Background Clinical laboratory patient databases are an untapped source of valuable diagnostic and prognostic information. However, the lack of associated clinical and/or demographic information and ...questionable generalizability to nonpatient populations often limit utility of these data. Objectives This study compared levels of cardiometabolic biomarkers between a national clinical laboratory patient cohort (Health Diagnostic Laboratory HD Lab) and the US population as inferred from the National Health and Nutrition Examination Survey (NHANES, 2011–2012). Methods Sample sizes for HD Lab ranged from 199,000 to 739,000 and for NHANES from 2200 to 5300. The latter were weighted to represent the adult US population (∼220 million). Descriptive statistics were compared for body mass index, 5 lipid biomarkers, and 3 glycemic biomarkers. Results Using age- and sex-matched data, mean biomarker values (mg/dL unless noted) and percent differences (%) for HD Lab vs NHANES were body mass index (kg/m2 ), 29.1 vs 28.6 (1.7%); total cholesterol, 185 vs 193 (–4.1%); apolipoprotein B, 92 vs 90 (2.2%); low-density lipoprotein cholesterol, 107 vs 115 (–7%); high-density lipoprotein cholesterol, 53 vs 53 (0%); triglycerides, 128 vs 127 (0.8%); glucose, 99 vs 108 (–8.3%); insulin (uU/mL), 13.7 vs 13.4 (2.2%); and hemoglobin A1c (%), 5.6 vs 5.8 (–3.4%). Although all differences were statistically significant, only low-density lipoprotein cholesterol and glucose differed by more than 5%. These may reflect a greater use of medications among HD Lab patients and/or preanalytical factors. Conclusions Cardiometabolic risk markers from a national clinical laboratory were broadly similar to those of the US population; thus, with certain caveats, data from the former may be generalizable to the latter.
It has been presumed that rheumatoid arthritis (RA) joint pain is related to inflammation in the synovium; however, recent studies reveal that pain scores in patients do not correlate with synovial ...inflammation. We developed a machine-learning approach (graph-based gene expression module identification or GbGMI) to identify an 815-gene expression module associated with pain in synovial biopsy samples from patients with established RA who had limited synovial inflammation at arthroplasty. We then validated this finding in an independent cohort of synovial biopsy samples from patients who had early untreated RA with little inflammation. Single-cell RNA sequencing analyses indicated that most of these 815 genes were most robustly expressed by lining layer synovial fibroblasts. Receptor-ligand interaction analysis predicted cross-talk between human lining layer fibroblasts and human dorsal root ganglion neurons expressing calcitonin gene-related peptide (CGRP
). Both RA synovial fibroblast culture supernatant and netrin-4, which is abundantly expressed by lining fibroblasts and was within the GbGMI-identified pain-associated gene module, increased the branching of pain-sensitive murine CGRP
dorsal root ganglion neurons in vitro. Imaging of solvent-cleared synovial tissue with little inflammation from humans with RA revealed CGRP
pain-sensing neurons encasing blood vessels growing into synovial hypertrophic papilla. Together, these findings support a model whereby synovial lining fibroblasts express genes associated with pain that enhance the growth of pain-sensing neurons into regions of synovial hypertrophy in RA.
The rapid global rise of COVID-19 from late 2019 caught major manufacturers of RT-qPCR reagents by surprise and threw into sharp focus the heavy reliance of molecular diagnostic providers on a ...handful of reagent suppliers. In addition, lockdown and transport bans, necessarily imposed to contain disease spread, put pressure on global supply lines with freight volumes severely restricted. These issues were acutely felt in New Zealand, an island nation located at the end of most supply lines. This led New Zealand scientists to pose the hypothetical question: in a doomsday scenario where access to COVID-19 RT-qPCR reagents became unavailable, would New Zealand possess the expertise and infrastructure to make its own reagents onshore? In this work we describe a review of New Zealand's COVID-19 test requirements, bring together local experts and resources to make all reagents for the RT-qPCR process, and create a COVID-19 diagnostic assay referred to as HomeBrew (HB) RT-qPCR from onshore synthesized components. This one-step RT-qPCR assay was evaluated using clinical samples and shown to be comparable to a commercial COVID-19 assay. Through this work we show New Zealand has both the expertise and, with sufficient lead time and forward planning, infrastructure capacity to meet reagent supply challenges if they were ever to emerge.
