AutoPeptideML: a study on how to build more trustworthy peptide bioactivity predictors.

MOTIVATION: Automated machine learning (AutoML) solutions can bridge the gap between new computational advances and their real-world applications by enabling experimental scientists to build their own custom models. We examine different steps in the development life-cycle of peptide bioactivity binary predictors and identify key steps where automation cannot only result in a more accessible method, but also more robust and interpretable evaluation leading to more trustworthy models. RESULTS: We present a new automated method for drawing negative peptides that achieves better balance between specificity and generalization than current alternatives. We study the effect of homology-based partitioning for generating the training and testing data subsets and demonstrate that model performance is overestimated when no such homology correction is used, which indicates that prior studies may have overestimated their performance when applied to new peptide sequences. We also conduct a systematic analysis of different protein language models as peptide representation methods and find that they can serve as better descriptors than a naive alternative, but that there is no significant difference across models with different sizes or algorithms. Finally, we demonstrate that an ensemble of optimized traditional machine learning algorithms can compete with more complex neural network models, while being more computationally efficient. We integrate these findings into AutoPeptideML, an easy-to-use AutoML tool to allow researchers without a computational background to build new predictive models for peptide bioactivity in a matter of minutes. AVAILABILITY AND IMPLEMENTATION: Source code, documentation, and data are available at https://github.com/IBM/AutoPeptideML and a dedicated web-server at http://peptide.ucd.ie/AutoPeptideML. A static version of the software to ensure the reproduction of the results is available at https://zenodo.org/records/13363975.

Acute respiratory failure due to pulmonary exacerbation in children with cystic fibrosis admitted in a pediatric intensive care unit: outcomes and factors associated with mortality.

BACKGROUND: Children with advanced pulmonary disease due to cystic fibrosis (CF) are at risk of acute respiratory failure due to pulmonary exacerbations leading to their admission to pediatric intensive care units (PICU). The objectives of this study were to determine short and medium-term outcomes of children with CF admitted to PICU for acute respiratory failure due to pulmonary exacerbation and to identify prognosis factors. METHODS: This retrospective monocentric study included patients less than 18 years old admitted to the PICU of a French university hospital between 2000 and 2020. Cox proportional hazard regression methods were used to determine prognosis factors of mortality or lung transplant. RESULTS: Prior to PICU admission, the 29 patients included (median age 13.5 years) had a severe lung disease (median Forced Expiratory Volume in 1 s percentage predicted at 29%). Mortality rates were respectively 17%, 31%, 34%, 41% at discharge and at 3, 12 and 36 months post-discharge. Survival rates free of lung transplant were 34%, 32%, 24% and 17% respectively. Risk factors associated with mortality or lung transplant using the univariate analysis were female sex and higher pCO2 and chloride levels at PICU admission, and following pre admission characteristics: home respiratory and nutritional support, registration on lung transplant list and Stenotrophomonas Maltophilia bronchial colonization. CONCLUSION: Children with CF admitted to PICU for acute respiratory failure secondary to pulmonary exacerbations are at high risk of death, both in the short and medium terms. Lung transplant is their main chance of survival and should be considered early.

Epigenomic Blood-Based Early Detection of Pancreatic Cancer Employing Cell-Free DNA.

BACKGROUND & AIMS: Early detection of pancreatic cancer (PaC) can drastically improve survival rates. Approximately 25% of subjects with PaC have type 2 diabetes diagnosed within 3 years prior to the PaC diagnosis, suggesting that subjects with type 2 diabetes are at high risk of occult PaC. We have developed an early-detection PaC test, based on changes in 5-hydroxymethylcytosine (5hmC) signals in cell-free DNA from plasma. METHODS: Blood was collected from 132 subjects with PaC and 528 noncancer subjects to generate epigenomic and genomic feature sets yielding a predictive PaC signal algorithm. The algorithm was validated in a blinded cohort composed of 102 subjects with PaC, 2048 noncancer subjects, and 1524 subjects with non-PaCs. RESULTS: 5hmC differential profiling and additional genomic features enabled the development of a machine learning algorithm capable of distinguishing subjects with PaC from noncancer subjects with high specificity and sensitivity. The algorithm was validated with a sensitivity for early-stage (stage I/II) PaC of 68.3% (95% confidence interval [CI], 51.9%-81.9%) and an overall specificity of 96.9% (95% CI, 96.1%-97.7%). CONCLUSIONS: The PaC detection test showed robust early-stage detection of PaC signal in the studied cohorts with varying type 2 diabetes status. This assay merits further clinical validation for the early detection of PaC in high-risk individuals.

