Natural organic matter (NOM) can increase the uptake fluxes of three critical metals (Ga, La, Pt) in a unicellular green alga.

Critical metals such as gallium, lanthanum and platinum are considered essential in a modern economy and for the required energy transition. Their relatively recent and increasing use in new technologies have led to an increase in their environmental mobility. As they reach aquatic systems, these metals can interact with organic ligands and especially Natural Organic Matter (NOM). The formation of organic complexes would be expected to reduce metal bioavailability and uptake by living cells, according to the Biotic Ligand Model (BLM). However, exceptions to this model have been determined for several critical metals in the past. The present work compared internalization kinetics of Ga, La and Pt in the green alga Chlamydomonas reinhardtii in the presence of NOMs from different origins: humic and fulvic acids from Suwannee River as well as NOMs from Ontario (Bannister Lake and Luther Marsh). Complexation was determined using a partial ultrafiltration method allowing for a normalization of data based on speciation to compare all conditions based on the concentration of the metal that was not bound to NOM. While internalization metal fluxes varied greatly from one NOM source to the other, uptake was almost always significantly higher than expected based on metal speciation. Quite often, metal internalization fluxes were even significantly increased in the presence of NOM, for the same total metal exposure concentration. For instance, Pt internalization was twice greater in the presence of Bannister Lake NOM than it was in the absence of NOM. The assumption that such exceptions could be explained by NOM characteristics was contradicted by the variable results from one metal to another. To further explore this phenomenon, internalization mechanisms for these individual metals need to be elucidated. This is a necessary step to accurately estimate the risk posed by the presence of these metals in humic aquatic systems.

Understanding decision-makers and their needs: framing Global Burden of Animal Diseases offerings to enhance relevance and increase impact.

In a world characterised by data deserts and data swamps, translating evidence into actionable policies and practices is not easy. This article addresses this challenge through the lens of evidence emerging from the Global Burden of Animal Diseases (GBADs) initiative. It emphasises the need for an intentional approach that connects research information with the specific needs of decision-makers and identifies specific impact pathways associated with different groups of decision-makers. The GBADs programme aims to support animal health decisions, and the authors outline the diverse landscape of decision-makers in this field, encompassing the public and private sectors, livestock keepers, civil society and international development agencies. Key issues such as disease prioritisation and lobbying are also discussed. The authors propose an â€Ëœevidence ecosystem'approach, one that understands data users and their interactions, for analysing the needs of decision-makers, and framing GBADs offerings according to these needs. Two case studies, a recently concluded global case study of disease prioritisation decision-making and an ongoing policy analysis and needs assessment for GBADs in Indonesia, are presented to demonstrate how evidence ecosystem analysis and audience segmentation could be used to tailor GBADs information offerings for different decision-making groups. The article concludes by recommending that GBADs'future applications prioritise information offerings, adapt them to decision-makers'needs and consider how different segments of decision-makers will utilise the information to achieve real-world impacts.

Dans un monde où l'on rencontre aussi bien des déserts de données que des marécages de données, il n'est guère facile d'utiliser avec succès des données probantes pour les traduire en politiques et en pratiques exploitables. Les auteurs abordent cette difficulté dans l'optique des données actuellement générées dans le cadre de l'initiative " Impact mondial des maladies animales " (GBADs). Ils soulignent l'importance de disposer d'une méthode volontariste capable de relier l'information issue de la recherche avec les besoins spécifiques des décideurs, en tenant compte des chemins d'impact spécifiques associés à chaque catégorie de décideurs. Le programme GBADs vise à soutenir les décisions relatives à la santé animale ; les auteurs donnent une vue d'ensemble de la diversité des décideurs intervenant dans ce domaine, qui recouvre les secteurs public et privé, les éleveurs, la société civile et les organismes internationaux de développement. Certaines questions majeures comme le classement des maladies par ordre de priorité et les activités des groupes de pression sont également abordées. Afin de pouvoir analyser les besoins de ces décideurs et d'encadrer les propositions du GBADs en conséquence, les auteurs proposent une approche qualifiée d'" écosystème d'éléments probants ", qui permet de comprendre les utilisateurs de données et leurs interactions. À travers deux études de cas, l'une récemment achevée sur l'établissement des priorités sanitaires dans les prises de décision à l'échelle mondiale et l'autre actuellement en cours sur l'analyse des politiques et l'évaluation des besoins dans le cadre du GBADs en Indonésie, les auteurs démontrent comment l'analyse de l'écosystème d'éléments probants et la segmentation des destinataires permettent de moduler les informations proposées par le GBADs en fonction des différents groupes de décideurs auxquels elle sont destinées. Les auteurs concluent en recommandant que les applications futures du GBADs établissent des priorités parmi les informations proposées, en les adaptant aux besoins des décideurs et en considérant le nombre de segments différents de décideurs qui vont utiliser l'information en vue de résultats tangibles.

