bluuebunny/crossref_metadata_2025 huggingface dataset:
Global Evaluation of Seasonal Precipitation and Temperature Forecasts from NMME
Authors: Roy Tirthankar , He Xiaogang , Lin Peirong , Beck Hylke E. , Castro Christopher , Wood Eric F.
Published: August 2020

We present a comprehensive global evaluation of monthly precipitation and temperature forecasts from 16 seasonal forecasting models within the NMME Phase-1 system, using Multi-Source Weighted-Ensemble Precipitation version 2 (MSWEP-V2; precipitation) and Climate Research Unit TS4.01 (CRU-TS4.01; temperature) data as reference. We first assessed the forecast skill for lead times of 1–8 months using Kling–Gupta efficiency (KGE), an objective performance metric combining correlation, bias, and variability. Next, we carried out an empirical orthogonal function (EOF) analysis to compare the spatiotemporal variability structures of the forecasts. We found that, in most cases, precipitation skill was highest during the first lead time (i.e., forecast in the month of initialization) and rapidly dropped thereafter, while temperature skill was much higher overall and better retained at higher lead times, which is indicative of stronger temporal persistence. Based on a comprehensive assessment over 21 regions and four seasons, we found that the skill showed strong regional and seasonal dependencies. Some tropical regions, such as the Amazon and Southeast Asia, showed high skill even at longer lead times for both precipitation and temperature. Rainy seasons were generally associated with high precipitation skill, while during winter, temperature skill was low. Overall, precipitation forecast skill was highest for the NASA, NCEP, CMC, and GFDL models, and for temperature, the NASA, CFSv2, COLA, and CMC models performed the best. The spatiotemporal variability structures were better captured for precipitation than temperature. The simple forecast averaging did not produce noticeably better results, emphasizing the need for more advanced weight-based averaging schemes.
Turbulence Asymmetries in Bottom Boundary Layer Velocity Pulses Associated with Onshore-Propagating Nonlinear Internal Waves
Authors: Becherer Johannes , Moum James N. , Colosi John A. , Lerczak James A. , McSweeney Jacqueline M.
Published: August 2020

The inner shelf is a region inshore of that part of the shelf that roughly obeys Ekman dynamics and offshore of the surf zone. Importantly, this is where surface and bottom boundary layers are in close proximity, overlap, and interact. The internal tide carries a substantial amount of energy into the inner shelf region were it eventually dissipates and contributes to mixing. A part of this energy transformation is due to a complex interaction with the bottom, where distinctions between nonlinear internal waves of depression and elevation are blurred, indeed, where polarity reversals of incoming waves take place. From an intensive set of measurements over the inner shelf off central California, we identify salient differences between onshore pulses from waves with properties of elevation waves and offshore pulses from shallowing depression waves. While the velocity structures and amplitudes of on/offshore pulses 1 m above the seafloor are not detectably different, onshore pulses are both more energetically turbulent and carry more sediments than offshore pulses. Their turbulence is also oppositely skewed: onshore pulses slightly to the leading edges, offshore pulses to the trailing edges of the pulses. We consider in turn three independent mechanisms that may contribute to the observed asymmetry: propagation in adverse pressure gradients and the resultant inflection point instability, residence time of a fluid parcel in the pulse, and turbulence suppression by stratification. The first mechanism may largely explain higher turbulence in the trailing edge of offshore pulses. The extended residence time may be responsible for the high and more uniform turbulence distribution across onshore compared to offshore pulses. Stratification does not play a leading role in turbulence modification inside of the pulses 1 m above the bed.
Surface Drift Currents Induced by Waves and Wind in a Large Tank
Authors: Polnikov Vladislav , Qiao Fangli , Ma Hongyu
Published: August 2020

The empirical features of surface drift currents induced by both mechanical and wind waves are presented. The measurements were made by using surface floats in a large tank with dimensions of 32.5 × 1 × 2 m3. Three cases were studied: (i) regular (narrowband) mechanical waves, (ii) irregular (wideband) mechanical waves, and (iii) wind waves. The measured surface drift currents induced by mechanical waves Ud are compared with the Stokes drift at the surface USt estimated by a well-known formula with an integral over the wave spectrum. In this case, the ratio Ud/USt varies in the range of 0.5–0.93 and slightly increases with decreasing wave steepness. No visible dependence on the breaking intensity is observed. In the case of wind waves, the wind-induced part of the surface drift Udw is compared with the friction velocity u*. In our measurements, the ratio Udw/u* varies systematically in the range of 0.65–1.2. Considering the percentage of wave breaking Br, the wave age A, and the wave steepness Ϭ, the parameterization of Udw was obtained in the form Udw = (Br + ϬA)u*, which corresponds to the observations with a mean error of 10%. For the first time, this ratio provides the dependence of wind-induced drift on the surface wave parameters. The obtained results and problems related to measuring surface drift currents are discussed.
Improving Nonlinear and Nonhydrostatic Ocean Lee Wave Drag Parameterizations
Authors: Mayer Frederick T. , Fringer Oliver B.
Published: August 2020

