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The millions of specimens stored in entomological collections provide a unique opportunity to study historical insect diversity. Current technologies allow to sequence entire genomes of historical specimens and estimate past genetic diversity of present-day endangered species, advancing our understanding of anthropogenic impact on genetic diversity and enabling the implementation of conservation strategies. A limiting challenge is the extraction of historical DNA (hDNA) of adequate quality for sequencing platforms. We tested four hDNA extraction protocols on five body parts of pinned false heath fritillary butterflies, Melitaea diamina, aiming to minimise specimen damage, preserve their scientific value to the collections, and maximise DNA quality and yield for whole-genome re-sequencing. We developed a very effective approach that successfully recovers hDNA appropriate for short-read sequencing from a single leg of pinned specimens using silica-based DNA extraction columns and an extraction buffer that includes SDS, Tris, Proteinase K, EDTA, NaCl, PTB, and DTT. We observed substantial variation in the ratio of nuclear to mitochondrial DNA in extractions from different tissues, indicating that optimal tissue choice depends on project aims and anticipated downstream analyses. We found that sufficient DNA for whole genome re-sequencing can reliably be extracted from a single leg, opening the possibility to monitor changes in genetic diversity maintaining the scientific value of specimens while supporting current and future conservation strategies. [ABSTRACT FROM AUTHOR]

As an integral part of the European strategy for advancing fusion-generated electricity, IFMIF-DONES represents a high-intensity neutron irradiation plant with the main purpose of assessing the suitability of materials for fusion reactor applications. Its primary mission is to examine how materials respond to irradiation within a neutron flux that mimics the conditions expected in the first wall of the proposed DEMO reactor, which is intended to succeed ITER. Consequently, IFMIF-DONES, whose construction is slated to commence shortly, plays a pivotal role in aiding the development, approval, and safe operation of DEMO, as well as future fusion power plants. This paper provides a quick overview of the current development of the IFMIF-DONES neutron source with a particular snapshot of the present engineering design status for what concerns the instrumentation and control systems together with its complex diagnostics, that guarantees the safe monitoring, supervision and regulation of all operations. The current status of design, after the completion of the preliminary design phase is presented, as well as the existing and future plans for their integration also using some of the new capabilities offered by Artificial Intelligence tools. [ABSTRACT FROM AUTHOR]

Digestive Chagas disease (DCD) is an enteric neuropathy caused by Trypanosoma cruzi infection. There is a lack of evidence on the mechanism of pathogenesis and rationales for treatment. We used a female C3H/HeN mouse model that recapitulates key clinical manifestations to study how infection dynamics shape DCD pathology and the impact of treatment with the front-line, anti-parasitic drug benznidazole. Curative treatment 6 weeks post-infection resulted in sustained recovery of gastrointestinal transit function, whereas treatment failure led to infection relapse and gradual return of DCD symptoms. Neuro/immune gene expression patterns shifted from chronic inflammation to a tissue repair profile after cure, accompanied by increased cellular proliferation, glial cell marker expression and recovery of neuronal density in the myenteric plexus. Delaying treatment until 24 weeks post-infection led to partial reversal of DCD, suggesting the accumulation of permanent tissue damage over the course of chronic infection. Our study shows that murine DCD pathogenesis is sustained by chronic T. cruzi infection and is not an inevitable consequence of acute stage denervation. The risk of irreversible enteric neuromuscular tissue damage and dysfunction developing highlights the importance of prompt diagnosis and treatment. These findings support the concept of treating asymptomatic, T. cruzi-infected individuals with benznidazole to prevent DCD development. The digestive form of Chagas disease (American trypanosomiasis) involves damage to the nervous system of the gastrointestinal tract and problems with peristalsis. Here, Khan et al show that infection causes damage to the colon that can be reversed if it is successfully treated early in the process. [ABSTRACT FROM AUTHOR]

With 54 new drugs and seven cellular and gene therapy products, the approvals by the US Food and Drug Administration (FDA) recovered 2023 from the 2022 dent back to the levels of 2020–2021. As in previous years of this annual review, we assign these new drugs to one of three levels of innovation: first drug against a condition ("first-in-indication"), first drug using a novel molecular mechanism ("first-in-class"), and "next-in-class," i.e., a drug using an already exploited molecular mechanism. We identify four (7%) "first-in-indication," 22 (36%) "first-in-class," and 35 (57%) "next-in-class" drugs. By treatment area, rare diseases (54%) and cancer drugs (23%) were once again the most prevalent (and partly overlapping) therapeutic areas. Other continuing trends were the use of accelerated regulatory approval pathways and the reliance on biopharmaceuticals (biologics). 2023 marks the approval of a first therapy based on CRISPR/Cas9 gene editing. [ABSTRACT FROM AUTHOR]

With improvements in survival for patients with metastatic cancer, long-term local control of brain metastases has become an increasingly important clinical priority. While consensus guidelines recommend surgery followed by stereotactic radiosurgery (SRS) for lesions >3 cm, smaller lesions (≤3 cm) treated with SRS alone elicit variable responses. To determine factors influencing this variable response to SRS, we analyzed outcomes of brain metastases ≤3 cm diameter in patients with no prior systemic therapy treated with frame-based single-fraction SRS. Following SRS, 259 out of 1733 (15%) treated lesions demonstrated MRI findings concerning for local treatment failure (LTF), of which 202 /1733 (12%) demonstrated LTF and 54/1733 (3%) had an adverse radiation effect. Multivariate analysis demonstrated tumor size (>1.5 cm) and melanoma histology were associated with higher LTF rates. Our results demonstrate that brain metastases ≤3 cm are not uniformly responsive to SRS and suggest that prospective studies to evaluate the effect of SRS alone or in combination with surgery on brain metastases ≤3 cm matched by tumor size and histology are warranted. These studies will help establish multi-disciplinary treatment guidelines that improve local control while minimizing radiation necrosis during treatment of brain metastasis ≤3 cm. Current guidelines recommend stereotactic radiosurgery for brain metastasis measuring less than 3 cm but there is significant variability in outcomes following treatment. This study shows that in treatment naïve brain metastasis less than 3 cm, intrinsic biological differences across multiple histologies may influence response to stereotactic radiosurgery. [ABSTRACT FROM AUTHOR]