En un mundo caracterizado por los desiertos y los pantanos de datos, no es una misión fácil traducir los datos en políticas y prácticas viables. Este artículo aborda este reto desde la óptica de los datos procedentes de la iniciativa sobre el impacto global de las enfermedades animales (GBADs). Asimismo, subraya la necesidad de un planteamiento intencionado que conecte la información de las investigaciones con las necesidades específicas de los responsables de la toma de decisiones e identifique vías de impacto concretas asociadas a los distintos grupos de decisores. El programa del GBADs busca respaldar las decisiones en materia de sanidad animal y, a este respecto, los autores del artículo describen la diversidad de responsables de la toma de decisiones en dicho ámbito, entre los que figuran los sectores público y privado, los ganaderos, la sociedad civil y los organismos internacionales de desarrollo. También se abordan cuestiones clave como la priorización de enfermedades y los grupos de presión. Los autores proponen un enfoque basado en un "ecosistema de datos" que tenga en cuenta a los usuarios de los datos y sus interacciones a fin de analizar las necesidades de los responsables de la toma de decisiones y enmarcar los servicios del GBADs en función de dichas necesidades. Se presentan dos estudios de casos, uno mundial sobre la toma de decisiones en materia de priorización de enfermedades, que concluyó recientemente, y otro en curso sobre análisis de políticas y evaluación de necesidades del GBADs en Indonesia, con miras a demostrar cómo el análisis del ecosistema de datos y la segmentación de la audiencia podrían utilizarse para adaptar los servicios de información del GBADs a los distintos grupos de responsables de la toma de decisiones. El artículo concluye recomendando que las futuras aplicaciones del GBADs prioricen los servicios de información, los adapten a las necesidades de los responsables de la toma de decisiones y tengan en cuenta cómo utilizarán la información los distintos grupos de responsables para lograr repercusiones en el mundo real.

The effects of dissolved organic carbon and model compounds (DOC analogues) on diffusive water flux, oxygen consumption, nitrogenous waste excretion rates and gill transepithelial potential in Pacific sanddab (Citharichthys sordidus) at two salinities.

Many flatfish species are partially euryhaline, such as the Pacific sanddab which spawn and feed in highly dynamic estuaries ranging from seawater to near freshwater. With the rapid increase in saltwater invasion of freshwater habitats, it is very likely that in these estuaries, flatfish will be exposed to increasing levels of dissolved organic carbon (DOC) of freshwater origin at a range of salinities. As salinity fluctuations often coincide with changes in DOC concentration, two natural freshwater DOCs [Luther Marsh (LM, allochthonous) and Lake Ontario (LO, autochthonous) were investigated at salinities of 30 and 7.5 ppt. Optical characterization of the two natural DOC sources indicate salinity-dependent differences in their physicochemistry. LO and LM DOCs, as well as three model compounds [tannic acid (TA), sodium dodecyl sulfate (SDS) and bovine serum albumin (BSA)] representing key chemical moieties of DOC, were used to evaluate physiological effects on sanddabs. In the absence of added DOC, an acute decrease in salinity resulted in an increase in diffusive water flux (a proxy for transcellular water permeability), ammonia excretion and a change in TEP from positive (inside) to negative (inside). The effects of DOC (10 mg C L-1) were salinity and source-dependent, with generally more pronounced effects at 30 than 7.5 ppt, and greater potency of LM relative to LO. Both LM DOC and SDS increased diffusive water flux at 30 ppt but only SDS had an effect at 7.5 ppt. TA decreased ammonia excretion at 7.5 ppt. LO DOC decreased urea-N excretion at both salinities whereas the stimulatory effect of BSA occurred only at 30 ppt. Likewise, the effects of LM DOC and BSA to reduce TEP were present at 30 ppt but not 7.5 ppt. None of the treatments affected oxygen consumption rates. Our results demonstrate that DOCs and salinity interact to alter key physiological processes in marine flatfish, reflecting changes in both gill function and the physicochemistry of DOCs between 30 and 7.5 ppt.

