Primary Ciliary Dyskinesia Due to Microtubular Defects is Associated with Worse Lung Clearance Index.

PURPOSE: Primary ciliary dyskinesia (PCD) is characterised by repeated upper and lower respiratory tract infections, neutrophilic airway inflammation and obstructive airway disease. Different ultrastructural ciliary defects may affect lung function decline to different degrees. Lung clearance index (LCI) is a marker of ventilation inhomogeneity that is raised in some but not all patients with PCD. We hypothesised that PCD patients with microtubular defects would have worse (higher) LCI than other PCD patients. METHODS: Spirometry and LCI were measured in 69 stable patients with PCD. Age at testing, age at diagnosis, ethnicity, ciliary ultrastructure, genetic screening result and any growth of Pseudomonas aeruginosa was recorded. RESULTS: Lung clearance index was more abnormal in PCD patients with microtubular defects (median 10.24) than those with dynein arm defects (median 8.3, p = 0.004) or normal ultrastructure (median 7.63, p = 0.0004). Age is correlated with LCI, with older patients having worse LCI values (p = 0.03, r = 0.3). CONCLUSION: This study shows that cilia microtubular defects are associated with worse LCI in PCD than dynein arm defects or normal ultrastructure. The patient's age at testing is also associated with a higher LCI. Patients at greater risk of obstructive lung disease should be considered for more aggressive management. Differences between patient groups may potentially open avenues for novel treatments.

COVID, Vulnerability, and the Death of Solidarity: "Who Do We Not Save?"

Solidarity between more and less vulnerable groups is fundamental to an effective public health response to a global pandemic. Yet in the case of COVID-19, a focus on deciding who can and who cannot be protected from harm has shaped the pandemic experience and continues to determine the post-pandemic trajectory of life with SARS-CoV-2. In this paper I discuss how this has affected our understanding and acceptance of solidarity.

The Radiation Environment of Ceres and Implications for Surface Sampling.

Ceres is a large water-rich dwarf planet located within the asteroid belt. Its surface displays evidence of material sourced from a deep subsurface liquid brine layer within recent geologic time, making it a candidate ocean world with possible present-day activity. However, Ceres lacks a substantial atmosphere and likely does not possess a global magnetic field. Therefore, any material emplaced or exposed on the surface will be subject to weathering by charged particles of solar and galactic origin. We have evaluated the effect of charged particle radiation on material within the near-surface of Ceres and find that the timescale for radiation-induced modification and destruction of organics and endogenic material is ∼100 Myr to 1 Gyr within the top 10-20 cm of the surface. Furthermore, we find that the timescale for sterilization of any putative living organisms contained within material at these depths is <500 kyr. Future missions to the surface may therefore consider targeting regions with geologic ages that fall between these two timescales to avoid the risk of backward contamination while ensuring that sampled material is not heavily radiation processed.

Impact heat driven volatile redistribution at Occator crater on Ceres as a comparative planetary process.

Hydrothermal processes in impact environments on water-rich bodies such as Mars and Earth are relevant to the origins of life. Dawn mapping of dwarf planet (1) Ceres has identified similar deposits within Occator crater. Here we show using Dawn high-resolution stereo imaging and topography that Ceres' unique composition has resulted in widespread mantling by solidified water- and salt-rich mud-like impact melts with scattered endogenic pits, troughs, and bright mounds indicative of outgassing of volatiles and periglacial-style activity during solidification. These features are distinct from and less extensive than on Mars, indicating that Occator melts may be less gas-rich or volatiles partially inhibited from reaching the surface. Bright salts at Vinalia Faculae form thin surficial precipitates sourced from hydrothermal brine effusion at many individual sites, coalescing in several larger centers, but their ages are statistically indistinguishable from floor materials, allowing for but not requiring migration of brines from deep crustal source(s).

The varied sources of faculae-forming brines in Ceres' Occator crater emplaced via hydrothermal brine effusion.

Before acquiring highest-resolution data of Ceres, questions remained about the emplacement mechanism and source of Occator crater's bright faculae. Here we report that brine effusion emplaced the faculae in a brine-limited, impact-induced hydrothermal system. Impact-derived fracturing enabled brines to reach the surface. The central faculae, Cerealia and Pasola Facula, postdate the central pit, and were primarily sourced from an impact-induced melt chamber, with some contribution from a deeper, pre-existing brine reservoir. Vinalia Faculae, in the crater floor, were sourced from the laterally extensive deep reservoir only. Vinalia Faculae are comparatively thinner and display greater ballistic emplacement than the central faculae because the deep reservoir brines took a longer path to the surface and contained more gas than the shallower impact-induced melt chamber brines. Impact-derived fractures providing conduits, and mixing of impact-induced melt with deeper endogenic brines, could also allow oceanic material to reach the surfaces of other large icy bodies.

