Quantifying regulatory limits for multiple stressors in an open and transparent way.

Biodiversity is confronted globally by multiple stressors. Environmental policies must regulate these stressors to achieve targets, but how should that be done when the outcomes of limits on one stressor are contingent on other stressors, about which there is imperfect knowledge? Deriving regulatory frameworks that incorporate these contingencies is an emerging challenge at the science-policy interface. To be fit for implementation, these frameworks need to facilitate the inherently sociopolitical process of policy implementation and account transparently for uncertainty, such that practitioners and other stakeholders can more realistically anticipate the range of potential outcomes to policy. We developed an approach to quantify stressor limits that explicitly accounts for multistressor contingencies. Using an invertebrate data set collected over 30 years throughout New Zealand, we combined ecological and ecotoxicological models to predict biodiversity loss as a function of one stressor, treating multistressor contingencies as a form of uncertainty about the outcomes of limits on that stressor. We transparently accounted for that uncertainty by presenting regulatory limits as bands bounded between optimistic and pessimistic views that practitioners may have about the local context within which limits are applied. In addition to transparently accounting for uncertainties, our framework also leaves room for practitioners to build stakeholder consensus when refining limits to suit different local contexts. A criticism of this open, transparent approach is that it creates too much scope for choosing limits that are lenient on polluters, paralyzing on-the-ground management of multiple stressors, but we demonstrate that this is not necessarily the case.

Cuantificación abierta y transparente de los límites regulatorios para varios estresantes Resumen La biodiversidad enfrenta a múltiples estresantes en todo el mundo. Las políticas ambientales deben regularlos para alcanzar los objetivos fijados, pero ¿cómo hacerlo cuando los resultados de la limitación de un estresante dependen de otros factores, de los que se conoce muy poco? La elaboración de marcos reguladores que incorporen estas contingencias es un reto emergente en la interfaz ciencia­política. Para aplicar estos marcos, se debe facilitar el proceso sociopolítico inherente a la aplicación de políticas y tener en cuenta de forma transparente la incertidumbre, de modo que los profesionales y otras partes interesadas puedan anticipar de forma más realista la variedad de posibles resultados de las políticas. Desarrollamos un método para cuantificar los límites de los estresantes que considera explícitamente las contingencias de múltiples factores. Usamos un conjunto de datos sobre invertebrados recolectados durante 30 años en toda Nueva Zelanda. Después combinamos modelos ecológicos y eco­toxicológicos para predecir la pérdida de biodiversidad en función de un estresante y tratamos las contingencias de múltiples estresantes como una forma de incertidumbre sobre los resultados de los límites de ese mismo estresante. Explicamos esa incertidumbre de forma transparente con los límites normativos como bandas delimitadas entre las opiniones optimistas y pesimistas que los profesionales pueden tener sobre el contexto local en el que se aplican los límites. Además de hacer lo anterior, nuestro marco también deja margen para que los profesionales lleguen a un consenso con las partes interesadas a la hora de perfeccionar los límites para adaptarlos a los distintos contextos locales. Una crítica a este enfoque abierto y transparente crea demasiado margen para elegir límites indulgentes con los contaminadores, paralizando la gestión sobre el terreno de múltiples estresantes, pero demostramos que no es necesariamente así.

Prior traumatic brain injury is a risk factor for in-hospital mortality in moderate to severe traumatic brain injury: a TRACK-TBI cohort study.

Objectives: An estimated 14-23% of patients with traumatic brain injury (TBI) incur multiple lifetime TBIs. The relationship between prior TBI and outcomes in patients with moderate to severe TBI (msTBI) is not well delineated. We examined the associations between prior TBI, in-hospital mortality, and outcomes up to 12 months after injury in a prospective US msTBI cohort. Methods: Data from hospitalized subjects with Glasgow Coma Scale score of 3-12 were extracted from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study (enrollment period: 2014-2019). Prior TBI with amnesia or alteration of consciousness was assessed using the Ohio State University TBI Identification Method. Competing risk regressions adjusting for age, sex, psychiatric history, cranial injury and extracranial injury severity examined the associations between prior TBI and in-hospital mortality, with hospital discharged alive as the competing risk. Adjusted HRs (aHR (95% CI)) were reported. Multivariable logistic regressions assessed the associations between prior TBI, mortality, and unfavorable outcome (Glasgow Outcome Scale-Extended score 1-3 (vs. 4-8)) at 3, 6, and 12 months after injury. Results: Of 405 acute msTBI subjects, 21.5% had prior TBI, which was associated with male sex (87.4% vs. 77.0%, p=0.037) and psychiatric history (34.5% vs. 20.7%, p=0.010). In-hospital mortality was 10.1% (prior TBI: 17.2%, no prior TBI: 8.2%, p=0.025). Competing risk regressions indicated that prior TBI was associated with likelihood of in-hospital mortality (aHR=2.06 (1.01-4.22)), but not with hospital discharged alive. Prior TBI was not associated with mortality or unfavorable outcomes at 3, 6, and 12 months. Conclusions: After acute msTBI, prior TBI history is independently associated with in-hospital mortality but not with mortality or unfavorable outcomes within 12 months after injury. This selective association underscores the importance of collecting standardized prior TBI history data early after acute hospitalization to inform risk stratification. Prospective validation studies are needed. Level of evidence: IV. Trial registration number: NCT02119182.

