High-frequency QRS analysis compared to conventional ST-segment analysis in patients with chest pain and normal ECG referred for exercise tolerance test

Background: The novel analysis of high-frequency QRS components (HFQRS-analysis) has been proposed in patients with chest pain (CP) and normal electrocardiography (ECG) referred for exercise tolerance test (ex-ECG). The aim of the study was to compare the diagnostic value of ex-ECG with ex-HFQRS-analysis. Methods: Patients with CP and normal ECG, troponin, and echocardiography were consid­ered. All patients underwent ex-ECG for conventional ST-segment-analysis and ex-HFQRS-analysis. A decrease ≥ 50% of the HFQRS signal intensity recorded in at least 2 contiguous leads was considered an index of ischemia, as ST-segment depression ≥ 2 mm or ≥ 1 mm and CP on ex-ECG. Exclusion criteria were: QRS duration ≥ 120 ms and inability to exercise. End-point: The composite of coronary stenosis ≥ 70% or acute coronary syndrome, revascu­larization, cardiovascular death at 3-month follow-up. Results: Three-hundred thirty-seven patients were enrolled (age 60 ± 15 years). The percent­age of age-adjusted maximal predicted heart rate was 89 ± 10 beat per minute and the maximal systolic blood pressure was 169 ± 23 mm Hg. Nineteen patients achieved the end-point. In multivariate analysis, both ex-ECG and ex-HFQRS were predictors of the end-point. The ex-HFQRS-analysis showed higher sensitivity (63% vs. 26%; p < 0.05), lower specificity (68% vs. 95%; p < 0.001), and comparable negative predictive value (97% vs. 96%; p = 0.502) when compared to ex-ECG-analysis. Receiver operator characteristics analysis showed the incremental diagnostic value of HFQRS (area: 0.655, 95% CI 0.60–0.71) over conventional ex-ECG (0.608, CI 0.55–0.66) and CP score (0.530, CI 0.48–0.59), however without statistical significance in pairwise comparison by C-statistic. Conclusions: In patients with CP submitted to ex-ECG, the novel ex-HFQRS-analysis shows a valuable incremental diagnostic value over ST-segment-analysis

Do you Trust your Device? Open Challenges in IoT Security Analysis

Several critical contexts, such as healthcare, smart cities, drones, transportation, and agriculture, nowadays rely on IoT, or more in general embedded, devices that require comprehensive security analysis to ensure their integrity before deployment. Security concerns are often related to vulnerabilities that result from inad- equate coding or undocumented features that may create significant privacy issues for users and companies. Current analysis methods, albeit dependent on complex tools, may lead to superficial assessments due to compatibility issues, while authoritative entities struggle with specifying feasible firmware analysis requests for manufacturers within operational contexts. This paper urges the scientific community to collaborate with stakeholders—manufacturers, vendors, security analysts, and experts—to forge a cooperative model that clari- fies manufacturer contributions and aligns analysis demands with operational constraints. Aiming at a modular approach, this paper highlights the crucial need to refine security analysis, ensuring more precise requirements, balanced expectations, and stronger partnerships between vendors and analysts. To achieve this, we propose a threat model based on the feasible interactions of actors involved in the security evaluation of a device, with a particular emphasis on the responsibilities and necessities of all entities involved

Contribution of MUTYH variants to male breast cancer risk: results from a multicenter study in Italy

Inherited mutations in BRCA1, and, mainly, BRCA2 genes are associated with increased risk of male breast cancer (MBC). Mutations in PALB2 and CHEK2 genes may also increase MBC risk. Overall, these genes are functionally linked to DNA repair pathways, highlighting the central role of genome maintenance in MBC genetic predisposition. MUTYH is a DNA repair gene whose biallelic germline variants cause MUTYH-associated polyposis (MAP) syndrome. Monoallelic MUTYH variants have been reported in families with both colorectal and breast cancer and there is some evidence on increased breast cancer risk in women with monoallelic variants. In this study, we aimed to investigate whether MUTYH germline variants may contribute to MBC susceptibility. To this aim, we screened the entire coding region of MUTYH in 503 BRCA1/2 mutation negative MBC cases by multigene panel analysis. Moreover, we genotyped selected variants, including p.Tyr179Cys, p.Gly396Asp, p.Arg245His, p.Gly264Trpfs*7, and p.Gln338His, in a total of 560 MBC cases and 1,540 male controls. Biallelic MUTYH pathogenic variants (p.Tyr179Cys/p.Arg241Trp) were identified in one MBC patient with phenotypic manifestation of adenomatous polyposis. Monoallelic pathogenic variants were identified in 14 (2.5%) MBC patients, in particular, p.Tyr179Cys was detected in seven cases, p.Gly396Asp in five cases, p.Arg245His and p.Gly264Trpfs*7 in one case each. The majority of MBC cases with MUTYH pathogenic variants had family history of cancer including breast, colorectal, and gastric cancers. In the case-control study, an association between the variant p.Tyr179Cys and increased MBC risk emerged by multivariate analysis [odds ratio (OR) = 4.54; 95% confidence interval (CI): 1.17-17.58; p = 0.028]. Overall, our study suggests that MUTYH pathogenic variants may have a role in MBC and, in particular, the p.Tyr179Cys variant may be a low/moderate penetrance risk allele for MBC. Moreover, our results suggest that MBC may be part of the tumor spectrum associated with MAP syndrome, with implication in the clinical management of patients and their relatives. Large-scale collaborative studies are needed to validate these findings

