Use and misuse of P-values: a conditional approach to post-model-selection inference

Adaptive generation of hypotheses is among the main culprits of the lack of replicability in science. Under conditions of uncertainty, the statements, or the process that generates them, can only be trusted if the reported error rates are reflected in the replication attempts. The discrepancy between the two is due to many factors, but interactive data analysis plays a major role in the inflation of type I error. In this regard, inference after model selection is of particular interest because its misuse can be analyzed through a Monte Carlo simulation. As the findings of this thesis show, inflation of type I error can be quite severe even in low dimensional scenarios, with up to 40% of false positives in the selected set of variables. Depending on the model selection strategy and the structure of the true data-generating mechanism, this percentage varies greatly. The results of the simulation show different performances between the Least Absolute Shrinkage and Selection Operator (LASSO) and the Forward Selection (FS). In particular, the LASSO yields a type I error lower than the FS when the structure of the true data-generating mechanism is additive and a higher one when the structure is multiplicative. The results also provide additional empirical evidence that given an extensive class of problems, most methods will provide on average comparable solutions. As shown in this thesis, the conditional probability approach to selective inference represents a viable solution to control type I error while avoiding any data loss due to data splitting. In the current research environment, incentives and funding policies need to be reshaped in order to bring about effective changes on the overall reliability of the published papers, but the tools to provide rigorous results, while meeting the needs of the researchers, are available for anyone conscientious enough.Adaptive generation of hypotheses is among the main culprits of the lack of replicability in science. Under conditions of uncertainty, the statements, or the process that generates them, can only be trusted if the reported error rates are reflected in the replication attempts. The discrepancy between the two is due to many factors, but interactive data analysis plays a major role in the inflation of type I error. In this regard, inference after model selection is of particular interest because its misuse can be analyzed through a Monte Carlo simulation. As the findings of this thesis show, inflation of type I error can be quite severe even in low dimensional scenarios, with up to 40% of false positives in the selected set of variables. Depending on the model selection strategy and the structure of the true data-generating mechanism, this percentage varies greatly. The results of the simulation show different performances between the Least Absolute Shrinkage and Selection Operator (LASSO) and the Forward Selection (FS). In particular, the LASSO yields a type I error lower than the FS when the structure of the true data-generating mechanism is additive and a higher one when the structure is multiplicative. The results also provide additional empirical evidence that given an extensive class of problems, most methods will provide on average comparable solutions. As shown in this thesis, the conditional probability approach to selective inference represents a viable solution to control type I error while avoiding any data loss due to data splitting. In the current research environment, incentives and funding policies need to be reshaped in order to bring about effective changes on the overall reliability of the published papers, but the tools to provide rigorous results, while meeting the needs of the researchers, are available for anyone conscientious enough

Inguino-abdominal combined approach for laterally extended pelvic resection: a step by step procedure

This video article demonstrates an inguino-abdominal combined approach for laterally extended pelvic resection, a major surgical procedure for locally advanced primary or recurrent gynecological cancer infiltrating the pelvic sidewall, for which palliative therapy is the only alternative.1 After local institutional review board approval (protocol No CICOG 02/03/62), we made a step by step surgical video of an inguino-abdominal combined approach for laterally extended pelvic resection , defined as an en bloc resection of a pelvic tumor with pelvic sidewall structures, including the iliopsoas and/or obturator internus muscles.2 3 The patient, a 48-year-old woman, diagnosed with single pelvic platinum resistant recurrence after five lines of chemotherapy for serous ovarian cancer G3, International Federation of Gynecology and Obstetrics (FIGO) stage IIIC, BRCA wild type. The preoperative positron emission tomography/computed tomography scan detected uptake on the right side at the level of the external iliac region and obturator fossa: the tumor surrounded the right external iliac vessels by more than 50% of their circumferences, with possible involvement of the vascular wall and venous vascular compression (Tinelli's score=4).4 The tumor extended towards the obturator fossa, with possible involvement of the inguinal canal. Due to an uncertain pathological response, the size of the recurrence, and its close contiguity with the ureter and bowel, we decided to avoid radiation therapy as it could result in a ureteral or intestinal fistula. We performed a laterally extended pelvic resection, as shown step by step in the video.The procedure was conducted until complete removal of recurrence (R0). Estimated blood loss was 1000 mL and total operative time was 240 min. The patient was discharged after 15 days; we reported a urinary infection, a likely postoperative complication. The pathology report described a lymphnodal relapse of ovarian cancer (diameter=6 cm) with infiltration of surrounding tissue and in the sano margins. Six months after surgery, the patient is alive without evidence of relapse.The borders of pelvic surgical anatomy are continually extending, requiring surgeons to use a personalized approach and to continually update their anatomic knowledge. In this context, laterally extended pelvic resection could be a feasible surgical procedure, representing a salvage treatment in recurrent or persistent primary gynecological malignancies infiltrating the pelvic sidewall, when other approaches have failed. However, additional clinical trials are needed to confirm these results.

