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Brain dissection is typically an important part of teaching neuroscience in health professional programs. This results in the need to effectively remove brains, which is often performed in a gross anatomy laboratory in the same curriculum. The aim of this study was to determine the most effective method of brain removal based on the time required for removal, difficulty of removal, and preservation of key brain structures for educational purposes. Six different dissectors performed each of the three calvaria removal approaches and three different spinal cord transection methods rating them for difficulty and tracking the time required. The combination of calvaria and brainstem approaches and the order of completion was randomized to control for fatigue and previous individual experience. After all brains were removed, each was evaluated by neuroscience faculty for utility in education contexts. The study found little difference between the individual approaches for both calvaria removal and spinal cord transection in regards to quality of outcome. The use of a circumferential cut only proved to be the most time-effective method for calvaria removal while a posterior cut between C1 and C2 was the most time-effective and least difficult method for brainstem release. There was no one technique that proved to be most beneficial across all three measures. However, different approaches resulted in a different combination of benefits across the time, difficulty, and outcome ratings that should be considered in light of the individual needs of any program or researcher.

BACKGROUND: It is well established that unstable shoe constructions with rounded soles have the potential to induce acute and long-term effects on muscle activity during standing and walking. However, it is unresolved whether functional footwear with regularly shaped soles may have similar effects. OBJECTIVE: Thus, the objective of this study was to compare measures of postural control and muscle activity during quiet standing and locomotion for women using a new sandal construction with an unstable element integrated into the sole of the shoe (Biodyn sandal), a conventional stable control sandal, and a barefoot condition. METHODS: Twenty-two healthy women between the ages of 30 and 50 years participated in this study. During standing, sway area was analysed in monopedal and bipedal stance by means of a computerised balance platform. During walking, temporal and spatial stride-to-stride variability was determined using a pressure-sensitive treadmill. Surface electromyography data of lower leg muscles was simultaneously collected during stance and walk tests. RESULTS: With the Biodyn sandal, significantly larger sway area during bipedal stance (p

Abstract Introduction Similar Patient-Reported Outcomes (PROs) at diagnosis for localized prostate cancer among countries may indicate that different treatments are recommended to the same profile of patients, regardless the context characteristics (health systems, medical schools, culture, preferences…). The aim of this study was to assess such comparison. Methods We analyzed the EPIC-26 results before the primary treatment of men diagnosed of localized prostate cancer from January 2017 onwards (revised data available up to September 2019), from a multicenter prospective international cohort including seven regions: Australia/New Zealand, Canada, Central Europe (Austria / Czech Republic / Germany), United Kingdom, Italy, Spain, and the United States. The EPIC-26 domain scores and pattern of three selected items were compared across regions (with Central Europe as reference). All comparisons were made stratifying by treatment: radical prostatectomy, external radiotherapy, brachytherapy, and active surveillance. Results The sample included a total of 13,483 men with clinically localized or locally advanced prostate cancer. PROs showed different domain patterns before treatment across countries. The sexual domain was the most impaired, and the one with the highest dispersion within countries and with the greatest medians’ differences across countries. The urinary incontinence domain, together with the bowel and hormonal domains, presented the highest scores (better outcomes) for all treatment groups, and homogeneity across regions. Conclusions Patients with localized or locally advanced prostate cancer undergoing radical prostatectomy, EBRT, brachytherapy, or active surveillance presented mainly negligible or small differences in the EPIC-26 domains before treatment across countries. The results on urinary incontinence or bowel domains, in which almost all patients presented the best possible score, may downplay the baseline data role for evaluating treatments’ effects. However, the heterogeneity within countries and the magnitude of the differences found across countries in other domains, especially sexual, support the need of implementing the PRO measurement from diagnosis.

This visualization provides a snapshot of social isolation in America over a 20-year period. The author leverages data from the American Time Use Survey to estimate the percentage of Americans who report a complete lack of social contact during a single day. Contrary to prior claims, there was no clear evidence of increasing isolation during the 2000s and 2010s. There was, however, a marked increase in the percentage of Americans who were socially isolated during the coronavirus pandemic. Adopting a micro view of social isolation contributes to contemporary debates by highlighting social interactions rather than broad assessments of social integration such as social relationships or group participation. Although these latter concepts are important in their own ways, focusing on social interactions speaks to issues that are often considered synonymous with social integration such as the exchange of support, resources, and feelings of belongingness.