Direct probing of low-energy intra d-band transitions in gas-phase cobalt clusters.

The interplay between constituent localized and itinerant electrons of metal clusters defines their physical and chemical properties. In turn, the electronic and geometrical structures are strongly entwined and exhibit strong size-dependent variations. Current understanding of low-energy excited states of metal clusters relies on stand-alone theoretical investigations and few comparisons with measured properties, since direct identification of low-lying states is lacking hitherto. Here, we report on the measurement of low-lying electronic transitions in cationic cobalt clusters using infrared photofragmentation spectroscopy. Broad and size-dependent absorption features were observed within 0.056 - 0.446 eV, well above the energies of the sharp absorption bands caused by cluster vibrations. Complementary time-dependent density functional theory calculations reproduce the main observed absorption features, providing direct evidence that they correspond to transitions between electronic states of mainly d-character, arising from the open d-shells of the Co atoms and the high spin multiplicity of the clusters.

Early versus delayed cranioplasty after decompressive craniectomy in traumatic brain injury: a multicenter observational study within CENTER-TBI and Net-QuRe.

OBJECTIVE: The aim of this study was to compare the outcomes of early (≤ 90 days) and delayed (> 90 days) cranioplasty following decompressive craniectomy (DC) in patients with traumatic brain injury (TBI). METHODS: The authors analyzed participants enrolled in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) and the Neurotraumatology Quality Registry (Net-QuRe) studies who were diagnosed with TBI and underwent DC and subsequent cranioplasty. These prospective, multicenter, observational cohort studies included 5091 patients enrolled from 2014 to 2020. The effect of cranioplasty timing on functional outcome was evaluated with multivariable ordinal regression and with propensity score matching (PSM) in a sensitivity analysis of functional outcome (Glasgow Outcome Scale-Extended [GOSE] score) and quality of life (Quality of Life After Brain Injury [QOLIBRI] instrument) at 12 months following DC. RESULTS: Among 173 eligible patients, 73 (42%) underwent early cranioplasty and 100 (58%) underwent delayed cranioplasty. In the ordinal logistic regression and PSM, similar 12-month GOSE scores were found between the two groups (adjusted odds ratio [aOR] 0.87, 95% CI 0.61-1.21 and 0.88, 95% CI 0.48-1.65, respectively). In the ordinal logistic regression, early cranioplasty was associated with a higher risk for hydrocephalus than that with delayed cranioplasty (aOR 4.0, 95% CI 1.2-16). Postdischarge seizure rates (early cranioplasty: aOR 1.73, 95% CI 0.7-4.7) and QOLIBRI scores (ß -1.9, 95% CI -9.1 to 9.6) were similar between the two groups. CONCLUSIONS: Functional outcome and quality of life were similar between early and delayed cranioplasty in patients who had undergone DC for TBI. Neurosurgeons may consider performing cranioplasty during the index admission (early) to simplify the patient's chain of care and prevent readmission for cranioplasty but should be vigilant for an increased possibility of hydrocephalus. Clinical trial registration nos.: CENTER-TBI, NCT02210221 (clinicaltrials.gov); Net-QuRe, NTR6003 (trialsearch.who.int) and NL5761 (onderzoekmetmensen.nl).

External Quality Assessment on Molecular Tumor Profiling with Circulating Tumor DNA-Based Methodologies Routinely Used in Clinical Pathology within the COIN Consortium.

