental question is how to incorporate the tasks structure in the learning problem. We tackle this question by studying a general computational framework that allows to encode a-priori knowledge of the tasks structure in the form of a convex penalty; in this setting a variety of previously proposed methods can be recovered as special cases, including linear and non-linear approaches. Within this framework, we show that tasks and their structure can be efficiently learned considering a convex optimization problem that can be approached by means of block coordinate methods such as alternating minimization and for which we prove convergence to the global minimum

Economic Evaluation of Different Organizational Models for the Management of Patients with Hepatitis C

BACKGROUND: Access to Directly Acting Antivirals (DAAs) for Hepatitis C Virus (HCV) treatment in Italy was initially restricted to severe patients. In 2017, AIFA expanded access to all patients, to achieve elimination by 2030.AIM: To investigate the impact of different hospitals’ organizational models on elimination timing, treatment capacity and direct costs.METHODS: Most Regional healthcare systems in Italy deploy a Center of Excellence (CoE) organizational model, where patients are referred to a single major hospital in the area, which is the only one that can prescribe and deliver DAAs. The study was conducted at Bergamo’s (Lombardy, Italy) Papa Giovanni XXIII hospital (PG-23), which deploys a Hub&Spoke model: the Hub (PG-23) prescribes and delivers DAAs while Spokes (four smaller hospitals) can only prescribe them. The study compares the two models (CoE vs. H&S). Patient journey and workloads were mapped and quantified through interviews with hospital stakeholders. Cost data were collected through the hospital’s IT system; the sample comprised 2,277 HCV patients, over one year.RESULTS: The study calculated the average cost to treat HCV patients (~ € 1,470 per patient). Key cost drivers are lab tests (60%) and specialist visits (30%). Over one year, H&S can treat 68% more patients than CoE. As deferred patients absorb up to 40% of total costs, the “Optimized” model was designed by streamlining specialists’ visits and involving general practitioners during follow-up. “Optimized” model increases treatment capacity and reduces costs of deferred patients by 72% vs CoE.CONCLUSION: The study demonstrates the importance of organizational models in efficiently achieving 2030 elimination

Excess of NPM-ALK oncogenic signaling promotes cellular apoptosis and drug dependency.

Most of the anaplastic large-cell lymphoma (ALCL) cases carry the t(2;5; p23;q35) that produces the fusion protein NPM-ALK (nucleophosmin-anaplastic lymphoma kinase). NPM-ALK-deregulated kinase activity drives several pathways that support malignant transformation of lymphoma cells. We found that in ALK-rearranged ALCL cell lines, NPM-ALK was distributed in equal amounts between the cytoplasm and the nucleus. Only the cytoplasmic portion was catalytically active in both cell lines and primary ALCL, whereas the nuclear portion was inactive because of heterodimerization with NPM1. Thus, about 50% of the NPM-ALK is not active and sequestered as NPM-ALK/NPM1 heterodimers in the nucleus. Overexpression or relocalization of NPM-ALK to the cytoplasm by NPM genetic knockout or knockdown caused ERK1/2 (extracellular signal-regulated protein kinases 1 and 2) increased phosphorylation and cell death through the engagement of an ATM/Chk2- and γH2AX (phosphorylated H2A histone family member X)-mediated DNA-damage response. Remarkably, human NPM-ALK-amplified cell lines resistant to ALK tyrosine kinase inhibitors (TKIs) underwent apoptosis upon drug withdrawal as a consequence of ERK1/2 hyperactivation. Altogether, these findings indicate that an excess of NPM-ALK activation and signaling induces apoptosis via oncogenic stress responses. A 'drug holiday' where the ALK TKI treatment is suspended could represent a therapeutic option in cells that become resistant by NPM-ALK amplification.We thank Maria Stella Scalzo for technical support, Dr Emanuela Colombo for kindly providing MEFs that lack NPM1 (MEF NPM−/−p53−/−) and control fibroblasts (MEF p53−/−), Dr Guido Serini for the use of his confocal microscopy unit at the Candiolo Cancer Institute—IRCCS, Torino, Italy. We also thank Ariad Pharmaceutical, Pfizer, Astellas and Novartis that kindly provided all drugs used in this study. This work was supported by the Regione Lombardia (ID14546A) and Fondazione Berlucchi Onlus Grant 2014 (to CGP), and by grants FP7 ERC-2009-StG (Proposal No. 242965—‘Lunely’); Associazione Italiana per la Ricerca sul Cancro (AIRC) Grant IG-12023; Koch Institute/DFCC Bridge Project Fund; Ellison Foundation Boston; Worldwide Cancer Research Association (former AICR) grant 12-0216; the Grant for Oncology Innovation by Merck-Serono and R01 CA196703-01 (to RC).This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/onc.2015.45

Complete response for advanced liver cancer during sorafenib therapy: Case Report