Ocean lee waves occur on length scales that are smaller than the grid scale of global circulation models (GCMs). Therefore, such models must parameterize the drag associated with launching lee waves. This paper compares the lee wave drag predicted by existing parameterizations with the drag measured in high-resolution nonhydrostatic numerical simulations of a lee wave over periodic sinusoidal bathymetry. The simulations afford a time-varying glimpse at the nonlinear and nonhydrostatic oceanic lee wave spinup process and identify a characteristic time scale to reach steady state. The maximum instantaneous lee wave drag observed during the spinup period is found to be well predicted by linear lee wave theory for all hill heights. In steady state, the simulations demonstrate the applicability of parameterizing the drag based on applying linear theory to the lowest overtopping streamline of the flow (LOTS), as is currently employed in GCMs. However, because existing parameterizations are based only on the height of the LOTS, they implicitly assume hydrostatic flow. For hills tall enough to trap water in their valleys, the simulations identify a set of nonhydrostatic processes that can result in a reduction of the lee wave drag from that given by hydrostatic parameterizations. The simulations suggest implementing a time-dependent nonhydrostatic version of the LOTS-based parameterization of lee wave drag and demonstrate the remarkable applicability of linear lee wave theory to oceanic lee waves.
Correcting Biases in Historical Bathythermograph Data Using Artificial Neural Networks
Authors: Bagnell Aaron , DeVries Timothy
Published: August 2020

Historical estimates of ocean heat content (OHC) are important for understanding the climate sensitivity of the Earth system and for tracking changes in Earth’s energy balance over time. Prior to 2004, these estimates rely primarily on temperature measurements from mechanical and expendable bathythermograph (BT) instruments that were deployed on large scales by naval vessels and ships of opportunity. These BT temperature measurements are subject to well-documented biases, but even the best calibration methods still exhibit residual biases when compared with high-quality temperature datasets. Here, we use a new approach to reduce biases in historical BT data after binning them to a regular grid such as would be used for estimating OHC. Our method consists of an ensemble of artificial neural networks that corrects biases with respect to depth, year, and water temperature in the top 10 m. A global correction and corrections optimized to specific BT probe types are presented for the top 1800 m. Our approach differs from most prior studies by accounting for multiple sources of error in a single correction instead of separating the bias into several independent components. These new global and probe-specific corrections perform on par with widely used calibration methods on a series of metrics that examine the residual temperature biases with respect to a high-quality reference dataset. However, distinct patterns emerge across these various calibration methods when they are extrapolated to BT data that are not included in our cross-instrument comparison, contributing to uncertainty that will ultimately impact estimates of OHC.
Impact of Synthetic Arctic Argo-Type Floats in a Coupled Ocean–Sea Ice State Estimation Framework
Authors: Nguyen An T. , Heimbach Patrick , Garg Vikram V. , Ocaña Victor , Lee Craig , Rainville Luc
Published: August 2020

The lack of continuous spatial and temporal sampling of hydrographic measurements in large parts of the Arctic Ocean remains a major obstacle for quantifying mean state and variability of the Arctic Ocean circulation. This shortcoming motivates an assessment of the utility of Argo-type floats, the challenges of deploying such floats due to the presence of sea ice, and the implications of extended times of no surfacing on hydrographic inferences. Within the framework of an Arctic coupled ocean–sea ice state estimate that is constrained to available satellite and in situ observations, we establish metrics for quantifying the usefulness of such floats. The likelihood of float surfacing strongly correlates with the annual sea ice minimum cover. Within the float lifetime of 4–5 years, surfacing frequency ranges from 10–100 days in seasonally sea ice–covered regions to 1–3 years in multiyear sea ice–covered regions. The longer the float drifts under ice without surfacing, the larger the uncertainty in its position, which translates into larger uncertainties in hydrographic measurements. Below the mixed layer, especially in the western Arctic, normalized errors remain below 1, suggesting that measurements along a path whose only known positions are the beginning and end points can help constrain numerical models and reduce hydrographic uncertainties. The error assessment presented is a first step in the development of quantitative methods for guiding the design of observing networks. These results can and should be used to inform a float network design with suggested locations of float deployment and associated expected hydrographic uncertainties.
A Spherical Temperature Sensor Array Design for Near-Surface Atmospheric Temperature Studies
Authors: Yang Jie , Liu Qingquan , Ding Feng , Ding Renhui
Published: August 2020

The observation accuracy of the surface air temperature less than 0.1 K is a requirement, stated by the meteorological and climatological community. However, the accuracy of a temperature sensor inside a shield is affected by a number of factors including solar radiation, wind speed, upwelling longwave radiation, air density, sun elevation angle, sun azimuth angle, underlying surface, precipitation, moisture, structure, and coating of the radiation shield. Due to these factors, the temperature error of the temperature sensor may be much larger than 1 K under adverse conditions. To improve the observation accuracy, this paper proposed a spherical temperature sensor array. A series of analytical calculations based on a computational fluid dynamics (CFD) method is performed to verify the design principle of this sensor array. The calculation results show that the temperature error ratio can be assumed as a constant. To verify the accuracy of this sensor array, simulations and observation experiments are conducted. The simulation results show that the mean difference between the temperature provided by this sensor array and the reference air temperature is 0.072 K. The field experiment results show that a root-mean-square error (RMSE) and a mean absolute error (MAE) between the temperature provided by this sensor array and the reference air temperature are 0.173 and 0.153 K, respectively.
Assessment of ECMWF Subseasonal Temperature Predictions for an Anomalously Cold Week Followed by an Anomalously Warm Week in Central and Southeastern South America during July 2017
Authors: Alvarez M. S. , Coelho C. A. S. , Osman M. , Firpo M. Â. F. , Vera C. S.
Published: August 2020

