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Anticoagulant rodenticides (ARs) are potent pesticides acting as vitamin K epoxide reductase inhibitors causing haemorrhaging or external bleeding from orifices and/or skin lesions in intoxicated rodents. However, their non-selective mode of action makes them particularly harmful for non-target wildlife, which may be exposed to ARs via ingestion of AR-containing baits (primary exposure), feeding on AR-intoxicated rodents and carrions (secondary exposure), consuming AR-contaminated necrophagous species (tertiary exposure), and exposure to surface waters receiving baited sewer systems and ARs from outdoor-placed traps after heavy rain events. In the present study, we assessed the suitability of hairs as a non-invasive matrix for monitoring the possible exposure of mammals to ARs with a focus on the first-generation anticoagulant rodenticides (FGARs) warfarin, coumatetralyl, and chlorophacinone and the second-generation anticoagulant rodenticides (SGARs) brodifacoum, bromadiolone, difenacoum, flocoumafen, and difethialone. The Red fox (n = 24) was selected as the species representing the potentially exposed non-target wildlife in a littoral area of Northern Italy along the Adriatic coast (Cavallino-Treporti municipality). Half (n = 12) of the analysed hair samples were positive for at least one of the targeted ARs, with a higher prevalence of SGARs (n = 11; 46%) compared to FGARs (n = 1; 4%). The most frequently quantified ARs were brodifacoum (25%), difethialone (13%), and flocoumafen (13%), with concentrations ranging from 0.08 ng g -1 (difethialone) to 0.96 ng g -1 (brodifacoum). These data documented that a relevant part of the Red foxes living in the study area were exposed to ARs and, most importantly, provided the first evidence that hair residues can be used as a non-invasive matrix for assessing the possible exposure of mammals to ARs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

To quantify the possible impact of different wood protection techniques on the aquatic environment, we applied a tiered Integrated Testing Strategy (ITS) on leachates obtained from untreated (UTW) Norway spruce (Picea abies), specimens treated with a copper-ethanolamine-based preservative solution, complying with the Use Class 3 (UC3), and specimens thermally modified (TM). Different maturation times in water were tested to verify whether toxicant leaching is time-dependent. Tier I tests, addressing acute effects on Aliivibrio fischeri, Raphidocelis subcapitata, and Daphnia magna, evidenced that TM toxicity was comparable or even lower than in UTW. Conversely, UC3 significantly affected all species compared to UTW, also after 30 days of maturation in water, and was not considered an environmentally acceptable wood preservation solution. Tier II (effects on early-life stages of Lymnea auricularia) and III (chronic effects on D. magna and L. auricularia) performed on UTW and TM confirmed the latter as an environmentally acceptable treatment, with increasing maturation times resulting in decreased adverse effects. The ITS allowed for rapid and reliable identification of potentially harmful effects due to preservation treatments, addressed the choice for a less impacting solution, and can be effective for manufacturers in identifying more environmentally friendly solutions while developing their products., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Feather analysis is an ethical and effective method for assessing the exposure of wild birds to environmental contamination due to trace elements and organic pollutants. We used feather to monitor the exposure to three toxic and non-essential metals (Hg, Cd, and Pb) and rare earth elements (REEs) of Kentish plover (Charadrius alexandrinus) breeding in different coastal areas (Veneto, Emilia-Romagna, Marche, Abruzzo, and Apulia) along the Italian coast of the Adriatic Sea. Feathers (n = 113) were collected from April to June. Feather concentrations evidenced a significant exposure to Hg (13.05 ± 1.71 mg kg -1 dw) and REEs (447.3 ± 52.8 ng g -1 dw) in the Kentish plover breeding in Veneto (n = 21) compared to the other coastal areas, with several individuals showing Hg concentrations above the adverse effect (5 mg kg -1 dw) and high-risk (9.14 mg kg -1 dw) thresholds reported for birds. Higher REE concentrations compared to Marche (n = 29), Abruzzo (n = 11) and Apulia (n = 13) were also reported for birds breeding in Emilia-Romagna (474.9 ± 41.9 ng g -1 dw; n = 29). The exposure to Cd and Pb was low in all the coastal areas, and only a few samples (n = 6 and n = 4 for Cd and Pb, respectively) exceeded the adverse effect thresholds (0.1 and 4 mg kg -1 for Cd and Pb, respectively). A significant sex-related difference was observed for REE-concentrations, with females showing higher concentration than males. These data highlight the need to monitor the exposure of the Kentish plover to Hg and REEs, especially in the northern basin of the Adriatic Sea, since these elements might negatively affect species' reproductive success and threaten its conservation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Considerable efforts have been devoted to develop or adapt existing guidelines and protocols, to obtain robust and reproducible results from (eco)toxicological assays on engineered nanomaterials (NMs). However, while many studies investigated adverse effects of NMs on freshwater species, less attention was posed to the marine environment, a major sink for these contaminants. This review discusses the procedures used to assess the ecotoxicity of NMs in the marine environment, focusing on the use of protocols and methods for preparing NMs dispersions and on the NMs physicochemical characterization in exposure media. To this purpose, a critical analysis of the literature since 2010 was carried out, based on the publication of the first NMs dispersion protocols. Among the 89 selected studies, only <5 % followed a standardized dispersion protocol combined with NMs characterization in ecotoxicological media, while more than half used a non-standardized dispersion method but performed NMs characterization. In the remaining studies, only partial or no information on dispersion procedures or on physicochemical characterization was provided. This literature review also highlighted that metal oxides NMs were the most studied (42 %), but with an increasing interest in last years towards nanoplastics (14 %) and multicomponent nanomaterials (MCNMs, 7 %), in line with the growing attention on these emerging contaminants. For all these NMs, primary producers as algae and bacteria were the most studied groups of marine species, in addition to mollusca, while organisms at higher trophic levels were less represented, likely due to challenges in evaluating adverse effects on more complex organisms. Thus, despite the wide use of NMs in different applications, standard dispersion protocols are not often used for ecotoxicity testing with marine species. However, the efforts to characterize NMs in ecotoxicological media recognize the importance of following conditions that are as standardized as possible to support the ecological hazard assessment of NMs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: This study aimed to characterize patient-reported outcomes from social media conversations in the gout community. The impact of management strategy differences on the community's emotional states was explored., Methods: We analyzed two social media sources using a variety of natural language processing techniques. We isolated conversations with a high probability of discussing disease management (score > 0.99). These conversations were stratified by management type: proactive or reactive. The polarity (positivity/negativity) of language and emotions conveyed in statements shared by community members was assessed by management type., Results: Among the statements related to management, reactive management (e.g., urgent care) was mentioned in 0.5% of statements, and proactive management (e.g., primary care) was mentioned in 0.6% of statements. Reactive management statements had a significantly larger proportion of negative words (59%) than did proactive management statements (44%); "fear" occurred more frequently with reactive statements, whereas "trust" predominated in proactive statements. Allopurinol was the most common medication in proactive management statements, whereas reactive management had significantly higher counts of prednisone/steroid mentions., Conclusions: A unique aspect of examining gout-related social media conversations is the ability to better understand the intersection of clinical management and emotional impacts in the gout community. The effect of social media statements was significantly stratified by management type for gout community members, where proactive management statements were characterized by more positive language than reactive management statements. These results suggest that proactive disease management may result in more positive mental and emotional experiences in patients with gout., (© 2024. The Author(s).)

