Post-mortem radiology in fetal and neonatal death: the diagnostic value of post-mortem MRI versus autopsy regarding non-cardiac thoracic and abdominal abnormalities.

AIM: To compare the diagnostic value and accuracy of post-mortem magnetic resonance imaging (PMMRI) and autopsy for non-cardiac thoracic and abdominal abnormalities in fetal death. MATERIALS AND METHODS: This single-institution retrospective study included all consecutive cases of fetal and perinatal death between January 2015 and December 2021 for which PMMRI followed by autopsy was conducted. These cases comprised fetuses at >18 weeks of gestation and preterm and term neonates who lived for <24 h. All PMMRI and autopsy reports were re-assessed and scored for seven non-cardiac thoracic and 52 abdominal abnormalities, and concordance between autopsy and PMMRI findings was determined as the primary outcome. RESULTS: Eighty cases were included in this study. Fetal loss was caused by termination of pregnancy in 80% of cases. Further, the mean gestational age was 166 days (23 weeks and 5 days, range 126-283 days). The concordance between PMMRI and autopsy for non-cardiac thoracic and abdominal abnormalities was 83.1% (95% confidence interval [CI] 71.3-83.3) and 76.3% (95% CI 65.8-84.2%), respectively, with a substantial and moderate strength of agreement (Cohen's kappa = 0.63 and 0.51 respectively). CONCLUSION: PMMRI exhibited good overall diagnostic value for non-cardiac thoracic and abdominal abnormalities, specifically large structural abnormalities. PMMRI may offer parents and physicians a valuable addition to autopsy for the detection of non-cardiac thoracic and abdominal abnormalities, or even an alternative option when parents do not consent to autopsy.

Disclosure of cardiac variants of uncertain significance results in an exome cohort.

This study examined the impact of disclosing subclassifications of genetic variants of uncertain significance (VUS) on behavioral intentions. We studied return of VUS results to 79 individuals with a cardiomyopathy-associated VUS, subclassified into VUS-high or VUS-low. Primary outcomes were perceived risk (absolute and comparative), perceived severity, perceived value of information, self-efficacy, decision regret, and behavioral intentions to share results and change behaviors. There was no significant difference between the 2 subclasses in overall behavioral intentions (t = 0.023, P = .982) and each of the individual items on the behavioral intentions scale; absolute (t = -1.138, P = .259) or comparative (t = -0.463, P = .645) risk perceptions; perceived value of information (t = 0.582, P = .563) and self-efficacy (t = -0.733, P = .466). Decision regret was significantly different (t = 2.148, P = .035), with VUS-low (mean = 17.24, SD = 16.08) reporting greater regret. Combining the subclasses, perceived value of information was the strongest predictor of behavioral intentions (ß = 0.524, P < .001). Participants generally understood the meaning of a genetic VUS result classification and reported satisfaction with result disclosure. No differences in behavioral intentions were found, but differences in decision regret suggest participants distinguish subclasses of VUS results. The perceived value of VUS may motivate recipients to pursue health-related behaviors.

Dutch guideline for clinical foetal-neonatal and paediatric post-mortem radiology, including a review of literature.

Clinical post-mortem radiology is a relatively new field of expertise and not common practice in most hospitals yet. With the declining numbers of autopsies and increasing demand for quality control of clinical care, post-mortem radiology can offer a solution, or at least be complementary. A working group consisting of radiologists, pathologists and other clinical medical specialists reviewed and evaluated the literature on the diagnostic value of post-mortem conventional radiography (CR), ultrasonography, computed tomography (PMCT), magnetic resonance imaging (PMMRI), and minimally invasive autopsy (MIA). Evidence tables were built and subsequently a Dutch national evidence-based guideline for post-mortem radiology was developed. We present this evaluation of the radiological modalities in a clinical post-mortem setting, including MIA, as well as the recently published Dutch guidelines for post-mortem radiology in foetuses, neonates, and children. In general, for post-mortem radiology modalities, PMMRI is the modality of choice in foetuses, neonates, and infants, whereas PMCT is advised in older children. There is a limited role for post-mortem CR and ultrasonography. In most cases, conventional autopsy will remain the diagnostic method of choice. CONCLUSION: Based on a literature review and clinical expertise, an evidence-based guideline was developed for post-mortem radiology of foetal, neonatal, and paediatric patients. What is Known: • Post-mortem investigations serve as a quality check for the provided health care and are important for reliable epidemiological registration. • Post-mortem radiology, sometimes combined with minimally invasive techniques, is considered as an adjunct or alternative to autopsy. What is New: • We present the Dutch guidelines for post-mortem radiology in foetuses, neonates and children. • Autopsy remains the reference standard, however minimal invasive autopsy with a skeletal survey, post-mortem computed tomography, or post-mortem magnetic resonance imaging can be complementary thereof.