The demand of subseasonal predictions (from one to about four weeks in advance) has been considerably increasing as these predictions can potentially help prepare for the occurrence of high-impact events such as heat or cold waves that affect both social and economic activities. This study aims to assess the subseasonal temperature prediction quality of the European Centre for Medium-Range Weather Forecasts (ECMWF) against the Japan Meteorological Agency reanalyses. Two consecutive weeks of July 2017 were analyzed, which presented anomalously cold and warm conditions over central South America. The quality of 20 years of hindcasts for the two investigated weeks was compared to that for similar weeks during the JJA season and of 3 years of real-time forecasts for the same season. Anomalously cold temperatures observed during the week of 17–23 July 2017 were well predicted one week in advance. Moreover, the warm anomalies observed during the following week of 24–30 July 2017 were well predicted two weeks in advance. Higher linear association and discrimination (ability to distinguish events from nonevents), but reduced reliability, was found for the 20 years of hindcasts for the target week than for the hindcasts produced for all of the JJA season. In addition, the real-time forecasts showed generally better performance over some regions of South America than the hindcasts. The assessment provides robust evidence about temperature prediction quality to build confidence in regional subseasonal forecasts as well as to identify regions in which the predictions have better performance.
The Relationship between the Madden–Julian Oscillation and Tropical Cyclone Rapid Intensification
Authors: Aberson Sim D. , Kaplan J.
Published: August 2020

The relationship between the Madden–Julian oscillation (MJO) and tropical cyclone rapid intensification in the northern basins of the Western Hemisphere is examined. All rapid intensification events in the part of the Western Hemisphere north of the equator and the MJO phase and amplitude are compiled from 1974 to 2015. Rapid intensification events and the MJO tend to move in tandem with each other from west to east across the hemisphere, though rapid intensification appears most likely during a neutral MJO phase. The addition of this information to an operational statistical rapid intensification forecasting scheme does not significantly improve forecasts.
Psychoanalysis and the Maltreatment of Children
Authors: Steele Brandt F.
Published: August 2020

This essay presents some of the ideas derived from 30 years of observing and treating abused children and those who abuse them. Although most of these patients have not been in what could be called classical analysis, psychoanalytic principles have been crucially important in understanding their behavior and psychodynamics. I also believe that the study of their life histories can often enhance and sometimes broaden many of our psychoanalytic concepts, especially of ego and superego development and expresssion.
Establishing Trauma: The Difficulty Distinguishing between Memories and Fantasies
Authors: Spector Person Ethel , Klar Howard
Published: August 2020

This paper is intended as a contribution to understanding why, up until recently, there have been so few case reports of actual abuse and its sequelae in the psychoanalytic literature. We suggest that psychoanalytic insights into the nature of psychic reality, while indispensable to the evolution of psychoanalytic thinking, have nonetheless had the adverse effect of collapsing any distinction between unconscious fantasies and repressed memories. Moreover, the idea that knowledge of external reality is itself mentally constructed also has diminished interest in uncovering trauma and “real” history. We present a report of an adult analysis that illustrates the recovery of a dissociated memory of sexual abuse that occurred during adolescence, as a springboard to discuss problems analysts have had in dealing with trauma theoretically. We hypothesize that repressed memories and conscious fantasies can often be distinguished insofar as they may be “stored” or encoded differently, and that consequently the sequelae of trauma and fantasy often, but not always, can be disentangled. We describe some different modes of encoding trauma and some different ways of remembering, reexperiencing, and reenacting it. And, finally, we suggest why traumatic memories are increasingly accessible to patients today.
Addictive Sexual Behavior
Authors: Myers Wayne A.
Published: August 2020

Case material is presented from two patients suffering from addictive sexual behavior. The term addiction is used because of the intense, driven quality of the behavior and because of its mood-elevating effects.

Psychodynamically, the patients’ sexual acts helped to undo feelings of rejection at the hands of their mothers and to enhance feelings of lovability and of self-esteem. The behavior also helped to neutralize powerful feelings of rage toward the mother. In one patient, the acts also helped to ease inner turmoil related to an underlying attention deficit disorder. I speculate that some adults with addictive sexual behavior may have underlying attention deficit disorders. In both my patients, the sexual behaviors served the self-regulatory function of alleviating inner feelings of anhedonia and depression. When they decreased their sexual activities during the course of the treatment, they required adjunctive antidepressant medication. The underlying meaning of the medication and countertransference attitudes toward such patients are explored.
Attitudes and Experiences of Psychoanalysts in Analyzing Homosexual Patients
Authors: Macintosh Houston
Published: August 2020