At the cellular level, membrane damage is a fundamental cause of yield loss at high temperatures (HT). We report our investigations on a subset of a peanut (Arachis hypogaea) recombinant inbred line population, demonstrating that the membrane lipid remodeling occurring at HT is consistent with homeoviscous adaptation to maintain membrane fluidity. A major alteration in the leaf lipidome at HT was the reduction in the unsaturation levels, primarily through reductions of 18:3 fatty acid chains, of the plastidic and extra-plastidic diacyl membrane lipids. In contrast, levels of 18:3-containing triacylglycerols (TGs) increased at HT, consistent with a role for TGs in sequestering fatty acids when membrane lipids undergo remodeling during plant stress. Polyunsaturated acyl chains from membrane diacyl lipids were also sequestered as sterol esters (SEs). The removal of 18:3 chains from the membrane lipids decreased the availability of susceptible molecules for oxidation, thereby minimizing oxidative damage in membranes. Our results suggest that transferring 18:3 chains from membrane diacyl lipids to TGs and SEs is a key feature of lipid remodeling for HT adaptation in peanut. Finally, QTL-seq allowed the identification of a genomic region associated with heat-adaptive lipid remodeling, which would be useful for identifying molecular markers for heat tolerance.

Huntington’s disease (HD) is a neurodegenerative disease characterized by movement and cognitive dysfunction. HD is caused by a CAG expansion in exon 1 of the HTT gene that leads to a polyglutamine (PQ) repeat in the huntingtin protein, which aggregates in the brain and periphery. Previously, we used Drosophila models to determine that Htt-PQ aggregation in the heart causes shortened lifespan and cardiac dysfunction that is ameliorated by promoting chaperonin function or reducing oxidative stress. Here, we further study the role of neuronal mutant huntingtin and how it affects peripheral function. We overexpressed normal (Htt-PQ25) or expanded mutant (Htt-PQ72) exon 1 of huntingtin in Drosophila neurons and found that mutant huntingtin caused age-dependent Htt-PQ aggregation in the brain and could cause a loss of synapsin. To determine if this neuronal dysfunction led to peripheral dysfunction, we performed a negative geotaxis assay to measure locomotor performance and found that neuronal mutant huntingtin caused an age-dependent decrease in locomotor performance. Next, we found that rapamycin reduced Htt-PQ aggregation in the brain. These results demonstrate the role of neuronal Htt-PQ in dysfunction in models of HD, suggest that brain-periphery crosstalk could be important to the pathogenesis of HD, and show that rapamycin reduces mutant huntingtin aggregation in the brain.

Darier, Hailey-Hailey, and Grover diseases are rare acantholytic skin diseases. While these diseases have different underlying causes, they share defects in cell-cell adhesion in the epidermis and desmosome organization. To better understand the underlying mechanisms leading to disease in these conditions, we performed RNA-seq on lesional skin samples from patients. The transcriptomic profiles of Darier, Hailey-Hailey, and Grover diseases were found to share a remarkable overlap, which did not extend to other common inflammatory skin diseases. Analysis of enriched pathways showed a shared increase in keratinocyte differentiation, and a decrease in cell adhesion and actin organization pathways in Darier, Hailey-Hailey, and Grover diseases. Direct comparison to atopic dermatitis and psoriasis showed that the downregulation in actin organization pathways was a unique feature in the acantholytic skin diseases. Furthermore, upstream regulator analysis suggested that a decrease in SRF/MRTF activity was responsible for the downregulation of actin organization pathways. Staining for MRTFA in lesional skin samples showed a decrease in nuclear MRTFA in patient skin compared with normal skin. These findings highlight the significant level of similarity in the transcriptome of Darier, Hailey-Hailey, and Grover diseases, and identify decreases in actin organization pathways as a unique signature present in these conditions.