Gestational long-term hypoxia induces metabolomic reprogramming and phenotypic transformations in fetal sheep pulmonary arteries.

Gestational long-term hypoxia increases the risk of myriad diseases in infants including persistent pulmonary hypertension. Similar to humans, fetal lamb lung development is susceptible to long-term intrauterine hypoxia, with structural and functional changes associated with the development of pulmonary hypertension including pulmonary arterial medial wall thickening and dysregulation of arterial reactivity, which culminates in decreased right ventricular output. To further explore the mechanisms associated with hypoxia-induced aberrations in the fetal sheep lung, we examined the premise that metabolomic changes and functional phenotypic transformations occur due to intrauterine, long-term hypoxia. To address this, we performed electron microscopy, Western immunoblotting, calcium imaging, and metabolomic analyses on pulmonary arteries isolated from near-term fetal lambs that had been exposed to low- or high-altitude (3,801 m) hypoxia for the latter 110+ days of gestation. Our results demonstrate that the sarcoplasmic reticulum was swollen with high luminal width and distances to the plasma membrane in the hypoxic group. Hypoxic animals were presented with higher endoplasmic reticulum stress and suppressed calcium storage. Metabolically, hypoxia was associated with lower levels of multiple omega-3 polyunsaturated fatty acids and derived lipid mediators (e.g., eicosapentaenoic acid, docosahexaenoic acid, α-linolenic acid, 5-hydroxyeicosapentaenoic acid (5-HEPE), 12-HEPE, 15-HEPE, prostaglandin E3, and 19(20)-epoxy docosapentaenoic acid) and higher levels of some omega-6 metabolites (P < 0.02) including 15-keto prostaglandin E2 and linoleoylglycerol. Collectively, the results reveal broad evidence for long-term hypoxia-induced metabolic reprogramming and phenotypic transformations in the pulmonary arteries of fetal sheep, conditions that likely contribute to the development of persistent pulmonary hypertension.

Anesthetic management for percutaneous reverse Potts shunt creation in children with refractory idiopathic pulmonary arterial hypertension: A case series.

Percutaneous reverse Potts shunt improves right ventricular function in patients with suprasystemic idiopathic pulmonary arterial hypertension. There are no data regarding the anesthesia in this high-risk procedure. We report our experience of the anesthetic management for the creation of percutaneous reverse Potts shunt in children with suprasystemic idiopathic pulmonary arterial hypertension. This study included 10 patients presenting with symptomatic idiopathic pulmonary arterial hypertension despite undergoing medical treatment. All patients underwent gradual induction of anesthesia to maintain hemodynamic stability (etomidate, n = 8; ketamine, n = 4). Four patients needed extracorporeal life support: 2 were rescued after cardiac arrest and 2 had elective extracorporeal life support due to preprocedural dysfunctional right ventricle and/or small left ventricle volumes with reduced cardiac output. All patients were admitted to the pediatric cardiac intensive care unit (4 [2-5] days). All patients with extracorporeal life support died. None of the six survivors needed pulmonary transplantation. Both ketamine and etomidate support hemodynamics. High-dose opioid technique has the advantage of blunting noxious stimuli and subsequent increase in pulmonary vascular resistance. We recommend using multimodal monitoring with transesophageal echocardiography. The 100% mortality of extracorporeal life support patients, probably too sick to undergo such procedure, may question its usefulness. Further studies should identify suitable candidates for percutaneous reverse Potts shunt creation.

Long-term neurobehavioural symptom reporting following mild, moderate, severe, and penetrating traumatic brain injury in U.S. military service members.