Background: Lung volume optimization maneuvers (LVOM) are necessary to make physiologic use of high-frequency oscillatory ventilation (HFOV), but lung behavior during such maneuvers has not been studied to determine lung volume changes after initiation of HFOV, to quantify recruitment versus derecruitment during the LVOM and to calculate the time to stabilization after a pressure change. Methods: We performed a secondary analysis of prospectively collected data in subjects < 18 years on HFOV. Uncalibrated respiratory inductance plethysmography (RIP) tracings were used to quantify lung recruitment and derecruitment during the LVOM inflation and deflation. The time constant was calculated according to the Niemann model. Results: RIP data of 51 subjects (median age 3.5 [1.7–13.3] months) with moderate-to-severe pediatric acute respiratory distress syndrome (PARDS) in 85.4% were analyzed. Lung recruitment and derecruitment occurred during the LVOM inflation phase upon start of HFOV and between and within pressure changes. At 90% of maximum inflation pressure, lung derecruitment already started during the deflation phase. Time to stable lung volume (time constant) could only be calculated in 26.2% of all pressure changes during the inflation and in 21.4% during the deflation phase, independent of continuous distending pressure (CDP). Inability to calculate the time constant was due to lack of stabilization of the RIP signal or no change in any direction. Conclusions: Significant heterogeneity in lung behavior during a staircase incremental–decremental LVOM occurred, underscoring the need for higher initial inflation pressures when transitioning from conventional mechanical ventilation (CMV) and a longer time between pressure changes to allow for equilibration. [ABSTRACT FROM AUTHOR]

Microsatellite instability-high (MSI-H) is a tumor-agnostic biomarker for immune checkpoint inhibitor therapy. However, MSI status is not routinely tested in prostate cancer, in part due to low prevalence and assay cost. As such, prediction of MSI status from hematoxylin and eosin (H&E) stained whole-slide images (WSIs) could identify prostate cancer patients most likely to benefit from confirmatory testing to evaluate their eligibility for immunotherapy and need for Lynch syndrome testing. Prostate biopsies and surgical resections from prostate cancer patients referred to our institution were analyzed. MSI status was determined by next-generation sequencing. Patients sequenced before a cutoff date formed an algorithm development set (n = 4015, MSI-H 1.8%) and a paired validation set (n = 173, MSI-H 19.7%) that consisted of two serial sections from each sample, one stained and scanned internally and the other at an external site. Patients sequenced after the cutoff date formed a temporally independent validation set (n = 1350, MSI-H 2.3%). Attention-based multiple instance learning models were trained to predict MSI-H from H&E WSIs. The predictor achieved area under the receiver operating characteristic curve values of 0.78 (95% CI [0.69–0.86]), 0.72 (95% CI [0.63–0.81]), and 0.72 (95% CI [0.62–0.82]) on the internally prepared, externally prepared, and temporal validation sets, respectively, showing effective predictability and generalization to both external staining/scanning processes and temporally independent samples. While MSI-H status is significantly correlated with Gleason score, the model remained predictive within each Gleason score subgroup. [ABSTRACT FROM AUTHOR]

Copyright of Die Unfallchirurgie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Publishing in reputable peer-reviewed journals is an integral step of the clinical pharmacy research process, allowing for knowledge transfer and advancement in clinical pharmacy practice. Writing a manuscript for publication in a journal requires several careful considerations to ensure that research findings are communicated to the satisfaction of editors and reviewers, and effectively to the readers. This commentary provides a summary of the main points to consider, outlining how to: (1) select a suitable journal, (2) tailor the manuscript for the journal readership, (3) organise the content of the manuscript in line with the journal's guidelines, and (4) manage feedback from the peer review process. This commentary reviews the steps of the writing process, identifies common pitfalls, and proposes ways to overcome them. It aims to assist both novice and established researchers in the field of clinical pharmacy to enhance the quality of writing in a research paper to maximise impact. [ABSTRACT FROM AUTHOR]

The glymphatic movement of fluid through the brain removes metabolic waste1–4. Noninvasive 40 Hz stimulation promotes 40 Hz neural activity in multiple brain regions and attenuates pathology in mouse models of Alzheimer’s disease5–8. Here we show that multisensory gamma stimulation promotes the influx of cerebrospinal fluid and the efflux of interstitial fluid in the cortex of the 5XFAD mouse model of Alzheimer’s disease. Influx of cerebrospinal fluid was associated with increased aquaporin-4 polarization along astrocytic endfeet and dilated meningeal lymphatic vessels. Inhibiting glymphatic clearance abolished the removal of amyloid by multisensory 40 Hz stimulation. Using chemogenetic manipulation and a genetically encoded sensor for neuropeptide signalling, we found that vasoactive intestinal peptide interneurons facilitate glymphatic clearance by regulating arterial pulsatility. Our findings establish novel mechanisms that recruit the glymphatic system to remove brain amyloid.Audio and visual stimulation at 40 Hz promote cerebrospinal and interstitial fluid flux in mouse brain and result in amyloid clearance via the glymphatic system in a mouse model of Alzheimer’s disease. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer is a major global health concern, disproportionately affecting women in developing countries. Cervical cancer has two primary subtypes, squamous cell carcinoma (SCC) and adenocarcinoma (AC), each with distinct characteristics and screening effectiveness. In this study, we aimed to estimate the global incidence of cervical cancer according to histological subtype to inform prevention strategies. Methods: Using data from population-based cancer registries, we computed the rates of SCC, AC, and other specified histology among all cervical cancer cases by country and by 5-year age group. Proportions were subsequently applied to the estimated number of cervical cancer cases from the Global Cancer Observatory 2020. Age-standardized incidence rates were calculated. Results: SCC accounted for 82.72% of global cervical cancer cases, with AC contributing 12.18%. The highest SCC incidence was in Sub-Saharan Africa (29.79 per 100,000 population). The AC incidence was highest in South-Eastern Asia (3.67 per 100,000 population). Age-specific trends showed SCC peaking at approximately age 55 years and AC plateauing after age 45 years. Conclusions: This study provided a comprehensive estimate of cervical cancer incidence by histological subtype. SCC remained the dominant subtype globally, whereas the incidence of AC varied across regions. These findings highlighted the need for tailored prevention strategies, especially testing for human papillomavirus to detect AC in high burden areas. [ABSTRACT FROM AUTHOR]