We present a case report of treatment using interstitial and surface high-dose-rate (HDR) brachytherapy for cutaneous squamous cell carcinoma (SCC) involving the interspace of the third and fourth ...digits. The patient refused two-ray amputation and the lesion was not amenable for external beam radiation therapy (EBRT). This is the first report detailing combined interstitial and surface HDR brachytherapy for a hand SCC.
The patient received 4050 cGy in 9 fractions, twice daily using 6 interstitial catheters and 8 Freiburg flap catheters. The clinical target was defined by MRI and ultrasound as a dorsal mass to the interspace between the heads of the third and fourth metacarpals measuring approximately 7 mm transverse × 5 mm volar-dorsal × 16 mm proximal-distal.
The treatment resulted in radiographic and clinical tumor control. The patient retained functional use of her hand. However, there were both acute and late treatment-related side effects. Acutely, inpatient admission for pain control with a nerve block was needed. Long-term toxicity was notable for grade 2 skin necrosis treated with hyperbaric oxygen.
The first interstitial and surface HDR brachytherapy for cutaneous squamous cell carcinoma of a finger interspace for hand function preservation is presented. The initial experience revealed that brachytherapy was tolerated but with notable acute and late side effects. Treatment did result in tumor shrinkage with organ preservation and function of two rays. A larger cohort of patients will be required for additional conclusions related to long-term clinical benefits in patients who refuse ray amputation.
Nearly half a century ago, two papers postulated the likelihood of lunar lava tube caves using mathematical models. Today, armed with an array of orbiting and fly‐by satellites and survey ...instrumentation, we have now acquired cave data across our solar system—including the identification of potential cave entrances on the Moon, Mars, and at least nine other planetary bodies. These discoveries gave rise to the study of planetary caves. To help advance this field, we leveraged the expertise of an interdisciplinary group to identify a strategy to explore caves beyond Earth. Focusing primarily on astrobiology, the cave environment, geology, robotics, instrumentation, and human exploration, our goal was to produce a framework to guide this subdiscipline through at least the next decade. To do this, we first assembled a list of 198 science and engineering questions. Then, through a series of social surveys, 114 scientists and engineers winnowed down the list to the top 53 highest priority questions. This exercise resulted in identifying emerging and crucial research areas that require robust development to ultimately support a robotic mission to a planetary cave—principally the Moon and/or Mars. With the necessary financial investment and institutional support, the research and technological development required to achieve these necessary advancements over the next decade are attainable. Subsequently, we will be positioned to robotically examine lunar caves and search for evidence of life within Martian caves; in turn, this will set the stage for human exploration and potential habitation of both the lunar and Martian subsurface.
Plain Language Summary
We have now acquired cave data across our solar system—including the identification of potential cave entrances on the Moon, Mars, and at least nine other planetary bodies. These discoveries gave rise to the study of planetary caves. To help advance this field, we conducted an expert‐opinion based social survey to identify a strategy to explore caves beyond Earth. We focused primarily on astrobiology, the cave environment, geology, robotics, instrumentation, and human exploration. First, we assembled a list of 198 science and engineering questions. Then, through a series of social surveys, 114 scientists and engineers winnowed down the list to the top 53 highest priority questions. This exercise resulted in identifying emerging and crucial research areas that require robust development to ultimately support a robotic mission to a planetary cave—principally the Moon and/or Mars. With the necessary financial investment and institutional support, the research and technological development required to achieve these necessary advancements over the next decade are attainable. Subsequently, we will be positioned to robotically examine lunar caves and search for evidence of life within Martian caves; in turn, this will set the stage for human exploration and potential habitation of both the lunar and Martian subsurface.