Biochemical Effects on the Liver of 1 Month of Alcohol Abstinence in Moderate Alcohol Consumers.

SHORT SUMMARY: : In this study in healthy moderate alcohol consumers, we observe that one month of alcohol abstinence results in decreased gamma-glutamyl transferase levels, which return to baseline levels after resumption of alcohol consumption.

PUGS: A novel scale to assess perceptions of uncertainties in genome sequencing.

Expectations of results from genome sequencing by end users are influenced by perceptions of uncertainty. This study aimed to assess uncertainties about sequencing by developing, evaluating, and implementing a novel scale. The Perceptions of Uncertainties in Genome Sequencing (PUGS) scale comprised ten items to assess uncertainties within three domains: clinical, affective, and evaluative. Participants (n=535) from the ClinSeq® NIH sequencing study completed a baseline survey that included the PUGS; responses (mean = 3.4/5, SD=0.58) suggested modest perceptions of certainty. A confirmatory factor analysis identified factor loadings that led to elimination of two items. A revised eight-item PUGS scale was used to test correlations with perceived ambiguity (r = -0.303, p < 0.001), attitudinal ambivalence (r = -0.111, p = 0.011), and ambiguity aversion (r = -0.093, p = 0.033). Results support nomological validity. A correlation with the MICRA uncertainty subscale was found among 175 cohort participants who had received results (r = -0.335, p < 0.001). Convergent and discriminant validity were also satisfied in a second sample of 208 parents from the HudsonAlpha CSER Project who completed the PUGS (mean = 3.4/5, SD = 0.72), and configural invariance was supported across the two datasets. As such, the PUGS is a promising scale for evaluating perceived uncertainties in genome sequencing, which can inform interventions to help patients form realistic expectations of these uncertainties.

Evidence that small molecule enhancement of ß-hexosaminidase activity corrects the behavioral phenotype in Dutch APP(E693Q) mice through reduction of ganglioside-bound Aß.

Certain mutant Alzheimer's amyloid-ß (Aß) peptides (that is, Dutch mutant APP(E693Q)) form complexes with gangliosides (GAß). These mutant Aß peptides may also undergo accelerated aggregation and accumulation upon exposure to GM2 and GM3. We hypothesized that increasing ß-hexosaminidase (ß-hex) activity would lead to a reduction in GM2 levels, which in turn, would cause a reduction in Aß aggregation and accumulation. The small molecule OT1001 is a ß-hex-targeted pharmacological chaperone with good bioavailability, blood-brain barrier penetration, high selectivity for ß-hex and low cytotoxicity. Dutch APP(E693Q) transgenic mice accumulate oligomeric Aß as they age, as well as Aß oligomer-dose-dependent anxiety and impaired novel object recognition (NOR). Treatment of Dutch APP(E693Q) mice with OT1001 caused a dose-dependent increase in brain ß-hex levels up to threefold over those observed at baseline. OT1001 treatment was associated with reduced anxiety, improved learning behavior in the NOR task and dramatically reduced GAß accumulation in the subiculum and perirhinal cortex, both of which are brain regions required for normal NOR. Pharmacological chaperones that increase ß-hex activity may be useful in reducing accumulation of certain mutant species of Aß and in preventing the associated behavioral pathology.

Foreshock and aftershocks in simple earthquake models.

Many models of earthquake faults have been introduced that connect Gutenberg-Richter (GR) scaling to triggering processes. However, natural earthquake fault systems are composed of a variety of different geometries and materials and the associated heterogeneity in physical properties can cause a variety of spatial and temporal behaviors. This raises the question of how the triggering process and the structure interact to produce the observed phenomena. Here we present a simple earthquake fault model based on the Olami-Feder-Christensen and Rundle-Jackson-Brown cellular automata models with long-range interactions that incorporates a fixed percentage of stronger sites, or asperity cells, into the lattice. These asperity cells are significantly stronger than the surrounding lattice sites but eventually rupture when the applied stress reaches their higher threshold stress. The introduction of these spatial heterogeneities results in temporal clustering in the model that mimics that seen in natural fault systems along with GR scaling. In addition, we observe sequences of activity that start with a gradually accelerating number of larger events (foreshocks) prior to a main shock that is followed by a tail of decreasing activity (aftershocks). This work provides further evidence that the spatial and temporal patterns observed in natural seismicity are strongly influenced by the underlying physical properties and are not solely the result of a simple cascade mechanism.