The purpose of this study was to examine long-term neurobehavioural symptom reporting following mild, moderate, severe, or penetrating TBI in U.S. military service members and veterans (SMV). Participants were 445 SMVs divided into four groups: 158 uncomplicated mild TBI ("unMTBI" group), 105 penetrating, severe, moderate, or complicated mild TBI ("smcTBI" group), 101 injured controls (IC), and 81 non-injured controls (NIC). Two independent cohorts were examined that included participants 5-years or 10-year post-injury. Participants completed the TBI-Quality of Life, Neurobehavioural Symptom Inventory, and Post-traumatic Stress Disorder Checklist. At 5-years and 10-years post-injury, there were significant main effects for the majority of measures (all p's < .005). At 10-years post-injury, the NIC group had consistently better scores compared to the IC, unMTBI, and smcTBI groups. At 5-years post-injury, either (a) the IC and NIC group had better scores compared to both TBI groups, or (b) the NIC group had better scores compared to the IC, unMTBI, and smcTBI groups. A high proportion of SMVs reported poor long-term neurobehavioural symptoms following TBI or bodily injury without TBI. Injured SMVs (regardless of injury type) can have long-term symptoms that impact mental health and overall quality of life requiring long-term follow-up and care.

Metabolism of Benzalkonium Chlorides by Human Hepatic Cytochromes P450.

Benzalkonium chlorides (BACs) are widely used as disinfectants in cleaning products, medical products, and the food processing industry. Despite a wide range of reported toxicities, limited studies have been conducted on the metabolism of these compounds in animal models and none in human-derived cells or tissues. In this work, we report on the metabolism of BACs in human liver microsomes (HLM) and by recombinant human hepatic cytochrome P450 (CYP) enzymes. BAC metabolism in HLM was NADPH-dependent and displayed apparent half-lives that increased with BAC alkyl chain length (C10 < C12 < C14 < C16), suggesting enhanced metabolic stability of the more lipophilic, longer chain BACs. Metabolites of d7-benzyl labeled BAC substrates retained all deuteriums and there was no evidence of N-dealkylation. Tandem mass spectrometry fragmentation of BAC metabolites confirmed that oxidation occurs on the alkyl chain region. Major metabolites of C10-BAC were identified as ω-hydroxy-, (ω-1)-hydroxy-, (ω, ω-1)-diol-, (ω-1)-ketone-, and ω-carboxylic acid-C10-BAC by liquid chromatography-mass spectrometry comparison with synthetic standards. In a screen of hepatic CYP isoforms, recombinant CYP2D6, CYP4F2, and CYP4F12 consumed substantial quantities of BAC substrates and produced the major microsomal metabolites. The use of potent pan-CYP4 inhibitor HET0016, the specific CYP2D6 inhibitor quinidine, or both confirmed major contributions of CYP4- and CYP2D6-mediated metabolism in the microsomal disappearance of BACs. Kinetic characterization of C10-BAC metabolite formation in HLM demonstrated robust Michaelis-Menten kinetic parameters for ω-hydroxylation (Vmax = 380 pmol/min/mg, Km = 0.69 µM) and (ω-1)-hydroxylation (Vmax = 126 pmol/min/mg, Km = 0.13 µM) reactions. This work illustrates important roles for CYP4-mediated ω-hydroxylation and CYP2D6/CYP4-mediated (ω-1)-hydroxylation during the hepatic elimination of BACs, an environmental contaminant of emerging concern. Furthermore, we demonstrate that CYP-mediated oxidation of C10-BAC mitigates the potent inhibition of cholesterol biosynthesis exhibited by this short-chain BAC.

Efficiency of the modified Sims maternal position in the rotation of persistent occiput posterior position during labor: A randomized clinical trial.

BACKGROUND: Fetal occiput posterior position in labor is associated with more painful and prolonged labor, and an increase in both maternal and fetal morbidity. The aim of this study is to assess whether the modified Sims position on the side of the fetal spine increases the rotation to occiput anterior position in women with epidural analgesia and a fetus in persistent occiput posterior (POP) position. METHODS: This is an open, randomized controlled, clinical trial. One hundred and twenty women in labor with fetuses in POP position were included. The diagnosis was performed through digital vaginal examination and confirmed with an ultrasound scan. Women were randomized into the free position group or the modified Sims on the side of the fetal spine. The primary outcome was rotation to occiput anterior, and secondary outcomes were type of delivery, postpartum perineal condition, perinatal results, and maternal satisfaction. RESULTS: In pregnant women undergoing labor in the Sims position, fetuses in POP rotated to occiput anterior in 50.8% of cases, whilst in the free position group, the rotation occurred in 21.7% (P = .001). The rate of vaginal deliveries was higher in the Sims group compared with the free position group (84.7% vs 68.3%, P = .035). DISCUSSION: The modified Sims position is a maternal posture intervention efficient in POP rotation, which decreases cesarean delivery rate. It is a simple and noninvasive intervention, reproducible, and well tolerated by pregnant women.