Key Points
Robotics and instrument advancements identified as linchpin focal areas for in situ study of planetary caves
Research and technological development required for lunar and/or Martian cave exploration is achievable in next decade with proper investment
First application of systematic and statistically rigorous social survey to identify science and engineering requirements in planetary science
The folk psychology of souls Bering, Jesse M
The Behavioral and brain sciences,
10/2006, Letnik:
29, Številka:
5
Journal Article
Recenzirano
The present article examines how people's belief in an afterlife, as well as closely related supernatural beliefs, may open an empirical backdoor to our understanding of the evolution of human social ...cognition. Recent findings and logic from the cognitive sciences contribute to a novel theory of existential psychology, one that is grounded in the tenets of Darwinian natural selection. Many of the predominant questions of existential psychology strike at the heart of cognitive science. They involve: causal attribution (why is mortal behavior represented as being causally related to one's afterlife? how are dead agents envisaged as communicating messages to the living?), moral judgment (why are certain social behaviors, i.e., transgressions, believed to have ultimate repercussions after death or to reap the punishment of disgruntled ancestors?), theory of mind (how can we know what it is "like" to be dead? what social-cognitive strategies do people use to reason about the minds of the dead?), concept acquisition (how does a common-sense dualism interact with a formalized socio-religious indoctrination in childhood? how are supernatural properties of the dead conceptualized by young minds?), and teleological reasoning (why do people so often see their lives as being designed for a purpose that must be accomplished before they perish? how do various life events affect people's interpretation of this purpose?), among others. The central thesis of the present article is that an organized cognitive "system" dedicated to forming illusory representations of (1) psychological immortality, (2) the intelligent design of the self, and (3) the symbolic meaning of natural events evolved in response to the unique selective pressures of the human social environment.
Acute febrile illness (AFI) is one of the most common reasons for seeking medical care in low-income and middle-income countries. Bacterial infections account for a relatively small proportion of ...AFIs; however, in the absence of a simple diagnostic test to guide clinical decisions, healthcare professionals often presume that a non-malarial febrile illness is bacterial in origin, potentially resulting in inappropriate antibiotic use. An accurate differential diagnostic tool for AFIs is thus essential, to both limit antibiotic use to bacterial infections and address the antimicrobial resistance crisis that is emerging globally, without resorting to multiple or complex pathogen-specific assays. The Biomarker for Fever-Diagnostic (BFF-Dx) study is one of the largest fever biomarker studies ever undertaken. We collected samples and classified disease aetiology in more than 1900 individuals, distributed among enrolment centres in three countries on two continents. Identical protocols were followed at each study site, and the same analyses were conducted in each setting, enabling like-with-like comparisons to be made among the large sample set generated. The BFF-Dx methodology can act as a model for other researchers, facilitating wider utility of the work in the future. The established sample collection is now accessible to researchers and companies and will facilitate the development of future fever-related diagnostic tests. Here, we outline the methodology used to determine the sample populations and to differentiate bacterial versus non-bacterial AFIs. Future publications will set out in more detail the study’s demographics, the causes of fever identified and the performance of selected biomarkers.
Pelvic fracture urethral injuries (PFUI) occur in up to 10% of pelvic fractures. It remains controversial whether initial primary urethral realignment (PR) after PFUI decreases the incidence of ...urethral obstruction and the need for subsequent urethral procedures. We present methodology for a prospective cohort study analyzing the outcomes of PR versus suprapubic cystostomy tube (SPT) after PFUI.
A prospective cohort trial was designed to compare outcomes between PR (group 1) and SPT placement (group 2). Centers are assigned to a group upon entry into the study. All patients will undergo retrograde attempted catheter placement; if this fails a cystoscopy exam is done to confirm a complete urethral disruption and attempt at gentle retrograde catheter placement. If catheter placement fails, group 1 will undergo urethral realignment and group 2 will undergo SPT. The primary outcome measure will be the rate of urethral obstruction preventing atraumatic passage of a flexible cystoscope. Secondary outcome measures include: subsequent urethral interventions, post-injury complications, urethroplasty complexity, erectile dysfunction (ED) and urinary incontinence rates.
Prior studies demonstrate PR is associated with a 15% to 50% reduction in urethral obstruction. Ninety-six men (48 per treatment group) are required to detect a 15% treatment effect (80% power, 0.05 significance level, 20% loss to follow up/death rate). Busy trauma centers treat complete PFUI approximately 1-6 times per year, thus our goal is to recruit 25 trauma centers and enroll patients for 3 years with a goal of 100 or more total patients with complete urethral disruption.
The proposed prospective multi-institutional cohort study should determine the utility of acute urethral realignment after PFUI.
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