In this work, we analyze 12 meteorological events that occurred in the Mediterranean Sea during the period November 2011-November 2021 from a seismic point of view. In particular, we consider 8 Medicanes and 4 more common storms. Each of these events, in spite of the marked differences between them, caused heavy rainfall, strong wind gusts and violent storm surge with significant wave heights usually >3 m. We deal with the relationships between these meteorological events and the features of microseism (the most continuous and widespread seismic signal on Earth) in terms of spectral content, space-time variation of the amplitude and source locations tracked employing two different methods (amplitude decay-based grid search and array techniques). By comparing the positions of the microseism sources with the areas of significant storm surges, we observe that the microseism locations align with the actual locations of the storm surges for 10 out of 12 events analyzed (two Medicanes present very low intensity in terms of meteorological parameters and the microseism amplitude does not show significant variations during these two events). We also perform two analyses that allowed us to obtain both the seismic signature of these events, by using a method that exploits the coherence of continuous seismic noise, and their strength from a seismic point of view, called Microseism Reduced Amplitude. In addition, by integrating the results obtained from these two methods, we are able to "seismically" distinguish Medicanes and common storms. Consequently, we demonstrate the possibility of creating a novel monitoring system for Mediterranean meteorological events by incorporating microseism information alongside with other commonly employed techniques for studying meteorological phenomena. The integration of microseism with the data provided by routinely used techniques in sea state monitoring (e.g., wave buoy and HF radar) has the potential to offer valuable insights into the examination of historical extreme weather events within the context of climate change., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Prior research has established a link between thalamic pathology and cognitive impairment (CI) in people with multiple sclerosis (pwMS). However, the translation of these findings to pwMS in everyday clinical settings has been insufficient., Objective: To assess which global and/or thalamic imaging biomarkers can be used to identify pwMS at risk for CI and cognitive worsening (CW) in a real-world setting., Methods: This was an international, multi-center (11 centers), longitudinal, retrospective, real-word study of people with relapsing-remitting MS (pwRRMS). Brain MRI exams acquired at baseline and follow-up were collected. Cognitive status was evaluated using the Symbol Digit Modalities Test (SDMT). Thalamic volume (TV) measurement was performed on T2-FLAIR, as well as on T1-WI, when available. Thalamic dysconnectivity, T2-lesion volume (T2-LV), and volumes of gray matter (GM), whole brain (WB) and lateral ventricles (LVV) were also assessed., Results: 332 pwMS were followed for an average of 2.8 years. At baseline, T2-LV, LVV, TV and thalamic dysconnectivity on T2-FLAIR (p < 0.016), and WB, GM and TV volumes on T1-WI (p < 0.039) were significantly worse in 90 (27.1 %) CI vs. 242 (62.9 %) non-CI pwRRMS. Greater SDMT decline over the follow-up was associated with lower baseline TV on T2-FLAIR (standardized β = 0.203, p = 0.002) and greater thalamic dysconnectivity (standardized β = -0.14, p = 0.028) in a linear regression model., Conclusions: PwRRMS with thalamic atrophy and worse thalamic dysconnectivity present more frequently with CI and experience greater CW over mid-term follow-up in a real-world setting., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Robert Zivadinov has received personal compensation from Bristol Myers Squibb, EMD Serono, Sanofi, Janssen, Protembis, Filterlex and Novartis for speaking and consultant fees. He received financial support for research activities from Novartis, Bristol Myers Squibb, Octave, Mapi Pharma, Protembis, CorEvitas and V-WAVE Medical. Niels Bergsland and Dejan Jakimovski have nothing to disclose. Myassar Zarif, Samuel Hunter, Stephen Newman, Tom Fuchs and Mary Ann Picone have not declared any conflict of interest. Bianca Weinstock-Guttman received honoraria as a speaker and/or as a consultant for Biogen Idec, Sanofi &Genzyme, Genentech, Novartis, BMS, Bayer, Horizon and Janssen. Dr Weinstock-Guttman received research funds from Biogen Idec, Genentech and Novartis. Lorena Lorefice received honoraria for consultancy and speaking from Biogen, Novartis, Sanofi, Genzyme, Merck and Bristol Myers Squibb. Menno Schoonheim: Serves on the editorial board of Neurology and Frontiers in Neurology, receives research support from the Dutch MS Research Foundation, Eurostars-EUREKA, ARSEP, Amsterdam Neuroscience, MAGNIMS and ZonMW (Vidi grant, project number 09150172010056) and has served as a consultant for or received research support from Atara Biotherapeutics, Biogen, Celgene/Bristol Meyers Squibb, EIP, Sanofi, MedDay and Merck. Sarah A. Morrow, in the last 3 years, has served as an advisory board member or received consulting fees from Biogen Idec; BMS/Celgene; EMDSerono; Novartis; Roche; Sanofi. She has participated in a speaker’s bureau for Biogen Idec; BMS/Celgene; EMDSerono; Novartis; Roche; Sanofi. She has received research support from Biogen Idec; EMDSerono, Novartis, Roche; Sanofi Genzyme. She has participated as a site investigator in clinical trials sponsored by Bristol Myers Squibb/Celgene; EMDSerono; Novartis; Roche; Sanofi. Gabriel Pardo received grants (to the institution) from Biogen, EMD Serono, Roche/Genentech, Sanofi Genzyme, Novartis, Abbvie, and BMS; consultant and/or speaker bureau for Biogen, EMD Serono, Roche/Genentech, Sanofi Genzyme, Novartis, Janssen, BMS, TG Therapeutics, PRIME Education, and MSAA. Mark Gudesblatt received honoraria from Biogen and Genentech. Jacqueline Nicholas received research grants from Biogen, Novartis, PCORI, Genentech, University of Buffalo, EMD Serono; Consulting for EMD Serono, Genentech, Greenwich Biosciences, Novartis, TG Therapeutics and Sanofi; Speaking honoraria for BMS, EMD Serono, Horizon, TG Therapeutics. Andrew Smith received honorariums from EMD Serono and Sanofi Genzyme for speaking bureau and combination for Genzyme for an advisory board. Mahmoud A. AbdelRazek received consultant fees from Bristol Myers Squibb. Wachy Vongchucherd, Jon Riolo and Diego Silva are employees of Bristol Myers Squibb. Michael G. Dwyer has received personal compensation from Bristol Myers Squibb and Filterlex for consultant fees. He received financial support for research activities from Novartis, Bristol Myers Squibb, Octave, Mapi Pharma, Protembis, CorEvitas and V-WAVE Medical. Ralph HB. Benedict has received consultation or speaking fees from Bristol Myer Squibb, Biogen, Merck, EMD Serono, Roche, Immune Therapeutics, Novartis, and Sanofi-Genzyme., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Ultrathin strut coronary drug-eluting stents (DES) have demonstrated improved safety and efficacy in large contemporary trials. The evaluation of an ultrathin strut DES in a post-market United States (US) patient population was undertaken., Objective: The purpose of this post-approval study is to confirm that the clinical performance of an ultrathin strut bioresorbable polymer sirolimus-eluting stent (BP SES) in clinical practice is similar to that observed with BP SES in the BIOFLOW V pivotal trial., Methods: BIOFLOW VII is a prospective, multicenter, single-arm US post-market approval study to confirm the clinical performance of BP SES in a real-world setting. The primary endpoint of 1-year target lesion failure (TLF) was compared with a performance goal of 6.9% based on an adapted BIOFLOW V trial BP SES TLF rate and TLF rates from other US market-released DES utilizing the Society for Cardiovascular Angiography and Interventions definition for peri-procedural myocardial infarction (MI). Subjects undergoing percutaneous coronary intervention with BP SES were consented within 24 h post-index procedure with planned follow-up through 5 years., Results: Among 556 enrolled patients, clinical demographics included: 34.7% female, 35.6% with diabetes mellitus, and 56.8% with acute coronary syndromes. The average stent length (mean ± standard deviation) was 20.2 ± 11.8 mm, and the mean number of stents per patient was 1.3 ± 0.6. Procedure success was 99.1% (551/556), and device success was 99.9% (689/690). Among 531 subjects included in the primary endpoint analysis, the 1-year rate of TLF rate was 1.7% (9/531), and the primary endpoint was met compared with the performance goal (p < 0.0001, 95% confidence interval: 0.69%, 3.43%). Rates of target vessel MI and clinically driven target lesion revascularization were 1.3% (7/531) and 0.9% (5/531), with no occurrence of cardiac death. Definite stent thrombosis was observed for two cases (0.4%; 2/556) with one acute (≤24 h) and one late (>30 days and ≤1 year) event., Conclusion: In a post-approval study, 1-year clinical outcomes with BP SES were consistent with prior trials supporting the safety and effectiveness of ultrathin BP SES., (© 2023 Wiley Periodicals LLC.)