Abstract Objective Charcot–Marie–Tooth type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsy (HNPP) are caused by mutations to the peripheral myelin protein 22 (PMP22) gene. A need exists for sensitive and reliable biomarkers of progression and treatment response. Magnetic resonance imaging (MRI) metrics of nerve pathology and morphology were investigated for this purpose. Methods MRI was performed at 3.0 T in the thigh of CMT1A (N = 11) and HNPP patients (N = 12) and controls (N = 23). Three potential imaging biomarkers of the sciatic nerve were investigated: 1) magnetization transfer ratio (MTR), which assays myelin content, and 2) cross‐sectional area (CSA) and 3) circularity, which assay morphological changes. Potential imaging biomarkers were compared across cohorts and assessed for relationships with disability in the legs (CMTESL), compound motor action potentials (CMAP), and motor conduction velocities (MCV). Inter‐rater reliability and test–retest repeatability were established for each imaging metric. Results Significant differences in MTR, CSA, and circularity were observed in CMT1A relative to controls (p = 0.02, p 0.999, CV = 0.30%) and repeatable (ICC = 0.84, CV = 3.16%). Interpretation MTR, CSA, and circularity showed promise as reliable and sensitive biomarkers of CMT1A, but not HNPP. These warrant longitudinal investigation as response biomarkers in upcoming clinical trials of CMT1A, while other methods should be considered for HNPP.

We present theoretical ground state energies and their uncertainties for p-shell nuclei obtained from chiral effective field theory internucleon interactions as a function of chiral order, fitted to two- and three-body data only. We apply a Similary Renormalization Group transformation to improve the numerical convergence of the many-body calculations, and discuss both the numerical uncertainties arising from basis truncations and those from omitted induced many-body forces, as well as chiral truncation uncertainties. With complete Next-to-Next-to-Leading (N2LO) order two- and three-body interactions, we find significant overbinding for the ground states in the upper p-shell, but using higher-order two-body potentials, in combination with N2LO three-body forces, our predictions agree with experiment throughout the p-shell to within our combined estimated uncertainties. The uncertainties due to chiral order truncation are noticeably larger than the numerical uncertainties, but they are expected to become comparable to the numerical uncertainties at complete N3LO.

The fine structure of the IsoVector Giant Dipole Resonance (IVGDR) in the doubly-magic nuclei 40,48Ca observed in inelastic proton scattering experiments under 0∘ is used to investigate the role of different mechanisms contributing to the IVGDR decay width. Characteristic energy scales are extracted from the fine structure by means of wavelet analysis. The experimental scales are compared to different theoretical approaches allowing for the inclusion of complex configurations beyond the mean-field level. Calculations are performed in the framework of RPA and beyond-RPA in a relativistic approach based on an effective meson-exchange interaction, with the UCOM effective interaction and, for the first time, with realistic two- plus three-nucleon interactions from chiral effective field theory employing the in-medium similarity renormalization group. All models highlight the role of Landau fragmentation for the damping of the IVGDR, while the differences in the coupling strength between one particle-one hole (1p-1h) and two particle-two hole (2p-2h) correlated (relativistic) and non-correlated (non-relativistic) configurations lead to very different pictures of the importance of the spreading width resulting in wavelet scales being a sensitive measure of their interplay. The relativistic approach with particle-vibration coupling, in particular, shows impressive agreement with the number and absolute values of the scales extracted from the experimental data.

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The ExoClock project has been created to increase the efficiency of the Ariel mission. It will achieve this by continuously monitoring and updating the ephemerides of Ariel candidates, in order to produce a consistent catalog of reliable and precise ephemerides. This work presents a homogenous catalog of updated ephemerides for 450 planets, generated by the integration of ∼18,000 data points from multiple sources. These sources include observations from ground-based telescopes (the ExoClock network and the Exoplanet Transit Database), midtime values from the literature, and light curves from space telescopes (Kepler, K2, and TESS). With all the above, we manage to collect observations for half of the postdiscovery years (median), with data that have a median uncertainty less than 1 minute. In comparison with the literature, the ephemerides generated by the project are more precise and less biased. More than 40% of the initial literature ephemerides had to be updated to reach the goals of the project, as they were either of low precision or drifting. Moreover, the integrated approach of the project enables both the monitoring of the majority of the Ariel candidates (95%), and also the identification of missing data. These results highlight the need for continuous monitoring to increase the observing coverage of the candidate planets. Finally, the extended observing coverage of planets allows us to detect trends (transit-timing variations) for a sample of 19 planets. All the products, data, and codes used in this work are open and accessible to the wider scientific community.

