Model-Based ISO 14971 Risk Management of EEG-Based Medical Devices.

Risk management (RM) is a key component of the development of modern medical devices (MD) to achieve acceptable functional safety and pass the regulatory process. The emerging availability of various techniques, languages, and tools that use model-based system engineering (MBSE) promises to facilitate the development and analysis of complex MD. In this paper, we show how to integrate RM principles and activities recommended in ISO 14971 medical standard into an MBSE-driven MD development process. We propose a method and framework capable of modeling essential RM concepts and performing RM and safety analysis in the early stages of the MD development life cycle. The framework extends OMG RAAML (Object Management Group Risk Analysis and Assessment Modeling Language) to the medical domain according to ISO 14971. We illustrate our approach using a case study of the e-Glass system developed for real-time EEG-based subject monitoring with the intended use of stress monitoring.Clinical Relevance-This facilitates the MD certification process by semi-automation of RM based on ISO 14971 and obtaining safe MD by design.

Approximate zero-crossing: a new interpretable, highly discriminative and low-complexity feature for EEG and iEEG seizure detection.

Objective. Long-term monitoring of people with epilepsy based on electroencephalography (EEG) and intracranial EEG (iEEG) has the potential to deliver key clinical information for personalised epilepsy treatment. More specifically, in outpatient settings, the available solutions are not satisfactory either due to poor classification performance or high complexity to be executed in resource-constrained devices (e.g. wearable systems). Therefore, we hypothesize that obtaining high discriminative features is the main avenue to improve low-complexity seizure-detection algorithms.Approach. Inspired by how neurologists recognize ictal EEG data, and to tackle this problem by targeting resource-constrained wearable devices, we introduce a new interpretable and highly discriminative feature for EEG and iEEG, namely approximate zero-crossing (AZC). We obtain AZC by applying a polygonal approximation to mimic how our brain selects prominent patterns among noisy data and then using a zero-crossing count as a measure of the dominating frequency. By employing Kullback-Leiber divergence, leveraging CHB-MIT and SWEC-ETHZ iEEG datasets, we compare the AZC discriminative power against a set of 56 classical literature features (CLF). Moreover, we assess the performances of a low-complexity seizure detection method using only AZC features versus employing the CLF set.Main results. Three AZC features obtained with different approximation thresholds are among the five with the highest median discriminative power. Moreover, seizure classification based on only AZC features outperforms an equivalent CLF-based method. The former detects 102 and 194 seizures, against 99 and 161 for the latter (CHB-MIT and SWEC-ETHZ, respectively). Moreover, the AZC-based method keeps a similar false-alarm rate (i.e. an average of 2.1 and 1.0, against 2.0 and 0.5, per day).Significance. We propose a new feature and demonstrate its capability in seizure classification for both scalp and intracranial EEG. We envision the use of such a feature to improve outpatient monitoring with resource-constrained devices.

Unmanned aerial vehicles (UAVs) as a tool for hazard assessment: The 2021 eruption of Cumbre Vieja volcano, La Palma Island (Spain).

Monitoring for assessment of natural disasters, such as volcanic eruptions, presents a methodological challenge for the scientific community. Here, we present Unmanned Aerial Vehicles (UAVs) as a feasible, precise, rapid and safe tool for real time monitoring of the impacts of a volcanic event during the Cumbre Vieja eruption on La Palma Island, Spain (2021). UAV surveys with optical RGB (Red-Green-Blue), thermal and multispectral sensors, and a water sampling device, were carried out in different areas affected by the lava flow, including the upper volcanic edifice and the lava delta formed on the coastal fringe of the island. Our results have provided useful information for the monitoring of the advance of the lava flow and its environmental consequences during the volcanic emergency. Our data shows how La Palma island's growth, with the formation of a new lava delta of 28 ha and a total volume of lava injected into the sea of 5,138,852 m3. Moreover, our Digital Elevation Model (DEM) simulated, with a 70 % accuracy, the probabilistic simulation of the possible path followed by the lava flow in the vicinity of the fissure from which the magma emanates. In addition, significant changes of seawater physical-chemical parameters were registered in coastal surface waters by the in situ seawater samples collected with the automatic water sampling device of our UAV. The first meters of the water column, due to the instant evaporation of the seawater in contact with the hot lava, produce an increase of temperature and salinity of up to 4-5 °C and up to 5 units, respectively.

Predicted vitamin D status and colon cancer recurrence and mortality in CALGB 89803 (Alliance).