A chronic toxicity test (21 d exposure) with the model organism Daphnia magna was performed to study the single-compound and combined effects of four fragrance materials (FMs), including musk xylene (MX), Celestolide™ (ADBI), Galaxolide™ (HHCB), and ethylene brassylate (MT). Furthermore, the transcriptional responses of ten target genes related to detoxification, molting and reproduction (DHR96, P-gp, CYP360A8, GST, CYP314, EcRb, Vtg, CAT, GPX, and GCLC) were determined by performing a quantitative real-time polymerase chain reaction (qRT‒PCR) after juvenile D. magna was exposed for 48 h. The results showed that MX, ADBI and HHCB affected development and reproduction after chronic exposure at a concentration of 10 μg L -1 . Conversely, MT did not affect reproduction, growth or molting during the 21 d exposure. In juvenile D. magna, gene expression was significantly altered by ADBI (DHR96, CYP260A8, and GCLC) and MX (DHR96, CYP360A8, EcRb, Vtg, CYP314, and GCLC) but not by HHCB. These results suggest that compared to biochemical measures, conventional biological endpoints provide more informative data regarding the effects of this FM. Compared to single substances in the chronic test, the mixture of the four FMs showed effects at lower concentrations and increased gene expression for EcRb and CYP314 during juvenile exposure, indicating a possible additive or synergistic effect of the four FMs compared to single compound exposure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Neonicotinoids (NEOs) and active pharmaceuticals ingredients (API) are contaminants widely diffused worldwide, causing increasing concern for potential adverse effects on wildlife. However, research on these contaminants have focused on target and non-target invertebrates, while information on potential effects in terrestrial mammals is lacking. We performed preliminary non-invasive monitoring of NEOs and API in a suburban and agricultural area using hair of the Red fox. The Red fox is a widely diffused mesopredator in Europe, and its plasticity in feeding habits makes it an excellent indicator for assessing exposure to environmental contamination. We observed the presence of NEOs in many Red fox hair samples (n = 11), including imidacloprid (IMI), acetamiprid (ACE), and clothianidin (CLO). The highest quantified concentrations were 6.4 ng g -1 dry weight (dw), 6.7 ng g -1 dw, and 0.9 ng g -1 dw for IMI, ACE, and CLO, respectively. The targeted APIs included non-steroidal anti-inflammatory drugs (NSAIDs) and antidepressants. APIs were less frequently detected than NEOs, and the compounds with the highest prevalence were the NSAID ketoprofen (36%), the antidepressant sertraline (36%), and its active metabolite norsertraline (27%). The presence of human pharmaceuticals such as the NSAID ibuprofen and the antidepressants sertraline, fluoxetine, and their active metabolites norsertraline and norfluoxetine suggest environmental contamination due to untreated and partially treated wastewater discharged in surface waters and soils of the study area. The detection and quantification of ketoprofen and flunixin also suggest the possible use of contaminated manure on farmland. Findings indicate that hair may be used for monitoring environmental exposure to NEOs and provide evidence that hair is a good marker of exposure for antidepressants and certain NSAIDs, including ibuprofen, ketoprofen, and flunixin., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Technological development in terms of the power requirement for data acquisition and processing opens new perspectives in the field of environmental monitoring. Near real-time data flow about the sea condition and a possible direct interface with applications and services devoted to marine weather networks would have a significant impact on several aspects, such as, for example, safety and efficiency. In this scenario, the needs of buoy networks have been analyzed, and the estimation of directional wave spectra from buoys' data has been deeply investigated. Two methods have been implemented, namely the truncated Fourier series and the weighted truncated Fourier series, and they have been tested by both simulated and real experimental data, representative of typical Mediterranean Sea conditions. From simulation, the second method proved to be more efficient. From the application to real case studies, it emerged that it works effectively in real conditions, as confirmed by parallel meteorological observations. The estimation of the main propagation direction was possible with a small uncertainty of a few degrees, yet the method exhibits a limited directional resolution, which suggests the need for undertaking further studies, briefly addressed in the conclusions.

Exhaust Gas Cleaning Systems (EGCS), operating in open-loop mode, continuously release acidic effluents (scrubber waters) to marine waters. Furthermore, scrubber waters contain high concentrations of metals, polycyclic aromatic hydrocarbons (PAHs), and alkylated PAHs, potentially affecting the plankton in the receiving waters. Toxicity tests evidenced significant impairments in planktonic indicators after acute, early-life stage, and long-term exposures to scrubber water produced by a vessel operating with high sulphur fuel. Acute effects on bacterial bioluminescence (Aliivibrio fischeri), algal growth (Phaeodactylum tricornutum, Dunaliella tertiolecta), and copepod survival (Acartia tonsa) were evident at 10 % and 20 % scrubber water, while larval development in mussels (Mytilus galloprovincialis) showed a 50 % reduction at ∼5 % scrubber water. Conversely, larval development and reproductive success of A. tonsa were severely affected at scrubber water concentrations ≤1.1 %, indicating the risk of severe impacts on copepod populations which in turn may result in impairment of the whole food web., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Marco Picone reports financial support was provided by European Union., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: The current study attempted to expand the literature on cognition and mood in MS by determining if illness intrusiveness may potentially serve as an intermediary factor in the well-established cognition-mood relationship in people with MS., Method: This study employed a retrospective cross-sectional design to answer this question. Baseline neuropsychological test data and mood questionnaires from 199 participants with clinically definite MS were used in this study. The sample was middle-aged ( M = 48.4, SD = 11.8), highly educated ( M = 14.6, SD = 2.2), majority female (76.9%) and majority White (74.5%). Assumptions for parametric statistics and ordinary least squares regression were met. Conditional process models evaluated whether illness intrusiveness mediated the relationship between cognitive functioning and psychiatric symptoms., Results: In total, 33.2% of the sample met criteria for clinically significant anxiety, 41.7% met criteria for depression, and 27.8% of the sample met criteria for processing speed impairment, consistent with other MS samples. Illness intrusiveness was found to mediate the relationship between processing speed and depression, ab = -.07, 95% CI [-.15, -.002], processing speed and anxiety, ab = -.06, 95% CI [-.12, -.02], and processing speed and more general mood disturbance, ab = -.08, 95% CI [-.13, -.0005]., Conclusions: Illness intrusiveness was found to be a potential important intermediary mechanism by which the primary cognitive impairment in MS, processing speed, impacts mood in this disease population. Conclusions, treatment implications, and directions for future research in light of these findings were discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Introduction: SLC6A1 Neurodevelopmental Disorder (SLC6A1-NDD), first described in 2015, is a rare syndrome caused by a mutation in the SLC6A1 gene which encodes for the GABA Transporter 1 (GAT-1) protein. Epilepsy is one of the most common symptoms in patients and is often the primary treatment target, though the severity of epilepsy is variable. The impact of seizures and other symptoms of SLC6A1-NDD on patients and caregivers is wide-ranging and has not been described in a formal disease concept study., Methods: A literature search was performed using the simple search term, "SLC6A1." Papers published before 2015, and those which did not describe the human neurodevelopmental disorder were removed from analysis. Open-ended interviews on lived experiences were conducted with two patient advocate key opinion leaders. An analysis of de-identified conversations between families of people with SLC6A1-NDD on social media was performed to quantify topics of concern., Results: Published literature described symptoms in all of the following domains: neurological, visual, motor, cognitive, communication, behavior, gastrointestinal, sleep, musculo-skeletal, and emotional in addition to epilepsy. Key opinion leaders noted two unpublished features: altered hand use in infants, and developmental regression with onset of epilepsy. Analysis of social media interactions confirmed that the core symptoms of epilepsy and autistic traits were prominent concerns, but also demonstrated that other symptoms have a large impact on family life., Discussion: For rare diseases, analysis of published literature is important, but may not be as comprehensive as that which can be gleaned from spontaneous interactions between families and through qualitative interviews. This report reflects our current understanding of the lived experience of SLC6A1-NDD. The discrepancy between the domains of disease reported in the literature and those discussed in patient conversations suggests that a formal qualitative interview-based disease concept study of SLC6A1-NDD is warranted., Competing Interests: KH, AP, MX, and TB were employed by COMBINEDBrain. MP was employed by TREND Community. KG provided consultation to Astellas Gene Therapies and Jaguar Gene Therapies for work unrelated to this research. TB has provided consultation to H. LaRoche Pharmaceuticals and Ovid Therapeutics for work unrelated to this research. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Goodspeed, Mosca, Weitzel, Horning, Simon, Pfalzer, Xia, Langer, Freed, Bone, Picone and Bichell.)