Involvement in social media activities has become a significant aspect of adolescents’ lives. Participation in numerous social media challenges with a variety of goals is also common among youth across platforms. Recently, the new app called TikTok has resulted in an increased level and variety of social media activities among youth. This study examines the factors related to participation in TikTok challenges, their potential impacts on adolescents and young adults, and participant reflection after performing a challenge. We recruited 25 adolescents and young adults who were actively involved in TikTok challenges from several secondary schools and colleges in South India. We administered a semi-structured, retrospective interview after screening participants through an online survey. The interview assessed motivations for participation, content of social media posts, and perceived consequences of participation. Based on the integrated behavior model, we conducted a theoretically grounded thematic analysis of the data. Our thematic analysis revealed that the factors closely related to the integrated behavior model motivated participation, such as attitudes, norms, personal agency, knowledge and skill, environmental constraints, habits, and individual differences. Further, one of the most frequent reasons reported as a motivational factor was being affirmed by others or peer pressure. Participants typically reported enjoying these challenges and experiencing positive feelings after completing the challenge. Overall, the participants seemed to have positive views of TikTok challenges and enjoyed the views and likes that came from posting about their participation in the challenge. Irrespective of the type of challenge participated in, the participants commented that taking part in online challenges is enjoyable and makes them feel confident. In sum, these adolescents appear to spend large amounts of time on TikTok due to the lure of online challenges and associated emotional states.

Genome-wide association studies identified the BIN1 locus as a leading modulator of genetic risk in Alzheimer’s disease (AD). One limitation in understanding BIN1’s contribution to AD is its unknown function in the brain. AD-associated BIN1 variants are generally noncoding and likely change expression. Here, we determined the effects of increasing expression of the major neuronal isoform of human BIN1 in cultured rat hippocampal neurons. Higher BIN1 induced network hyperexcitability on multielectrode arrays, increased frequency of synaptic transmission, and elevated calcium transients, indicating that increasing BIN1 drives greater neuronal activity. In exploring the mechanism of these effects on neuronal physiology, we found that BIN1 interacted with L-type voltage-gated calcium channels (LVGCCs) and that BIN1–LVGCC interactions were modulated by Tau in rat hippocampal neurons and mouse brain. Finally, Tau reduction prevented BIN1-induced network hyperexcitability. These data shed light on BIN1’s neuronal function and suggest that it may contribute to Tau-dependent hyperexcitability in AD.

Thomas M. Franck's The Emerging Right to Democratic Governance has lived a dual existence. On the one hand, it is almost universally cited as having brought international lawyers into the freewheeling debate of the early 1990s among scholars of international relations, comparative politics, and political theory about the so-called “Third Wave” of democratization. On the other hand, the article is not infrequently described as a legal avatar of post-Cold War Western triumphalism, often sharing a sentence or a footnote with Francis Fukuyama's The End of History and the Last Man. From the standpoint of the two authors of this essay—one a long-time defender of Franck's thesis and the other a long-time critic—both of these broad-brush characterizations of the article contain elements of truth, but both are also woefully incomplete.

