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Cyanobacteria proliferate in warm, nutrient-rich environments and release toxic secondary metabolites into natural waters. Using cyanotoxin-contaminated water to irrigate crops could expose humans and biota, but the risk may be low if agricultural soils can sorb and retain cyanotoxins. In this report, we compared the sorption and desorption capacities of multi-class cyanotoxins/anabaenopeptins in soils of variable properties with a batch sorption procedure. The target compounds were anabaenopeptin-A, anabaenopeptin-B, anatoxin-a, cylindrospermopsin, and microcystins -LR, -RR, -LA, -LY, -LW, and -LF. Based on solid-liquid distribution coefficients (Kd), we classified cylindrospermopsin and microcystin-LA/-LY as "very low sorptivity", anabaenopeptin-A, -B and microcystin-LR, -LF, and -LW as "low sorptivity", and anatoxin-a and microcystin-RR as "medium sorptivity". We remain concerned about irrigating agricultural land with water contaminated with high levels of CYN and MC-LA/-LY because of their relatively low affinity and high desorption proportion in soils. The results also suggest that soil sorption can be an effective immobilization pathway for anatoxin-a and microcystin-RR. The generated data will be useful for prioritizing research on the most bioavailable cyanotoxins/anabaenopeptins that are likely to be released by the soil matrix, for environmental risk assessment.
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Background: Advances in the development of neurotechnologies have the potential to revolutionize treatment of brain-based conditions. However, a critical concern revolves around the willingness of the public to embrace these technologies, especially considering the tumultuous histories of certain neurosurgical interventions. Therefore, examining public attitudes is paramount to uncovering potential barriers to adoption ensuring ethically sound innovation. Methods: In the present study, we investigate public attitudes towards the use of four neurotechnologies (within-subjects conditions): deep brain stimulation (DBS), transcranial magnetic stimulation (TMS), pills, and MRI-guided focused ultrasound (MRgFUS) as potential treatments to a person experiencing either mood, memory, or motor symptoms (between-subjects conditions). US-based participants (N=1052; stratified to be nationally representative based on sex, race, age) were asked about their perceptions of risk, benefit, invasiveness, acceptability, perceived change to the person, and personal interest in using these neurotechnologies for symptom alleviation. Results: Descriptive results indicate variability between technologies that the U.S. public is willing to consider if experiencing severe mood, memory, or motor symptoms. The main effect of neurotechnology revealed DBS was viewed as the most invasive and risky treatment and was perceived to lead to the greatest change to who someone is as a person. DBS was also viewed as least likely to be personally used and least acceptable for use by others. When examining the main effects of symptomatology, we found that all forms of neuromodulation were perceived as significantly more beneficial, acceptable, and likely to be used by participants for motor symptoms, followed by memory symptoms, and lastly mood symptoms. Neuromodulation (averaging across neurotechnologies) was perceived as significantly riskier, more invasive, and leading to a greater change to person for mood versus motor symptoms; however, memory and motor symptoms were perceived similarly with respect to risk, invasiveness, and change to person. Conclusion: These results suggest that the public views neuromodulatory approaches that require surgery (i.e., DBS and MRgFUS) as riskier, more invasive, and less acceptable than those that do not. Further, findings suggest individuals may be more reluctant to alter or treat psychological symptoms with neuromodulation compared to physical symptoms.
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Recent advances in psychiatric genetics have enabled the use of polygenic risk scores (PRS) to estimate genetic risk for psychiatric disorders. However, the potential use of PRS in child and adolescent psychiatry has raised concerns. This study provides an in-depth examination of attitudes among child and adolescent psychiatrists (CAP) regarding the use of PRS in psychiatry. We conducted semi-structured interviews with U.S.-based CAP (n = 29) who possess expertise in genetics. The majority of CAP indicated that PRS have limited clinical utility in their current form and are not ready for clinical implementation. Most clinicians stated that nothing would motivate them to generate PRS at present; however, some exceptions were noted (e.g., parent/family request). Clinicians spoke to challenges related to ordering, interpreting, and explaining PRS to patients and families. CAP raised concerns regarding the potential for this information to be misinterpreted or misused by patients, families, clinicians, and outside entities such as insurance companies. Finally, some CAP noted that PRS may lead to increased stigmatization of psychiatric disorders, and at the extreme, could be used to support eugenics. As PRS testing increases, it will be critical to examine CAP and other stakeholders' views to ensure responsible implementation of this technology.