BACKGROUND: Identification of tumor-derived variants in circulating tumor DNA (ctDNA) has potential as a sensitive and reliable surrogate for tumor tissue-based routine diagnostic testing. However, variations in pre(analytical) procedures affect the efficiency of ctDNA recovery. Here, an external quality assessment (EQA) was performed to determine the performance of ctDNA mutation detection work flows that are used in current diagnostic settings across laboratories within the Dutch COIN consortium (ctDNA on the road to implementation in The Netherlands). METHODS: Aliquots of 3 high-volume diagnostic leukapheresis (DLA) plasma samples and 3 artificial reference plasma samples with predetermined mutations were distributed among 16 Dutch laboratories. Participating laboratories were requested to perform ctDNA analysis for BRAF exon 15, EGFR exon 18-21, and KRAS exon 2-3 using their regular circulating cell-free DNA (ccfDNA) analysis work flow. Laboratories were assessed based on adherence to the study protocol, overall detection rate, and overall genotyping performance. RESULTS: A broad range of preanalytical conditions (e.g., plasma volume, elution volume, and extraction methods) and analytical methodologies (e.g., droplet digital PCR [ddPCR], small-panel PCR assays, and next-generation sequencing [NGS]) were used. Six laboratories (38%) had a performance score of >0.90; all other laboratories scored between 0.26 and 0.80. Although 13 laboratories (81%) reached a 100% overall detection rate, the therapeutically relevant EGFR p.(S752_I759del) (69%), EGFR p.(N771_H773dup) (50%), and KRAS p.(G12C) (48%) mutations were frequently not genotyped accurately. CONCLUSIONS: Divergent (pre)analytical protocols could lead to discrepant clinical outcomes when using the same plasma samples. Standardization of (pre)analytical work flows can facilitate the implementation of reproducible liquid biopsy testing in the clinical routine.

Extensor tendon transfer for fracture-related extensor pollicis longus rupture: Long-term outcome case series.

BACKGROUND: Spontaneous rupture of the extensor pollicis longus (EPL) tendon following both nonoperative and operative treatment of distal radius fractures has been well described. PURPOSE: The purpose of this study was to assess long-term outcomes of extensor indicis proprius to EPL tendon transfers for patients following distal radius fracture and EPL tendon repair. STUDY DESIGN: Retrospective case series focusing on long-term clinical outcomes. METHODS: A retrospective review was conducted for patients who sustained a distal radius fracture and subsequently underwent extensor tendon transfer from 2005-2015 at a private practice center. Outcome measures including index finger (IF) metacarpophalangeal (MCP) and thumb interphalangeal (IP) active range of motion (ROM), digital extension against resistance, subjective complaints, and QuickDASH scores were recorded at final follow-up. RESULTS: Seven patients were included in the study. There were six females and one male subject, mean age of 54 ± 13 years at injury of EPL, and 5/7 involved the left upper extremity. For isolated function, 7/7 (100%) patients had isolated, active IF MCP extension, 6/7 (86%) could extend IF MCP and thumb IP against resistance. Mean IF MCP extension was 1° ± 2°, mean IF MCP flexion was 89° ± 2°, mean thumb IP extension was -5° ± 4°, and mean thumb IP flexion was 67° ± 15°. Mean QuickDASH score was 16 ± 14. CONCLUSIONS: This series shows good long-term functional and patient reported outcomes in patients following extensor indicis proprius to EPL tendon transfers at a single center.

Polycyclic Aromatic Hydrocarbons and Pancreatic Cancer: An Analysis of the Blood Biomarker, r-1,t-2,3,c-4-Tetrahydroxy-1,2,3,4-tetrahydrophenanthrene and Selected Metabolism Gene SNPs.