Management of Asymptomatic Sporadic Nonfunctioning Pancreatic Neuroendocrine Neoplasms (ASPEN) <= 2 cm: Study Protocol for a Prospective Observational Study

Introduction: The optimal treatment for small, asymptomatic, nonfunctioning pancreatic neuroendocrine neoplasms (NF-PanNEN) is still controversial. European Neuroendocrine Tumor Society (ENETS) guidelines recommend a watchful strategy for asymptomatic NF-PanNEN <2 cm of diameter. Several retrospective series demonstrated that a non-operative management is safe and feasible, but no prospective studies are available. Aim of the ASPEN study is to evaluate the optimal management of asymptomatic NF-PanNEN ≤2 cm comparing active surveillance and surgery. Methods: ASPEN is a prospective international observational multicentric cohort study supported by ENETS. The study is registered in ClinicalTrials.gov with the identification code NCT03084770. Based on the incidence of NF-PanNEN the number of expected patients to be enrolled in the ASPEN study is 1,000 during the study period (2017–2022). Primary endpoint is disease/progression-free survival, defined as the time from study enrolment to the first evidence of progression (active surveillance group) or recurrence of disease (surgery group) or death from disease. Inclusion criteria are: age >18 years, the presence of asymptomatic sporadic NF-PanNEN ≤2 cm proven by a positive fine-needle aspiration (FNA) or by the presence of a measurable nodule on high-quality imaging techniques that is positive at 68Gallium DOTATOC-PET scan. Conclusion: The ASPEN study is designed to investigate if an active surveillance of asymptomatic NF-PanNEN ≤2 cm is safe as compared to surgical approach

Secure and User-Friendly Commissioning and Bootstrapping of Constrained Devices

The spread of Internet of Things (IoT) systems, based on the introduction of constrained devices into physical objects, has required particular efforts to improve security, privacy and simplicity of such systems. The goal of this work is to find secure and user-friendly ways for the commissioning and bootstrapping of constrained devices, working with Bluetooth Low Energy (BLE) as the main wireless communication technology. An important assumption for future constrained devices is the absence of input/output interfaces like keyboards and displays. That represents the real challenge which makes the traditional security mechanisms unfeasible. At first, an analysis of some products from the current generation of IoT systems has shown a lack in term of security or simplicity. Starting from these results this work defines the security requirements to ensure authentication and confidentiality/integrity for the information exchanged. Then it presents some user-friendly solutions to initiate such devices based on the security requirements defined. These solutions require only few interactions and knowledge for the final users. After a study of the security features offered by BLE and defined the user-friendliness level required, scenarios that combine BLE and NFC technologies seem to be the best solutions. NFC can be used as the Out-of- Band (OOB) channel for BLE pairing method, providing authentication and limiting the risk of Man In The Middle (MITM) attacks and passive eavesdropping. This combination also increase the simplicity and avoid typical authentication techniques like passkey insertion. The conjunction BLE-NFC can be easily managed to produce several solutions for different scenarios. Scenario with movable devices represents the easiest solution. Instead, fixed targets require support devices, like smartphone or tablet, to reach the goal. However, both are based on the same principles. The presented solutions aim to be considered for the next generation of IoT systems, increasing security and user-friendly level. Current and near future chips combine BLE and NFC in a unique product which make the solutions low cost and easy to implement

The early Pleistocene vertebrate fauna of Mulhuli-Amo (Buia area, Danakil Depression, Eritrea)