Low perfusion pressure is associated with renal tubular injury in infants undergoing cardiac surgery with cardiopulmonary bypass: A secondary analysis of an observational study.

BACKGROUND: Earlier work on adults undergoing surgery with cardiopulmonary bypass suggests that there is a close relationship between the lower limit of the cerebral and renal autoregulation pressures. Although cerebral autoregulation during bypass in infants has been extensively investigated, the impact of bypass on kidney function is not well known. It is, nevertheless, acknowledged that the main pathophysiological process involved in cardiac surgery-related kidney damage is tubular injury, and that urine neutrophil gelatinase-associated lipocaline (uNGAL) is a reliable biomarker of injury. OBJECTIVE: To identify the most predictive bypass variable for the measurement of renal injury, its threshold value and the most predictive time below that threshold. DESIGN: Observational study linking electronically recorded bypass perfusion pressure and oxygen delivery rate with intra-operative uNGAL excretion. Variations in bypass variables were accounted for by their excursions below several thresholds. SETTING: French tertiary referral paediatric cardiac centre. PATIENTS: A total of 72 infants in whom uNGAL was measured within 1 h of bypass. INTERVENTIONS: None. MAIN OUTCOME MEASURE: Renal injury, identified by a high creatinine normalised uNGAL concentration (>21.2 µg mmol). RESULTS: At the end of bypass, 43.75% of infants had high uNGAL. A more than 40% pressure drop below the normal age-standardised mean arterial pressure was associated with high uNGAL. Receiver operating curve [interquartile range] areas were 0.626 [0.501 to 0.752] for a more than 40% drop, and 0.679 [0.555 to 0.804] for a more than 50% drop. A more than 40% pressure drop for 19.5 min provided a 0.65 negative predictive value for high uNGAL, and a more than 50% pressure drop for 5.4 min provided a 0.67 negative predictive value. The link between uNGAL and oxygen delivery rate was negligible. CONCLUSION: Maintaining the perfusion pressure above 60% of the normal age-standardised mean arterial pressure may provide an effective renal protective strategy. TRIAL REGISTRATION: Registered on October 11, 2010, ClinicalTrials.gov Identifier: NCT01219998.

[Implementation and operation of protected residences for people with serious mental illness in Iquitos, Peru (2013-2016)Implementação e funcionamento de residências terapêuticas para pessoas com transtornos mentais graves em Iquitos, Peru (2013-2016)]. / Implementación y funcionamiento de hogares protegidos para personas con trastornos mentales graves en Iquitos, Perú (2013-2016).

OBJECTIVE: Evaluate the implementation and operation of protected residences for people with serious mental illness in Iquitos, based on the benefits and perceived improvement in their quality of life. METHODS: Qualitative and cross-cutting study. Thirty-six in-depth interviews of residents, caregivers, neighbors, and health professionals were conducted. A sociodemographic and clinical file was completed for each resident, along with a file on managerial processes for each facility. Focus groups were conducted with managers and caregivers. RESULTS: Residents' previous length of stay in a psychiatric hospital was 7 years and 3 months. Only 28 % had suffered a clinical relapse in the past year. Residents reported an improvement in their quality of life and greater satisfaction with their stay in the facility compared with their stay in the psychiatric hospital. The residences evaluated are located in areas accessible to social and community services, with adequate access to transportation. Periodic supervision of caregivers, infrastructure, and residence maintenance was performed. CONCLUSIONS: Caregivers, managers, residents, and neighbors have a positive view of residence operations.