Centering the person in development of a model of care for people with Parkinson's disease: a qualitative study.

PURPOSE: Obtain the perspectives of people with Parkinson's disease (PwPD) and their care partners (CPs) about their lived experiences with Parkinson's Disease (PD) to characterize a new model of care that meets their biopsychosocial and healthcare needs. METHODS: This phenomenological study included semi-structured focus groups exploring PD diagnosis/care experiences and conceptualizations of an ideal model of care among PwPD and CPs. Data were analyzed via thematic analysis. RESULTS: Twenty-five individuals (PwPD, n = 18; CPs, n = 7) participated across four focus groups. Researchers developed four themes to describe participants' lived experience with, barriers to, and needs for PD care. These themes characterize key hopes for care as: 1) person-centered, 2) coordinated, 3) provides access to education and information, and 4) builds on the benefits of community. CONCLUSIONS: Participants emphasized that, beyond clinical interactions and diagnosis-centered conversations, they wished for holistic healthcare that acknowledged the larger picture of their life with PD. An ideal model of care for PwPD should aim to be person centered, maximize collaboration and coordination across multiple disciplines, provide access to a wide range of information and resources, refer to community centers and support groups, and be designed with ease of navigation in mind.

Health professionals need to inquire about an individual's lived experience and employ strategies that center the person and personalizes their care while also integrating a coordinated interdisciplinary approach.An ideal model of care needs to integrate healthcare professionals as part of a larger care team that includes the person with Parkinson's disease, and facilitates communication and planning with those team membersAn ideal model of care needs to integrate the larger community and seek to refer and build relationships with health professionals, organizations, and non-medical providers that will facilitate holistic care and advocate for people with Parkinson's disease.

Pharmacokinetics and Pharmacogenomics of Ribociclib in Black Patients with Metastatic Breast Cancer: The LEANORA study.

Underrepresented populations' participation in clinical trials remains limited, and the potential impact of genomic variants on drug metabolism remains elusive. This study aimed to assess the pharmacokinetics (PK) and pharmacogenomics (PGx) of ribociclib in self-identified Black women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2) advanced breast cancer. LEANORA (NCT04657679) was a prospective, observational, multicenter cohort study involving 14 Black women. PK and PGx were evaluated using tandem mass spectrometry and PharmacoScan™ microarray (including CYP3A5*3 , *6 , and *7 ). CYP3A5 phenotypes varied among participants: 7 poor metabolizers (PM), 6 intermediate metabolizers (IM), and one normal metabolizer (NM). The area-under-the-curve did not significantly differ between PMs (39,230 hr*ng/mL) and IM/NMs (43,546 hr*ng/mL; p = 0.38). The incidence of adverse events (AEs) was also similar. We found no association between CYP3A5 genotype and ribociclib exposure. Continued efforts are needed to include diverse populations in clinical trials to ensure equitable treatment outcomes.

Who's in control? Situating expertise, (mis)trust, and power among the Latine/Hispanic community in COVID-19's liminal moments.