In response to a survey, 285 psychoanalysts reported having analyzed 1215 homosexual patients, resulting in 23 percent changing to heterosexuality and 84 percent receiving significant therapeutic benefit. Various statistics and individual comments are reported. Virtually all of the respondents rejected the idea that a homosexual patient in analysis “can and should” change to heterosexuality, although 17 percent had changed their opinion during the last 10 years. Over a third believed that most other psychoanalysts hold this opinion even though they themselves do not. The contention of some gay activists that “traditionally trained” psychoanalysts harm and “abuse” their patients is examined and rejected.
Machine Learning in Laryngoscopy Analysis: A Proof of Concept Observational Study for the Identification of Post-Extubation Ulcerations and Granulomas
Authors: Parker Felix , Brodsky Martin B. , Akst Lee M. , Ali Haider
Published: August 2020

Objective:

Computer-aided analysis of laryngoscopy images has potential to add objectivity to subjective evaluations. Automated classification of biomedical images is extremely challenging due to the precision required and the limited amount of annotated data available for training. Convolutional neural networks (CNNs) have the potential to improve image analysis and have demonstrated good performance in many settings. This study applied machine-learning technologies to laryngoscopy to determine the accuracy of computer recognition of known laryngeal lesions found in patients post-extubation.

Methods:

This is a proof of concept study that used a convenience sample of transnasal, flexible, distal-chip laryngoscopy images from patients post-extubation in the intensive care unit. After manually annotating images at the pixel-level, we applied a CNN-based method for analysis of granulomas and ulcerations to test potential machine-learning approaches for laryngoscopy analysis.

Results:

A total of 127 images from 25 patients were manually annotated for presence and shape of these lesions—100 for training, 27 for evaluating the system. There were 193 ulcerations (148 in the training set; 45 in the evaluation set) and 272 granulomas (208 in the training set; 64 in the evaluation set) identified. Time to annotate each image was approximately 3 minutes. Machine-based analysis demonstrated per-pixel sensitivity of 82.0% and 62.8% for granulomas and ulcerations respectively; specificity was 99.0% and 99.6%.

Conclusion:

This work demonstrates the feasibility of machine learning via CNN-based methods to add objectivity to laryngoscopy analysis, suggesting that CNN may aid in laryngoscopy analysis for other conditions in the future.
Book review: Jean A. Berlie (Ed.), China’s Globalization and the Belt and Road Initiative
Authors: Amarasinghe Punsara , Rajhans Sanjay Kumar
Published: August 2020

Jean A. Berlie (Ed.), China’s Globalization and the Belt and Road Initiative. (London, Palgrave Macmillan, 2020), pp. 342, €88.39, ISBN: 978-3-030-22289-5
Fertility Technology Research and the Use of Human Beings as Property
Authors: Jones-Nosacek Cynthia
Published: August 2020

In January 2020, an article in the Journal of Human Reproduction exploring whether human embryos could be obtained via uterine lavage and to compare their quality to embryos created via in vitro fertilization. Any embryo that was not removed via lavage was either prevented from implanting by giving the women injections of gonadotropin releasing hormone antagonists or aborted with either methotrexate or uterine curettage. This research was done using women in Mexico, who were paid the equivalent of over two months’ wages and who signed away their rights to their embryos, including agreeing to have an abortion if implantation did occur. Not only is this another instance of human beings being treated as property but is against the dignity of these women by turning them into, as one ethicist says, “human petri dishes.”

Researchers continue to use people as objects to obtain their goals. In this case, it was poor women in Mexico and their embryos. The Editors of Journal of Human Reproduction enabled this by publishing the report.
What Kind of Dignity?
Authors: Smith Janet E.
Published: August 2020

We tend to think that “dignity” means that someone is sophisticated and well-mannered or that human dignity points to great achievements. There is, though, a special dignity in those who are vulnerable for they provide a focal point for love and generally respond enthusiastically to that love; they draw love out of others.
Keep Them Apart or Join Them Together? How Identification Processes Shape Orientations to Network Brokerage
Authors: Endacott Camille G. , Leonardi Paul M.
Published: August 2020

This article investigates how the targets with which brokers identify shape the orientation with which they approach their network position. Brokers are often thought of as exhibiting a tertius gaudens orientation toward their network position through their efforts to keep disconnected groups apart, thereby maintaining their ability to control the flow of information between the groups. However, brokers may also exhibit a tertius iungens orientation if they make decisions to join disconnected groups together, bridging structural holes and enabling information to flow freely between them. Drawing on data from an in-depth field study, this article shows that when brokers identify with their community of practice or their profession, they are more likely to exhibit a tertius iungens orientation than when brokers identify with personal or workgroup targets. The qualitative data suggest that this relationship between identification with targets and brokerage orientation was guided by the rules and resources of the identities they enacted. The targets with which brokers identified shaped how they took perspectives in their work and the flexibility with which they enacted their role, which in turn shaped their decisions about whether to join people together or to keep them apart.
Transoral Endoscopic Thyroidectomy via Vestibular Approach With 4 Trocars: A New Technique
Authors: Ngo Duy Quoc , Tran Toan Duc , Ngo Quy Xuan , Van Le Quang
Published: August 2020

Objectives:

The objective of this study was to report the feasibility and safety of a novel 4-trocar approach for transoral endoscopic thyroidectomy via the vestibular.