Microseism is the continuous background seismic signal caused by the interaction between the atmosphere, the hydrosphere and the solid Earth. Several studies have dealt with the relationship between microseisms and the tropical cyclones, but none focused on the small-scale tropical cyclones that occur in the Mediterranean Sea, called Medicanes. In this work, we analysed the Medicane Apollo which impacted the eastern part of Sicily during the period 25 October-5 November 2021 causing heavy rainfall, strong wind gusts and violent sea waves. We investigated the microseism accompanying this extreme Mediterranean weather event, and its relationship with the sea state retrieved from hindcast maps and wave buoys. The spectral and amplitude analyses showed the space-time variation of the microseism amplitude. In addition, we tracked the position of Apollo during the time using two different methods: (i) a grid search method; (ii) an array analysis. We obtained a good match between the real position of Apollo and the location constraint by both methods. This work shows that it is possible to extract information on Medicanes from microseisms for both research and monitoring purposes., (© 2022. The Author(s).)

Seabirds accumulate mercury (Hg) due to their long-life span together with their high trophic position. A Hg monitoring in Venice's Lagoon using three seabird species occupying different trophic habitat (Thalasseus sandvicensis, Ichthyaetus melanocephalus, and Chroicocephalus ridibundus) confirmed that fledgelings might effectively be used as sentinels of Hg bioavailability. The significant differences in Hg residues in feathers observed among the species highlighted a possible differential exposure due to different diets, with C. ridibundus accumulating more Hg than the other species. Average residues in feathers were not above the threshold associated with adverse effects on birds (5 mg kg - 1 ). Nevertheless, a large part of the C. ridibundus individuals (58%) exceeded the adverse effect level, underlining the need for strengthening Hg monitoring. Seabirds indeed may provide relevant insight on Hg transfer in food webs and a better picture of the hazards to men when bird species forage on species exploited for human consumption., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Neonicotinoids (NEOs) are neurotoxic pesticides acting as nicotinic acetylcholine receptor agonists. NEOs' efficacy against pest insects has favoured their spreading use in agriculture, but their proven effectiveness against non-target insects in terrestrial and aquatic ecosystems also raised concern over their environmental impact. Crustaceans were often studied for the impacts of NEOs due to their economic values and nervous' system similarity with insects. However, most studies on crustaceans focused on acute effects or exposure of early-life stages, while long-term effects were seldom explored. The present study aimed to assess the potential long-term effects of four commercially available NEOs on the reproduction and offspring of the calanoid copepod Acartia tonsa, a key species in the food webs of several coastal and estuarine environments. NEOs were confirmed as potent interferents of copepod reproduction. The first-generation compound acetamiprid significantly inhibited egg production and hatching ratio at 10 ng L -1 , while larval survival and development were affected at 81 ng L -1 . Similarly, the first-generation compound thiacloprid significantly inhibited the hatching ratio and larval development at 9 ng L -1 , while it did not affect egg production and larval survival. Second-generation compounds were less toxic than acetamiprid and thiacloprid: clothianidin affected significantly only larval development of the offspring at 62 ng L -1 , while thiamethoxam was not toxic at both the tested concentrations (8 ng L -1 and 84 ng L -1 ). These data evidenced that effects on copepods may occur at concentrations below the chronic aquatic life benchmarks reported by USEPA for acetamiprid (2100 ng L -1 ) and thiacloprid (970 ng L -1 ), suggesting that long-term effects of NEOs have been underestimated. A comparison with environmental concentrations evidenced that NEO-mediated effects on copepods are more liable in coastal areas receiving discharge from wastewater treatment plants or diffuse inputs from agricultural land during pesticide application periods., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Clinical experience and a growing body of evidence suggest that sleep disturbances are common in people with Prader-Willi syndrome (PWS). PWS is a rare neuroendocrine disorder characterized by early hypotonia and feeding difficulties; developmental delays; endocrinopathies; and behavioral concerns, especially rigidity, anxiety, and behavioral outbursts. PWS is also characterized by decreased resting energy expenditure and transition to hyperphagia and obesity. We propose that, for many people with PWS, clinical diagnosis and management of sleep disorders is an unmet need. We present current information to suggest disordered sleep is a significant burden for individuals with PWS and often overlooked. While central and obstructive sleep apnea are more widely recognized in PWS, other sleep disorders have increasingly gained recognition, including hypersomnia, narcolepsy-like phenotypes, and insomnia. Sleep disorders can impact behavior, cognition, and quality of life and health for individuals with PWS. Our goal is to bring sleep disorders to the forefront of therapeutic intervention for patients with PWS. This paper presents a review of the literature and recommendations for clinical practice based on published research and our clinical experience as sleep specialists, geneticists, psychiatrists, pediatricians, otolaryngologists, and pulmonologists with extensive experience with this patient population. We recommend that management of sleep be considered an integral part of successful medical management of PWS. Further research concerning sleep problems in PWS is urgently needed to develop best practices and work toward a consensus statement for medical management to meet the needs of people with PWS., Citation: Duis J, Pullen LC, Picone M, et al. Diagnosis and management of sleep disorders in Prader-Willi syndrome. J Clin Sleep Med . 2022;18(6):1687-1696., (© 2022 American Academy of Sleep Medicine.)