Advanced chemical stability diagrams to predict the formation of complex zinc compounds in a chloride environment.

A chemical stability map is advanced by incorporating ion complexation, solubility, and chemical trajectories to predict ZnO, Zn(OH)2, ZnCO3, ZnCl2, Zn5(CO3)2(OH)6, and Zn5(OH)8Cl2·H2O precipitation as a function of the total Zn content and pH of an NaCl solution. These calculations demonstrate equilibrium stability of solid Zn products often not considered while tracking the consumed and produced aqueous Zn ion species concentrations through chemical trajectories. The effect of Cl-based ligand formation is incorporated into these stability predictions, enabling enhanced appreciation for the local corrosion conditions experienced at the Zn surface in chloride-containing environments. Additionally, the complexation of Cl- with Zn2+ is demonstrated to compete with the formation of solid phases, making precipitation more difficult. The present work also extends the chemical stability diagram derivations by incorporating a Gibbs-Thompson curvature relation to predict the effect of nanoscale precipitate phase formation on species solubility. These thermodynamic predictions correlate well with experimental results for Zn corrosion in full and alternate NaCl immersion, and have far-reaching utility in a variety of fields requiring nanoscale, semiconductor, and/or structural materials.

Landslides on Ceres: Diversity and Geologic Context.

Landslides are among the most widespread geologic features on Ceres. Using data from Dawn's Framing Camera, landslides were previously classified based upon geomorphologic characteristics into one of three archetypal categories, Type 1(T1), Type 2 (T2), and Type 3 (T3). Due to their geologic context, variation in age, and physical characteristics, most landslides on Ceres are, however, intermediate in their morphology and physical properties between the archetypes of each landslide class. Here we describe the varied morphology of individual intermediate landslides, identify geologic controls that contribute to this variation, and provide first-order quantification of the physical properties of the continuum of Ceres's surface flows. These intermediate flows appear in varied settings and show a range of characteristics, including those found at contacts between craters, those having multiple trunks or lobes; showing characteristics of both T2 and T3 landslides; material slumping on crater rims; very small, ejecta-like flows; and those appearing inside of catenae. We suggest that while their morphologies can vary, the distribution and mechanical properties of intermediate landslides do not differ significantly from that of archetypal landslides, confirming a link between landslides and subsurface ice. We also find that most intermediate landslides are similar to Type 2 landslides and formed by shallow failure. Clusters of these features suggest ice enhancement near Juling, Kupalo and Urvara craters. Since the majority of Ceres's landslides fall in the intermediate landslide category, placing their attributes in context contributes to a better understanding of Ceres's shallow subsurface and the nature of ground ice.

Tripartite sequences within and 3' to the sea urchin H2A histone gene display properties associated with a transcriptional termination process.

We have defined a DNA sequence that behaves as an RNA polymerase II termination signal by using the human HeLa cell transient expression system. Surprisingly, this sequence is tripartite, including part of the coding region of the sea urchin H2A histone gene together with two separate sequences in the 3' flanking region of the gene. We demonstrate that this signal functions both in its normal gene environment and also when placed within the human alpha-globin gene. However, we have failed to detect a discrete 3' terminus. Rather, our data indicate the presence of an extremely heterogeneous series of nonpolyadenylated RNAs. These heterogeneous nonpolyadenylated RNAs are stable when transcribed from the intact histone gene but are highly unstable within the human alpha-globin gene. This provides evidence for the role of poly(A) in the stability of mRNA.

Controlling the corrosion and cathodic activation of magnesium via microalloying additions of Ge.

The evolution of corrosion morphology and kinetics for magnesium (Mg) have been demonstrated to be influenced by cathodic activation, which implies that the rate of the cathodic partial reaction is enhanced as a result of anodic dissolution. This phenomenon was recently demonstrated to be moderated by the use of arsenic (As) alloying as a poison for the cathodic reaction, leading to significantly improved corrosion resistance. The pursuit of alternatives to toxic As is important as a means to imparting a technologically safe and effective corrosion control method for Mg (and its alloys). In this work, Mg was microalloyed with germanium (Ge), with the aim of improving corrosion resistance by retarding cathodic activation. Based on a combined analysis herein, we report that Ge is potent in supressing the cathodic hydrogen evolution reaction (reduction of water) upon Mg, improving corrosion resistance. With the addition of Ge, cathodic activation of Mg subject to cyclic polarisation was also hindered, with beneficial implications for future Mg electrodes.