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Psiquiatria do Adolescente , Transtornos Mentais , Herança Multifatorial , Humanos , Transtornos Mentais/genética , Masculino , Feminino , Adolescente , Psiquiatria Infantil , Criança , Atitude do Pessoal de Saúde , Adulto , Predisposição Genética para Doença , Pessoa de Meia-Idade , Estratificação de Risco Genético , PsiquiatrasRESUMO
Neurosurgery is a field with complex ethical issues. In this article, we aim to provide an overview of key and emerging ethical issues in neurosurgery with a focus on issues relevant to practicing neurosurgeons. These issues include those of informed consent, capacity, clinical trials, emerging neurotechnology, innovation, equity and justice, and emerging bioethics areas including community engagement and organizational ethics. We argue that bioethics can help neurosurgeons think about and address these issues, and, in turn, the field of bioethics can benefit from engagement by neurosurgeons. Several ideas for increasing engagement in bioethics are proposed.
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In April 2023, symptomatic strawberry (Fragaria × ananassa) plants (cv. 'Camarosa' and 'Florida Brilliance') were observed at a commercial farm in Worth County, GA (USA). Symptoms included foliar, irregularly distributed, and different-sized spots (dark brown with light brown centers) and dark brown V-shaped necrotic areas starting at the leaf edge. By the time of sample collection, ~50% incidence was reported in the field. Leaf samples were collected and shipped overnight to the laboratory. Black acervuli were observed readily on old necrotic foliar lesions. Conidial morphology was consistent with that observed with Neopestalotiopsis species (Maharachchikumbura et al. 2014). Conidia were ellipsoid to fusiform, five-celled, with three light brown median cells and one hyaline apical and basal cell. Apical cells had two-to-four flexuous appendages, and the basal cell had one non-flexuous appendage (Fig 1). The average (n = 20) conidia length, not including the appendages, was 26.6 µm (SD: 2.8), and width was 6.3 µm (SD: 0.94). Fungal isolation was conducted on acidified PDA and incubated at 25°C for 6 days. Dense, white mycelia were observed on the upper plate surface, while a pale pink/orange coloration was observed on the underside (Fig 1). Black acervuli formed on the surface of the white mycelial mat. Six isolates were purified and selected to confirm the species identity. DNA was extracted from 6-day-old cultures and PCR was conducted following Kaur et al. (2023). Amplified DNA was digested with the restriction enzyme BsaWI and two bands were clearly visualized (~130 and ~290 bp), along with a faint band of 20-bp (Fig 2). Four of the six isolates were selected for sequencing of the ß-tubulin gene. BLAST queries using the consensus sequence showed that all isolates had 100% identity to strain N21002 from Florida (FL), characterized as Neopestalotiopsis sp. (Kaur et al. 2023). One representative isolate (AJ07-2023) was deposited in GenBank (accession No. PP316103). Pathogenicity tests were performed on 27-day-old transplants of Sensation 'Florida127' provided by Natalia Peres from the UF. Plants were grown in 10.5 cm pots in the greenhouse. Isolate AJ07-2023 was grown on PDA for 30 days at 25°C, and the spore suspension was adjusted at 106 spore/ml. Five strawberry plants were sprayed with 5 ml of inoculum using a Preval sprayer with a CO2 canister, and 5 plants were sprayed with sterile distilled water. Plants were placed in a growth chamber for 6 days and covered with plastic bags after the sixth day to maintain ~85% relative humidity and 25°C. Foliar symptoms, including dark-brown circular lesions occurring towards the edge of leaves with light-brown center and light-yellow halo, developed 13 days after inoculation. No symptoms were observed on control plants. Neopestalotiopsis sp. was reisolated from inoculated plants as described above. Colony, conidial morphology, and PCR results were consistent with the original isolates. Neopestalotiopsis disease has been reported on strawberry in FL (Baggio et al. 2021), OH (Rotondo et al. 2022) and IN (Guan et al. 2023). Although the disease has been observed sporadically in GA since 2020 (Brannen, personal communication), to our knowledge, this is the first official report of the new Neopestalotiopsis sp. in GA. It has been reported that this new strain is more aggressive on fruits and leaves than other Neopestalotiopsis spp. (Baggio et al. 2021), therefore, accurate identification is critical for proper management.