Membranes Matter: Preventing Ammonia Crossover during Electrochemical Ammonia Synthesis.

The electrochemical nitrogen and nitrate reduction reactions (E-NRR and E-NO3RR) promise to provide decentralized and fossil-fuel-free ammonia synthesis, and as a result, E-NRR and E-NO3RR research has surged in recent years. Membrane NH3/NH4+ crossover during E-NRR and E-NO3RR decreases Faradaic efficiency and thus the overall yield. During catalyst evaluation, such unaccounted-for crossover results in measurement error. Herein, several commercially available membranes were screened and evaluated for use in ammonia-generating electrolyzers. NH3/NH4+ crossover of the commonly used cation-exchange membrane (CEM) Nafion 212 was measured in an H-cell architecture and found to be significant. Interestingly, some anion exchange membranes (AEMs) show negligible NH4+ crossover, addressing the problem of measurement error due to NH4+ crossover. Further investigation of select membranes in a zero-gap gas diffusion electrode (GDE)-cell determines that most membranes show significant NH3 crossover when the cell is in an open circuit. However, uptake and crossover of NH3 are mitigated when -1.6 V is applied across the GDE-cell. The results of this study present AEMs as a useful alternative to CEMs for H-cell E-NRR and E-NO3RR electrolyzer studies and present critical insight into membrane crossover in zero-gap GDE-cell E-NRR and E-NO3RR electrolyzers.

Ergodicity breaking in geometric Brownian motion.

Geometric Brownian motion (GBM) is a model for systems as varied as financial instruments and populations. The statistical properties of GBM are complicated by nonergodicity, which can lead to ensemble averages exhibiting exponential growth while any individual trajectory collapses according to its time average. A common tactic for bringing time averages closer to ensemble averages is diversification. In this Letter, we study the effects of diversification using the concept of ergodicity breaking.

Liquid to solid nucleation via onion structure droplets.

We study homogeneous nucleation from a deeply quenched metastable liquid to a spatially modulated phase. We find, for a general class of density functional theories, that the universally favored nucleating droplet in dimensions d ≥ 3 is spherically symmetric with radial modulations resembling the layers of an onion. The existence of this droplet has important implications for systems with effective long-range interactions, and potentially applies to polymers, plasmas, and metals.

Cluster scaling and critical points: A cautionary tale.

Many systems in nature are conjectured to exist at a critical point, including the brain and earthquake faults. The primary reason for this conjecture is that the distribution of clusters (avalanches of firing neurons in the brain or regions of slip in earthquake faults) can be described by a power law. Because there are other mechanisms such as 1/f noise that can produce power laws, other criteria that the cluster critical exponents must satisfy can be used to conclude whether or not the observed power-law behavior indicates an underlying critical point rather than an alternate mechanism. We show how a possible misinterpretation of the cluster scaling data can lead one to incorrectly conclude that the measured critical exponents do not satisfy these criteria. Examples of the possible misinterpretation of the data for one-dimensional random site percolation and the one-dimensional Ising model are presented. We stress that the interpretation of a power-law cluster distribution indicating the presence of a critical point is subtle and its misinterpretation might lead to the abandonment of a promising area of research.

New approach to Gutenberg-Richter scaling.

We introduce a new model for an earthquake fault system that is composed of noninteracting simple lattice models with different levels of damage denoted by q. The undamaged lattice models (q=0) have Gutenberg-Richter scaling with a cumulative exponent ß=1/2, whereas the damaged models do not have well defined scaling. However, if we consider the "fault system" consisting of all models, damaged and undamaged, we get excellent scaling with the exponent depending on the relative frequency with which faults with a particular amount of damage occur in the fault system. This paradigm combines the idea that Gutenberg-Richter scaling is associated with an underlying critical point with the notion that the structure of a fault system also affects the statistical distribution of earthquakes. In addition, it provides a framework in which the variation, from one tectonic region to another, of the scaling exponent, or b value, can be understood.