Anadromous salmonid species vary in their use of open ocean, coastal, and inland marine waters. To better understand this diversity in behavior and habitat use, 120 coastal cutthroat trout, Oncorhynchus clarkii clarkii, were caught in southern Puget Sound, Washington, USA, tagged with acoustic transmitters, and 95 were detected by a network of receiver stations. Despite sufficient time to reach other parts of the Salish Sea where many receivers operated, none was detected beyond southern Puget Sound, indicating localized movements. Within southern Puget Sound, fish were detected at 34 of 127 receivers in marine sites throughout the year but especially in spring and fall. Most detection events (between first and last detections at a given receiver) were brief (60.5% were ≤ 2 h and 76.8% ≤ 6 h), indicating movement along the shoreline. However, 823 events (12.8%) exceeded 12 h and 222 (3.4%) exceeded 24 h at a receiver, indicating longer occupancy at certain sites and by certain individuals. The detections also indicated that cutthroat trout were active throughout the 24-h period, but they moved more often at night and less often in other periods than would occur by chance, and they moved more often on ebbing and flooding tides and less often at slack periods. Fish with pressure-sensitive transmitters were almost always (97.3% of records) within 2.5 m of the surface and 76.8% between 1 – 2 m, despite deeper and shallower waters nearby where they could have been detected. The data provide new insights into the behavior of this species, whose marine ecology has not been extensively studied, and differs markedly from the region's other native salmonids. [ABSTRACT FROM AUTHOR]

There are no therapeutic predictive biomarkers or representative preclinical models for high-grade gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN), a highly aggressive, fatal, and heterogeneous malignancy. We established patient-derived (PD) tumoroids from biobanked tissue samples of advanced high-grade GEP-NEN patients and applied this model for targeted rapid ex vivo pharmacotyping, next-generation sequencing, and perturbational profiling. We used tissue-matched PD tumoroids to profile individual patients, compared ex vivo drug response to patients' clinical response to chemotherapy, and investigated treatment-induced adaptive stress responses. PD tumoroids recapitulated biological key features of high-grade GEP-NEN and mimicked clinical response to cisplatin and temozolomide ex vivo. When we investigated treatment-induced adaptive stress responses in PD tumoroids in silico, we discovered and functionally validated Lysine demethylase 5 A and interferon-beta, which act synergistically in combination with cisplatin. Since ex vivo drug response in PD tumoroids matched clinical patient responses to standard-of-care chemotherapeutics for GEP-NEN, our rapid and functional precision oncology approach could expand personalized therapeutic options for patients with advanced high-grade GEP-NEN. [ABSTRACT FROM AUTHOR]

Copyright of Fire Ecology is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Coal mining is known for its contributions to climate change, but its impacts on the environment and human lives near mine sites are less widely recognised. This study integrates remote sensing, GIS, stakeholder interviews and extensive review of provincial data and documents to identify patterns of infringement, risk and impact driven by coal mining expansion across East Kalimantan, Indonesia. Specifically, we map and analyse patterns of mining concessions, land clearing, water cover, human settlement, and safety risks, and link them with mining governance and regulatory infractions related to coal mining permits. We show that excessive, improper permit granting and insufficient monitoring and oversight have led to deforestation, widespread overlaps of concessions with settlements, extensive boundary and regulatory violations, lacking reclamation, and numerous deaths. As the world's largest thermal coal exporter, Indonesia's elevated coal infringements, risks, and impacts translate to supply chain, sustainability, and human rights concerns for global coal markets. [ABSTRACT FROM AUTHOR]

Copyright of Die Unfallchirurgie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

ThTi2O6 derived compounds with the brannerite structure were designed, synthesised, and characterised with the aim of stabilising incorporation of U5+ or U6+, at dilute concentration. Appropriate charge compensation was targeted by co-substitution of Gd3+, Ca2+, Al3+, or Cr3+, on the Th or Ti site. U L3 edge X-ray Absorption Near Edge Spectroscopy (XANES) and High Energy Resolution Fluorescence Detected U M4 edge XANES evidenced U5+ as the major oxidation state in all compounds, with a minor fraction of U6+ (2–13%). The balance of X-ray and Raman spectroscopy data support uranate, rather than uranyl, as the dominant U6+ speciation in the reported brannerites. It is considered that the U6+ concentration was limited by unfavourable electrostatic repulsion arising from substitution in the octahedral Th or Ti sites, which share two or three edges, respectively, with neighbouring polyhedra in the brannerite structure. [ABSTRACT FROM AUTHOR]

The Saiga are migratory antelopes inhabiting the grasslands of Eurasia. Over the last century, Saiga have been pushed to the brink of extinction by mass mortality events and intense poaching. Yet, despite the high profile of the Saiga as an animal of conservation concern, little is known of its biology. In particular, the gut microbiota of Saiga has not been studied, despite its potential importance in health. Here, we characterise the gut microbiota of Saiga from two geographically distinct populations in Kazakhstan and compare it with that of other antelope species. We identified a consistent gut microbial diversity and composition among individuals and across two Saiga populations during a year without die-offs, with over 85% of bacterial genera being common to both populations despite vast geographic separation. We further show that the Saiga gut microbiota resembled that of five other antelopes. The putative causative agent of Saiga mass die-offs, Pasteurella multocida, was not detected in the Saiga microbiota. Our findings provide the first description of the Saiga gut microbiota, generating a baseline for future work investigating the microbiota's role in health and mass die-offs, and supporting the conservation of this critically endangered species. [ABSTRACT FROM AUTHOR]