BACKGROUND: Research has established the disproportionate impact of COVID-19 on Black, Indigenous, and People of color (BIPOC) communities, and the barriers to vaccine trust and access among these populations. Focusing on perceptions of safety, access, and trustworthiness, studies often attach barriers to community-members, and discuss vaccines as if developed from an objective perspective, or "view from nowhere" (Haraway). OBJECTIVE: We sought to follow Haraway's concept of "situated knowledges," whereby no one truth exists, and information is understood within its context, to understand the exertions of expertise surrounding vaccines. We focused on perceptions of power among a BIPOC community during a relatively unexamined moment, wherein the status of the pandemic and steps to prevent it were particularly uncertain. METHODS: We report the findings of ten focus groups conducted among members of Rhode Island's Latine/Hispanic communities between December 2021 and May 2022. We called this time COVID-19's liminal moment because vaccines were distributed, mandates were lifted, vaccine efficacy was doubted, and new strains spread. We translated, transcribed, and analyzed focus groups using thematic analysis. RESULTS: Community-member (n = 65) perceptions of control aligned with three key themes: (1) no power is capable of controlling COVID-19, (2) we are the objects of scientific and political powers, and (3) we, as individuals and communities, can control COVID-19 through our decisions and actions. CONCLUSIONS: By centering the perspectives of a minoritized community, we situated the scientific knowledge produced about COVID-19 within the realities of imperfect interventions, uncontrollable situations, and medical power-exertions. We argue that medical knowledge should not be assumed implicitly trustworthy, or even capable, but instead seen as one of many products of human labor within human systems. Trust and trustworthiness must be mutually negotiated between experts, contexts, and communities through communication, empowerment, and justice.

von Willebrand factor antigen, von Willebrand factor propeptide and ADAMTS13 activity in TIA or ischaemic stroke patients changing antiplatelet therapy.

Data are limited on the impact of commencing antiplatelet therapy on von Willebrand Factor Antigen (VWF:Ag) or von Willebrand Factor propeptide (VWFpp) levels and ADAMTS13 activity, and their relationship with platelet reactivity following TIA/ischaemic stroke. In this pilot, observational study, VWF:Ag and VWFpp levels and ADAMTS13 activity were quantified in 48 patients ≤4 weeks of TIA/ischaemic stroke (baseline), and 14 days (14d) and 90 days (90d) after commencing aspirin, clopidogrel or aspirin+dipyridamole. Platelet reactivity was assessed at moderately-high shear stress (PFA-100® Collagen-Epinephrine / Collagen-ADP / INNOVANCE PFA P2Y assays), and low shear stress (VerifyNow® Aspirin / P2Y12, and Multiplate® Aspirin / ADP assays). VWF:Ag levels decreased and VWFpp/VWF:Ag ratio increased between baseline and 14d and 90d in the overall population (P ≤ 0.03). In the clopidogrel subgroup, VWF:Ag levels decreased and VWFpp/VWF:Ag ratio increased between baseline and 14d and 90d (P ≤ 0.01), with an increase in ADAMTS13 activity between baseline vs. 90d (P ≤ 0.03). In the aspirin+dipyridamole subgroup, there was an inverse relationship between VWF:Ag and VWFpp levels with both PFA-100 C-ADP and INNOVANCE PFA P2Y closure times (CTs) at baseline (P ≤ 0.02), with PFA-100 C-ADP, INNOVANCE PFA P2Y and C-EPI CTs at 14d (P ≤ 0.05), and between VWF:Ag levels and PFA-100 INNOVANCE PFA P2Y CTs at 90d (P = 0.03). There was a positive relationship between ADAMTS13 activity and PFA-100 C-ADP CTs at baseline (R2 = 0.254; P = 0.04). Commencing/altering antiplatelet therapy, mainly attributed to commencing clopidogrel in this study, was associated with decreasing endothelial activation following TIA/ischaemic stroke. These data enhance our understanding of the impact of VWF:Ag and VWFpp especially on ex-vivo platelet reactivity status at high shear stress after TIA/ischaemic stroke.

Strategies for DPYD testing prior to fluoropyrimidine chemotherapy in the US.