The missing large impact craters on Ceres.

Asteroids provide fundamental clues to the formation and evolution of planetesimals. Collisional models based on the depletion of the primordial main belt of asteroids predict 10-15 craters >400 km should have formed on Ceres, the largest object between Mars and Jupiter, over the last 4.55 Gyr. Likewise, an extrapolation from the asteroid Vesta would require at least 6-7 such basins. However, Ceres' surface appears devoid of impact craters >∼280 km. Here, we show a significant depletion of cerean craters down to 100-150 km in diameter. The overall scarcity of recognizable large craters is incompatible with collisional models, even in the case of a late implantation of Ceres in the main belt, a possibility raised by the presence of ammoniated phyllosilicates. Our results indicate that a significant population of large craters has been obliterated, implying that long-wavelength topography viscously relaxed or that Ceres experienced protracted widespread resurfacing.

The geomorphology of Ceres.

Analysis of Dawn spacecraft Framing Camera image data allows evaluation of the topography and geomorphology of features on the surface of Ceres. The dwarf planet is dominated by numerous craters, but other features are also common. Linear structures include both those associated with impact craters and those that do not appear to have any correlation to an impact event. Abundant lobate flows are identified, and numerous domical features are found at a range of scales. Features suggestive of near-surface ice, cryomagmatism, and cryovolcanism have been identified. Although spectroscopic analysis has currently detected surface water ice at only one location on Ceres, the identification of these potentially ice-related features suggests that there may be at least some ice in localized regions in the crust.

Backbone flexibility and stability of reverse turn conformation in a model system.

Molecular dynamics simulations have been used to study differences in propensity to form a disulfide-bridged turn conformation by peptides with sequence Ac-Cys-Pro-Xaa-Cys-NMe. The calculations were limited to three peptides, with Xaa = Aib, Gly and Val. The experimental differences in propensity (in terms of free energy differences delta delta G degree) were reproduced within 2 kJ/mol. The use of a reduced 1-4 non-bonded interaction potential was tested in this system, but was found to give slightly worse agreement with experiment. The stability of alternate conformations was determined systematically. Type I and II turn conformations of the Aib compound have similar free energy; the Val compound is most stable in a type I turn conformation (by 8 kJ/mol), while the Gly compound is most stable in a type II turn conformation (by 5 kJ/mol). Different backbone conformations were obtained for the valine compound in simulations in solution and in the crystal. It is concluded that turn conformations with psi i+2 near 0, as typically seen in proteins, are stabilized by intramolecular hydrogen bonding in the confined environment. However, when exposed to solvent, hydrogen bonds with water stabilize conformations with larger or smaller values of psi i+2 that are more similar to free energy minima in the isolated, terminally blocked, residue.

When norms normalize: the case of genetic "enhancement".

As the possibility of genetic intervention becomes more concrete, defining and regulating ethically permissible interventions must include a consideration of the implicit as well as explicit consequences. These include the moral implications of defining "enhancement" by reference to a standard of normality. Some authors have called into question the standard ethical concerns about genetic enhancement, but the distinction between enhancing and therapeutic interventions is still structured as relatively unproblematic. However, determining the boundary between therapy and enhancement will have feedback effects on the socially implemented definitions of what counts as normal in human embodiment. Positioning the interface between permissible and nonpermissible interventions at the same place as the boundaries between therapy and enhancement, and between normal and abnormal embodiment, (1) uses biology to justify a moral evaluation, (2) privileges the single standpoint of the genetically canonical person, and (3) enhances the dichotomy between "normal" and "not normal". Assuming that the limit of permissibility along the interventional continuum is coterminous with the definitions of enhancement and of normality, distracts from the work of uncovering the real grounds to setting limits to genetic manipulation.

Suicide by burning.

Of 164 patients admitted to a university hospital burn unit, 15 (9%) had attempted suicide, and 5 of the 15 died. The use of a flammable liquid was the most common method of attempted suicide; the most common psychiatric diagnosis was schizophrenia.

Ratings of videotaped simulated patient interviews and four other methods of evaluating a psychiatry clerkship.