Exposure to polycyclic aromatic hydrocarbons (PAHs), byproducts of incomplete combustion, and their effects on the development of cancer are still being evaluated. Recent studies have analyzed the relationship between PAHs and tobacco or dietary intake in the form of processed foods and smoked/well-done meats. This study aims to assess the association of a blood biomarker and metabolite of PAHs, r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene (PheT), dietary intake, selected metabolism SNPs, and pancreatic cancer. Demographics, food-frequency data, SNPs, treatment history, and levels of PheT in plasma were determined from 400 participants (202 cases and 198 controls) and evaluated based on pancreatic adenocarcinoma diagnosis. Demographic and dietary variables were selected based on previously published literature indicating association with pancreatic cancer. A multiple regression model combined the significant demographic and food items with SNPs. Final multivariate logistic regression significant factors (p-value < 0.05) associated with pancreatic cancer included: Type 2 Diabetes [OR = 6.26 (95% CI = 2.83, 14.46)], PheT [1.03 (1.02, 1.05)], very well-done red meat [0.90 (0.83, 0.96)], fruit/vegetable servings [1.35 (1.06, 1.73)], recessive (rs12203582) [4.11 (1.77, 9.91)], recessive (rs56679) [0.2 (0.06, 0.85)], overdominant (rs3784605) [3.14 (1.69, 6.01)], and overdominant (rs721430) [0.39 (0.19, 0.76)]. Of note, by design, the level of smoking did not differ between our cases and controls. This study does not provide strong evidence that PheT is a biomarker of pancreatic cancer susceptibility independent of dietary intake and select metabolism SNPs among a nonsmoking population.

Water footprints and crop water use of 175 individual crops for 1990-2019 simulated with a global crop model.

The water footprint of a crop (WF) is a common metric for assessing agricultural water consumption and productivity. To provide an update and methodological enhancement of existing WF datasets, we apply a global process-based crop model to quantify consumptive WFs of 175 individual crops at a 5 arcminute resolution over the 1990-2019 period. This model simulates the daily crop growth and vertical water balance considering local environmental conditions, crop characteristics, and farm management. We partition WFs into green (water from precipitation) and blue (from irrigation or capillary rise), and differentiate between rainfed and irrigated production systems. The outputs include gridded datasets and national averages for unit water footprints (expressed in m3 t-1 yr-1), water footprints of production (m3 yr-1), and crop water use (mm yr-1). We compare our estimates to other global studies covering different historical periods and methodological approaches. Provided outputs can offer insights into spatial and temporal patterns of agricultural water consumption and serve as inputs for further virtual water trade studies, life cycle and water footprint assessments.

United States Experience With a Femoral Neck Retaining Total Hip Arthroplasty Stem: A Retrospective Study With Control Comparison From the Literature.

BACKGROUND: Femoral neck retaining prostheses have gained popularity in Europe, but the United States has not seen the same trends occurring. Previous reports demonstrate high survivorship for these implants, but to our knowledge, there are no reports examining US data. METHODS: After institutional review board approval, 824 primary total hip arthroplasties utilizing a femoral neck-retaining prosthesis were examined for femoral component survivorship rates. European studies were systematically reviewed to determine survivorship rates. The data were used to formulate a Kaplan-Meier survivorship curve and compare US data to that of the European studies. RESULTS: European studies demonstrated survivorship rates for all causes of 97.7 and 99.0% for aseptic loosening at an average of 6 years (range, 4.5 to 10). The current study demonstrated an all-cause 94% Kaplan-Meier survivorship estimate at 5 years and when aseptic loosening only was considered, survivorship increased to 99.4% at 5 years and 98.4% at 11 years. CONCLUSION: This femoral neck-retaining prosthesis demonstrated excellent survivorship that is comparable to the rates seen in European studies as well as the rates of standard and mid-stem prostheses in the United States.

Monitoring for the adaptive management of rivers.

Monitoring for adaptive management (AM) involves collection of data with the aim of reducing uncertainty about links between human pressures (e.g. water abstraction from rivers), consequent stressors (e.g. low river flows) and environmental state (e.g. biodiversity). 'Surveillance monitoring' involves documenting trends in state, without the aim of understanding relationships between state, stressors, and pressures. Critics have highlighted that surveillance monitoring dominates monitoring investments but is not supporting AM. Decision-makers continue to be disappointed by monitoring data that are unsuitable for AM, yet designers of monitoring programs tend to make decisions that reinforce rather than reimagine the status quo. We argue that a structured, collaborative approach to objective-setting is required to break the status quo. We collaborated with regional management authorities to develop monitoring objectives and implementation strategies to support AM of New Zealand's rivers. Our collaborative approach discouraged 'failure fearing' and encouraged reimagining 'what could be' as opposed to 'what is.' Seventeen monitoring objectives were identified based on the AM requirements of national policy and regional authorities. Several objectives-particularly those arising from national policy-stretch the limits of what environmental science can currently provide. There were also strong trade-offs among objectives. We offer practical implementation strategies for overcoming the technical challenges of, and reducing trade-offs among, monitoring objectives. These strategies point to a monitoring program that contrasts strongly with one aimed at surveillance. Monitoring for AM is more complex than monitoring for surveillance, so strong leadership is required for successful implementation.