PURPOSE: Patients with dihydropyrimidine dehydrogenase (DPD) deficiency are at high risk for severe and fatal toxicity from fluoropyrimidine (FP) chemotherapy. Pre-treatment DPYD testing is standard of care in many countries, but not the United States (US). This survey assessed pre-treatment DPYD testing approaches in the US to identify best practices for broader adoption. METHODS: From August to October 2023, a 22-item QualtricsXM survey was sent to institutions and clinicians known to conduct pre-treatment DPYD testing and broadly distributed through relevant organizations and social networks. Responses were analyzed using descriptive analysis. RESULTS: Responses from 24 unique US sites that have implemented pre-treatment DPYD testing or have a detailed implementation plan in place were analyzed. Only 33% of sites ordered DPYD testing for all FP-treated patients; at the remaining sites, patients were tested depending on disease characteristics or clinician preference. Almost 50% of sites depend on individual clinicians to remember to order testing without the assistance of electronic alerts or workflow reminders. DPYD testing was most often conducted by commercial laboratories that tested for at least the four or five DPYD variants considered clinically actionable. Approximately 90% of sites reported receiving results within 10 days of ordering. CONCLUSION: Implementing DPYD testing into routine clinical practice is feasible and requires a coordinated effort among the healthcare team. These results will be used to develop best practices for the clinical adoption of DPYD testing to prevent severe and fatal toxicity in cancer patients receiving FP chemotherapy.

Yttrium-90 anti-CD25 BEAM conditioning for autologous hematopoietic cell transplantation in Peripheral T-cell lymphoma.

ABSTRACT: Peripheral T-cell lymphomas (PTCLs) have a poor prognosis with current treatments. High-dose chemotherapy followed by autologous hematopoietic cell transplant (AHCT) is used as a consolidation strategy after achieving clinical remission with first-line therapy, as well as in chemotherapy-sensitive relapse if allogeneic transplant is not an option. CD25 is a targetable protein often highly expressed in PTCLs. In this phase 1 clinical trial, we tested the addition of ß-emitting 90yttrium (90Y)-labeled chimeric anti-CD25 basiliximab (aTac) to BEAM (carmustine, etoposide, cytarabine, and melphalan) as conditioning for AHCT for patients with PTCL. Twenty-three AHCT-eligible patients were enrolled, and 20 received therapeutic 90Y-aTac-BEAM AHCT. Radiation doses of 0.4, 0.5, and 0.6 mCi/kg were tested. With no observed dose-limiting toxicities, 0.6 mCi/kg was deemed the recommended phase 2 dose. The most prevalent adverse effect, grade 2 mucositis, was experienced by 80% of patients. As of this report, 6 (30%) of the treated patients had died, 5 due to progressive disease and 1 due to multiple organ failure (median time of death, 17 months [range, 9-21]) after AHCT. Median follow-up was 24 months (range, 9-26) overall and 24 months (range, 13-26) for surviving patients. For patients who received therapeutic 90Y-aTac-BEAM AHCT, the 2-year progression-free and overall survival were 59% (95% confidence interval [CI], 34-77) and 68% (95% CI, 42-84), respectively. 90Y-aTac-BEAM appears to be safe as an AHCT conditioning regimen for PTCL, with no increased toxicity over the toxicities historically seen with BEAM alone in this patient population. This trial was registered at www.ClinicalTrials.gov as #NCT02342782.

Perinatal optimisation for periviable birth and outcomes: a 4-year network analysis (2018-2021) across a change in national guidance.

Introduction: The British Association of Perinatal Medicine (BAPM) released their revised framework for extremely preterm infant management in 2019. This revised framework promotes consideration of perinatal optimisation and survival-focused care from 22 weeks gestation onwards. This was a departure from the previous BAPM framework which recommended comfort care as the only recommended management for infants <23 + 0 weeks. Methods: Our study evaluates the clinical impact that this updated framework has had across the Northwest of England. We utilised anonymised network data from periviable infants delivered across the region to examine changes in perinatal optimisation practices and survival outcomes following the release of the latest BAPM framework. Results: Our data show that after the introduction of the updated framework there has been an increase in perinatal optimisation practices for periviable infants and an 80% increase in the number of infants born at 22 weeks receiving survival-focused care and admission to a neonatal unit. Discussion: There remain significant discrepancies in optimisation practices by gestational age, which may be contributing to the static survival rates that were observed in the lowest gestational ages.

Predicting consequences of COVID-19 control measure de-escalation on nosocomial transmission and mortality: a modelling study in a French rehabilitation hospital.