A challenge in establishing new ground-based stations for monitoring snowpack accumulation and ablation is to locate the sites in areas that represent the key processes affecting snow accumulation and ablation. This is especially challenging in forested montane watersheds where the combined effects of terrain, climate, and land cover affect seasonal snowpack. We present a coupled modeling approach used to objectively identify representative snow-monitoring locations in a forested watershed in the western Oregon Cascades mountain range. We used a binary regression tree (BRT) non-parametric statistical model to classify peak snow water equivalent (SWE) based on physiographic landscape characteristics in an average snow year, an above-average snow year, and a below-average snow year. Training data for the BRT classification were derived using spatially distributed estimates of SWE from a validated physically based model of snow evolution. The optimal BRT model showed that elevation and land cover type were the most significant drivers of spatial variability in peak SWE across the watershed (R2 = 0.93, p value

Objective: While small non-obstructive stones in the adult population are usually observed with minimal follow-up, the same guidelines for management in the pediatric population have not been well-studied. We evaluate the clinical outcomes of small non-obstructing kidney stones in the pediatric population to better define the natural history of the disease.Methods: In this IRB-approved retrospective study, patients with a diagnosis of kidney stones from January 2011 to March 2017 were identified using ICD9 and ICD10 codes. Patients with ureteral stones, obstruction, or stones >5 mm in size were excluded. Patients with no follow-up after initial imaging were also excluded. Patients with a history of stones or prior stone interventions were included in our population. Frequency of follow-up ultrasounds while on observation were noted and any ER visits, stone passage episodes, infections, and surgical interventions were documented.Results: Over the 6-year study period, 106 patients with non-obstructing kidney stones were identified. The average age at diagnosis was 12.5 years and the average stone size was 3.6 mm. Average follow-up was 17 months. About half of the patients had spontaneous passage of stones (54/106) at an average time of 13 months after diagnosis. Stone location did not correlate with spontaneous passage rates. Only 6/106 (5.7%) patients required stone surgery with ureteroscopy and/or PCNL at an average time of 12 months after initial diagnosis. The indication for surgery in all 6 cases was pain. 17/106 (16%) patients developed febrile UTIs and a total of 43 ER visits for stone-related issues were noted, but no patients required urgent intervention for an infected obstructing stone. Median interval for follow-up was every 6 months with renal ultrasounds, which then was prolonged to annual follow up in most cases.Conclusions: The observation of pediatric patients with small non-obstructing stones is safe with no episodes of acute obstructive pyelonephritis occurring in these patients. The sole indication for intervention in our patient population was pain, which suggests that routine follow-up ultrasounds may not be necessary for the follow-up of pediatric non-obstructive renal stones ≤5 mm in size.

Previous work has demonstrated that plant leaf polar lipid fatty acid composition varies during the diurnal (dark-light) cycle. Fatty acid synthesis occurs primarily during the light, but fatty acid desaturation continues in the absence of light, resulting in polyunsaturated fatty acids reaching their highest levels toward the end of the dark period. In this work, Arabidopsis thaliana were grown at constant (21°C) temperature with 12-h light and 12-h dark periods. Collision induced dissociation time-of-flight mass spectrometry demonstrated that 16:3 and 18:3 fatty acid content in membrane lipids of leaves are higher at the end of the dark than at the end of the light period, while 16:1, 16:2, 18:0, and 18:1 content are higher at the end of the light period. Lipid profiling of membrane galactolipids, phospholipids, and lysophospholipids by electrospray ionization triple quadrupole mass spectrometry indicated that the monogalactosyldiacylglycerol, phosphatidylglycerol, and phosphatidylcholine classes include molecular species whose levels are highest at end of the light period and others that are highest at the end of the dark period. The levels of phosphatidic acid and phosphatidylserine classes were higher at the end of the dark period, and molecular species within these classes either followed the class pattern or were not significantly changed in the diurnal cycle. Phospholipase D (PLD) is a family of enzymes that hydrolyzes phospholipids to produce phosphatidic acid. Analysis of several PLD mutant lines suggests that PLDζ2 and possibly PLDα1 may contribute to diurnal cycling of phosphatidic acid. The polar lipid compositional changes are considered in relation to recent data that demonstrate phosphatidylcholine acyl editing.