Ratings of videotaped interviews with simulated patients were compared with four other measures commonly used to evaluate medical students during their psychiatry clerkship. Intercorrelations among self-reported attitude change, written examination grade, and student rating of satisfaction with the clerkship suggest that each measures different processes. Low but significant correlations between preceptor ratings of interaction skills and data-gathering skills and process and content scores based on an end-of-course videotaped interview suggest that preceptor ratings and the videotaped interview method evaluated the same skills. The authors conclude that preceptor evaluations supplemented by objective ratings of videotaped interviews show promise for evaluating the development of interviewing skills.

Undergraduate education and recruitment into psychiatry.

From 1969 to 1979 senior medical students from the University of Colorado School of Medicine entered psychiatric residencies at an average rate of 3.8%. The university gradually instituted a series of changes in its undergraduate psychiatric education program for medical students, and the senior class of 1980 was the first to be exposed to all of the changes. In 1980-1982 7.7% of the seniors went into psychiatric residencies. The authors describe the curriculum changes and speculate that more attention to the quality of medical students' psychiatric education at the undergraduate level enhances recruitment into psychiatric residencies.

Training directors' opinions about the psychiatry resident in-training examination (PRITE).

OBJECTIVE: The American College of Psychiatrists conducted research to validate the content outline of the Psychiatry Resident In-Training Examination (PRITE) and to assess what residency training directors think about the examination. METHOD: A mail survey was sent to the 218 psychiatry residency training directors who subscribe to the PRITE. RESULTS: The survey response rate was 70%. A majority of the respondents indicated agreement with the relative emphasis given to each content area in the PRITE (range = 52%-80% agreement). Eighty-one percent of the respondents were strongly in favor of continuing the practice of releasing the examination and the correct responses each year after the examinations have been scored. The majority of the respondents use results on the PRITE for individual resident evaluation and program evaluation (90% and 94%, respectively). Very few respondents use the PRITE results as the sole measure for assessing residents' cognitive competence or use it for marketing their residency programs. CONCLUSIONS: The survey provided strong support for the content areas covered in the PRITE and their relative emphases. The current practice of releasing PRITE items and answers (a main difference between the PRITE and the certification examination of the American Board of Psychiatry and Neurology) was well supported by the survey results. The stated purpose of the PRITE, to provide educationally useful feedback for individuals and groups in the form of comparisons with peers in specific areas of knowledge, was supported by a large majority of the respondents.

How well does the psychiatry residency in-training examination predict performance on the American Board of Psychiatry and Neurology. Part I. Examination?

OBJECTIVE: Scores on the American College of Psychiatrists' Psychiatry Residency In-Training Examination (PRITE) were correlated with scores on the American Board of Psychiatry and Neurology (ABPN) Part I examination in psychiatry. METHOD: Pearson correlations between 1992 PRITE scores and 1994 ABPN Part I psychiatry scores were calculated. Analyses were based on 701 examinees. RESULTS: There was a moderate correlation between scores on the PRITE and ABPN Part I examination in psychiatry and a low correlation of neurology scores. CONCLUSIONS: These correlations were observed even though the two examinations differ in their purposes, content outlines, development, and administration.

Neurotrophin expression modulated by glucocorticoids and oestrogen in immortalized hippocampal neurons.

We have used reverse transcription followed by polymerase chain reaction amplification to investigate changes in expression of nerve growth factor (NGF) mRNA in immortalized hippocampal neurons after treatment with the glucocorticoids dexamethasone and corticosterone, the glucocorticoid antagonist RU38486, and the gonadal steroids progesterone and 17-beta oestradiol. We found that NGF mRNA levels rise after application of either dexamethasone or corticosterone, and that this rise is prevented by the antagonist. Thus, neurotrophin expression is modulated by the physiological glucocorticoid and is mediated by type II glucocorticoid receptors. Progesterone has no effect, while 17-beta oestradiol suppresses NGF mRNA in a postnatally-derived cell line but does not change levels in an embryonic line. An increase in neurotrophin expression is therefore not a general response to steroid hormone application, and may be a specific defence against the presence of metabolically endangering glucocorticoids.

Increased levels of NGF in sera of systemic lupus erythematosus patients.

Using a specific enzyme-linked immunosorbent assay (ELISA) for human nerve growth factor (NGF), serum levels in patients with systemic lupus erythematosus (SLE) were measured. We found a consistent increase in NGF levels in SLE patients compared with controls. A good correlation exists between serum NGF level and severity of clinical manifestation. We hypothesize that NGF might play a role in the pathogenesis of autoimmune disorders such as SLE.