Background: Randomized clinical trials have demonstrated efficacy and safety of erenumab. The aim of this study is to evaluate the effectiveness and safety of erenumab in a real-world setting in French patients with migraine associated with extreme unmet needs. Methods: This is a one year-prospective real-word study with enrolment of all consecutive adult patients included in the FHU InovPain registry who participated in a compassionate erenumab use program. Results: Of 144 patients included, 140 patients (82.1% female / mean age of 50.9 ± 11.4) received at least one dose of erenumab and were concerned by effectiveness and safety assessment. All patients had failed 11 oral preventive treatments. Most of them suffered from chronic migraine (88.6%) and presented a medication overuse (90.7%) at baseline. Thirty-eight (27.1%) discontinued treatment during the 12-month follow-up, with 22 (15.7%), 11 (7.9%) and 5 (3.6%) patients before 3, 6 or 9 months of treatment. The proportion of ≥ 50% responders at M3, M6, M9 and M12 was 74/140 (52.9%), 69/118 (58.5%), 61/107 (57.0%) and 60/102 (58.8%) respectively. At M3, the rate of reversion from chronic migraine to episodic migraine was 57.3% and the rate of transition from medication overuse to non-overuse was 46.5%. For monthly migraine days, the median (IQR) was 18.0 (13.0–26.0), 9.0 (5.0–17.0), 7.5 (5.0–14.0), 8.0 (5.0–12.5) and 8.0 (5.0–12.0) at M0, M3, M6, M9 and M12 respectively. For HIT-6 score, the median (IQR) was 68.0 (63.8–73.3), 60.0 (54.0–65.0), 60.0 (50.3–53.0), 59.0 (50.0–63.0) and 58.0 (50.0–62.9) at M0, M3, M6, M9 and M12 respectively. Fifty-three (37.9%) patients reported at least one of the following adverse events: cutaneous erythema and/or pain at the injection site for 42 (30%) patients, constipation for 22 (15.7%) patients, muscle spasm for 2 (1.4%) patients, alopecia for one (0.7%) patient and blood pressure increase in one (0.7%) patient. There was no serious adverse event. One female patient became pregnant after 5 months of exposure to erenumab with a safe evolution after treatment discontinuation. Conclusion: This first French real-world study related to migraine prevention with CGRP-mAbs confirms effectiveness and safety of erenumab in patients with extreme unmet needs. [ABSTRACT FROM AUTHOR]

Copyright of Innere Medizin (2731-7080) is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Melanoma of the skin is the most dangerous skin cancer in the world, though the numbers of reported new cases and melanoma-related deaths are low. Objective: This study evaluated the global incidence, mortality, risk factors and temporal trends by age, sex and locations of melanoma skin cancer. Patients and Methods: Cancer Incidence in Five Continents (CI5) volumes I–XI; the Nordic Cancer Registries (NORDCAN); the Surveillance, Epidemiology and End Results (SEER) Program; and the World Health Organization (WHO) International Agency for Research on Cancer (IARC) mortality database were accessed for worldwide incidence and mortality rates. Average Annual Percentage Change (AAPC) was calculated using a Joinpoint regression to examine trends. Results: Age-standardized rates of cancer incidence and mortality were 3.4 and 0.55 per 100,000 worldwide in 2020. Australia and New Zealand reported the highest incidence and mortality rates. Associated risk factors included higher prevalence of smoking, alcohol consumption, unhealthy diet, obesity and metabolic diseases. Increasing incidence trends were observed mostly in European countries, whilst mortality displayed an overall decreasing trend. For both sexes in the age group 50 years and above, a significant increase in incidence trend was observed. Conclusions: Although mortality rates and trends were found to decrease, global incidence has increased, especially in older age groups and males. Whilst incidence increase may be attributed to improved healthcare infrastructure and cancer detection methods, the growing prevalence of lifestyle and metabolic risk factors in developed countries should not be discounted. Future research should explore underlying variables behind epidemiological trends. [ABSTRACT FROM AUTHOR]

Copyright of Die Urologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The secretome of adipose-derived stromal cells (ASC) is a heterogeneous mixture of components with a beneficial influence on cellular microenvironments. As such, it represents a cell-free alternative in regenerative medicine therapies. Pathophysiological conditions increase the therapeutic capacity of ASC and, with this, the benefits of the secretome. Such conditions can be partially mimicked in vitro by adjusting culturing conditions. Secretomics, the unbiased analysis of a cell secretome by mass spectrometry, is a powerful tool to describe the composition of ASC secretomes. In this proteomics databases review, we compared ASC secretomic studies to retrieve persistently reported proteins resulting from the most explored types of culturing conditions used in research, i.e., exposure to normoxia, hypoxia, or cytokines. Our comparisons identified only eight common proteins within ASC normoxic secretomes, no commonalities within hypoxic ASC secretomes, and only nine within secretomes of ASC exposed to proinflammatory cytokines. Within these, and regardless of the culturing condition that stimulated secretion, a consistent presence of extracellular matrix-related pathways associated with such proteins was identified. Confounders such as donors' age, sex, body mass index, the anatomical area where ASC were harvested, secretome collection method, data description, and how the data is shared with the scientific community are discussed as factors that might explain our outcomes. We conclude that standardization is imperative as the currently available ASC secretomic studies do not facilitate solid conclusions on the therapeutic value of different ASC secretomes. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the distribution and severity of muscle atrophy in diabetic patients with active Charcot foot (CF) compared to diabetic patients without CF. Furthermore, to correlate the muscle atrophy with severity of CF disease. Material/methods: In this retrospective study, MR images of 35 diabetic patients (21 male, median:62.1 years ± 9.9SD) with active CF were compared with an age- and gender-matched control group of diabetic patients without CF. Two readers evaluated fatty muscle infiltration (Goutallier-classification) in the mid- and hindfoot. Furthermore, muscle trophic (cross-sectional muscle area (CSA)), intramuscular edema (none/mild versus moderate/severe), and the severity of CF disease (Balgrist Score) were assessed. Results: Interreader correlation for fatty infiltration was substantial to almost perfect (kappa-values:0.73–1.0). Frequency of fatty muscle infiltration was high in both groups (CF:97.1–100%; control:77.1–91.4%), but severe infiltration was significantly more frequent in CF patients (p-values: < 0.001–0.043). Muscle edema was also frequently seen in both groups, but significantly more often in the CF group (p-values: < 0.001–0.003). CSAs of hindfoot muscles were significantly smaller in the CF group. For the flexor digitorum brevis muscle, a cutoff value of 139 mm2 (sensitivity:62.9%; specificity:82.9%) in the hindfoot was found to differentiate between CF disease and the control group. No correlation was seen between fatty muscle infiltration and the Balgrist Score. Conclusion: Muscle atrophy and muscle edema are significantly more severe in diabetic patients with CF disease. Muscle atrophy does not correlate with the severity of active CF disease. A CSA < 139 mm2 of the flexor digitorum brevis muscle in the hindfoot may indicate CF disease. [ABSTRACT FROM AUTHOR]