Leitfäden für die Ausbildung im Deutschen Wetterdienst, Nr. 1: Allgemeine Meteorologie. Dritte, vollständig neubearbeitete Auflage. - Selbstverlag des Deutschen Wetterdienstes, Offenbach am Main, 1987; Fluggestützte Messungen von Luftverunreinigungen. - Beiträge eines VDI-Workshops in Trier im Oktober 1988, herausgegeben von der VDI-Kommission Reinhaltung der Luft (RdL), erschienen in der VDI-RdL-Schriftenreihe B. 9, Düsseldorf, 1989; Schwarzbach, M.: Alfred Wegener und die Drift der Kontinente. - 2., neu bearbeitete Aufl., Wissenschaftliche Verlagsgesellschaft Stuttgart, 1989; Jessberger, Hans Ludwig: Geotechnische Aufgaben der Deponietechnik und der Altlastensanierung und Krause, Egon: Numerische Strömungssimulation. - Rheinisch-Westfälische Akademie der Wissenschaften. Vorträge: Natur-, Ingenieur- und Wirtschaftswissenschaften, Reihe N, Bd. 364. Vieweg, Wiesbaden, 1990; Hoffmann, Geerd-R. & Maretis, Dimitris K. (Eds.): The Dawn of Massively Parallel Processing in Meteorology. Proceedings of the 3rd Workshop on Use of Parallel Processors in Meteorology. - In: Ghil, M., Sadourny, R. & Sündermann, J. (Eds.): Topics in Atmospheric and Oceanic Sciences. Springer, Berlin, 1990; Gerüche: Stand der Erkenntnisse zur Ermittlung von Belastung und Belästigung. - VDI Kommission Reinhaltung der Luft, Düsseldorf, 1990; Scharnow, U., Berth, W., Keller, W.: Maritime Wetterkunde. Transpress, Berlin, 1990; Crutzen, P. J. & Müller, M.: (Hrsg.): Das Ende des blauen Planeten? Der Klimakollaps. Gefahren und Auswege. - Becksche Reihe Nr. 385, 2. Aufl., Verlag C. H. Beck, München, 1990; Brosche, P. & Sündermann, J. (Eds.): Earth Rotation from Eons to Days. - Springer Verlag, Berlin, 1990; Müller-Westermeier, G.: Klimadaten der Bundesrepublik Deutschland. Zeitraum 1951-1980 (Temperatur, Luftfeuchte, Niederschlag, Sonnenschein, Bewölkung). - Selbstverlag des Deutschen Wetterdienstes, Offenbach, 1990; Kurz, Manfred: Synoptische Meteorologie. - 2., vollständig neu bearbeitete Aufl. - In: Leitfäden für die Ausbildung im Deutschen Wetterdienst 8. Selbstverlag des Deutschen Wetterdienstes, Offenbach/ M. 1990;

Mit Hilfe dreier Flugzeuge wurden während des Experiments FRONTEX' 89 meteorologische Parameter im Bereich einer Kaltfront über der Nordsee bestimmt. Die hochauflösenden flugzeuggestützten Messungen ermöglichten dabei die Erfassung mesoskaliger Phänomene in der gesamten Grenzschicht. Die Darstellungen der Temperatur weisen die Front als eine breite Zone mit allmählicher Luftmassenänderung aus. In den unteren Höhen macht sich über dem Meer der dämpfende Einfluß der Wasseroberfläche auf die Temperaturgegensätze bemerkbar. Die größten Temperaturkontraste sind daher in etwa 600 m Höhe zu finden. Über der Bodenfront ist in 600 m Höhe ein Maximum der frontparallelen Windkomponente zu erkennen. Entsprechend den nicht sehr großen Temperaturkontrasten ist dieser Jet allerdings weniger stark ausgeprägt als in der Literatur beschriebene Strahlströme. Hinter der Front bildet sich ein Wirbel mit horizontaler Achse aus. Dazu gehört ein ausgedehntes Gebiet hinter der Front mit frontsenkrechten Windkomponenten, die größer als die Frontverlagerungsgeschwindigkeit sind. Vor der Bodenfront tritt ein ausgedehntes Gebiet mit aufsteigender Luftbewegung auf. Die stärksten Aufwinde sind in einer schmalen Zone direkt vor der Bodenfront zu finden.