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A rapid on-line solid-phase extraction liquid chromatography high-resolution mass spectrometry (on-line SPE-LC-HRMS) method was developed to analyze 11 ultra-short and short-chain PFAS in surface water. Analytical optimization involved screening 7 chromatographic columns and 5 on-line SPE columns, as well as evaluating SPE loading conditions, filters, sample acidification, chromatographic mobile phases, and SPE loading mobile phases. The optimized method was then applied to 44 river water samples collected in Eastern Canada, including sites near airports with fire-training areas. Among the 11 targeted PFAS, the most frequently detected were trifluoroacetic acid (TFA, 4.6-220 ng/L), perfluorobutanoic acid (PFBA, 0.85-33 ng/L), perfluoropentanoic acid (PFPeA, 1.2-2100 ng/L), trifluoromethane sulfonic acid (TMS, 0.01-4.3 ng/L), and perfluorobutane sulfonic acid (PFBS, 0.07-450 ng/L). Levels of C3-C5 perfluoroalkyl carboxylic acids (PFCAs), C2-C4 perfluoroalkyl sulfonates (PFSAs) and n:3 polyfluoroalkyl acids (n = 2,3; n:3 acids) were significantly higher in water bodies near fire-training area sites compared with rivers in urban areas. In contrast, TFA, TMS, and 1:3 acid were not significantly elevated, likely reflecting atmospheric deposition or other diffuse sources for these compounds. Nontarget and suspect screening analysis revealed an abundance of other ultra-short and short-chain PFAS in AFFF-impacted water bodies. Perfluoroalkyl sulfonamides (FASA, C2, C3, and C5), perfluoroalkyl sulfonamide propanoic acids (FASA-PrA, C1-C2) and n:3 acids (n = 1, 4, and 5) were detected for the first time in environmental surface waters.
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Importance: Polygenic embryo screening (PES) is a novel technology that estimates the likelihood of developing future conditions (eg, diabetes or depression) and traits (eg, height or cognitive ability) in human embryos, with the goal of selecting which embryos to use. Given its commercial availability and concerns raised by researchers, clinicians, bioethicists, and professional organizations, it is essential to inform key stakeholders and relevant policymakers about the public's perspectives on this technology. Objective: To survey US adults to examine general attitudes, interests, and concerns regarding PES use. Design, Setting, and Participants: For this survey study, data were collected from 1 stratified sample and 1 nonprobability sample (samples 1 and 2, respectively) between March and July 2023. The surveys measured approval, interest, and concerns regarding various applications of PES. In the second sample, presentation of a list of potential concerns was randomized (presented at survey onset vs survey end). The survey was designed using Qualtrics and distributed to participants through Prolific, an online sampling firm. Sample 1 was nationally representative with respect to gender, age, and race and ethnicity; sample 2 was recruited without specific demographic criteria. Analyses were conducted between March 2023 and February 2024. Main Outcomes and Measures: Participants reported their approval, interest, and concerns regarding various applications of PES and outcomes screened (eg, traits and conditions). Statistical analysis was conducted using independent samples t tests and repeated-measures analyses of variance. Results: Of the 1435 respondents in sample 1, demographic data were available for 1427 (mean [SD] age, 45.8 [16.0] years; 724 women [50.7%]). Among these 1427 sample 1 respondents, 1027 (72.0%) expressed approval for PES and 1169 (81.9%) expressed some interest in using PES if already undergoing in vitro fertilization (IVF). Approval among these respondents for using PES for embryo selection was notably high for physical health conditions (1109 [77.7%]) and psychiatric health conditions (1028 [72.0%]). In contrast, there was minority approval for embryo selection based on PES for behavioral traits (514 [36.0%]) and physical traits (432 [30.3%]). Nevertheless, concerns about PES leading to false expectations and promoting eugenic practices were pronounced, with 787 of 1422 (55.3%) and 780 of 1423 (54.8%) respondents finding them very to extremely concerning, respectively. Sample 2 included 192 respondents (mean [SD] age 37.7 [12.2] years; 110 men [57.3%]). These respondents were presented concerns at survey onset (n = 95) vs survey end (n = 97), which was associated with less approval (28-percentage point decrease) and more uncertainty (24 percentage-point increase) but with only slightly higher disapproval (4 percentage-point increase). Conclusions and Relevance: These findings suggest that it is critical for health care professionals and medical societies to consider and understand the perspectives of diverse stakeholders (eg, patients undergoing IVF, clinicians, and the general public), given the absence of regulation and the recent commercial availability of PES.