Hemodynamic Parameters in the Parent Arteries of Unruptured Intracranial Aneurysms Depend on Aneurysm Size and Are Different Compared to Contralateral Arteries: A 7 Tesla 4D Flow MRI Study.

BACKGROUND: Different Circle of Willis (CoW) variants have variable prevalences of aneurysm development, but the hemodynamic variation along the CoW and its relation to presence and size of unruptured intracranial aneurysms (UIAs) are not well known. PURPOSE: Gain insight into hemodynamic imaging markers of the CoW for UIA development by comparing these outcomes to the corresponding contralateral artery without an UIA using 4D flow magnetic resonance imaging (MRI). STUDY TYPE: Retrospective, cross-sectional study. SUBJECTS: Thirty-eight patients with an UIA, whereby 27 were women and a mean age of 62 years old. FIELD STRENGTH/SEQUENCE: Four-dimensional phase-contrast (PC) MRI with a 3D time-resolved velocity encoded gradient echo sequence at 7 T. ASSESSMENT: Hemodynamic parameters (blood flow, velocity pulsatility index [vPI], mean velocity, distensibility, and wall shear stress [peak systolic (WSSMAX ), and time-averaged (WSSMEAN )]) in the parent artery of the UIA were compared to the corresponding contralateral artery without an UIA and were related to UIA size. STATISTICAL TESTS: Paired t-tests and Pearson Correlation tests. The threshold for statistical significance was P < 0.05 (two-tailed). RESULTS: Blood flow, mean velocity, WSSMAX , and WSSMEAN were significantly higher, while vPI was lower, in the parent artery relative to contralateral artery. The WSSMAX of the parent artery significantly increased linearly while the WSSMEAN decreased linearly with increasing UIA size. CONCLUSIONS: Hemodynamic parameters and WSS differ between parent vessels of UIAs and corresponding contralateral vessels. WSS correlates with UIA size, supporting a potential hemodynamic role in aneurysm pathology. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Observations of COVID-19 vaccine coverage and vaccine hesitancy on COVID-19 outbreak: An American ecological study.

In this ecological study, we aim to establish the role vaccines play in bringing the pandemic under control, as well as the impact of pathogen variants, vaccine hesitancy, and medical resource availability during the process by utilizing publicly available data. The study spans a three-year data collection period for daily hospital admissions due to COVID-19 and the daily reported cases of COVID-19 across all 50 states in the USA. In doing so, we aim to demonstrate the difference in severity of the SARS-CoV-2 pathogen among vaccinated and unvaccinated populations in the USA. The study assesses the correlation of COVID-19 vaccines (e.g., Pfizer, Moderna, and Janssen) and disease outcomes (transmissibility, severity, and deaths) caused by different strains of SARS-CoV-2 and establishes a negative correlation between COVID-19 vaccine and disease outcomes. By considering potential confounders in vaccine hesitancy, medical resource availability and vaccine dosage, we demonstrate the aforementioned to be insubstantial in predicting disease outcomes while the latter displays a contrasting significance in terms of disease outcomes. Between all the major variants of concern, the Delta and Omicron variants in particular have been associated with higher virulence and transmissibility factors respectively. Hence, the CDC continues to encourage the US population to get vaccinated since vaccines are one of the most effective ways to protect the community from potential outbreaks and prevent severe disease manifestations.

Large-scale violence in Late Neolithic Western Europe based on expanded skeletal evidence from San Juan ante Portam Latinam.

This paper explores the nature and extent of conflict in Late Neolithic Europe based on expanded skeletal evidence for violence from the San Juan ante Portam Latinam rockshelter in present-day Spain (ca. 3380-3000 cal. BC). The systematic osteological re-examination has identified 65 unhealed and 89 healed traumas-of which 77 were previously undocumented-consistent with aggression. They affect 23.1% of the 338 individuals represented. Adolescent and adult males are particularly affected (44.9% of the 107 identified), comprising 97.6% of unhealed trauma and 81.7% of healed trauma recorded in individuals whose sex could be estimated and showing higher frequencies of injuries per individual than other demographic subgroups. Results suggest that many individuals, essentially men, were exposed to violence and eventually killed in battle and raids, since warriorship is mainly restricted to this demographic in many societies. The proportion of casualties is likely to have been far greater than indicated by the 10.1% individuals exhibiting unhealed trauma, given the presence of isolated cases of unhealed postcranial trauma and of arrowheads potentially having impacted into soft tissues. This, together with skeletal indicators of poor health and the possible socioeconomic outcomes evidenced in the region, suggest wider social impacts, which may relate to a more sophisticated and formalized way of warfare than previously appreciated in the European Neolithic record.