BACKGROUND: Observational studies suggest that higher levels of 25-hydroxyvitamin D3 (25(OH)D) are associated with a reduced risk of colorectal cancer and improved survival of colorectal cancer patients. However, the influence of vitamin D status on cancer recurrence and survival of patients with stage III colon cancer is unknown. PATIENTS AND METHODS: We prospectively examined the influence of post-diagnosis predicted plasma 25(OH)D on outcome among 1016 patients with stage III colon cancer who were enrolled in a National Cancer Institute-sponsored adjuvant therapy trial (CALGB 89803). Predicted 25(OH)D scores were computed using validated regression models. We examined the influence of predicted 25(OH)D scores on cancer recurrence and mortality (disease-free survival; DFS) using Cox proportional hazards. RESULTS: Patients in the highest quintile of predicted 25(OH)D score had an adjusted hazard ratio (HR) for colon cancer recurrence or mortality (DFS) of 0.62 (95% confidence interval [CI], 0.44-0.86), compared with those in the lowest quintile (Ptrend = 0.005). Higher predicted 25(OH)D score was also associated with a significant improvement in recurrence-free survival and overall survival (Ptrend = 0.01 and 0.0004, respectively). The benefit associated with higher predicted 25(OH)D score appeared consistent across predictors of cancer outcome and strata of molecular tumor characteristics, including microsatellite instability and KRAS, BRAF, PIK3CA, and TP53 mutation status. CONCLUSION: Higher predicted 25(OH)D levels after a diagnosis of stage III colon cancer may be associated with decreased recurrence and improved survival. Clinical trials assessing the benefit of vitamin D supplementation in the adjuvant setting are warranted. CLINICALTRIALS.GOV IDENTIFIER: NCT00003835.

[A new species of amphipod crustacean of the genus Amphilochus (Crustacea, Amphipoda, Amphilochidae) from Venezuela]. / Una nueva especie de anfípodo del género Amphilochus (Crustacea, amphipoda, Amphilochidae) de Venezuela.

A new species of amphipod Crustacea (Gammaridea, Amphilochidae) of the genus Amphilochus Bate, 1862, is described. The species was collected in Phallusia nigra (Savigny, 1816) at depths between 0 and 2 m, in the pier piles of the Marina El Ancla and Los Manglares gas station in Morrocoy National Park (Falcón State, Venezuela), during the months of June and July 1998. The main differences between A. ascidicola new species and all others species of the genus recorded from the Gulf of Mexico and the Caribbean Sea, are given.

Phase II study of oral etoposide for patients with advanced breast cancer.

BACKGROUND: The objective of this study was to define the activity and toxicity of etoposide for patients with previously treated metastatic breast cancer. METHODS: Thirty patients with measurable metastatic breast cancer who progressed after prior chemotherapy, hormonal therapy, or both, either as adjuvant therapy or for metastatic disease, were enrolled. There were 26 patients evaluable for response and 30 evaluable for toxicity. Treatment consisted of oral etoposide at a dose of 50 mg/m2/day administered for 21 consecutive days. Doses were modified depending on toxicity. Patients were evaluable for response after at least one cycle of therapy. RESULTS: One complete response and four partial responses were observed. The overall objective response rate was 19% (5/26). Six patients had stable disease. Toxicity consisted mainly of Grade 4 neutropenia for 24% and Grade 4 thrombocytopenia for 13% of patients. There was one death due to neutropenic sepsis. CONCLUSION: Oral etoposide is an effective, easily administered outpatient regimen with minimal toxicities. Etoposide is effective for patients with pretreated metastatic breast cancer.

Severe diabetic retinopathy after cataract surgery.

We retrospectively compared the visual acuity and degree of background diabetic retinopathy in 32 consecutive patients with diabetes who had cataract surgery in one eye (study group) and compared them with the visual acuity and degree of diabetic retinopathy in 32 patients with diabetes who had not had cataract surgery (control group) to determine if the retinopathy was asymmetric and worse in the operated-on eye. Twenty-three (72%) of the 32 study patients had asymmetric retinopathy (with the more severe retinopathy in the eye that underwent cataract surgery in each case) compared with three (9%) of the control group (P < .0005). The eyes that had cataract surgery did poorly in terms of visual acuity with no eyes achieving 20/20 or 20/25, only three eyes achieving 20/30 or 20/40, and 16 achieving 20/100 or worse.

Prolactin-producing pituitary carcinoma with pulmonary metastases.

Pituitary adenomas rarely are metastatic. Extracranial visceral metastases of prolactinomas were not previously reported. The authors report a case of a 34-year-old man with a prolactin-producing pituitary carcinoma and histologically proven lung metastases. Pathologic examination of the pulmonary spread included electron microscopy and immunohistochemistry; these confirmed prolactin production by the tumor. The patient's presentation at initial diagnosis, disease recurrence, clinical course, management, and response to therapy (with its theoretic basis) are detailed. Despite the use of dopamine analogues (to tolerance and in combination), there was documented intracranial and extracranial disease progression. Possible future therapeutic maneuvers are discussed.