Exposure to active pharmaceutical ingredients (APIs) from both human and veterinary sources is an increasing threat to wildlife welfare and conservation. Notwithstanding, tracking the exposure to pharmaceuticals in non-target and sensitive vertebrates, including birds, is seldom performed and relies almost exclusively on analysing internal organs retrieved from carcasses or from experimentally exposed and sacrificed birds. Clearly, this excludes the possibility of performing large-scale monitoring. Analysing feathers collected from healthy birds may permit this, by detecting APIs in wild birds, including protected and declining species of waterbirds, without affecting their welfare. To this end, we set up a non-destructive method for analysing the presence of non-steroidal anti-inflammatory drugs (NSAIDs), selective serotonin reuptake inhibitors (SSRIs) and noradrenaline reuptake inhibitors (SNRIs) in the feathers of fledglings of both the Mediterranean gull (Ichtyaetus melanocephalus) and the Sandwich tern (Thalasseus sandvicensis). The presence of several NSAIDs and SSRIs above the method quantification limits have confirmed that feathers might be a suitable means of evaluating the exposure of birds to APIs. Moreover, the concentrations indicated that waterbirds are exposed to NSAIDs, such as diclofenac, ibuprofen and naproxen, and SSRIs, such as citalopram, desmethylcitalopram, fluvoxamine and sertraline, possibly due to their widespread use and incomplete removal in wastewater treatment plants (WWTPs). The active ingredient diclofenac raises a the primary concern for the ecosystem and the welfare of the waterbirds, due to its high prevalence (100% and 83.3% in Mediterranean gull and Sandwich tern, respectively), its concentrations detected in feathers (11.9 ng g -1 and 6.7 ng g -1 in Mediterranean gull and Sandwich tern, respectively), and its documented toxicity toward certain birds., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Laboratory testing with spiked sediments with organic contaminants is a valuable tool for ecotoxicologists to study specific processes such as effects of known concentrations of toxicants, interactions of the toxicants with sediment and biota, and uptake kinetics. Since spiking of the sediment may be performed by using different strategies, a plethora of procedures was proposed in the literature for spiking organic chemicals onto sediments to perform ecotoxicological analyses. In this paper, we reviewed the scientific literature intending to characterise the kind of substrates that were used for spiking (i.e. artificial or field-collected sediment), how the substrates were handled before spiking and amended with the organic chemical, how the spiked sediment was mixed to allow the homogenisation of the chemical on the substrate and finally how long the spiked sediment was allowed to equilibrate before testing. What emerged from this review is that the choice of the test species, the testing procedures and the physicochemical properties of the organic contaminant are the primary driving factors affecting the selection of substrate type, sediment handling procedures, solvent carrier and mixing method. Finally, we provide recommendations concerning storage and characterization of the substrate, equilibrium times and verification of both equilibration and homogeneity., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Neonicotinoids are one of the most diffusely used classes of pesticides whose level of danger toward non-target invertebrate and vertebrate species has raised increasing concern in the last decades. Among vertebrates, birds are particularly susceptible to unintentional neonicotinoid poisoning since they can be exposed through different pathways, including ingestion of dressed seeds, sucking of contaminated pollen, ingestion of sprayed insects, predation on contaminated aquatic and terrestrial preys. In the present study, we investigated the possible exposure of seabirds by measuring the residues of five neonicotinoids (acetamiprid, clothianidin, imidacloprid, thiacloprid and thiamethoxam) in samples of pooled feathers collected from fledglings of the strictly piscivorous Sandwich tern (Thalasseus sandvicensis) and the mixotrophic species Mediterranean gull (Ichthyaetus melanocephalus). At least one neonicotinoid was quantified in all the Mediterranean gull samples (n = 11) and 89% of the analysed Sandwich tern samples (n = 36). The active principles with the highest quantification rates were imidacloprid (100% in Mediterranean gulls and 58% in Sandwich terns) and clothianidin (100% in Mediterranean gulls and 61% in Sandwich terns), while thiacloprid was the less frequently detected pesticide (<20% of samples in both species). Mean concentrations ± standard error for imidacloprid, clothianidin and thiamethoxam were 8.8 ± 1.4, 4.5 ± 0.19 and 0.16 ± 0.02 ng g -1 for the Mediterranean gull, and 5.8 ± 0.55, 0.60 ± 0.08 and 0.36 ± 0.03 ng g -1 for the Sandwich tern, respectively. Our data evidenced the exposure of seabirds to neonicotinoids and the further need to investigate the extent of neonicotinoid contamination in non-agricultural ecosystems., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Neonicotinoids (NEOs) are neurotoxic pesticides widely used in agriculture due to their high effectiveness against pest insects. Despite their widespread use, very little is known about their toxicity towards marine organisms, including sensitive and ecologically relevant taxa such as copepods. Thus, we investigated the toxicity of five widely used NEOs, including acetamiprid (ACE), clothianidin (CLO), imidacloprid (IMI), thiacloprid (THI), and thiamethoxam (TMX), to assess their ability to inhibit the larval development of the copepod Acartia tonsa . The more toxic NEOs were ACE (EC 50 = 0.73 μg L -1 ), TMX (EC 50 = 1.71 μg L -1 ) and CLO (EC 50 = 1.90 μg L -1 ), while the less toxic compound was IMI (EC 50 = 8.84 μg L -1 ). Early life-stage mortality was unaffected by NEOs at all of the tested concentrations. The calculated toxicity data indicated that significant effects due to ACE (EC 20 = 0.12 μg L -1 ), THI (EC 20 = 0.88 μg L -1 ) and TMX (EC 20 = 0.18 μg L -1 ) are observed at concentrations lower than established chronic aquatic life benchmarks reported by USEPA for freshwater invertebrates. Nevertheless, since environmental concentrations of NEOs are generally lower than the threshold concentrations we calculated for A. tonsa , the effects may be currently of concern only in estuaries receiving wastewater discharges or experiencing intense runoff from agriculture.

Rare Earth Elements (REEs) are increasingly exploited for crucial new technologies, and their massive use in the past decades has significantly increased their environmental concentrations. Although their effects have been extensively studied in vitro and in vivo in model species, little is known of their accumulation and potential toxic effects in wildlife, including waterbirds. In the present work, we measured the concentrations of REEs in feathers of young Sandwich tern (Thalasseus sandvicensis) about 16-20 days old to assess whether the accumulation of these elements may be a concern in Venice's Lagoon, one of the most important wetlands of the Mediterranean area for breeding and migrating birds. The REE concentrations detected in the Sandwich tern were the highest among those reported in the literature for bird's feathers (940.9 ± 223.0 ng g -1 ), although in the study area industrial activities related to REEs mining, processing and disposal are absent. In particular, Lanthanum (La) was more abundant in the feathers than other REEs and accounted for 73-97% of total REEs detected. Analysis of bird's food indicated that diet is a relevant route of exposure to REEs for young terns; however, concentration in fishes are relevantly higher than in the feathers for all REEs other than La. The study evidenced the need to collect more information concerning the occurrence of REEs both in the abiotic matrices (i.e. water and sediments) and in living organisms of different trophic levels to improve the general knowledge concerning the fate of REEs in the aquatic ecosystems., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Although deep inspiratory breath-hold (DIBH) is routinely used for left-sided breast cancers, its benefits for right-sided breast cancer (rBC) have yet to be established. We compared free-breathing (FB) and DIBH treatment plans for a cohort of rBC undergoing regional nodal irradiation (RNI) to determine its potential benefits., Methods and Materials: rBC patients considered for RNI (internal mammary nodal chains, supraclavicular field, with or without axilla) from October 2017 to May 2020 were included in this analysis. For each patient, FB versus DIBH plans were generated and dose volume histograms evaluated the following parameters: mean lung dose, ipsilateral lung V 20 /V 5 (volumes of lung receiving 20 Gy and 5 Gy, respectively); mean heart dose and heart V 5 (volumes of heart receiving 5 Gy); liver V 20 absolute /V 30 absolute (absolute volume of liver receiving 20 Gy and 30 Gy, respectively), liver D max , and total liver volume irradiated (TVI liver ). The dosimetric parameters were compared using Wilcoxon signed-rank testing., Results: Fifty-four patients were eligible for analysis, comparing 108 FB and DIBH plans. DIBH significantly decreased all lung and liver parameters: mean lung dose (19.7 Gy-16.2 Gy, P < .001), lung V 20 (40.7%-31.7%, P < .001), lung V 5 (61.2%-54.5%, P < .001), TVI liver (1446 cc vs 1264 cc; P = .006) liver D max (50.2 Gy vs 48.9 Gy; P = .023), liver V 20 (78.8-23.9 cc, P < .001), and liver V 30 (58.1-14.6 cc, P < .001) compared with FB. DIBH use did not significantly improve heart parameters, although the V 5Heart trended on significance (1.25-0.6, P = .067)., Conclusions: This is the largest cohort to date analyzing DIBH for RNI-rBC. Our findings demonstrate significant improvement in all lung and liver parameters with DIBH, supporting its routine consideration for rBC patients undergoing comprehensive RNI., (Copyright © 2021. Published by Elsevier Inc.)