Methods:

In this study, we first used 4 trocars via vestibular area to perform transoral endoscopic thyroidectomy. We reported the safety and surgical feasibility of transoral endoscopic thyroidectomy using a 4-trocar technique in our institute from February 1, 2020, to May 10, 2020.

Results:

Transoral endoscopic thyroidectomy via the vestibular approach using 4 trocars was carried out in 5 patients. No complications such as bleeding, mental nerve injury, recurrent laryngeal nerve injury, or hypoparathyroidism were reported. All patients were completely satisfied with the cosmetic results.

Conclusions:

Transoral endoscopic thyroidectomy with 4 trocars via vestibular approach is an effective and feasible method. Markedly, this technique can assist surgeons to expose and preserve both parathyroid glands and recurrent laryngeal nerve easily when performing transoral endoscopic thyroidectomy.
Delayed-Onset NOG Gene-Related Syndromic Conductive Deafness: A Case Report
Authors: Sun Huiying , Qiao Yufei , Chen Na , Yang Hua , Gao Zhiqiang , Shang Yingying
Published: August 2020

We report a 6-year-old girl with progressive bilateral conductive hearing loss for 2 years. She passed the newborn hearing screening conducted with otoacoustic emissions testing and had a normal development of speech and language, which indicated that her deafness was delayed-onset. She also had congenital proximal interphalangeal joints. Proximal symphalangism was confirmed by genetic testing ( NOG gene: c.406C > T, p.R136C). Bilateral stapes ankyloses were proved by surgery and her hearing was improved after stapedotomy by over 30 dB. Besides, this case should remind clinicians to carefully distinguish NOG gene-related deafness from congenital ossicular malformation and pediatric otosclerosis.
Primary Combined Small-Cell and Squamous Cell Carcinoma of the Supraglottis: Case Report and Literature Review
Authors: Cox Eric L. , Lepoudre Christine , Schwartz Erich
Published: August 2020

Combined small-cell carcinoma and squamous cell carcinoma of the larynx is an exquisitely rare and underreported primary tumor the head and neck region, with an English literature review revealing only 17 documented cases. There is limited information on how best to treat these patients oncologically, given the low number of reported cases. A subset of the reported cases also detail a unique local spread of this combined carcinoma, further obscuring the clinical picture of these patients. Here, we detail an 18th case, with nodal metastasis of only one component of the primary tumor, and discuss the published literature surrounding this etiology.
Swim Program Pilot for Children with Autism: Impact on Behaviors and Health
Authors: Johnson Norah L. , Bekhet Abir K. , Karenke Tana , Garnier-Villarreal Mauricio
Published: August 2020

The purpose of this mixed methods pre-/post-pilot intervention study was to assess parental psychological health and child challenging behaviors before and after a swimming program for children with autism. Participants were 10 parent–child dyads. Child’s challenging behaviors were lower in the post testing (Cohen’s d = 0.07–0.45). Mean scores were improved for parent perception of general health (Cohen’s d = 0.22). Three themes emerged from the post swim program focus group: (a) Parent satisfaction with instructors with sub themes (i) firmness (ii) creativity, and (iii) promotion of social interaction and sharing, (b) improved child sleeping, and (c) family dynamics with sub themes (i) siblings wanted to swim and (ii) parents’ fear of drowning. Preliminary results point to improved child behaviors and parent perception of general health. Future studies can focus on expanding the swim program to include all family members.
The Bovine Lens as a Model for Osmotic Cataract
Authors: Marcantonio Julia M.
Published: August 2020

Summary

Bovine lenses, obtained from a commercial slaughterhouse, have been cultured successfully in a completely defined medium, for periods of up to two weeks. In control lenses, transparency is maintained, ionic balance and hydration are normal, and the amino acid L-tyrosine is in a steady state. Synthesis of the lens specific proteins continues throughout the culture period and there is no evidence of crystallin breakdown.

Cultured lenses have been subjected to insult by various substances known to affect membrane function. In each case, ionic balance was disturbed, hydration was increased and there was gradual opacification of the lens. In addition, in the presence of ouabain, amino acid transport was decreased after a delay, while there was a very rapid reduction in protein synthesis.

The cultured lens seems to be a very sensitive system which can be used as a model for investigations of normal function and for in vitro testing.
To What is the Alternative?
Authors: Worden Alastair N.
Published: August 2020

Summary

The value of conventional long-term, carcinogenicity or reproductive studies would in many instances appear to depend upon the “insurance” they are held to provide and upon “no effect” levels, rather than upon the production of adverse effects that can be extrapolated to man. The development of alternatives to such studies necessitates refinement of the latter and the investigation of specific components and mechanisms of toxicity.
Further Investigations on the Ileum Model as a Possible Alternative to In Vivo Eye Irritancy Testing
Authors: Muir C.K.
Published: August 2020

Summary

The concentration of six surfactants required to block spontaneous contractions of rabbit isolated ileum by 50% (EC50) correlated well with in vivo eye irritancy (correlation coefficient -0.996) only when fresh ileum was tested at 35°C. Storage of ileum for 2 hr or 4 hr before testing did not significantly alter the potency of five of the surfactants, but the potency of triethanolamine decyl sulphate (TDS), the only C-10 surfactant tested, was significantly reduced as compared to fresh controls. When tested on fresh ileum at 29°C all the surfactants, except TDS, were more potent at blocking contractions while TDS was significantly less potent.