Fogli 609-596, Termini Imerese-Capo Plaia

Il Servizio Geologico Nazionale ha unificato i Fogli 609 "Termini Imerese" e 596 "Capo Plaia" in un unico Foglio denominato 609/596 "Termini Imerese-Capo Plaia" allo scopo di uniformare i rilievi e raccoglierne la descrizione in un unico volume delle Note Illustrative. Il Foglio 609/596 "Termini Imerese-Capo Plaia" della Carta Geologica d’Italia in scala 1:50.000 è stato realizzato nell’ambito del Progetto CARG con i fondi della Legge 67/88 - Legge 226/99 con una convenzione tra Servizio Geologico Nazionale ora ISPRA) e Regione Siciliana. Le aree ricadono interamente nella Provincia di Palermo, comprendono la fascia marina del Golfo di Termini Imerese fino al promontorio di Capo Plaia, la regione dei Monti di Termini Imerese e Trabia ad ovest e il settore occidentale del gruppo montuoso delle Madonie ad est. Tra questi rilievi si sviluppa un’ampio settore collinare inciso dai fiumi Torto e Imera settentrionale (o Fiume Grande)

Epidemiology and Microbiology of Skin and Soft Tissue Infections: Preliminary Results of a National Registry

Skin and soft tissue infections (SSTIs) represent a wide range of clinical conditions characterized by a considerable variety of clinical presentations and severity. Their aetiology can also vary, with numerous possible causative pathogens. While other authors previously published analyses on several types of SSTI and on restricted types of patients, we conducted a large nationwide surveillance programme on behalf of the Italian Society of Infectious and Tropical Diseases to assess the clinical and microbiological characteristics of the whole SSTI spectrum, from mild to severe life-threatening infections, in both inpatients and outpatients. Twenty-five Infectious Diseases (ID) Centres throughout Italy collected prospectively data concerning both the clinical and microbiological diagnosis of patients affected by SSTIs via an electronic case report form. All the cases included in our database, independently from their severity, have been managed by ID specialists joining the study while SSTIs from other wards/clinics have been excluded from this analysis. Here, we report the preliminary results of our study, referring to a 12-month period (October 2016–September 2017). During this period, the study population included 254 adult patients and a total of 291 SSTI diagnoses were posed, with 36 patients presenting more than one SSTIs. The type of infection diagnosed, the aetiological micro-organisms involved and some notes on their antimicrobial susceptibilities were collected and are reported herein. The enrichment of our registry is ongoing, but these preliminary results suggest that further analysis could soon provide useful information to better understand the national epidemiologic data and the current clinical management of SSTIs in Italy

Chest wall TB and low 25-hidroxy-vitamin D levels in a 15-month-old girl

Parietal chest wall tuberculosis is an extremely rare manifestation of tuberculosis (TB) in children. We present the case of a 15 month-old girl presenting with a chest wall lesion initially thought to be of neoplastic origin and eventually diagnosed as chest wall TB, which was treated with surgical debridement and specific antitubercular therapy. The girl had not-measurable 25-hidroxy-vitamin D levels, an increasingly recognized risk factor for the development of active TB. To our knowledge, in the English literature there are no similar described cases in such young infants. This case highlight the possibility of dealing with TB and its different manifestations also in low TB burden countries, due to continuously increasing migration flows. A detailed history is a key point to reach the diagnosis. Moreover, our case confirm the possible non casual relationship between TB and low 25-hidroxy-vitamin D levels, pointing out the importance of measuring its levels in all TB patients and considering its supplementation in addition to specific antitubercular therapy

Malaria and the heart: Two rare case reports of plasmodium falciparum-associated pericarditis

Malaria is one of the most important parasitic diseases in the world, causing significant mortality and morbidity in the tropical regions1 . Although symptoms can range from a mild fever to severe complicated forms, there are limited published data on cardiac involvement of malaria and only a few studies have been carried out regarding cardiac function in severe malaria2–3. Cardiac involvement in the course of malaria ranges from severe forms with hypatension, shock, circulatory collapse and impaired haemodynamic function, to mild disorders documented by Electrocardiogram (ECG) and echocardiography4–6. Pericardial involvement in malaria is a very rare event7–8. We report here two cases of falciparum malaria complicated with pericardial effusion

Efficacy and safety of dolutegravir and doravirine dual therapy in the context of antiretroviral therapy switch: 48 weeks analysis.

Dual therapy in HIV represents an attractive opportunity for HIV infected people in virologic suppression Dual therapy regimens should achieve and maintain viral suppression and immunologic control while minimizing short and long term AEs, improve adherence and convenience and reduce drug drug interactions and costs To date, there are few clinical data to support a dual regimen with dolutegravir and doravirine 1 The individual efficacy of both doravirine and dolutegravir suggests that concomitant administration of these two molecules as part of an NRTI sparing regimen could be a viable option, although to date there are no studies in the HIV infected population The aim of our study is to investigate whether a dual therapy regimen containing dolutegravir and doravirine is effective and saf

Exploratory thermal and fluid-dynamic assessment of a pin of the Helium cooled pebble bed breeding blanket concept with a modular pin monoblock design for the EU DEMO nuclear fusion reactor

The Helium-Cooled Pebble-Bed (HCPB) Breeding Blanket (BB) concept is one of the two candidates eligible for the driver blanket for the EU-DEMO nuclear fusion reactor. It foresees gaseous helium at high pressure as a coolant and tritium carrier, and solid tritium breeder and neutron multiplier. In order to overcome the potential showstoppers that emerged during its pre-conceptual design phase, alternative HCPB BB variants are under consideration in the frame of the DEMO studies. Among them, the concept envisaging a modular pin monoblock presents the advantages of having all the functional materials contained in a pin structure and of avoiding the need for a first wall, remarkably simplifying manufacturing. Hence, in this work, a campaign of thermofluid-dynamic scoping analyses aimed at assessing the performances of this novel BB concept is presented. To this scope, different geometric layouts have been assessed under a wide range of loading conditions and evaluating the sensitivity to key parameters, through cost-effective 2D CFD models. As an outcome, two promising geometric configurations ensuring both temperatures in line with the design requirements and an acceptable pressure drop have been found to be further assessed from the structural standpoint in a second phase of the activity