[Development of an emergency room algorithm for treatment of multiple trauma. Wolfsburg model]. / Entwicklung eines Schockraumalgorithmus für die Polytraumaversorgung. "Wolfsburger Modell."

Within the framework of restructuring for the certification to a regional trauma centre of the DGU (German Society for Casualty Surgery), a uniform algorithm for multiple trauma was developed in the medical centre of Wolfsburg. The Wolfsburg multiple trauma algorithm is based on ATLS (advanced trauma life support) with integration of FAST (focused assessment with sonography for trauma), as well as the white paper of the DGU and regional-specific features. Thus structural, instrumental, organizational and personnel conditions were created to improve the care of multiply traumatized patients even further. The conditions for transition to a regional trauma centre of the DGU were confirmed by a successful audit.

Mean-field theory of an asset exchange model with economic growth and wealth distribution.

We develop a mean-field theory of the growth, exchange, and distribution (GED) model introduced by Liu et al. [K. K. L. Liu et al., preceding paper, Phys. Rev. E 104, 014150 (2021)10.1103/PhysRevE.104.014150] that accurately describes the phase transition in the limit that the number of agents N approaches infinity. The GED model is a generalization of the yard-sale model in which the additional wealth added by economic growth is nonuniformly distributed to the agents according to their wealth in a way determined by the parameter λ. The model is shown numerically to have a phase transition at λ=1 and be characterized by critical exponents and critical slowing down. Our mean-field treatment of the GED model correctly predicts the existence of the phase transition, a critical slowing down, and the values of the critical exponents and introduces an energy whose probability satisfies the Boltzmann distribution for λ<1, implying that the system is in thermodynamic equilibrium in the limit that N→∞. We show that the values of the critical exponents obtained by varying λ for a fixed value of N do not satisfy the usual scaling laws, but do satisfy scaling if a combination of parameters, which we refer to as the Ginzburg parameter, is much greater than one and is held constant. We discuss possible implications of our results for understanding economic systems and the subtle nature of the mean-field limit in systems with both additive and multiplicative noise.

Simulation of a generalized asset exchange model with economic growth and wealth distribution.

The agent-based yard-sale model of wealth inequality is generalized to incorporate exponential economic growth and its distribution. The distribution of economic growth is nonuniform and is determined by the wealth of each agent and a parameter λ. Our numerical results indicate that the model has a critical point at λ=1 between a phase for λ<1 with economic mobility and exponentially growing wealth of all agents and a nonstationary phase for λ≥1 with wealth condensation and no mobility. We define the energy of the system and show that the system can be considered to be in thermodynamic equilibrium for λ<1. Our estimates of various critical exponents are consistent with a mean-field theory [see W. Klein et al., following paper, Phys. Rev. E 104, 014151 (2021)10.1103/PhysRevE.104.014151]. The exponents do not obey the usual scaling laws unless a combination of parameters that we refer to as the Ginzburg parameter is held fixed as the phase transition is approached. The model illustrates that both poorer and richer agents benefit from economic growth if its distribution does not favor the richer agents too strongly. This work and the following theoretical paper contribute to our understanding of whether the methods of equilibrium statistical mechanics can be applied to economic systems.

Lymphocyte-mediated cytotoxicity in vitro. Effect of enhancing antisera.

The ability of antisera to suppress immune responses either in vivo or in vitro is well known. A variety of lymphocyte-target cell systems have been employed to demonstrate inhibition of cell-mediated immunity by antisera in vitro, and skin, tumor, and kidney graft survival have been prolonged by passively administered antiserum in vivo. An in vitro lymphocyte-tumor cell assay system was developed for the purpose of studying the effects of enhancing antisera (in vivo) on lymphocyte-mediated cytotoxicity in vitro. The characteristics of this system with respect to route of immunization, time of harvest of immune cells, lymphocyte:tumor cell ratio, and effect of nonimmune or nonspecifically immune lymphoid cells are presented. Sera capable of enhancement in vivo were tested in this system and shown to inhibit cell-mediated immunity in vitro. Further, in both instances the immunosuppressive effect is mediated by antigen-antibody complexes and not by free antibody alone. Experiments were also carried out to determine the site of action of these suppressive antigen-antibody complexes. Presensitized lymphocytes were exposed to antigen-antibody complexes, washed, and then allowed to interact with fresh tumor cells (not antibody treated). Lymphocytes treated in this manner are incapable of exhibiting cell-mediated immunity in vitro. This evidence supports the concept that the antigen-antibody complexes have a direct immunosuppressive effect on the lymphocyte.