Mulhuli-Amo is an early Pleistocene locality of the Buia area in the Dandiero Basin (Danakil Depression, Eritrea) already known for the presence of Homo remains and stone tools. Recent surface surveys lead to the retrieval of a rich vertebrate fauna that is here described for the first time in order to contribute to the palaeoenvironmental background to the Homo layers of the basin. The following 14 taxa (two fishes, four reptiles, one bird, and nine mammals) were identified: Clarias (Clarias) sp., ?Cichlidae indet., Crocodylus sp., Pelusios sinuatus, Varanus niloticus, Python gr. P. sebae, Ardeotis kori, Palaeoloxodon cf. P. recki, Ceratotherium simum, Equus cf. E. quagga, Hippopotamus gorgops, Kolpochoerus majus, Bos cf. B. buiaensis, and Kobus cf. K. ellipsiprymnus. With the exception of a fish and the bird that were identified at Mulhuli-Amo for the first time, the whole fauna is fully congruent with the taxa already described for the neighbouring locality of Uadi Aalad and confirms, in agreement with all the other proxies, an early Pleistocene age and the former presence of moist grassed habitats adjacent to persistent water.[I vertebrati del Pleistocene inferiore di Mulhuli-Amo (area di Buia, Depressione Dancala, Eritrea)] - Il Progetto Buia nasce nel 1994 come un progetto di ricognizione geologica finalizzato allo studio della geologia regionale di un'area circa 20 Km a sud di Buia nella Dancalia settentrionale (Eritrea) ma, già a partire dalle prime missioni, il rinvenimento di resti umani associati a strumenti litici e ad una ricca fauna di vertebrati ha ampliato notevolmente le prospettive di ricerca. I primi resti umani sono stati identificati nel 1995 in un livello della località Uadi Aalad attribuito al Subcrono Jaramillo e datato a circa 1.0 Ma. Successivamente, a partire dal dicembre 2000, ulteriori resti umani sono stati ritrovati a Mulhuli-Amo, una località lontana circa 5 Km dalla prima, già conosciuta per un eccezionale accumulo di strumenti litici e di resti di vertebrati. In questo lavoro viene descritta per la prima volta in modo unitario la fauna vertebrata non umana rinvenuta in superficie a Mulhuli-Amo. Complessivamente, sono stati identificati i seguenti 14 taxa: Clarias (Clarias) sp., ?Cichlidae indet., Crocodylus sp., Pelusios sinuatus, Varanus niloticus, Python gr. P. sebae, Ardeotis kori, Palaeoloxodon cf. P. recki, Ceratotherium simum, Equus cf. E. quagga, Hippopotamus gorgops, Kolpochoerus majus, Bos cf. B. buiaensis, Kobus cf. K. ellipsiprymnus. L'associazione faunistica è pienamente congruente con quella di Uadi Aalad e, nonostante sia meno diversificata di questa, presenta alcuni elementi di novità (?Cichlidae indet., Ardeotis kori). Alcuni mammiferi (Palaeoloxodon cf. P. recki, E. cf. E. quagga, H. gorgops, K. majus, B. cf. B. buiaensis) confermano l'attribuzione della fauna al Pleistocene inferiore finale. Da un punto di vista ambientale, l'associazione faunistica suggerisce la presenza di raccolte permanenti d'acqua circondate da praterie umide, in netto contrasto con gli ambienti attuali estremamente aridi

Integrated ultrasonographic approach to evaluate fluid responsiveness in critically ill patients

Abstract In patients with acute circulatory failure, we tested the feasibility of the evaluation of the fluid-responsiveness (FR) by a combined approach with echocardiography and lung ultrasound. We enrolled 113 consecutive patients admitted to the Emergency Department High-Dependency Unit of Careggi University-Hospital from January 2015 to June 2020. We assessed: (1) inferior vena cava collapsibility index (IVCCI); (2) the variation of aortic flow (VTIAo) during the passive leg raising test (PLR); (3) the presence of interstitial syndrome by lung ultrasound. FR was defined as an increase in the VTIAo > 10% during PLR or IVCCI ≥ 40%. FR patients were treated with fluid and those non-FR with diuretics or vasopressors. The therapeutic strategy was reassessed after 12 h. The goal was to maintain the initial strategy. Among 56 FR patients, at lung ultrasound, 15 patients showed basal interstitial syndrome and 4 all-lung involvement. One fluid bolus was given to 51 patients. Among 57 non-FR patients, 26 patients showed interstitial syndrome at lung ultrasound (basal fields in 14, all lungs in 12). We administered diuretics to 21 patients and vasopressors to 4 subjects. We had to change the initial treatment plan in 9% non-FR patients and in 12% FR patients (p = NS). In the first 12 h after the evaluation, non-FR patients received significantly less fluids compared to those FR (1119 ± 410 vs 2010 ± 1254 ml, p < 0.001). The evaluation of the FR based on echocardiography and lung ultrasound was associated with the reduction in fluid administration for non-FR patients compared with those FR