INTRODUCTION: Infection control measures are effective for nosocomial COVID-19 prevention but bear substantial health-economic costs, motivating their "de-escalation" in settings at low risk of SARS-CoV-2 transmission. Yet consequences of de-escalation are difficult to predict, particularly in light of novel variants and heterogeneous population immunity. AIM: To estimate how infection control measure de-escalation influences nosocomial COVID-19 risk. METHODS: An individual-based transmission model was used to simulate SARS-CoV-2 outbreaks and control measure de-escalation in a French long-term care hospital with multi-modal control measures in place (testing and isolation, universal masking, single-occupant rooms). Estimates of COVID-19 case fatality rates (CFRs) from reported outbreaks were used to quantify excess COVID-19 mortality due to de-escalation. RESULTS: In a population fully susceptible to infection, de-escalating both universal masking and single rooms resulted in hospital-wide outbreaks of 114 (95% CI: 103-125) excess infections, compared with five (three to seven) excess infections when de-escalating only universal masking or 15 (11-18) when de-escalating only single rooms. When de-escalating both measures and applying CFRs from the first wave of COVID-19, excess patient mortality ranged from 1.57 (1.41-1.71) to 9.66 (8.73-10.57) excess deaths/1000 patient-days. By contrast, when applying CFRs from subsequent pandemic waves and assuming susceptibility to infection among 40-60% of individuals, excess mortality ranged from 0 (0-0) to 0.92 (0.77-1.07) excess deaths/1000 patient-days. CONCLUSIONS: The de-escalation of bundled COVID-19 control measures may facilitate widespread nosocomial SARS-CoV-2 transmission. However, excess mortality is probably limited in populations at least moderately immune to infection and given CFRs resembling those estimated during the 'post-vaccine' era.

Telomere dynamics during hibernation in a tropical primate.

Hibernation is a widespread metabolic strategy among mammals for surviving periods of food scarcity. During hibernation, animals naturally alternate between metabolically depressed torpor bouts and energetically expensive arousals without ill effects. As a result, hibernators are promising models for investigating mechanisms that buffer against cellular stress, including telomere protection and restoration. In non-hibernators, telomeres, the protective structural ends of chromosomes, shorten with age and metabolic stress. In temperate hibernators, however, telomere shortening and elongation can occur in response to changing environmental conditions and associated metabolic state. We investigate telomere dynamics in a tropical hibernating primate, the fat-tailed dwarf lemur (Cheirogaleus medius). In captivity, these lemurs can hibernate when maintained under cold temperatures (11-15 °C) with limited food provisioning. We study telomere dynamics in eight fat-tailed dwarf lemurs at the Duke Lemur Center, USA, from samples collected before, during, and after the hibernation season and assayed via qPCR. Contrary to our predictions, we found that telomeres were maintained or even lengthened during hibernation, but shortened immediately thereafter. During hibernation, telomere lengthening was negatively correlated with time in euthermia. Although preliminary in scope, our findings suggest that there may be a preemptive, compensatory mechanism to maintain telomere integrity in dwarf lemurs during hibernation. Nevertheless, telomere shortening immediately afterward may broadly result in similar outcomes across seasons. Future studies could profitably investigate the mechanisms that offset telomere shortening within and outside of the hibernation season and whether those mechanisms are modulated by energy surplus or crises.

Proposing a new history of grief's medicalisation: A critical discourse analysis.

Conceptualisations of grief have transformed significantly in recent decades, from an experience accepted and expressed in community spaces to a diagnosable clinical phenomenon. Narratives of this transformation tend to focus on grief's relationship to major depression, or on recent nosological changes. This paper examines the possibility of a new narrative for medicalisation by grounding in the networks of language and power created around 'grief' through a critical discourse analysis of psy-discipline articles (n = 70) published between 1975 and 1995. Focusing on shifts in definitions of, methods used to approach, and rationales motivating study of the experience, it posits that the psy-disciplines exerted exclusive expertise over grief decades before its creation as a diagnosis. By reconceptualising grief in the terms of psy-specific symptoms and functional performance and by approaching it with the decontextualising and interventionist methods of an increasingly scientific psy-discipline, the psy-community medicalised grief between 1975 and 1995. Identifying neoliberal and other cultural influences shaping this process of medical construction and reconsidering narratives of grief's history mindful of the powers exerted in medicalisation, this paper establishes that these moments played a critical role in the development of the present's grief.

geoFOR: A collaborative forensic taphonomy database for estimating the postmortem interval.