Explaining the outcome of programs has become one of the main concerns in AI research. In constraint programming, a user may want the system to explain why a given variable assignment is not feasible or how it came to the conclusion that the problem does not have any solution. One solution to the latter is to return to the user a sequence of simple reasoning steps that lead to inconsistency. Arc consistency is a well-known form of reasoning that can be understood by a human. We consider explanations as sequences of propagation steps of a constraint on a variable (i.e. the ubiquitous revise function in arc-consistency algorithms) that lead to inconsistency. We characterize several cases for which providing a shortest such explanation is easy: For instance when constraints are binary and variables have maximum degree two. However, these polynomial cases are tight. For instance, providing a shortest explanation is NP-hard when constraints are binary and the maximum degree is three, even if the number of variables is bounded. It remains NP-hard on trees, despite the fact that arc consistency is a decision procedure on trees. The problem is not even FPT-approximable unless the FPT ≠ W[2] hypothesis is false. [ABSTRACT FROM AUTHOR]

This study presents a comparison between fishers' knowledge and fiscal records about the structure of inland fisheries in the Paraná River (Argentina). First of all, we characterized the fishing population according to the main demographic and economic indicators, identifying two different fishing areas: the northern and southern sections in the lower La Plata basin. Secondly, we carried out a comparative analysis of fiscal fishery records (from two commercial sets: 1930–1984 and 2011–2019) and local fishers' knowledge on inland commercial fisheries (frequency of occurrence and abundance). Finally, we contrasted current fishing regulations (allowed meshes and boats, fishing prohibitions, exports) to fishers' effective practices. The study area included 52 sites located along the floodplain of the middle and lower sections of the Paraná River, in the province of Santa Fe. Socioeconomic analyses identified two different groups of fishers throughout the river corridor. Results showed that fishers have detailed knowledge on nomenclature, ecology, reproductive strategy, habitat distribution, and usefulness of commercial fish species. By contrasting fishers' knowledge with fiscal records, we found similar and complementary information about the changes in abundance and frequency of occurrence in fisheries. These results highlight the need of including local knowledge as an outstanding source of information for well-planned management of fishing programs and sustainable policies. [ABSTRACT FROM AUTHOR]

While new drug approvals by the U.S. Food and Drug Administration (FDA) had remained stable or even increased in the first 2 years of the COVID-19 pandemic, the 37 newly approved drugs in 2022 are considerably less than the 53 and 50 new drugs approved in 2020 and 2021, respectively, and less than the rolling 10-year average of 43. As in previous years of this annual review, we assign these new drugs to one of three levels of innovation: first drug against a condition ("first-in-indication"), first drug using a novel molecular mechanism ("first-in-class"), and "next-in-class," i.e., a drug using an already exploited molecular mechanism. We identify two "first-in-indication" (ganaxolon and teplizumab), 20 (54%) "first-in-class," and 17 (46%) "next-in-class" drugs. By treatment area, rare diseases and cancer drugs were once again the most prevalent (partly overlapping) therapeutic areas. Other continuing trends were the use of accelerated regulatory approval pathways and the reliance on biopharmaceuticals (biologics). [ABSTRACT FROM AUTHOR]

Copyright of Die Urologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Selection of mosquito collection methods is of crucial importance to evaluate the impact of vector control tools on entomological outcomes. During a cluster randomised control trial evaluating the relative efficacy of two dual-active ingredient (a.i.) long-lasting insecticidal nets (LLINs) compared to pyrethroid-only LLINs, we assessed the performance of different mosquito collection methods: Human landing catches (HLC), Centers for Disease Control and Prevention (CDC) light traps, and pyrethrum spray catches (PSC). Anopheles mosquitoes were collected using three collection methods in 4 houses, in each of the 60 trial clusters at baseline and every quarter for 24 months using PSCs and HLCs, while CDC light traps were performed during two quarters only. Mean density of vectors collected per method per night was the highest with HLCs (15.9), followed by CDC light traps (6.8); with PSCs (1.1) collecting 10 times less mosquitoes than HLCs. All three collection methods collected fewer mosquitoes in the Interceptor G2® dual a.i. arm, compared to the other trial arms, although only HLCs and PSCs demonstrated strong evidence of this due to a greater number of collection rounds undertaken, than CDC light traps. The broadly similar results regarding the differential impact of the two dual a.i. LLINs showed by the three collection methods suggest that the more ethically acceptable, cheaper, and logistically simpler methods such as CDC light traps could be prioritised for use in large community trials for measuring the efficacy of vector control tools. [ABSTRACT FROM AUTHOR]

While immunologic correlates of COVID-19 have been widely reported, their associations with post-acute sequelae of COVID-19 (PASC) remain less clear. Due to the wide array of PASC presentations, understanding if specific disease features associate with discrete immune processes and therapeutic opportunities is important. Here we profile patients in the recovery phase of COVID-19 via proteomics screening and machine learning to find signatures of ongoing antiviral B cell development, immune-mediated fibrosis, and markers of cell death in PASC patients but not in controls with uncomplicated recovery. Plasma and immune cell profiling further allow the stratification of PASC into inflammatory and non-inflammatory types. Inflammatory PASC, identifiable through a refined set of 12 blood markers, displays evidence of ongoing neutrophil activity, B cell memory alterations, and building autoreactivity more than a year post COVID-19. Our work thus helps refine PASC categorization to aid in both therapeutic targeting and epidemiological investigation of PASC. Post-acute sequelae of COVID-19 (PASC) has heterogenous presentation and complex etiology. Here the authors profile peripheral blood of patients with PASC and analyze by machine-learning to identify immune and serology features that allow the stratification of PASC into inflammatory and non-inflammatory types for better diagnosis and therapy-planning. [ABSTRACT FROM AUTHOR]