<p>Abstract</p> <p>Background</p> <p>Hepatocellular carcinoma (HCC) is the fifth most common neoplasia in the world. In the past, treatment of advanced HCC with conventional antineoplastic drugs did not result in satisfactory outcomes: recently, in this patient population the oral multikinase inhibitor sorafenib has been able to induce a statistically significant improvement of overall survival. Similarly to other anti-angiogenic drugs employed in other tumour types, also sorafenib seldom induces the dimensional tumour shrinking usually observed with conventional cytotoxic drugs: data gathered from studies carried out with sorafenib and other competitors under development do not report any complete response in HCV-induced HCC.</p> <p>Case presentation</p> <p>An 84-year old man with a long-lasting history of chronic HCV hepatitis was referred to our Institution for an ultrasonography investigation of a focal hepatic lesion. To better characterize the liver disease and clearly define the diagnosis of the focal hepatic lesion, the patient was hospitalized in our department. Laboratory and instrumental investigations confirmed the clinical picture of HCV-related liver cirrhosis and identified a hepatic lesion of about 6 cm featuring infiltrating HCC with thrombosis of the portal trunk. Due to the advanced stage of the disease, therapy with sorafenib 400 mg bid was started. Right from one month after the treatment was started, a reduction of alpha-fetoprotein level was observed which, by the third month, turned down within the normal limits. In addition the CT scan showed 50% reduction of the neoplastic lesion along with canalization of the portal trunk. At the sixth month the normalization of the alpha-fetoprotein level at the lower limit of normality was confirmed and the MRI showed complete disappearance of the neoplasia. In addition a reduction of a metallo-proteinase serum level was obserdved. At the twelfth month a further MRI confirmed complete response had been maintained. At present the patient is in a follow-up program to evaluate the duration of the complete response.</p> <p>Conclusions</p> <p>This case is worth mentioning since, to the best of our knowledge, it represents the first evidence of complete response to sorafenib in an elderly patient with advanced HCV-related HCC.</p

Laser ablation is superior to TACE in large-sized hepatocellular carcinoma: A pilot case-control study

Background:Limited therapies are available for large ( 6540 mm) unresectable hepatocellular carcinoma (HCC). Currently, the standard treatment with transarterial chemoembolisation (TACE) is unsatisfactory with high recurrence rate and limited effect on survival. Laser Ablation (LA) has emerged as a relatively new technique characterized by high efficacy and good safety. This study is aimed to evaluate the efficacy of LA in comparison to TACE in patients with large HCC. Methods: Eighty-two patients with a single HCC nodule 6540 mm (BCLC stage A or B) were enrolled in this case-control study. Forty-one patients were treated with LA and 41 patients were treated with TACE. Response to therapy was evaluated according to the mRECIST criteria. Survival was calculated with Kaplan-Meier from the time of cancer diagnosis to death with values censored at the date of the last follow-up. Results: Twenty-six (63.4%) and 8 (19.5%) patients had a complete response after LA and TACE, respectively (p &lt; 0.001). Subsequently we stratified the HCCs in 3 categories according to the nodule size: 40-50 mm, 51-60 mm, and &gt; 60 mm. LA resulted superior to TACE especially in nodules ranging between 51 and 60 mm in diameter, with a complete response rate post-LA and post-TACE of 75% and 14.3%, respectively (p = 0.0133). The 36 months cumulative survival rate in patients treated with LA and TACE was 55.4% and 48.8%, respectively. The disease recurrence rates after LA and TACE were 19.5% and 75.0%, respectively. Conclusions: LA is a more effective therapeutic option than TACE in patients with solitary large HCC

Crescere a Trento. Indagine sui servizi socio-educativi per la prima infanzia

Nel primo semestre del 2010, il Dipartimento di Sociologia e Ricerca Sociale e il Servizio servizi all’Infanzia, Istruzione e Sport del Comune di Trento - in collaborazione con numerosi altri soggetti – hanno avviato e svolto l’indagine Crescere a Trento, sui servizi socio-educativi per la prima infanzia nel Comune di Trento. La ricerca era orientata a raccogliere dati utili per un’analisi su come le famiglie con bambine e bambini piccoli si organizzano per la loro cura ed educazione, sul bisogno di servizi e interventi per la prima infanzia, sui livelli di soddisfazione per i servizi esistenti, sulle ragioni della non frequenza dei nidi d’infanzia. La rilevazione ha coinvolto un campione probabilistico di famiglie, rappresentativo della popolazione di interesse. Il ricorso a un disegno di ricerca mixed-mode (questionario auto compilato via web, intervista telefonica, intervista faccia-a-faccia) fa di questa indagine anche un interessante esperimento metodologico. Questo quaderno presenta i principali risultati della ricerca e la metodologia adottata per l’indagine