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Opinião Pública , Humanos , Feminino , Adulto , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Estados Unidos , Herança Multifatorial , Testes Genéticos/estatística & dados numéricos , Testes Genéticos/métodosRESUMO
Importance: Establishing a formal definition for neurological device abandonment has the potential to reduce or to prevent the occurrence of this abandonment. Objective: To perform a systematic review of the literature and develop an expert consensus definition for neurological device abandonment. Evidence Review: After a Royal Society Summit on Neural Interfaces (September 13-14, 2023), a systematic English language review using PubMed was undertaken to investigate extant definitions of neurological device abandonment. Articles were reviewed for relevance to neurological device abandonment in the setting of deep brain, vagal nerve, and spinal cord stimulation. This review was followed by the convening of an expert consensus group of physicians, scientists, ethicists, and stakeholders. The group summarized findings, added subject matter experience, and applied relevant ethics concepts to propose a current operational definition of neurological device abandonment. Data collection, study, and consensus development were done between September 13, 2023, and February 1, 2024. Findings: The PubMed search revealed 734 total articles, and after review, 7 articles were found to address neurological device abandonment. The expert consensus group addressed findings as germane to neurological device abandonment and added personal experience and additional relevant peer-reviewed articles, addressed stakeholders' respective responsibilities, and operationally defined abandonment in the context of implantable neurotechnological devices. The group further addressed whether clinical trial failure or shelving of devices would constitute or be associated with abandonment as defined. Referential to these domains and dimensions, the group proposed a standardized definition for abandonment of active implantable neurotechnological devices. Conclusions and Relevance: This study's consensus statement suggests that the definition for neurological device abandonment should entail failure to provide fundamental aspects of patient consent; fulfill reasonable responsibility for medical, technical, or financial support prior to the end of the device's labeled lifetime; and address any or all immediate needs that may result in safety concerns or device ineffectiveness and that the definition of abandonment associated with the failure of a research trial should be contingent on specific circumstances.
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Consenso , Humanos , Estimulação Encefálica Profunda/instrumentação , Estimulação Encefálica Profunda/éticaRESUMO
The ongoing debate within neuroethics concerning the degree to which neuromodulation such as deep brain stimulation (DBS) changes the personality, identity, and agency (PIA) of patients has paid relatively little attention to the perspectives of prospective patients. Even less attention has been given to pediatric populations. To understand patients' views about identity changes due to DBS in obsessive-compulsive disorder (OCD), the authors conducted and analyzed semistructured interviews with adolescent patients with OCD and their parents/caregivers. Patients were asked about projected impacts to PIA generally due to DBS. All patient respondents and half of caregivers reported that DBS would impact patient self-identity in significant ways. For example, many patients expressed how DBS could positively impact identity by allowing them to explore their identities free from OCD. Others voiced concerns that DBS-related resolution of OCD might negatively impact patient agency and authenticity. Half of patients expressed that DBS may positively facilitate social access through relieving symptoms, while half indicated that DBS could increase social stigma. These views give insights into how to approach decision-making and informed consent if DBS for OCD becomes available for adolescents. They also offer insights into adolescent experiences of disability identity and "normalcy" in the context of OCD.
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The Deep Brain Stimulation (DBS) Think Tank XI was held on August 9-11, 2023 in Gainesville, Florida with the theme of "Pushing the Forefront of Neuromodulation". The keynote speaker was Dr. Nico Dosenbach from Washington University in St. Louis, Missouri. He presented his research recently published in Nature inn a collaboration with Dr. Evan Gordon to identify and characterize the somato-cognitive action network (SCAN), which has redefined the motor homunculus and has led to new hypotheses about the integrative networks underpinning therapeutic DBS. The DBS Think Tank was founded in 2012 and provides an open platform where clinicians, engineers, and researchers (from industry and academia) can freely discuss current and emerging DBS technologies, as well as logistical and ethical issues facing the field. The group estimated that globally more than 263,000 DBS devices have been implanted for neurological and neuropsychiatric disorders. This year's meeting was focused on advances in the following areas: cutting-edge translational neuromodulation, cutting-edge physiology, advances in neuromodulation from Europe and Asia, neuroethical dilemmas, artificial intelligence and computational modeling, time scales in DBS for mood disorders, and advances in future neuromodulation devices.