Screening for intracranial aneurysms in persons ⩾35 years with hypertension and atherosclerotic disease who smoke(d).

INTRODUCTION: Lifetime risk of aneurysmal subarachnoid haemorrhage (aSAH) is high (7%) in persons ⩾35 years with hypertension who smoke(d). Whether screening for intracranial aneurysms (IAs) to prevent aSAH is effective in these patients is unknown. PATIENTS AND METHODS: Participants were retrieved from a cohort of patients with clinically manifest atherosclerotic vascular disease included between 2012 and 2019 at the University Medical Centre Utrecht (SMART-ORACLE, NCT01932671) in whom CT-angiography (CTA) of intracranial arteries was performed. We selected patients ⩾35 years with hypertension who smoke(d). CTAs were reviewed for the presence of IAs by experienced neuroradiologists. Patients with IAs were offered follow-up imaging to detect aneurysmal growth. We determined aneurysm prevalence and developed a diagnostic model for IA risk at screening using multivariable logistic regression. RESULTS: IA were found in 25 of 500 patients (5.0% prevalence, 95%CI: 3.3%-7.3%). Median 5 year risk of rupture assessed with the PHASES score was 0.9% (IQR: 0.7%-1.3%). During a median follow-up of 57 months (IQR: 39-83 months) no patients suffered from aSAH. Aneurysmal growth was detected in one patient for whom preventive treatment was advised. IA risk at screening ranged between 1.6% and 13.4% with predictors being age, female sex and current smoking. DISCUSSION AND CONCLUSION: IA prevalence in persons ⩾35 years with hypertension and atherosclerotic vascular disease who smoke(d) was 5%. Given the very small proportion of IA that needed preventive treatment, we currently do not advise screening for Caucasian persons older than 35 years of age who smoke and have hypertension in general. Whether screening may be effective for certain subgroups (e.g. women older than 50 years of age) or other ethnic populations should be the subject of future studies.

Aneurysm Prevalence and Quality of Life During Screening in Relatives of Patients With Unruptured Intracranial Aneurysms: A Prospective Study.

BACKGROUND AND OBJECTIVES: Screening for unruptured intracranial aneurysms (UIAs) is effective for first-degree relatives (FDRs) of patients with aneurysmal subarachnoid hemorrhage (aSAH). Whether screening is also effective for FDRs of patients with UIA is unknown. We determined the yield of screening in such FDRs, assessed rupture risk and treatment decisions of aneurysms that were found, identified potential high-risk subgroups, and studied the effects of screening on quality of life (QoL). METHODS: In this prospective cohort study, we included FDRs, aged 20-70 years, of patients with UIA without a family history of aSAH who visited the Neurology outpatient clinic in 1 of 3 participating tertiary referral centers in the Netherlands. FDRs were screened for UIA with magnetic resonance angiography between 2017 and 2021. We determined UIA prevalence and developed a prediction model for UIA risk at screening using multivariable logistic regression. QoL was evaluated with questionnaires 6 times during the first year after screening and assessed with a linear mixed-effects model. RESULTS: We detected 24 UIAs in 23 of 461 screened FDRs, resulting in a 5.0% prevalence (95% CI 3.2-7.4). The median aneurysm size was 3 mm (interquartile range [IQR] 2-4 mm), and the median 5-year rupture risk assessed with the PHASES score was 0.7% (IQR 0.4%-0.9%). All UIAs received follow-up imaging, and none were treated preventively. After a median follow-up of 24 months (IQR 13-38 months), no UIA had changed. Predicted UIA risk at screening ranged between 2.3% and 14.7% with the highest risk in FDRs who smoke and have excessive alcohol consumption (c-statistic: 0.76; 95% CI 0.65-0.88). At all survey moments, health-related QoL and emotional functioning were comparable with those in a reference group from the general population. One FDR with a positive screening result expressed regret about screening. DISCUSSION: Based on the current data, we do not advise screening FDRs of patients with UIA because all identified UIAs had a low rupture risk. We observed no negative effect of screening on QoL. A longer follow-up should determine the risk of aneurysm growth requiring preventive treatment.