It is suggested that the penetration barrier to surfactants is considerably more complex than previously envisaged, possibly involving a transport system capable of concentrating TDS, but not the other agents tested.

It would appear that, provided experimental conditions are carefully controlled, the ileum model can yield results which correlate well with in vivo ocular irritancy and as such may provide the basis for the development of a viable screen for irritancy of surfactants and surfactant-based products.
Effects of Fungizone on the In Vitro Cytotoxicity of Other Chemicals
Authors: Horner Steven A. , Shah Minesh K.
Published: August 2020

Summary

Fungizone, the deoxycholate complex of Amphotericin B, is widely used in tissue culture media as a precaution against contamination. However, a number of reports indicate that the polyenes are toxic to certain mammalian cell lines at relatively low concentrations and can potentiate the effects of other chemicals. The effects of Fungizone on the growth of cultured V79 Chinese hamster lung fibroblasts were determined: growth was inhibited at concentrations above 10μg/ml (ID50 = 13μg/ml), but Fungizone did not affect cell growth when present at the concentration recommended for use in tissue culture media (2μg/ml). This concentration of Fungizone was found to significantly increase the growth inhibitory effects of four toxicants with different modes of action; however, this effect is not considered sufficient to invalidate the inclusion of Fungizone in media used in cytotoxicity tests on cultured V79 cells.
Assessment of the Skin Irritancy Potential of Synthetic Detergents (Syndets)
Authors: Dykes P.J. , Williams D.L. , Jenner L.A. , Marks R.
Published: August 2020

Summary

Among the factors which determine the degree of damage to the skin are (a) the resistance of the stratum corneum to the solubilisation of its components, (b) the intrinsic toxicity of the compound, and (c) the susceptibility of the viable cell layers to damage. In this study of the toxicity of syndets we have attempted to compare their properties in vivo and in vitro and relate these to cutaneous irritancy studies in normal volunteers. The “solubilising” effect of a series of syndets has been studied using the forced desquamation technique. Although no differences could be determined in terms of the corneocytes released from the skin surface, the protein solubilised did differ according to the syndet used and a rank order could be obtained. The susceptibility of viable cells to lysis by syndets has been studied in vitro, using human skin fibroblasts. This test system was able to discriminate between the different syndets and gave the same rank order as the in vivo human test. Comparison with the standard cutaneous irritancy test indicated some correlation between the two test systems and the irritancy test. However, the rank order correlation did show some discrepancy, and the use of such test systems as predictors of cutaneous irritancy is still being investigated.
Scientific Procedures on Living Animals: Proposals for Reform of the 1876 Cruelty to Animals Act
Authors: Balls Michael
Published: August 2020

The British Government plans to reform the legislation which has controlled animal experimentation in Britain since 1876. The background to this development is reviewed, the Government proposals are summarised and discussed, and the reactions of various interested parties are reported.
The Effects of Some Non-steroidal Antiinflammatory Drugs on Human Granulopoiesis In Vitro
Authors: Gyte Gillian M.L. , Williams J.R.B.
Published: August 2020

By measuring colony forming units in culture (CFU-C), the effects of the non-steroidal antiinflammatory drugs indoprofen (24mg/1; 39μM), indomethacin (24mg/1; 67μM), and phenylbutazone (12mg/l; 39μM) on human granulopoiesis in vitro were compared with those of chloramphenicol (57mg/l; 176μM) in 18 bone marrow samples. Inhibitions of 10–92% (median 54%) for indoprofen, -13–86% (median 34%) for ibuprofen, 0–86% (median 42%) for indomethacin and -26–75% (median 3%) for phenylbutazone were observed, with chloramphenicol showing inhibitions of 11–100% (median 70%). A further patient, who had developed agranulocytosis during indoprofen treatment, subsequently showed no greater sensitivity to that drug in vitro than the other patients studied. This in vitro technique may be useful in Phase I studies on new drugs.
The Limulus Amoebocyte Lysate Assay for Bacterial Endotoxins
Authors: McCartney A. Christine
Published: August 2020

The Limulus amoeboecyte lysate (LAL) test not only provides a means for the detection and quantitation of endotoxin in parenteral preparations and medical devices to be used for the benefit of man without recourse to the use of animals, but also provides a more precise assay than the traditional rabbit test.
Animals (Scientific Procedures) Act 1986: The Animal Procedures Committee
Authors: Balls Michael
Published: August 2020

A new British Act of Parliament on animal experimentation establishes a statutory body, the Animal Procedures Committee, which will advise the Government on the administration of the Act. The membership of this Committee will reflect the legitimate requirements of biomedical science and animal welfare, and the Committee will have the right to initiate its own investigations, commission research and publish reports. The establishment of this Committee is considered against its historical background and in terms of its significance as reflected in discussions which took place in Parliament during 1985 and 1986.
The Importance of Exposure Period and Cell Type in In Vitro Cytotoxicity Tests
Authors: Riddell R.J. , Panacer D.S. , Wilde S.M. , Clothier R.H. , Balls M.
Published: August 2020

The cytotoxicities of 50 coded chemicals from the FRAME blind trial set were estimated by the FRAME kenacid blue (KB) and Rockefeller neutral red (NR) assay methods after test periods of 24 hours and 72 hours with murine 3T3 fibroblasts.