Introduction: Cancers assume a variety of distinct histologies, and may originate from a myriad of sites including solid organs, hematopoietic cells, and connective tissue. Clinical decision-making based on consensus guidelines such as the National Comprehensive Cancer Network (NCCN) is often predicated on a specific histologic and anatomic diagnosis, supported by clinical features and pathologist interpretation of morphology and immunohistochemical (IHC) staining patterns. However, in patients with nonspecific morphologic and IHC findings—in addition to ambiguous clinical presentations such as recurrence versus new primary—a definitive diagnosis may not be possible, resulting in the patient being categorized as having a cancer of unknown primary (CUP). Therapeutic options and clinical outcomes are poor for patients with CUP, with a median survival of 8–11 months. Methods: Here, we describe and validate the Tempus Tumor Origin (Tempus TO) assay, an RNA-sequencing-based machine learning classifier capable of discriminating between 68 clinically relevant cancer subtypes. Model accuracy was assessed using primary and/or metastatic samples with known subtype. Results: We show that the Tempus TO model is 91% accurate when assessed on both a retrospectively held out cohort and a set of samples sequenced after model freeze that collectively contained 9210 total samples with known diagnoses. When evaluated on a cohort of CUPs, the model recapitulated established associations between genomic alterations and cancer subtype. Discussion: Combining diagnostic prediction tests (e.g., Tempus TO) with sequencing-based variant reporting (e.g., Tempus xT) may expand therapeutic options for patients with cancers of unknown primary or uncertain histology. [ABSTRACT FROM AUTHOR]

Purpose: Distinguishing radiation necrosis from tumor progression among patients with brain metastases previously treated with stereotactic radiosurgery represents a common diagnostic challenge. We performed a prospective pilot study to determine whether PET/CT with 18F-fluciclovine, a widely available amino acid PET radiotracer, repurposed intracranially, can accurately diagnose equivocal lesions. Methods: Adults with brain metastases previously treated with radiosurgery presenting with a follow-up tumor-protocol MRI brain equivocal for radiation necrosis versus tumor progression underwent an 18F-fluciclovine PET/CT of the brain within 30 days. The reference standard for final diagnosis consisted of clinical follow-up until multidisciplinary consensus or tissue confirmation. Results: Of 16 patients imaged from 7/2019 to 11/2020, 15 subjects were evaluable with 20 lesions (radiation necrosis, n = 16; tumor progression, n = 4). Higher SUVmax statistically significantly predicted tumor progression (AUC = 0.875; p = 0.011). Lesion SUVmean (AUC = 0.875; p = 0.018), SUVpeak (AUC = 0.813; p = 0.007), and SUVpeak-to-normal-brain (AUC = 0.859; p = 0.002) also predicted tumor progression, whereas SUVmax-to-normal-brain (p = 0.1) and SUVmean-to-normal-brain (p = 0.5) did not. Qualitative visual scores were significant predictors for readers 1 (AUC = 0.750; p < 0.001) and 3 (AUC = 0.781; p = 0.045), but not for reader 2 (p = 0.3). Visual interpretations were significant predictors for reader 1 (AUC = 0.898; p = 0.012) but not for reader 2 (p = 0.3) or 3 (p = 0.2). Conclusions: In this prospective pilot study of patients with brain metastases previously treated with radiosurgery presenting with a contemporary MRI brain with a lesion equivocal for radiation necrosis versus tumor progression, 18F-fluciclovine PET/CT repurposed intracranially demonstrated encouraging diagnostic accuracy, supporting the pursuit of larger clinical trials which will be necessary to establish diagnostic criteria and performance. [ABSTRACT FROM AUTHOR]

Crystal chemical design principles were applied to synthesise novel U4+ dominant and titanium excess betafite phases Ca1.15(5)U0.56(4)Zr0.17(2)Ti2.19(2)O7 and Ca1.10(4)U0.68(4)Zr0.15(3)Ti2.12(2)O7, in high yield (85–95 wt%), and ceramic density reaching 99% of theoretical. Substitution of Ti on the A-site of the pyrochlore structure, in excess of full B-site occupancy, enabled the radius ratio (rA/rB = 1.69) to be tuned into the pyrochlore stability field, approximately 1.48 ≲ rA/rB ≲ 1.78, in contrast to the archetype composition CaUTi2O7 (rA/rB = 1.75). U L3-edge XANES and U 4f7/2 and U 4f5/2 XPS data evidenced U4+ as the dominant speciation, consistent with the determined chemical compositions. The new betafite phases, and further analysis reported herein, point to a wider family of actinide betafite pyrochlores that could be stabilised by application of the underlying crystal chemical principle applied here. [ABSTRACT FROM AUTHOR]

Indium (In) is a neutron absorbing additive that could feasibly be used to mitigate criticality in ceramic wasteforms containing Pu in the immobilised form, for which zirconolite (nominally CaZrTi2O7) is a candidate host phase. Herein, the solid solutions Ca1-xZr1-xIn2xTi2O7 (0.10 ≤ x ≤ 1.00; air synthesis) and Ca1-xUxZrTi2-2xIn2xO7 (x = 0.05, 0.10; air and argon synthesis) were investigated by conventional solid state sintering at a temperature of 1350 °C maintained for 20 h, with a view to characterise In3+ substitution behaviour in the zirconolite phase across the Ca2+, Zr4+ and Ti4+ sites. When targeting Ca1-xZr1-xIn2xTi2O7, single phase zirconolite-2M was formed at In concentrations of 0.10 ≤ x ≤ 0.20; beyond x ≥ 0.20, a number of secondary In-containing phases were stabilised. Zirconolite-2M remained a constituent of the phase assemblage up to a concentration of x = 0.80, albeit at relatively low concentration beyond x ≥ 0.40. It was not possible to synthesise the In2Ti2O7 end member compound using a solid state route. Analysis of the In K-edge XANES spectra in the single phase zirconolite-2M compounds confirmed that the In inventory was speciated as trivalent In3+, consistent with targeted oxidation state. However, fitting of the EXAFS region using the zirconolite-2M structural model was consistent with In3+ cations accommodated within the Ti4+ site, contrary to the targeted substitution scheme. When deploying U as a surrogate for immobilised Pu in the Ca1-xUxZrTi2-2xIn2xO7 solid solution, it was demonstrated that, for both x = 0.05 and 0.10, In3+ was successfully able to stabilise zirconolite-2M when U was distributed predominantly as both U4+ and average U5+, when synthesised under argon and air, respectively, determined by U L3-edge XANES analysis. [ABSTRACT FROM AUTHOR]