Nuclear fluorescence employing antinucleoside immunoglobulins.

Fluoresceinated antinucleoside globulins were shown to react with the nuclei of L cells. The pattern of nuclear fluorescence was similar to the distribution of nuclear DNA. This reaction was shown to be specific by the following control experiments: 1. Absorption of the specific antibody from an antiadenosine globulin eliminated all fluorescence. 2. Treatment of the cells with nonfluorescent antiadenosine globulin, followed by staining with the fluorescent antiadenosine eliminated almost all of the fluorescence of the nucleus. 3. Treatment of the cells with DNase destroyed the ability of the nucleus to react with antiuridine fluorescent antibodies. 4. Fluoresceinated anti-BSA did not produce nuclear fluorescence. Nuclear fluorescence occurred only in cells harvested during the period of maximum DNA synthesis as measured by the uptake of thymidine. This correlates with the previously demonstrated specificity of the antibodies for denatured DNA.

MCAK is present at centromeres, midspindle and chiasmata and involved in silencing of the spindle assembly checkpoint in mammalian oocytes.

Mitotic centromere-associated kinesin (MCAK) is an ATP-dependent microtubule (MT) depolymerase regulated by Aurora kinase (AURK) phosphorylation and implicated in resolution of improper MT attachments in mitosis. Distribution of MCAK was studied in oocyte maturation by anti-MCAK antibody, anti-tubulin antibody, anti-AURKB antibody and anti-centromere antibody (ACA) and by the expression of MCAK-enhanced green fluorescent protein fusion protein in maturing mouse oocytes. Function was assessed by knockdown of MCAK and Mad2, by inhibiting AURK or the proteasome, by live imaging with polarization microscope and by chromosomal analysis. The results show that MCAK is transiently recruited to the nucleus and transits to spindle poles, ACA-positive domains and chiasmata at prometaphase I. At metaphase I and II, it is present at centrosomes and centromeres next to AURKB and checkpoint proteins Mad2 and BubR1. It is retained at centromeres at telophase I and also at the midbody. Knockdown of MCAK causes a delay in chromosome congression but does not prevent bipolar spindle assembly. MCAK knockdown also induces a meiosis I arrest, which is overcome by knockdown of Mad2 resulting in chiasma resolution, chromosome separation, formation of aberrant meiosis II spindles and increased hypoploidy. In conclusion, MCAK appears to possess a unique distribution and function in oocyte maturation. It is required for meiotic progression from meiosis I to meiosis II associated with silencing of the spindle assembly checkpoint. Alterations in abundance and activity of MCAK, as implicated in aged oocytes, may therefore contribute to the loss of control of cell cycle and chromosome behaviour, thus increasing risk for errors in chromosome segregation and aneuploidy.

Penile and preputial tumours in the horse: literature review and proposal of a standardised approach.

Penile and preputial tumours are not uncommon in the horse, but can cause discomfort and lead to serious complications. Several types of tumour of the male external genitalia have been described. The most common type is the squamous cell carcinoma (SCC), which is found mainly in older horses. Reports of a breed predilection for penile tumour formation are equivocal, but castration, coat colour, poor hygiene and various infectious agents have all been suggested to predispose to the development of some types of tumour (e.g. SCC, papilloma and melanoma). Careful assessment of the primary tumour is an important first step in the design of an optimal treatment protocol. Invasiveness, differentiation grade, tumour size and presence of metastases are all relevant to the decision to pursue additional diagnostic procedures or specific treatment options. To date, no standard protocol has been reported for the approach to penile tumours in the horse and treatments range from minimally invasive therapies (e.g. topical use of 5-fluorouracil) to radical surgical interventions (e.g. en bloc penile and preputial resection with penile retroversion). Completeness of removal of the neoplasm and therefore risk of recurrence is highly dependent on the type of therapy chosen. However, the size and histopathological features of the primary tumour are also important factors with respect to the likelihood of recurrence. This review describes the most common penile and preputial neoplasms in the horse, and outlines a standard protocol aimed at arriving at a specific diagnosis and tailoring the therapeutic approach accordingly.