OBJETIVO: Avaliar o processo de implementação e funcionamento de residências terapêuticas ("pensões protegidas") para pessoas portadoras de transtornos mentais graves segundo a percepção de benefício e melhoria da qualidade de vida. MÉTODOS: Trata-se de um estudo transversal qualitativo realizado em Iquitos, no Peru. Trinta e seis entrevistas em profundidade foram conduzidas com os moradores de residências terapêuticas, cuidadores, vizinhos e profissionais de saúde. Foi feito o preenchimento de uma ficha sociodemográfica e clínica para cada morador e uma ficha do processo de gestão por residência. Foram realizados grupos de discussão com gestores e cuidadores. RESULTADOS: A permanência prolongada anterior em instituição manicomial dos moradores das residências foi de 7 anos e 3 meses. Apenas 28% tiveram recaída clínica no último ano. Os moradores perceberam melhoria da qualidade de vida e informaram um nível maior de satisfação com a permanência nas residências terapêuticas em comparação à permanência anterior em instituição manicomial. As residências estudadas se situavam em locais acessíveis aos funcionários dos serviços sociais e comunitários, com acesso adequado ao transporte público. O trabalho dos cuidadores e a infraestrutura e manutenção das residências receberam supervisão periódica. CONCLUSÕES: O funcionamento das residências terapêuticas é percebido favoravelmente por cuidadores, gestores, moradores e vizinhos.

Controlled Synthesis of Nitrogen-Doped Graphene on Ruthenium from Azafullerene.

The controlled synthesis of high-quality nitrogen (N) doped single layer graphene on the Ru(0001) surface has been achieved using the N-containing sole precursor azafullerence (C59NH). The synthesis process and doping properties have been investigated on the atomic scale by combining scanning tunneling microscopy and X-ray photoelectron spectroscopy measurements. We find for the first time that the concentration of N-related defects on the N-doped graphene/Ru(0001) surface is tunable by adjusting the dosage of sole precursor and the number of growth cycles. Two primary types of N-related defects have been observed. The predominant bonding configuration of N atoms in the obtained graphene layer is pyridinic N. Our findings indicate that the synthesis from heteroatom-containing sole precursors is a very promising approach for the preparation of doped graphene materials with controlled doping properties.

Postanesthesia evaluation of emotional and psychological satisfaction in a Hispanic population.

BACKGROUND: Patient satisfaction has a positive impact on clinical care. Different strategies, such as questionnaires, have been developed to evaluate and improve patient satisfaction. A validated pediatric anesthesia questionnaire previously showed the importance of perioperative care built upon a relationship of trust between healthcare providers and children and parents, and a comfortable environment in which satisfactory answers are provided. However, the questionnaire was validated in English, and no research exists on the use of satisfaction questionnaires in Spanish. Given that there are 559 million Spanish speakers in the world, of which 53 million live in the United States, we intended to validate a Spanish version of this questionnaire to measure parental and pediatric satisfaction after anesthesia, and facilitate the provision and quality management of anesthesia care in Hispanic populations. METHODS: A questionnaire validated in English was translated to Spanish. Subsequently, it was administered to children who had undergone surgery and their parents to determine reliability, validity, acceptability, and reproducibility. RESULTS: Of the 228 recruited parents, a total of 221 agreed to participate, and 77 questionnaires were filled out completely by both parents and children. Overall response rates of 97% for parents and 90% for children were achieved. The reliability, test-retest reliability, and internal consistency were examined, and a McNemar coefficient of 0.97 and a Cronbach's alpha coefficient of 0.82 were obtained. Construct validity was obtained through comparisons of the following items: the child's perception of serenity imparted by the medical staff with the parent's satisfaction with conversations between the anesthesiologist and child, the nurse's ability to make the child feel better with the parent's satisfaction with the nurse's professionalism, and the nurse's kindness toward the child with the parent's perception of the care provided. CONCLUSION: This questionnaire proved to be simple and easy to understand within the literate Spanish-speaking population. It had adequate content validity and high reliability, acceptability, reproducibility, and construct validity. We believe that this Spanish questionnaire can be used with success among Hispanic populations resulting in improved care for those undergoing anesthesia, and therefore, patient satisfaction.

Wireless Sensor Platform for Cultural Heritage Monitoring and Modeling System.