Microplastic pollution in aquatic ecosystems presents an emerging environmental threat that can have adverse effects on ecology, endanger aquatic species, and result in economic damage. Despite the numerous studies reporting the presence of microplastics in marine environments, research into their presence in freshwater systems or inland waters remains limited. This study aimed to assess the level of microplastic pollution transported by the Munzur and Pülümür Rivers and some small rivers that flow into the Uzunçayır dam lake, which is the confluence of the Munzur and Pülümür Rivers in Türkiye. Samples were collected from 23 stations, with the concentration of microplastics ranging from 0.01 MP/m3 at P-4 station to 28.21 MP/m3 at P-10, a station located near a city. Microplastics comprise four types: fiber, film, fragment, and glitter. The average size of microplastics was 1.46 ± 0.05 mm, with the average size of fibers, films, fragments, and glitter-type microplastics being 1.58 ± 0.07 mm, 1.23 ± 0.10 mm, 1.21 ± 0.11 mm, and 0.78 ± 0.16 mm, respectively. The most frequent polymers were polyethylene (31.8%), polystyrene (21.1%), and polypropylene (10.5%). Despite being considered remote and less populated rivers compared to other river systems in Türkiye, all sampling sites showed varying concentrations of microplastics. [ABSTRACT FROM AUTHOR]

Background: Mechanical power is a major contributor to lung injury and mortality in adults receiving mechanical ventilation. Recent advances in our understanding of mechanical power have allowed the different mechanical components to be isolated. The preterm lung shares many of the same similarities that would indicate mechanical power may be relevant in this group. To date, the role of mechanical power in neonatal lung injury is unknown. We hypothesise that mechanical power maybe useful in expanding our understanding of preterm lung disease. Specifically, that mechanical power measures may account for gaps in knowledge in how lung injury is initiated. Hypothesis-generating data set: To provide a justification for our hypothesis, data in a repository at the Murdoch Children's Research Institute, Melbourne (Australia) were re-analysed. 16 preterm lambs 124–127d gestation (term 145d) who received 90 min of standardised positive pressure ventilation from birth via a cuffed endotracheal tube were chosen as each was exposed to three distinct and clinically relevant respiratory states with unique mechanics. These were (1) the respiratory transition to air-breathing from an entirely fluid-filled lung (rapid aeration and fall in resistance); (2) commencement of tidal ventilation in an acutely surfactant-deficient state (low compliance) and (3) exogenous surfactant therapy (improved aeration and compliance). Total, tidal, resistive and elastic-dynamic mechanical power were calculated from the flow, pressure and volume signals (200 Hz) for each inflation. Results: All components of mechanical power behaved as expected for each state. Mechanical power increased during lung aeration from birth to 5 min, before again falling immediately after surfactant therapy. Before surfactant therapy tidal power contributed 70% of total mechanical power, and 53.7% after. The contribution of resistive power was greatest at birth, demonstrating the initial high respiratory system resistance at birth. Conclusions: In our hypothesis-generating dataset, changes in mechanical power were evident during clinically important states for the preterm lung, specifically transition to air-breathing, changes in aeration and surfactant administration. Future preclinical studies using ventilation strategies designed to highlight different types of lung injury, including volu-, baro- and ergotrauma, are needed to test our hypothesis. [ABSTRACT FROM AUTHOR]

Purpose: The aims of the present study were to evaluate the development of untreated cervical intraepithelial neoplasia (CIN) 3 during pregnancy and to assess persistence, progression, and regression rates postpartum to identify factors associated with regression. Methods: In a tertiary gynecology and obstetrics department, a total of 154 pregnant women with CIN 3 were treated in the dysplasia unit. The follow-up findings were analyzed retrospectively on the basis of histological, cytological, and human papillomavirus (HPV) testing of 154 pregnant women confirmed as having CIN 3 in colposcopically guided biopsies. Results: The rates of persistence, regression, and progression of CIN 3 in these women were 76.1%, 20% and 3.2%, respectively. Data for the delivery mode was available for 126 women. The rate of regression was almost twice as high with vaginal delivery as with cesarean section, at 27.4 vs. 15.2%, whereas the rate of progression was lower with vaginal delivery, at 2.7 vs. 6.5%. Conclusion: The rate of persistence of CIN observed in this study is comparable to that reported in other studies. The study provides strong evidence for greater regression among women who have vaginal deliveries. Careful work-up is recommended postpartum for this group of women in order to rule out persistent CIN 3 or invasive disease. [ABSTRACT FROM AUTHOR]

Context: Rivers are heterogeneous landscapes characterised by distinct patches separated by boundaries. The significance of tributaries as dominant geomorphic boundaries in determining the character of the river discontinuum is a prevailing, yet largely unscrutinised, paradigm of river science. Objectives: This study examines the spatial organisation and strength of geomorphic boundaries within the river network of 10 drainage basins in the Kimberley region of NW Australia. The possible drivers of the spatial organisation of boundaries throughout the river networks are also identified. Methods: Using a suite of GIS tools and statistical analyses, distinct rivers zones or functional process zones (FPZs) and the strength of geomorphic boundaries between these FPZs were empirically determined for > 35,700 km of river network. The spatial distribution of boundary strengths throughout the river network was analysed against a set of environmental variables hypothesised to influence the location of boundaries, specifically: lithology, slope, elevation, and tributary confluences. Results: 1410 boundaries were identified in the river network of the Kimberley region, an average of one boundary every 25 km of river. Only 32% of these occurred at river confluences. Transitions between different FPZs – large scale river patches, present in the river network were the dominant geomorphic boundary. Although a range of boundary strengths occurred, some river confluences represented the strongest geomorphic boundaries. The location of geomorphic boundaries was significantly associated with the boundary between different types of lithologies. Conclusion: Our analysis shows that the river network of the Kimberley region is naturally highly fragmented, and that tributary confluences are not the dominant control on discontinuities in the river network. We suggest that the character of river network fragmentation depends not only on dams, waterfalls, and confluences, but also on the strength and spatial organisation of geomorphic boundaries between FPZs. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the incidence and mortality trend of thyroid cancer, and compare its global incidence trends among different countries by age group and sex. Methods: Data on age-standardized incidence and mortality rate of thyroid cancer among 50 countries were collected from the Cancer Incidence in Five Continents Volume XI; the Surveillance, Epidemiology, and End Results Program (SEER), the National Cancer Institute; the Nordic Cancer Registries (NORDCAN), and the WHO mortality database. The Average Annual Percent Change (AAPC) of the incidence and mortality trends was calculated by joinpoint regression analysis. Results: The age-standardized incidence of thyroid cancer was 3.1 and 10.1 cases per 100,000 persons in men and women, respectively. The incidence of thyroid cancer increased in most countries among individuals irrespective of age groups, and increased in populations aged <40 years in several countries, including Korea (male: AAPC 25.3, 95% C.I. 22.3–28.4, p < 0.001; female: AAPC 18.5, 95% C.I. 16.2–20.9, p < 0.001), Poland (male: AAPC 19.1, 95% C.I. 1.4–39.7, p = 0.036; female: AAPC 13.7, 95% C.I. 7.6–20.2), and China (male: AAPC 18.6, 95% C.I. 12.1–25.5, p < 0.001; female: AAPC 13.3, 95%C.I. 11.5–15.1, p < 0.001). Conclusion: An increasing incidence of thyroid cancer was observed in younger subjects in a majority of countries, highlighting the need for more preventive strategies in this population and possible avoidance of over-diagnosis. [ABSTRACT FROM AUTHOR]