Fragrance materials (FMs) are used in a variety of detergents and cosmetics, including household and personal care products. Despite their widespread use and the growing evidence of their occurrence in surface waters worldwide, very little is known about their toxicity towards marine species, including a key component of the marine food webs such as copepods. Thus, we investigated the toxicity of six of the more long-lasting and stable commercial fragrances, including Amyl Salicylate (AMY), Oranger Crystals (ORA), Hexyl Salicylate (HEX), Ambrofix (AMB), Peonile (PEO), and Benzyl Salicylate (BZS), to assess their ability to impair the larval development of the calanoid copepod Acartia tonsa. FMs inhibited the development of A. tonsa significantly at concentrations by far lower than the effect-concentrations reported in the literature for aquatic species. The more toxic FMs were HEX (EC 50 = 57 ng L -1 ), AMY (EC 50 = 131 ng L -1 ) and ORA (EC 50 = 766 ng L -1 ), while the other three compounds exerted toxic effects at concentrations higher than 1000 ng L -1 (LOEC at 1000 ng L -1 for PEO and BZS, and at 10,000 ng L -1 for AMB). Early life-stage mortality was unaffected by FMs at all the tested concentrations. A comparison with water concentrations of FMs reported in the literature confirmed that FMs, especially HEX and AMY, may act as contaminants of potential concern in many aquatic habitats, including urban areas and remote and polar environments., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Microplastics (MPs) are present in fresh, brackish, or marine waters. Micro- and macroinvertebrates can mistake MPs or small microplastics (SMPs, <100 μm) to be food particles and easily ingest them according to the size of their mouthparts. SMPs may then block the passage of food through the intestinal tract (i.e. hepatopancreas), accumulate within the organism, and enter the food web. Pacific oysters (Crassostrea gigas) are allochthonous filter-feeding bivalve mollusks, which have been introduced in coastal seas around the world in both natural banks and farms. Considering their economic and ecological value, these bivalves have been chosen as a model to study the ingestion of SMPs. A novel method for the extraction and purification of SMPs in bivalves was developed. Quantification and simultaneous polymer identification of SMPs using Micro-FTIR (Fourier Transform Infrared Spectroscopy) were performed, with a limit of detection for the particle size of 5 μm., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Given the severe and rapid impact of COVID-19, the pace of information sharing has been accelerated. However, traditional methods of disseminating and digesting medical information can be time-consuming and cumbersome. In a pilot study, the authors used social listening to quickly extract information from social media channels to explore what people with COVID-19 are talking about regarding symptoms and disease progression. The goal was to determine whether, by amplifying patient voices, new information could be identified that might have been missed through other sources. Two data sets from social media groups of people with or presumed to have COVID-19 were analyzed: a Facebook group poll, and conversation data from a Reddit group including detailed disease natural history-like posts. Content analysis and a customized analytics engine that incorporates machine learning and natural language processing were used to quickly identify symptoms mentioned. Key findings include more than 20 symptoms in the data sets that were not listed in online lists of symptoms from 4 respected medical information sources. The disease natural history-like posts revealed that people can experience symptoms for many weeks and that some symptoms change over time. This study demonstrates that social media can offer novel insights into patient experiences as a source of real-world data. This inductive research approach can quickly generate descriptive information that can be used to develop hypotheses and new research questions. Also, the method allows rapid assessments of large numbers of social media conversations that could be applied to monitor public health for emerging and rapidly spreading diseases such as COVID-19.

The COVID-19 pandemic zoonosis has determined extensive lockdowns worldwide that provide an unprecedented opportunity to understand how large-scale shifts of human activities can impact wildlife. We addressed the impacts of the COVID-19 lockdown on wildlife in Italy, the first European country that performed a countrywide lockdown, and identified potentially beneficial and negative consequences for wildlife conservation and management. We combined a qualitative analysis of social media information with field data from multiple taxa, data from citizen science projects, and questionnaires addressed to managers of protected areas. Both social media information and field data suggest that a reduction of human disturbance allowed wildlife to exploit new habitats and increase daily activity. The field data confirmed some positive effects on wildlife conservation, such as an increase in species richness in temporarily less-disturbed habitats, a higher breeding success of an aerial insectivorous bird, and reduction of road-killing of both amphibians and reptiles. Despite some positive effects, our data also highlighted several negative impacts of the COVID-19 crisis on wildlife. The lower human disturbance linked to lockdown was in fact beneficial for invasive alien species. Results from questionnaires addressed to managers of protected areas highlighted that the COVID-19 lockdown interrupted actions for the control of invasive alien species, and hampered conservation activities targeting threatened taxa. Furthermore, the reduction of enforcement could cause a surge of illegal killing of wildlife. The COVID-19 crisis, besides having deep socio-economic impacts, might profoundly affect wildlife conservation, with potentially long-lasting effects., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 Elsevier Ltd. All rights reserved.)

To evaluate the hazard assessment of dredging and disposal of sediments, an in-depth chemical and toxicological characterization of sediments was carried out in Venice Lagoon. The bioaccessible and mobile concentration of trace elements in superficial and deep sediments (in the Holocene-Pleistocene limit) can deeply affect the quality of the aquatic ecosystem. Geospeciation and total concentration of trace elements in sediment cores were assessed and several toxicological tests were carried out. The indices of contamination (e.g., geochemical accumulation index, I geo , pollution load index, PLI) and of speciation (individual contamination factor, ICF and global contamination factor, GCF) were evaluated. Factor Analysis (FA) was performed to explore possible significant correlations between toxicity data and sediment chemistry. Results underlined that the total concentration of trace elements cannot adequately assess the hazard, while bioavailability, mobility, and toxicity of trace elements allow a thorough evaluation of the environmental threats. The integration of results from chemical characterization ex ante and toxicity assays will provide for a better sustainable handling and management of sediments.