Results obtained after the two test periods were considered to be similar for 25 of the chemicals, but different for 25 others.

Our results indicate that a test period of 72 hours is more suitable for the assessment of potential cytotoxicity by the KB and NR methods than the 24 hour test period, which is less likely to allow sufficient time for certain chemicals to exert their toxic effects, particularly those that inhibit cell division or affect cell viability through other long-term effects.

A comparison of results obtained by the 72 hour KB method with 3T3 cells and with human BCL-D1 cells indicated that substantially different ID50 values were found for 8 of 48 chemicals.

These results are discussed in terms of the importance of choice of test period, assay method and cell type used in in vitro cytotoxicity tests.
Cytotoxic and Genotoxic Effects of Paracetamol in Cultured Mammalian Cells
Authors: Holme J.A. , Dybing E. , Soderlund E. , Gordon P. , Dahlin D. , Nelson S.
Published: August 2020

Paracetamol may cause liver damage by binding covalently and/or by directly or indirectly oxidising nucleophilic sites on cellular macromolecules. Lipid peroxidation has been postulated as a third alternative or additive mechanism. Under some experimental conditions genotoxic effects have also been observed.
Cytotoxicity of Vanadate on Chinese Hamster Ovary Cells
Authors: Jenssen J. , Syversen T.
Published: August 2020

The cytotoxicity of vanadate was tested in CHO-cells using uptake of neutral red (NR) and the MIT test as indicators. Cells were exposed to 1–500μM monovanadate for 2–72 hours. Cells exposed to 100μM monovanadate caused a 50% reduction in MIT activity measured after 30 hours, while a similar reduction in NR uptake was observed after 16 hours exposure to the same vanadate concentration. Monovanadate also caused a reduction in amount of cellular protein; a 50% reduction was observed after 24 hours exposure to 100μM monovanadate.
Simultaneous Exposure of Cell Cultures to High Hydrostatic Pressure and Chromate
Authors: Syversen T. , Jenssen J.
Published: August 2020

We have used a fibroblast-like cell line (Flow 5000) to investigate the effects of high pressure and chromate effects on cytoskeletal integrity. Pressure (1–150 bar) resulted in a rounding-up of cells, and changes were also observed in F-actin filament organisation. Addition of 1–5μM chromate to the cell culture media disrupted the F-actin fibres. The combined exposure to 100 bar and 1μM chromate for 18 hours caused an increase in the fraction of rounded cells higher than would be expected if the effects were purely additive. To study cell cycle kinetics, we used a rat glioma culture and measured the quenching of 32258 Hoechst fluorescence by bromodeoxyuridine incorporation. Exposure to 1 or 5μM chromate caused a prolongation of the DNA synthesis phase, and the application of high pressure did not affect this process further. When the cells were exposed to 1μM chromate and 100 bar pressure during the early part of cell cycle, we observed a delay in the cell cycle, which was not observed when cells were exposed to pressure or chromate separately.
A Comparison of Different Endpoints in Neuroblastoma Cell Toxicity Tests of Three Heavy Metal Compounds
Authors: Walum E.
Published: August 2020

The cytotoxicities of HgCl2 (MC), CH3Hg Cl (MMC) and (C2H5)3SnCl (TET) were investigated in a mouse neuroblastoma cell line (C1300, clone NB41A3). General cytotoxicity was determined as TD25 and TD50 values in a cell detachment test and a monolayer growth test, respectively. Membrane toxicity was studied as increase in the efflux of tritiated 2-deoxy- D-glucose-6-phosphate from exposed cells, and metabolic effects as inhibition of oxygen consumption. It was found that the general endpoints (detachment and growth) correlated better to both animal and human in vitro toxicity than the more specific endpoints.
Qualitative Differences in Opacification and Thickness of Bovine Cornea In Vitro Induced by Acid, Alkali, Surfactant or Methanol
Authors: Muir Colin K.
Published: August 2020

Bovine corneas incubated at pH 2 for 4.5 hours became opaque but did not thicken. Corneas incubated at pH 12 became opaque and thickened. Removal of epithelium indicated that pH 2 had caused opacity predominantly in the epithelium itself, while pH 12 had predominantly opacified the stroma.

With 5 x 10-3 M of the cationic surfactant, lauryl trimethylammonium bromide, in contact only with the outside (epithelium-side) of the cornea for up to 4 hours, the epithelium opacified but the stroma did not. There was no thickening for the first 2 hours of incubation, but significant thickening thereafter.

Methanol 50% v/v in contact only with the outside of the cornea caused the epithelium to opacify within 2 minutes, but this effect diminished and a profound opacification of stroma developed over 4 hours. Gross thickening to over three times normal had developed after 4 hours of incubation.