Carriers of the p.P522R variant in PLCγ2 have a slightly more responsive immune system.

BACKGROUND: The rs72824905 single-nucleotide polymorphism in the PLCG2 gene, encoding the p.P522R residue change in Phospholipase C gamma 2 (PLCγ2), associates with protection against several dementia subtypes and with increased likelihood of longevity. Cell lines and animal models indicated that p.P522R is a functional hypermorph. We aimed to confirm this in human circulating peripheral immune cells. METHODS: We compared effects of p.P522R on immune system function between carriers and non-carriers (aged 59-103y), using in-depth immunophenotyping, functional B-cell and myeloid cell assays, and in vivo SARS-CoV-2 vaccination. RESULTS: In line with expectations, p.P522R impacts immune cell function only slightly, but it does so across a wide array of immune cell types. Upon B-cell stimulation, we observed increased PLCγ2 phosphorylation and calcium release, suggesting increased B-cell sensitivity upon antigen recognition. Further, p.P522R-carriers had higher numbers of CD20++CD21-CD24+ naive B cells and IgG1+ memory B cells. In myeloid cells, normalized ROS production was higher upon PLCγ2-dependent stimulation. On classical monocytes, CD33 levels were elevated. Furthermore, carriers expressed lower levels of allergy-related FcεRI on several immune cell subsets. Nevertheless, carriers and non-carriers had similar serological responses to SARS-CoV-2 vaccination. CONCLUSION: The immune system from p.P522R-carriers is slightly more responsive to stimulation than in non-carriers.

Extraoral anterior approach for the treatment of os odontoideum: illustrative case.

BACKGROUND: Os odontoideum is typically treated with instrumented fusion through a posterior cervical approach. When this approach fails, limited options for revision are available. Occipitocervical fusion and transoral anterior fusions have been utilized in the past but are associated with high morbidity and complications. OBSERVATIONS: Here the authors report a case of os odontoideum that was treated with an anterior cervical extraoral approach after failed posterior instrumented fusion. They discuss the challenges that can be encountered with the failure of fusion and the limited options when it comes to approach and fixation of os odontoideum. LESSONS: To the authors' knowledge and based on a review of the literature, this case represents the first use of an anterior extraoral prevascular approach to the high cervical spine to address os odontoideum. They demonstrate that this approach can be utilized as a reasonable alternative to transoral surgery and should be considered in cases where additional or alternative fixation is desired without the morbidity and complications associated with occipitocervical fusion or a transoral approach, especially in a younger patient population.

Water pollution from pharmaceutical use in livestock farming: Assessing differences between livestock types and production systems.

Livestock production is a major source of pharmaceutical emissions to the environment. The current scientific discourse focuses on measuring and modeling emissions as well as assessing their risks. Although several studies corroborate the severity of pharmaceutical pollution resulting from livestock farming, differences in pollution between livestock types and production systems are largely unknown. In fact, there is no comprehensive analysis of factors influencing pharmaceutical use-the emission's source-in the diverse production systems. To address these knowledge gaps, we developed a framework to investigate pharmaceutical pollution from different livestock production systems and applied it in a first pilot assessment to compare pollution from organic and conventional cattle, pig, and chicken production systems on selected indicator substances, covering antibiotics, antiparasitics, hormones, and nonsteroidal anti-inflammatory drugs (NSAIDs). Given the lack of statistics, for this article we retrieved novel qualitative information about influential factors for pharmaceutical use and pollution from expert interviews and combined this with quantitative data on, among other factors, the environmental behavior of specific substances from the literature. Our analysis reveals that factors across a pharmaceutical's entire life cycle influence pollution. However, not all factors are livestock type or production-system dependent. The pilot assessment furthermore reveals that differences in pollution potential between conventional and organic production exist, but for antibiotics, NSAIDs, and partially for antiparasitics, some factors lead to greater pollution potential in conventional systems, and others in organic systems. For hormones, we identified a comparatively greater pollution potential from conventional systems. Among the indicator substances, the assessment over the entire pharmaceutical life cycle illustrates that flubendazole in broiler production has the greatest per unit impact. The framework and its application in the pilot assessment generated insights useful to identifying which substances, livestock types, production systems, or the combination thereof have great or little pollution potential, informing more sustainable agricultural management practices. Integr Environ Assess Manag 2023;19:1495-1509. © 2023 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).