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Per- and polyfluoroalkyl substances (PFAS) are a large chemical family, and numerous chemical species can co-exist in environmental samples, especially those impacted by aqueous film-forming foams (AFFFs). Given the limited availability of chemical standards, capturing the total amount of PFAS is challenging. Thus, the total oxidizable precursor (TOP) assay has been developed to estimate the total amount of PFAS via the oxidative conversion of precursors into perfluorocarboxylic acids (PFCAs). This study aims to enhance the robustness of the TOP assay by replacing heat activation with UV activation. We evaluated the molar yields of known precursors in water in the presence of varying levels of Suwannee River natural organic matter (SRNOM) and in two soils. The impact of UV activation was also evaluated in two soils spiked with three well-characterized AFFFs, six AFFF-impacted field soils, and nine rinse samples of AFFF-impacted stainless-steel pipe. In the presence of 100 mg/L SNROM, 6:2 fluorotelomer sulfonate (FTS), 8:2 FTS, and N-ethyl perfluorooctane sulfonamidoacetic acid (N-EtFOSAA) in deionized water had good molar recovery as PFCAs (average of 102 ± 9.8 %); at 500 mg/L SNROM, the recovery significantly dropped to an average of 51 ± 19 %. In two soils (with 4 % and 8.8 % organic matter) with individual precursor spikes, the average molar recovery was 101 ± 9.4 %, except N-EtFOSAA, which had a reduced recovery in the soil with 8.8 % organic matter (OM). UV-activated assays outperformed heat-activated ones, especially in AFFF-impacted soils and pipe extract samples, with an average of 1.4-1.5× higher PFCA recovery. In almost all test samples, UV activation resulted in a notable shift towards longer PFCA chain lengths, particularly for samples with high OM content. The study confirmed the advantages of UV activation, including a significantly shortened exposure time (1 h vs. 6 h) and reduced matrix effects from OM due to the dual functions of UV in activating persulfate and photodegrading OM.
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Cyclic nucleotide binding domains (CNB) confer allosteric regulation by cAMP or cGMP to many signaling proteins, including PKA and PKG. PKA of phylogenetically distant Trypanosoma is the first exception as it is cyclic nucleotide-independent and responsive to nucleoside analogues (Bachmaier et al., 2019). Here, we show that natural nucleosides inosine, guanosine and adenosine are nanomolar affinity CNB ligands and activators of PKA orthologs of the important tropical pathogens Trypanosoma brucei, Trypanosoma cruzi, and Leishmania. The sequence and structural determinants of binding affinity, -specificity and kinase activation of PKAR were established by structure-activity relationship (SAR) analysis, co-crystal structures and mutagenesis. Substitution of two to three amino acids in the binding sites is sufficient for conversion of CNB domains from nucleoside to cyclic nucleotide specificity. In addition, a trypanosomatid-specific C-terminal helix (αD) is required for high affinity binding to CNB-B. The αD helix functions as a lid of the binding site that shields ligands from solvent. Selectivity of guanosine for CNB-B and of adenosine for CNB-A results in synergistic kinase activation at low nanomolar concentration. PKA pulldown from rapid lysis establishes guanosine as the predominant ligand in vivo in T. brucei bloodstream forms, whereas guanosine and adenosine seem to synergize in the procyclic developmental stage in the insect vector. We discuss the versatile use of CNB domains in evolution and recruitment of PKA for novel nucleoside-mediated signaling.