A prospective trial comparing isotonic with hypotonic maintenance fluids for prevention of hospital-acquired hyponatraemia. 10.1007/s00467-010-1600-4. 20668885 5 Pemde HK, Dutta AK, Sodani R, Mishra K. Isotonic intravenous maintenance fluid reduces hospital acquired hyponatremia in young children with central nervous system infections. Importantly, the updated results do not alter, but rather strengthen the level of evidence for the PiCO2 recommendation: "in acutely and critically ill children, isotonic maintenance fluid should be used to reduce the risk of hyponatremia"; level of evidence A. The authors apologize for this error. [Extracted from the article]

In January 2021, the eHealth App was launched in Hong Kong by the Hong Kong government to support the Electronic Health Record Sharing System (eHRSS). A Health Management Module in the eHealth App introduced new functions to record blood pressure, blood sugar, and heart rate, and downloading and sharing records. This study aims to compare the level of glycaemic control between users of the eHealth App and non-users. Type 2 diabetes patients who have joined the eHRSS with existing haemoglobin A1c (HbA1c) level records are recruited. Correlations between predictors and optimal HbA1c control (<7%) are examined using logistic regression analyses. A total of 109,823 participants are included, with 76,356 non-users of eHealth App, 31,723 users of eHealth App, and 1744 users of the eHealth Management Module together with the App. We collect HbA1c values from Jan 2021 to May 2022, and they are 6 months after the use of the App on average. Users of the eHealth Management Module are found to have more optimal HbA1c levels across all subgroups, with the strongest effect observed in younger females (aOR = 1.66, 95% CI = 1.27–2.17). eHealth App usage is also positively associated with optimal HbA1c levels, particularly amongst younger females (aOR = 1.17, 95% CI = 1.08–1.26). Overall, users of eHealth App and eHealth Management Module demonstrate more optimal HbA1c levels when compared with non-users, particularly among younger adults and females. These findings support its potential adoption in diabetes patients. Future studies should examine the impact of eHealth interventions on other clinical targets and diabetes complications. [ABSTRACT FROM AUTHOR]

Precipitation events have been predicted and observed to become fewer, but larger, as the atmosphere warms. Water-limited ecosystems are especially sensitive to changes in water cycling, yet evidence suggests that productivity may either increase or decrease in response to precipitation intensification. Interactions among climate, soil properties, and vegetation type may explain different responses, but this is difficult to experimentally test over large spatial scales. Simulation modeling may reveal the mechanisms through which climate, soils, and vegetation interact to affect plant growth. We use an individual-based plant ecohydrological model to simulate the effects of 25%, 50%, and 100% increases in precipitation event sizes on water cycling and shrub, grass, and forb biomass in 200 shrub-steppe sites spanning 651,000 km2 of the Intermountain West, USA. Simulations did not change annual precipitation amounts and were performed for 0, 3, and 5 °C warming. Larger precipitation events decreased evaporation and 'pushed' water into shrub root zones in arid and semi-arid sites, but 'pushed' water below shrub root zones in mesic sites resulting in increased shrub biomass in arid and semi-arid, but not mesic, sites. Positive effects of precipitation intensification on shrub growth partially counteracted negative effects of warming. Grasses and forbs showed no consistent response to precipitation intensification. Results indicate that increased precipitation intensity creates a competitive advantage for shrubs in arid and semi-arid sites. This advantage results in greater shrub relative abundance and suggests that precipitation intensification contributes to woody plant encroachment observed globally in arid and semi-arid ecosystems. [ABSTRACT FROM AUTHOR]

Collecting job analysis ratings for a large number of jobs via surveys, interviews, or focus groups can put a very large burden on organizations. In this study, we describe and evaluate a streamlined, natural language processing-based approach to estimating (a) the importance of various knowledges, skills, abilities, and other characteristics (KSAOs) to jobs, and (b) how descriptive various interests are of work on a job. Specifically, we evaluate whether we can train a machine to accurately estimate KSAO ratings for jobs using job description and task statement text as the sole input. Data for 963 occupations from the U.S. Department of Labor's Occupational Information Network (O*NET) system and an independent set of 229 occupations from a large organization provided the basis for the evaluation. Our approach produced KSAO predictions that had cross-validated correlations with subject matter expert (SME) ratings of knowledges, skills, abilities, and interests of.74,.80,.75, and.84, respectively (on average, across the 126 KSAOs examined). We found clear evidence for the validity of machine-based predictions based on (a) convergence among machine-based and SME-furnished ratings, (b) conceptually meaningful patterns of prediction model regression coefficients among the KSAOs examined, and (c) conceptual relevance of top predictor models underlying related clusters of KSAOs. We also found that prediction models developed on O*NET data produced meaningful results when applied to an independent set of job descriptions and tasks. Implications of this work, as well as suggested directions for future job analysis research and practice, are discussed. [ABSTRACT FROM AUTHOR]