Accurately assessing the postmortem interval (PMI), or the time since death, remains elusive within forensic science research and application. This paper introduces geoFOR, a web-based collaborative application that utilizes ArcGIS and machine learning to deliver improved PMI predictions. The geoFOR application provides a standardized, collaborative forensic taphonomy database that gives practitioners a readily available tool to enter case information that automates the collection of environmental data and delivers a PMI prediction using statistically robust methods. After case submission, the cross-validating machine learning PMI predictive model results in a R² value of 0.82. Contributors receive a predicted PMI with an 80% confidence interval. The geoFOR database currently contains 2529 entries from across the U.S. and includes cases from medicolegal investigations and longitudinal studies from human decomposition facilities. We present the overall findings of the data collected so far and compare results from medicolegal cases and longitudinal studies to highlight previously poorly understood limitations involved in the difficult task of PMI estimation. This novel approach for building a reference dataset of human decomposition is forensically and geographically representative of the realities in which human remains are discovered which allows for continual improvement of PMI estimations as more data is captured. It is our goal that the geoFOR data repository follow the principles of Open Science and be made available to forensic researchers to test, refine, and improve PMI models. Mass collaboration and data sharing can ultimately address enduring issues associated with accurately estimating the PMI within medicolegal death investigations.

Enhancing the Standardized Field Sobriety Test to detect cannabis impairment: An observational study.

OBJECTIVE: The purpose of this study was to explore various tests of impairment that could potentially be added to the Standardized Field Sobriety Test (SFST) to enhance its sensitivity to identify drivers whose abilities are adversely affected by cannabis. METHODS: An observational study was conducted in which participants were invited to use their own cannabis at the research facility. Once prior to cannabis use and at four times during the 150 min after cannabis use, participants performed the three tests of the Standardized Field Sobriety Test (SFST) (i.e., Horizontal Gaze Nystagmus, Walk and Turn, and One Leg Stand) as well as the Modified Romberg Balance and Finger to Nose tests. In addition, assessments were made of physiological indicators (i.e., eyelid, leg and body tremors, rebound dilation, lack of convergence) and vital signs (pulse, blood pressure and body temperature). Participants also completed a digit-symbol substitution task at each testing interval. With the exception of vital signs and the digit symbol task, all tests and assessments were administered and scored by certified Drug Recognition Experts using the standard procedures of the Drug Evaluation and Classification Program. RESULTS: Twenty minutes after vaping cannabis (mean THC concentration = 6.34 ng/mL), participants displayed performance deficits on a variety of tasks; 67% met the criterion for suspected impairment on the SFST. Addition of the Finger-to-Nose (FTN) test along with observations of head movements and jerks (HMJ) increased the percentage of participants who met the criterion for suspected impairment by 33% and improved the sensitivity of the test from 0.67 to 0.88. CONCLUSIONS: The results of this study support supplementing the SFST with the Finger-to-Nose test and observations of HMJ to assist in the detection of drivers who are adversely affected by the use of cannabis. The observational study design and the use of assessors who were not blinded as to the use of cannabis by participants limits the strength of the evidence. Further research, including randomized trials and field studies of drivers, is required to confirm and validate this enhanced version of the SFST.

Prenatal cortisol exposure impairs adrenal function but not glucose metabolism in adult sheep.