Results from three years of continuous monitoring of environmental conditions using a wireless sensor platform installed at The Cloisters, the medieval branch of the New York Metropolitan Museum of Art, are presented. The platform comprises more than 200 sensors that were distributed in five galleries to assess temperature and air flow and to quantify microclimate changes using physics-based and statistical models. The wireless sensor network data shows a very stable environment within the galleries, while the dense monitoring enables localized monitoring of subtle changes in air quality trends and impact of visitors on the microclimate conditions. The high spatial and temporal resolution data serves as a baseline study to understand the impact of visitors and building operations on the long-term preservation of art objects.

Development of the Mexican Heart Team: The Long and Winding Road.

Heart failure (HF) is the leading cause of death worldwide. Efforts to decrease HF mortality rates include a multidisciplinary approach management. Although evidence suggests that this has been an optimal strategy for treating HF, the model remains not widely implanted. The current article explores the rationale behind the formation of a Heart Team in a developing country and its development despite the lack of an allocated budget.

Structural equation modelling exploration of the key pathophysiological processes involved in cardiac surgery-related acute kidney injury in infants.

BACKGROUND: Uncertainties about the pathophysiological processes resulting in cardiac surgery-related acute kidney injury (AKI) in infants concern the relative impact of the most prominent risk factors, the clinical relevance of changes in glomerular filtration rate vs tubular injury, and the usefulness of available diagnostic tools. Structural equation modelling could allow for the assessment of these complex relationships. METHODS: A structural model was specified using data from a prospective observational cohort of 200 patients <1 year of age undergoing cardiopulmonary bypass surgery. It included four latent variables: AKI, modelled as a construct of perioperative creatinine variation, of oliguria and of urine neutrophil gelatinase-associated lipocalin (uNGAL) concentrations; the cardiopulmonary bypass characteristics; the occurrence of a post-operative low cardiac output syndrome and the post-operative outcome. RESULTS: The model showed a good fit, and all path coefficients were statistically significant. The bypass was the most prominent risk factor, with a path coefficient of 0.820 (95 % CI 0.527-0.979), translating to a 67.2 % explanation for the risk of AKI. A strong relationships was found between AKI and early uNGAL excretion, and between AKI and the post-operative outcome, with path coefficients of 0.611 (95 % CI 0.347-0.777) and 0.741 (95 % CI 0.610-0.988), respectively. The path coefficient between AKI and a >50 % increase in serum creatinine was smaller, with a path coefficient of 0.443 (95 % CI 0.273-0.596), and was intermediate for oliguria, defined as urine output <0.5 ml kg(-1) h(-1), with a path coefficient of 0.495 (95 % CI 0.250-0.864). A path coefficient of -0.229 (95 % CI -0.319 to 0.060) suggested that the risk of AKI during the first year of life did not increase with younger age at surgery. CONCLUSIONS: These findings suggest that cardiac surgery-related AKI in infants is a translation of tubular injury, predominately driven by the cardiopulmonary bypass, and linked to early uNGAL excretion and to post-operative outcome. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01219998 . Registered 11 October 2010.

Agronomic Practices for Improving Gentle Remediation of Trace Element-Contaminated Soils.

The last few decades have seen the rise of Gentle soil Remediation Options (GRO), which notably include in situ contaminant stabilization ("inactivation") and plant-based (generally termed "phytoremediation") options. For trace element (TE)-contaminated sites, GRO aim to either decrease their labile pool and/or total content in the soil, thereby reducing related pollutant linkages. Much research has been dedicated to the screening and selection of TE-tolerant plant species and genotypes for application in GRO. However, the number of field trials demonstrating successful GRO remains well below the number of studies carried out at a greenhouse level. The move from greenhouse to field conditions requires incorporating agronomical knowledge into the remediation process and the ecological restoration of ecosystem services. This review summarizes agronomic practices against their demonstrated or potential positive effect on GRO performance, including plant selection, soil management practices, crop rotation, short rotation coppice, intercropping/row cropping, planting methods and plant densities, harvest and fertilization management, pest and weed control and irrigation management. Potentially negative effects of GRO, e.g., the introduction of potentially invasive species, are also discussed. Lessons learnt from long-term European field case sites are given for aiding the choice of appropriate management practices and plant species.