The results suggest that opacity can occur without thickening, but that thickening cannot occur without opacity. Opacity may therefore be a more reliable parameter than thickness for indicating toxic responses of the cornea.
The Opacification of the Bovine Isolated Cornea by Surfactants and Other Chemicals—A Process of Protein Denaturation?
Authors: Igarashi Haruyoshi
Published: August 2020

An attempt has been made to determine whether anionic, cationic and non-ionic surfactants and other chemicals opacify the various layers of bovine isolated corneas to the same or to differing degrees. In the intact cornea the opacifying ability of surfactants was in the following order: cationic>anionic>non-ionic. The chemicals tested spanned the range from virtually inactive to very active. However, in the isolated stroma, the anionic surfactants caused considerably more opacity than either the cationic or non-ionic compounds. The results indicate that cationic surfactants primarily opacify the epithelium. It is suggested that opacification of the cornea is due to precipitation of protein in its various layers. The surfactants opacify egg white solutions in the same order of potency as in the cornea, but within the anionic group the order of opacification produced was the reverse of that in the cornea.
Aquatic Pollutants Tested in vitro with Early Passage Fish Cells
Authors: Babich Harvey , Borenfreund Ellen
Published: August 2020

Epithelioid cells derived from fin tissues of bluegill sunfish fingerlings were used at early passage with the neutral red assay to assess the relative cytotoxicities of organochlorine pesticides. These fin cells were able to differentiate between the cytotoxicities of various test agents, although they were less sensitive than were the BF-2 cells, an established fibroblastic cell-line derived from the caudal trunk of bluegill fry. Both the fin epithelioid and the BF-2 fibroblast cells lacked significant xenobiotic metabolising capacity, based on determinations of 7-ethoxycoumarin O-deethylase as the indicator of monooxygenase activities. Such enzymatic activity could not be induced by exposure of the cultures to Arochlor 1254.
Brain Reaggregate Cultures in Neurotoxicological Investigations: Studies with Cholinergic Neurotoxins
Authors: Atterwill Christopher K.
Published: August 2020

The number of neurotoxicants which produce ‘lesions’ in organotypic brain reaggregate cultures in vitro, which correlate with known in vivo actions, is growing. With respect to cholinergic neurones, this includes kainic acid, organophosphorus compounds and, in our hands, ethylcholine mustard aziridinium (ECMA) and aluminium. We have demonstrated that in vitro exposure to low concentrations of ECMA (12.5μM) produces a two-stage lesion in rat whole-brain reaggregate cultures, corresponding to initial direct inhibition of choline acetyltransferase (ChAT), followed by a later loss of cholinergic neurones. Higher concentrations of ECMA (25–50μM) are more generally cytotoxic and also cause lesions in non-cholinergic cerebellar granule neurones in monolayer culture. Aluminium (0.1–0.01mM) similarly reduces ChAT activity in rat whole-brain reaggregate cultures. Both agents may be useful in providing brain cholinergic lesions in vitro analagous to those occurring in types of dementia in vivo. The use of brain reaggregates in a ‘stepwise’ procedure for testing potential neurotoxicants is also described.
Uptake of Sodium Valproate and Effects on GABA Transport in Astroglial Primary Culture
Authors: Nilsson Michael , Hansson Elisabeth , Rönnbäck Lars
Published: August 2020

The sodium salt of valproic acid (VPA) is an antiepileptic drug, which is effective in the treatment of several types of epilepsy. The drug has been postulated to exert its anticonvulsant effects by interaction with GABA-ergic systems in the brain. Results show a high-affinity uptake for sodium valproate in primary astroglial cultures from newborn rat cerebral cortex, with the kinetic parameters Km and Vmax not significantly different from those observed for GABA. This uptake was shown to interact with astroglial GABA transport in culture, with an increased Km value for GABA uptake. Since failure in GABA-ergic systems is postulated to be one of the major factors in the aetiology of epilepsy, it is interesting to note that the transport system for GABA in astrocytes is affected by sodium valproate.
Glial Cells in Primary Cultures Exposed to Mercury and Lead
Authors: Grundt Inger K. , Neskovic Nenad M.
Published: August 2020

Several toxic compounds of heavy metals (triethyllead, lead acetate, methylmercury, mercuric oxide and copper sulphate) stimulate oligodendroglial development in cultures when present at low levels in the culture medium. Studies of methylmercury and triethyllead show that astroglial cells respond to the same doses with an increase in glial fibrillary acidic protein (GFAP) content. Above a critical concentration, the stimulatory effect of a metal ceases, and the compounds begin to express individual toxic effects. We were not able to observe any differences microscopically in the number of microglia in the control and exposed cultures.
Phorbol Esters Stimulate Phospholipase D Activity in C-6 Glioma Cells
Authors: Gustavsson Lena , Lundqvist Christofer , Ailing Christer
Published: August 2020

The effects of phorbol esters on phospholipase D activity were studied in C-6 glioma cells. The cell lipids were prelabelled with [3H]-glycerol or [14C]-arachidonic acid. Phosphatidylethanol was formed during stimulation with 100nM 12-0-tetradecanoylphorbol-13-acetate (TPA), when ethanol was present in the culture medium. After 30 minutes of stimulation, phosphatidylethanol constituted 2.6% of the [3H]-glycerol-labelled lipids. Stimulating the cells with TPA in the absence of ethanol caused a significant increase in labelled phosphatidic acid. This increase was inhibited by ethanol. The present findings demonstrate that TPA stimulates phospholipase D activity in cultured C-6 glioma cells.