Adverse environmental conditions before birth are known to programme adult metabolic and endocrine phenotypes in several species. However, whether increments in fetal cortisol concentrations of the magnitude commonly seen in these conditions can cause developmental programming remains unknown. Thus, this study investigated the outcome of physiological increases in fetal cortisol concentrations on glucose-insulin dynamics and pituitary-adrenal function in adult sheep. Compared with saline treatment, intravenous fetal cortisol infusion for 5 days in late gestation did not affect birthweight but increased lamb body weight at 1-2 weeks after birth. Adult glucose dynamics, insulin sensitivity and insulin secretion were unaffected by prenatal cortisol overexposure, assessed by glucose tolerance tests, hyperinsulinaemic-euglycaemic clamps and acute insulin administration. In contrast, prenatal cortisol infusion induced adrenal hypo-responsiveness in adulthood with significantly reduced cortisol responses to insulin-induced hypoglycaemia and exogenous adrenocorticotropic hormone (ACTH) administration relative to saline treatment. The area of adrenal cortex expressed as a percentage of the total cross-sectional area of the adult adrenal gland was also lower after prenatal cortisol than saline infusion. In adulthood, basal circulating ACTH but not cortisol concentrations were significantly higher in the cortisol than saline-treated group. The results show that cortisol overexposure before birth programmes pituitary-adrenal development with consequences for adult stress responses. Physiological variations in cortisol concentrations before birth may, therefore, have an important role in determining adult phenotypical diversity and adaptability to environmental challenges.

Pharmacogenomic testing in oncology: a health system's approach to identify oncology provider perspectives.

Aim: Identify oncology healthcare providers' attitudes toward barriers to and use cases for pharmacogenomic (PGx) testing and implications for prescribing anticancer and supportive care medications. Materials & methods: A questionnaire was designed and disseminated to 71 practicing oncology providers across the MedStar Health System. Results: 25 of 70 (36%) eligible oncology providers were included. 88% were aware of PGx testing and 72% believed PGx can improve care. Of providers who had ordered a medication with PGx implications in the past month, interest in PGx for anticancer (90-100%) and supportive care medications (>75%) was high. Providers with previous PGx education were more likely to have ordered a test (odds ratio: 7.9; 95% CI: 1.1-56; p = 0.0394). Conclusion: Oncology provider prescribing practices and interest in PGx suggest opportunities for implementation.

Understanding the mechanism by which Gd(III) coiled coils achieve magnetic resonance relaxivity - a study into the water coordination chemistry.

A class of Gd(III) coiled coils achieve high MRI relaxivity, in part due to their slow rotational correlation time. However, extending their length is unable to further enhance performance, as the mechanism by which relaxivity is achieved is dominated by the presence of three inner sphere waters in rapid exchange, through an associative mechanism.

Phosphorus release and recovery by reductive dissolution of chemically precipitated phosphorus from simulated wastewater.

Chemically mediated recovery of phosphorous (P) as vivianite from the sludges generated by chemical phosphorus removal (CPR) is a potential means of enhancing sustainability of wastewater treatment. This study marks an initial attempt to explore direct P release and recovery from lab synthetic Fe-P sludge via reductive dissolution using ascorbic acid (AA) under acidic conditions. The effects of AA/Fe molar ratio, age of Fe-P sludge and pH were examined to find the optimum conditions for Fe-P reductive solubilization and vivianite precipitation. The performance of the reductive, chelating, and acidic effects of AA toward Fe-P sludge were evaluated by comparison with hydroxylamine (reducing agent), oxalic acid (chelating agent), and inorganic acids (pH effect) including HNO3, HCl, and H2SO4. Full solubilization of Fe-P sludge and reduction of Fe3+ were observed at pH values 3 and 4 for two Fe/AA molar ratios of 1:2 and 1:4. Sludge age (up to 11 days) did not affect the reductive solubilization of Fe-P with AA addition. The reductive dissolution of Fe-P sludge with hydroxylamine was negligible, while both P (95 ± 2%) and Fe3+ (90 ± 1%) were solubilized through non-reductive dissolution by oxalic acid treatment at an Fe/oxalic acid molar ratio 1:2 and a pH 3. With sludge treatment with inorganic acids at pH 3, P and Fe release was very low (<10%) compared to AA and oxalic acid treatment. After full solubilization of Fe-P sludge by AA treatment at pH 3 it was possible to recover the phosphorus and iron as vivianite by simple pH adjustment to pH 7; P and Fe recoveries of 88 ± 2% and 90 ± 1% respectively were achieved in this manner. XRD analysis, Fe/P molar ratio measurements, and magnetic attraction confirmed vivianite formation. PHREEQC modeling showed a reasonable agreement with the measured release of P and Fe from Fe-P sludge and vivianite formation.