A non-invasive study of trace element accumulation in tail feathers of the Kentish plover (Charadrius alexandrinus) was performed along the coastline of the northern littoral strip of the Venice Lagoon, with the aim to verify whether contamination may be a factor affecting conservation status of Kentish plover populations. Body burdens in feathers of 11 trace elements including toxic metals/metalloids and essential elements (As, Cd, Co, Cr, Cu, Hg, Ni, Pb, Se, V, Zn) were quantified by ICP-MS, then concentrations were normalized to feather's age calculated using ptilochronology in order to obtain daily deposition rates. Mercury emerged as a major threat to the conservation of the species, since average feather concentration was clearly above the adverse-effect threshold associated with impairment in the reproductive success in a number of bird species. Also Cd and Se occurred at levels that may impact on the conservation status of the studied species at local scale, even if to a lesser extent than Hg. Gender-related differences in trace element accumulation emerged only for As, although for this element the risks associated to environmental exposure seem to be negligible., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Nanotechnology provides innovative and promising solutions for the conservation of cultural heritage, but the development and application of new nano-enabled products pose concerns regarding their human health and environmental risks. To address these issues, we propose a sustainability framework implementing the Safe by Design concept to support product developers in the early steps of product development, with the aim to provide safer nano-formulations for conservation, while retaining their functionality. In addition, this framework can support the assessment of sustainability of new products and their comparison to their conventional chemical counterparts if any. The goal is to promote the selection and use of safer and more sustainable nano-based products in different conservation contexts. The application of the proposed framework is illustrated through a hypothetical case which provides a realistic example of the methodological steps to be followed, tailored and iterated along the decision-making process.

A sequential TIE procedure combining in a single framework Phase I manipulations and Phase II methods, including chemical analyses and complementary Phase I treatments, was proposed for characterization and identification of toxicants of concern in estuarine environments. Interstitial water was chosen as test matrix and embryo-larval development with the bivalve Crassostrea gigas as toxicity endpoint. TIE treatments included addition of Ulva rigida and elution through zeolite column for addressing effects due to ammonia, addition of EDTA and elution through a Cation-Exchange Solid-Phase Extraction column for characterize metals, and elution through two different type of polymers (XAD and DPA) with different affinity for polar and nonpolar organic pollutants. Chemical analyses concerned determination of ammonia and trace elements in the untreated sample and after manipulation intended to remove or modify bioavailability of ammonia and metals. The "hybrid" Phase I-Phase II TIE sequence proved to be a reliable and effective tool for the identification of main toxicant of concern in a highly toxic and contaminated interstitial water sample, also in presence of high concentration of potential confounding factors (ammonia). The addition of U. rigida was the more reliable treatment for the removal of ammonia, due to the concurrent release of particles and potentially toxic elements, such as Ba, Rb, and Tl by zeolite column, which may increase toxicity in the post-column sample. The combined use of polymers with different affinity for the various classes of organic pollutants was essential to identify the contribution of polar organic compounds to the observed toxicity.

A whole-sediment test with the infaunal amphipod Monocorophium insidiosum has been developed to assess the long-term effects exerted by sediment contamination on survival, growth rates and attainment of sexual maturity. Juvenile amphipods were exposed for 28 days to a control sediment (native sediment) and three sediment samples collected in sites of the Venice Lagoon, characterized by contamination levels ranging from low to moderate, and absence of acute toxicity toward amphipods. Growth rate was estimated as daily length (μm d -1 ) and weight increments (μg d -1 ). The long-term exposure to the test sediments affected significantly both growth rate and attainment of sexual maturity of the females of M. insidiosum. In contrast, survival was high and uniform among all the samples, despite the contamination gradient. The results suggest growth to be the more reliable and statistically relevant endpoint. Attainment of sexual maturity, although allowed the identification of detrimental effects, was affected by a higher among-replicates variance as compared with growth rates, and thus less reliable than growth for the identification of impairments. The significant impairments observed both on growth and attainment of maturity evidenced the need to address the monitoring, also in the Lagoon of Venice, towards the assessment of the long-term effects on benthic species.

The early-life stages of development of the calanoid copepod Acartia tonsa from egg to copepodite I is proposed as an endpoint for assessing sediment toxicity by exposing newly released eggs directly onto the sediment-water interface. A preliminary study of 5 sediment samples collected in the lagoon of Venice highlighted that the larval development rate (LDR) and the early-life stages (ELS) mortality endpoints with A. tonsa are more sensitive than the standard amphipod mortality test; moreover LDR resulted in a more reliable endpoint than ELS mortality, due to the interference of the sediment with the recovery of unhatched eggs and dead larvae. The LDR data collected in a definitive study of 48 sediment samples from the Venice Lagoon has been analysed together with the preliminary data to evaluate the statistical performances of the bioassay (among replicate variance and minimum significant difference between samples and control) and to investigate the possible correlation with sediment chemistry and physical properties. The results showed that statistical performances of the LDR test with A. tonsa correspond with the outcomes of other tests applied to the sediment-water interface (Strongylocentrotus purpuratus embryotoxicity test), sediments (Neanthes arenaceodentata survival and growth test) and porewater (S. purpuratus); the LDR endpoint did, however, show a slightly higher variance as compared with other tests used in the Lagoon of Venice, such as 10-d amphipod lethality test and larval development with sea urchin and bivalves embryos. Sediment toxicity data highlighted the high sensitivity and the clear ability of the larval development to discriminate among sediments characterized by different levels of contamination. The data of the definitive study evidenced that inhibition of the larval development was not affected by grain-size and the organic carbon content of the sediment; in contrast, a strong correlation between inhibition of the larval development and the sediment concentrations of some metals (Cu, Hg, Pb, Zn), acid-volatile sulphides (AVS), polychlorinated biphenyls (PCBs) and polynuclear aromatic hydrocarbons (PAHs) was found. No correlation was found with DDTs, hexachlorobenzene and organotin compounds., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Cognitive impairments are common in individuals with MS and adversely affect functioning. Early detection of cognitive impairment, therefore, would enable earlier, and possibly more effective, treatment. We sought to compare self-reports with a short neuropsychological test as possible screening tools for cognitive impairment., Methods: One hundred patients with MS were tested with the Minimal Assessment of Cognitive Function in Multiple Sclerosis; z scores were used to derive the Cognitive Index (CI). Receiver operator characteristic curve analyses were performed, with criteria for impairment set at -1.5 and -2.0 SD below the mean. Scores from two self-reports (the Multiple Sclerosis Neuropsychological Screening Questionnaire-Patient Version and the Behavior Rating Inventory of Executive Function-Adult Version [BRIEF-A]) and a neuropsychological test (the Symbol Digit Modalities Test [SDMT]) were entered as test variables. Exploratory regression analyses were conducted with 1) CI and self-reports and 2) CI and the Problem-Solving Inventory (PSI)., Results: Classification accuracy was high or moderately high for SDMT when the criterion was -2.0 or -1.5 SD, respectively, but low for the self-reports. Hierarchical linear regression showed that the SDMT alone was the best predictor of cognitive impairment; adding the self-reports did not improve the model. Exploratory analyses indicated that certain self-reports (BRIEF-A, PSI) provided some explanatory power in separate models., Conclusions: The SDMT is a more accurate screening tool for cognitive impairment; however, self-reports provide additional information and may complement objective testing. Results suggest that screening for cognitive impairment may require a multidimensional approach.