Assessing the flight capabilities of the goldspotted oak borer (Coleoptera: Buprestidae) with computerized flight mills.

The goldspotted oak borer, Agrilus auroguttatus Schaeffer (Coleoptera: Buprestidae), is native to southern Arizona and is an invasive wood-boring beetle that has caused considerable mortality to native oak species in southern California. Assessing the dispersal capabilities of this woodborer may help to determine its potential environmental and economic risk within the invaded region, and possibly assist with the development of species-specific management strategies. The flight performance of A. auroguttatus adults under different age, mating, and nutritional status was assessed by tethering individuals to computerized flight mills for a 24-h trial period to collect information on total distance flown, flight times and velocities, number and duration of flight bouts, and postflight weight. The nutritional status and body size (i.e., elytron length) of A. auroguttatus adults had a significant influence on overall flight performance. Mating status and gender had no significant influence on total flight distance, duration, velocity, and flight bout time. Significant interactions between nutritional status and age were observed in the overall flight performance of A. auroguttatus, with decreased flight activity in old (approximately 6 d of age) starved individuals during a 24-h trial period. Overall, results of these flight mill assays indicate that A. auroguttatus is unable to disperse long distances across habitats that lack suitable oak hosts. This work supports the hypothesis that human-aided transportation via infested oak firewood from southern Arizona across the Sonoran desert likely caused the initial introduction, and subsequent satellite infestations of A. auroguttatus within southern California's native oak woodlands.

A systematic review on cross-cultural validations and psychometric solidity of the orthotics and prosthetics user survey.

Research is essential to reflect patients' satisfaction with their devices in the field of Prosthetics and Orthotics, record their performance and health-related quality of life. This requires culturally adapted questionnaires for each country. Periodic assessment of validity and test fit are essential elements for the long-term utility and effectiveness of psychometric tests. This article reviews the psychometric properties of the Orthotics and Prosthetics Users Survey (OPUS). The purpose, in addition to its adaptation to the Spanish-speaking population, involves a review/update of content, statistical analyses, and validity studies, until a larger number of studies are conducted. Study design: a Systematic review. A systematic literature search was carried out in specialized search engines: Alcorze (University of Zaragoza), MEDLINE (PubMed), and EMBASE of original articles published since 2000. Eleven items belonging to the OPUS were obtained, according to the language of the country where they were validated, and promising psychometric properties were confirmed (reflecting reliability values between 0.62 and 0.95; Cronbach's α scores between 0.73 and 0.98) with sample sizes between 10 and 321. The study concluded by stating that the OPUS was validated in different languages, reporting good psychometric robustness so far. Further deployment, refinement, and validation of this survey by country is warranted in view of its promising use.

Analytical Validation of an Early Detection Pancreatic Cancer Test Using 5-Hydroxymethylation Signatures.

Early detection of pancreatic cancer has been shown to improve patient survival rates. However, effective early detection tools to detect pancreatic cancer do not currently exist. The Avantect Pancreatic Cancer Test, leveraging the 5-hydroxymethylation [5-hydroxymethylcytosine (5hmC)] signatures in cell-free DNA, was developed and analytically validated to address this unmet need. We report a comprehensive analytical validation study encompassing precision, sample stability, limit of detection, interfering substance studies, and a comparison with an alternative method. The assay performance on an independent case-control patient cohort was previously reported with a sensitivity for early-stage (stage I/II) pancreatic cancer of 68.3% (95% CI, 51.9%-81.9%) and an overall specificity of 96.9% (95% CI, 96.1%-97.7%). Precision studies showed a cancer classification of 100% concordance in biological replicates. The sample stability studies revealed stable assay performance for up to 7 days after blood collection. The limit of detection studies revealed equal results between early- and late-stage cancer samples, emphasizing strong early-stage performance characteristics. Comparisons of concordance of the Avantect assay with the enzymatic methyl sequencing (EM-Seq) method, which measures both methylation (5-methylcytosine) and 5hmC, were >95% for all samples tested. The Avantect Pancreatic Cancer Test showed strong analytical validation in multiple validation studies required for laboratory-developed test accreditation. The comparison of 5hmC versus EM-Seq further validated the 5hmC approach as a robust and reproducible assay.