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AMP Cíclico , Nucleosídeos de Purina , AMP Cíclico/metabolismo , Nucleosídeos/farmacologia , Regulação Alostérica , Nucleotídeos Cíclicos , Guanosina , AdenosinaRESUMO
Background: Artificial intelligence (AI)-based computer perception technologies (e.g., digital phenotyping and affective computing) promise to transform clinical approaches to personalized care in psychiatry and beyond by offering more objective measures of emotional states and behavior, enabling precision treatment, diagnosis, and symptom monitoring. At the same time, passive and continuous nature by which they often collect data from patients in non-clinical settings raises ethical issues related to privacy and self-determination. Little is known about how such concerns may be exacerbated by the integration of neural data, as parallel advances in computer perception, AI, and neurotechnology enable new insights into subjective states. Here, we present findings from a multi-site NCATS-funded study of ethical considerations for translating computer perception into clinical care and contextualize them within the neuroethics and neurorights literatures. Methods: We conducted qualitative interviews with patients (n = 20), caregivers (n = 20), clinicians (n = 12), developers (n = 12), and clinician developers (n = 2) regarding their perspective toward using PC in clinical care. Transcripts were analyzed in MAXQDA using Thematic Content Analysis. Results: Stakeholder groups voiced concerns related to (1) perceived invasiveness of passive and continuous data collection in private settings; (2) data protection and security and the potential for negative downstream/future impacts on patients of unintended disclosure; and (3) ethical issues related to patients' limited versus hyper awareness of passive and continuous data collection and monitoring. Clinicians and developers highlighted that these concerns may be exacerbated by the integration of neural data with other computer perception data. Discussion: Our findings suggest that the integration of neurotechnologies with existing computer perception technologies raises novel concerns around dignity-related and other harms (e.g., stigma, discrimination) that stem from data security threats and the growing potential for reidentification of sensitive data. Further, our findings suggest that patients' awareness and preoccupation with feeling monitored via computer sensors ranges from hypo- to hyper-awareness, with either extreme accompanied by ethical concerns (consent vs. anxiety and preoccupation). These results highlight the need for systematic research into how best to implement these technologies into clinical care in ways that reduce disruption, maximize patient benefits, and mitigate long-term risks associated with the passive collection of sensitive emotional, behavioral and neural data.
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Patient narratives from two investigational deep brain stimulation trials for traumatic brain injury and obsessive-compulsive disorder reveal that injury and illness rob individuals of personal identity and that neuromodulation can restore it. The early success of these interventions makes a compelling case for continued post-trial access to these technologies. Given the centrality of personal identity to respect for persons, a failure to provide continued access can be understood to represent a metaphorical identity theft. Such a loss recapitulates the pain of an individual's initial injury or illness and becomes especially tragic because it could be prevented by robust policy. A failure to fulfill this normative obligation constitutes a breach of disability law, which would view post-trial access as a means to achieve social reintegration through this neurotechnological accommodation.
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Estimulação Encefálica Profunda , Transtorno Obsessivo-Compulsivo , Humanos , Estimulação Encefálica Profunda/métodos , Transtorno Obsessivo-Compulsivo/terapia , Dever de Recontatar , Assistência ao Convalescente , Obrigações MoraisRESUMO
Over the past decades, single-molecule and super-resolution microscopy have advanced and represent essential tools for life science research. There is,however, a growing gap between the state-of-the-art and what is accessible to biologists, biochemists, medical researchers or labs with financial constraints. To bridge this gap, we introduce Brick-MIC, a versatile and affordable open-source 3D-printed micro-spectroscopy and imaging platform. Brick-MIC enables the integration of various fluorescence imaging techniques with single-molecule resolution within a single platform and exchange between different modalities within minutes. We here present variants of Brick-MIC that facilitate single-molecule fluorescence detection, fluorescence correlation spectroscopy and super-resolution imaging (STORM and PAINT). Detailed descriptions of the hardware and software components, as well as data analysis routines are provided, to allow non-optics specialist to operate their own Brick-MIC with minimal effort and investments. We foresee that our affordable, flexible, and opensource Brick-MIC platform will be a valuable tool for many laboratories worldwide.
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Mainstream virus detection relies on the specific amplification of nucleic acids via polymerase chain reaction, a process that is slow and requires extensive laboratory expertise and equipment. Other modalities, such as antigen-based tests, allow much faster virus detection but have reduced sensitivity. In this study, we report the development of a flow virometer for the specific and rapid detection of single nanoparticles based on confocal microscopy. The combination of laminar flow and multiple dyes enable the detection of correlated fluorescence signals, providing information on nanoparticle volumes and specific chemical composition properties, such as viral envelope proteins. We evaluated and validated the assay using fluorescent beads and viruses, including SARS-CoV-2. Additionally, we demonstrate how hydrodynamic focusing enhances the assay sensitivity for detecting clinically-relevant virus loads. Based on our results, we envision the use of this technology for clinically relevant bio-nanoparticles, supported by the implementation of the assay in a portable and user-friendly setup.