Within the framework of a Weight of Evidence (WoE) approach, a set of four toxicity bioassays involving the amphipod Corophium volutator (10 d lethality test on whole sediment), the sea urchin Paracentrotus lividus (fertilization and embryo toxicity tests on elutriate) and the pacific oyster Crassostrea gigas (embryo toxicity test on elutriate) was applied to sediments from 10 sampling sites of the Venice Lagoon (Italy). Sediments were collected during three campaigns carried out in May 2004 (spring campaign), October 2004 (autumn campaign) and February 2005 (winter campaign). Toxicity tests were performed on all sediment samples. Sediment grain-size and chemistry were measured during spring and autumn campaigns. This research investigated (i) the ability of toxicity tests in discriminating among sites with different contamination level, (ii) the occurrence of a gradient of effect among sampling sites, (iii) the possible correlation among toxicity tests, sediment chemistry, grain size and organic carbon, and (iv) the possible occurrence of toxicity seasonal variability. Sediment contamination levels were from low to moderate. No acute toxicity toward amphipods was observed, while sea urchin fertilization was affected only in few sites in just a single campaign. Short-term effects on larval development of sea urchin and oyster evidenced a clear spatial trend among sites, with increasing effects along the axis connecting the sea-inlets with the industrial area. The set of bioassays allowed the identification of a spatial gradient of effect, with decreasing toxicity from the industrial area toward the sea-inlets. Multivariate data analysis showed that the malformations of oyster embryos were significantly correlated to the industrial contamination (metals, polynuclear aromatic hydrocarbons, hexachlorobenzene and polychlorinated biphenyls), while sea urchin development to sediment concentrations of As, Cr and organic carbon. Both embryo toxicity tests were significantly affected by high ammonia concentrations found in the elutriates extracted from some mudflat and industrial sediments. No significant temporal variation of the toxicity was observed within the experimental period. Amendments to the set of bioassays, with inclusion of chronic tests, can certainly provide more reliability and consistency to the characterization of the (possible) toxic effects., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The spectrum of modern molecular high-throughput assaying includes diverse technologies such as microarray gene expression, miRNA expression, proteomics, DNA methylation, among many others. Now that these technologies have matured and become increasingly accessible, the next frontier is to collect "multi-modal" data for the same set of subjects and conduct integrative, multi-level analyses. While multi-modal data does contain distinct biological information that can be useful for answering complex biology questions, its value for predicting clinical phenotypes and contributions of each type of input remain unknown. We obtained 47 datasets/predictive tasks that in total span over 9 data modalities and executed analytic experiments for predicting various clinical phenotypes and outcomes. First, we analyzed each modality separately using uni-modal approaches based on several state-of-the-art supervised classification and feature selection methods. Then, we applied integrative multi-modal classification techniques. We have found that gene expression is the most predictively informative modality. Other modalities such as protein expression, miRNA expression, and DNA methylation also provide highly predictive results, which are often statistically comparable but not superior to gene expression data. Integrative multi-modal analyses generally do not increase predictive signal compared to gene expression data.

Purpose: Studies show that suicidality is greater in persons with multiple sclerosis (MS) than in the general population. In this study, we evaluated the consistency of suicidality over time in patients with MS., Method: Participants were patients (n = 344) at an outpatient clinic at a large medical center in New Jersey. Longitudinal data was collected as part of an ongoing research project. Binary logistic regression examined the effect of gender, age, depression and disability on level of suicidality at Time 1 versus Time 2., Results: Baseline depression and change in level of depression significantly predicted level of suicidality at Time 2, while demographic variables, baseline disability, change in level of disability, and the interaction between change in depression and change in disability over time did not., Conclusions: Interventions aimed at evaluating and monitoring depression over time should be considered in order to reduce the risk of suicidality. Implications for Rehabilitation Due to the inconsistency and unpredictability of MS, depression should be assessed routinely. Given the high prevalence of depression and suicidality in MS, mental health services should be available and encouraged by healthcare providers treating individuals with MS.

Objective: Clinical response to immunomodulatory therapies in multiple sclerosis (MS) is variable among patients. Currently, there are no validated biomarkers of clinical response to any of the approved treatments for MS. The objective of this study was to determine if HLA-class II alleles predict the clinical response to glatiramer acetate (GA)., Methods: This was a prospective study of 64 MS patients with relapsing-remitting disease. Patients were HLA-typed and classified as GA-responders or non-responders after 2 years of treatment based on a clinical criterion. Statistical models were used to determine whether HLA-DR and DQ alleles and haplotypes predict the clinical response to GA., Results: Tests of association of response singled out four alleles and two haplotypes with nominal p<0.01. The presence of alleles DR15 or DQ6 or the absence of DR17 and DQ2 alleles was associated with favorable clinical response. The presence of the DR15-DQ6 haplotype and the absence of the DR17-DQ2 haplotype were also associated with favorable treatment response. A best fitting two-haplotype model resulted in the identification of three prognostic categories (good, neutral, and poor). A DR15-DQ6 positive but DR17-DQ2 negative combination was strongly predictive of a favorable clinical response (71%). Conversely, a DR15-DQ6 negative but DR17-DQ2 positive combination was strongly predictive of poor clinical response to GA (17%)., Conclusion: HLA-DR and DQ typing may prove to be useful biomarkers of predicting response to GA in MS and may help select patients appropriate for this treatment., (Copyright © 2013 Elsevier B.V. All rights reserved.)

One of the major problems related to cancer treatment is its recurrence. Without knowing in advance how likely the cancer will relapse, clinical practice usually recommends adjuvant treatments that have strong side effects. A way to optimize treatments is to predict the recurrence probability by analyzing a set of bio-markers. The NeoMark European project has identified a set of preliminary bio-markers for the case of oral cancer by collecting a large series of data from genomic, imaging, and clinical evidence. This heterogeneous set of data needs a proper representation in order to be stored, computed, and communicated efficiently. Ontologies are often considered the proper mean to integrate biomedical data, for their high level of formality and for the need of interoperable, universally accepted models. This paper presents the NeoMark system and how an ontology has been designed to integrate all its heterogeneous data. The system has been validated in a pilot in which data will populate the ontology and will be made public for further research.

For an overwhelming majority of commentators, including many anthropologists, 'Japanese culture' is still associated with a positive view of suicide. Western-language writings have contributed by feedback loop to perpetuate this stereotype. Besides the local 'samurai ethic', Japanese Buddhism is also said not to prohibit taking one's life. However, the most popular examples of heroic self-sacrifice, from the Edo period to WWII, are fraught with covert contradictions. From ancient times to the present religious practitioners of all sorts have maintained that suicide creates unhappy, resentful spirits who harm the living. This article discusses many examples of a diverse series of narratives, from spirit medium's séances to drama to contemporary films, in which the anguished spirits of suicides are allowed to express themselves directly. After the figures rose alarmingly in the late 1990s various religious organisations have attempted to fight the stigma suffered by bereaved family members and have introduced new interpretations and new rituals.

Early prediction of cancer reoccurrence constitutes a challenge for oncologists and surgeons. This chapter describes one ongoing experience, the EU-Project NeoMark, where scientists from different medical and biology research fields joined efforts with Information Technology experts to identify methods and algorithms that are able to early predict the reoccurrence risk for one of the most devastating tumors, the oral cavity squamous cell carcinoma (OSCC). The challenge of NeoMark is to develop algorithms able to identify a "signature" or bio-profile of the disease, by integrating multiscale and multivariate data from medical images, genomic profile from tissue and circulating cells RNA, and other medical parameters collected from patients before and after treatment. A limited number of relevant biomarkers will be identified and used in a real-time PCR device for early detection of disease reoccurrence.

Objective: Pain physicians should also be aware of rare complications that can occur after intrathecal pump (ITP) placement. One such rare complication includes an acute exacerbation of hereditary coproporphyria (HCP)., Methods: We present a case report that illustrates how an acute exacerbation of HCP can mimic an early surgical post-procedure infection after ITP implantation., Results: The patient's rapid onset of symptoms two hours after the procedure keyed into HCP as the underlying cause, as acute wound infections rarely occur in the several hours following surgery. After symptomatic treatment of her HCP acute exacerbation, the patient clinically improved without the development of further symptoms or adverse sequelae. She reported considerable pain relief with the implanted drug delivery system., Conclusion: In a setting with multiple confounders, a methodical history and physical examination, close monitoring, and a comprehensive understanding of potential complications can prevent unnecessary ITP extraction and streamline the delivery of appropriate care., (© 2010 International Neuromodulation Society.)