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Psychiatry is rapidly adopting digital phenotyping and artificial intelligence/machine learning tools to study mental illness based on tracking participants' locations, online activity, phone and text message usage, heart rate, sleep, physical activity, and more. Existing ethical frameworks for return of individual research results (IRRs) are inadequate to guide researchers for when, if, and how to return this unprecedented number of potentially sensitive results about each participant's real-world behavior. To address this gap, we convened an interdisciplinary expert working group, supported by a National Institute of Mental Health grant. Building on established guidelines and the emerging norm of returning results in participant-centered research, we present a novel framework specific to the ethical, legal, and social implications of returning IRRs in digital phenotyping research. Our framework offers researchers, clinicians, and Institutional Review Boards (IRBs) urgently needed guidance, and the principles developed here in the context of psychiatry will be readily adaptable to other therapeutic areas.
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Transtornos Mentais , Psiquiatria , Humanos , Inteligência Artificial , Transtornos Mentais/terapia , Comitês de Ética em Pesquisa , PesquisadoresRESUMO
A reconnaissance survey was undertaken to evaluate the occurrence and risks of 27 pharmaceuticals and metabolites in the St. Lawrence watershed. Surface water samples were collected over a five-year period (2017-2021) along a 700-km reach of the St. Lawrence River as well as 55 tributary rivers (overall N = 406 samples). Additionally, depth water samples and sediments were collected near a major wastewater effluent. Caffeine, diclofenac, and venlafaxine were the most recurrent substances (detection rates >80 %), and extremely high levels were found near a municipal effluent (e.g., ibuprofen (860 ng/L), hydroxyibuprofen (1800 ng/L) and caffeine (7200 ng/L)). Geographical mapping and statistical analyses indicated that the St. Lawrence River water mass after the Montreal City effluent was significantly more contaminated than the other water masses, and that contamination could extend up to 70 km further downstream. This phenomenon was repeatedly observed over the five years of sampling, confirming that this is not a random trend. A slight increase in contamination was also observed near Quebec City, but concentrations rapidly declined in the estuarine transition zone. Tributaries with the highest pharmaceutical levels (ΣPharmas â¼400-900 ng/L) included the Mascouche, Saint-Régis, and Bertrand rivers, all located in the densely populated Greater Montreal area. When flowrate was factored in, the top five tributaries in terms of mass load (ΣPharmas â¼200-2000 kg/year) were the Des Prairies, Saint-François, Richelieu, Ottawa, and Yamaska rivers. All samples met the Canadian Water Quality Guideline for carbamazepine. Despite the large dilution effect of the St. Lawrence River, a risk quotient approach based on freshwater PNEC values suggested that four compounds (caffeine, carbamazepine, diclofenac, and ibuprofen) could present intermediate to high risks for aquatic organisms in terms of chronic exposure.
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Poluentes Químicos da Água , Canadá , Poluentes Químicos da Água/análise , Cafeína/análise , Diclofenaco , Ibuprofeno , Carbamazepina/análise , Preparações Farmacêuticas , Monitoramento AmbientalRESUMO
INTRODUCTION: Pediatric deep brain stimulation (pDBS) is commonly used to manage treatment-resistant primary dystonias with favorable results and more frequently used for secondary dystonia to improve quality of life. There has been little systematic empirical neuroethics research to identify ethical challenges and potential solutions to ensure responsible use of DBS in pediatric populations. METHODS: Clinicians (n = 29) who care for minors with treatment-resistant dystonia were interviewed for their perspectives on the most pressing ethical issues in pDBS. RESULTS: Using thematic content analysis to explore salient themes, clinicians identified four pressing concerns: (1) uncertainty about risks and benefits of pDBS (22/29; 72%) that poses a challenge to informed decision-making; (2) ethically navigating decision-making roles (15/29; 52%), including how best to integrate perspectives from diverse stakeholders (patient, caregiver, clinician) and how to manage surrogate decisions on behalf of pediatric patients with limited capacity to make autonomous decisions; (3) information scarcity effects on informed consent and decision quality (15/29; 52%) in the context of patient and caregivers' expectations for treatment; and (4) narrow regulatory status and access (7/29; 24%) such as the lack of FDA-approved indications that contribute to decision-making uncertainty and liability and potentially limit access to DBS among patients who may benefit from it. CONCLUSION: These results suggest that clinicians are primarily concerned about ethical limitations of making difficult decisions in the absence of informational, regulatory, and financial supports. We discuss two solutions already underway, including supported decision-making to address uncertainty and further data sharing to enhance clinical knowledge and discovery.