Christoffer, Jürgen und Monika Ulbricht-Eissing: Die bodennahen Windverhältnisse in der Bundesrepublik Deutschland. - Ber. Deutsch. Wetterdienst. Nr. 147, 2. Aufl., Selbstverlag des Deutschen Wetterdienstes, Offenbach 1989; Malberg, H.: Bauernregeln. Aus meteorologischer Sicht. - 2., erweiterte Auflage. Springer-Verlag, Berlin, Heidelberg usw., 1993; VDI-Richtlinie 3782, Blatt 1: Ausbreitung von Luftverunreinigungen in der Atmosphäre. Gaußsches Ausbreitungsmodell für Luftreinhaltepläne. VDI-Handbuch Reinhaltung der Luft, Bd. 1. - VDI Düsseldorf, Oktober 1992; Huijun Yang: Wave packets and their bifurcations in geophysical fluid dynamics. - Springer-Verlag, New York, Berlin, Heidelberg, 1990; Zilitinkevich, S. S. (Ed.): Modeling air - lake interaction, physical background. Research reports in physics. - Springer-Verlag, Berlin, Heidelberg, New York, 1991; Eine Bestandsaufnahme 1982-1992 / 10 Jahre deutsche Klimaforschung. - Herausgeber GSF, Kühbachstr. 11, D-81543 München, September 1993.

Abstract Infectious diseases continue to pose a significant public health burden despite the great progress achieved in their prevention and control over the last few decades. Our ability to disentangle the factors and mechanisms driving their propagation in space and time has dramatically advanced in recent years. The current era is rich in mathematical and computational tools and detailed geospatial information, including sociodemographic, geographic, and environmental data, which are essential to elucidate key drivers of infectious disease transmission from epidemiological and genetic data. Indeed, this paradigm shift was driven by dramatic advances in complex systems approaches along with substantial improvements in data availability and computational power. The burgeoning output of infectious disease spatial modeling suggests that we are close to a fully integrated approach for early epidemic detection and intervention. This special collection in BMC Medicine aims to bring together a broad range of quantitative investigations that improve our understanding of the spatiotemporal transmission dynamics of infectious diseases in order to mitigate their impact on the human population.

AbstractBackground and Purpose:The injection of dextranomer/hyaluronic acid (DHA) has become an accepted treatment for children with vesicoureteral reflux (VUR). Complete ureteral duplication has been considered by some practitioners as counterindication for its use. We reviewed the Texas Children's Hospital (TCH) records for children with complete ureteral duplication who were treated with DHA for VUR.Methods:We searched medical records at TCH for patients with a preoperative diagnosis of complete ureteral duplication who had undergone DHA injection between January 1, 2001, and October 15, 2008. Operative notes, imaging studies, and clinic notes were reviewed.Results:In this period, 28 kidneys in 24 children were treated. The average grade of reflux before injection was 3.44 (range 1–5). First injection resolution of reflux was 57% with an increase to 73% after a second injection with an average volume of DHA of 1.05 mL. New contralateral VUR developed postinjection in three (15%) children with unilateral VUR. There were no perioperative complications. The average age of the children who were treated was 41.4 months. Mean follow-up was 45.94 months. Success of DHA injection tended to be higher in girls (65%) and older children.Conclusions:High levels of success can be achieved with DHA injection in children with complete ureteral duplication. DHA injection is more likely to be successful for older girls with VUR and complete ureteral duplication. If initial injection does not result in VUR resolution, a second injection offers an opportunity for improved success. For physicians and families who are seeking an alternative to open surgical management, DHA represents an attractive option for selected children with complete ureteral duplication. [ABSTRACT FROM AUTHOR]

New genes with novel functions arise by duplication and divergence, but the process poses a problem. After duplication, an extra gene copy must rise to sufficiently high frequency in the population and remain free of common inactivating lesions long enough to acquire the rare mutations that provide a new selectable function. Maintaining a duplicated gene by selection for the original function would restrict the freedom to diverge. (We refer to this problem as Ohno's dilemma). A model is described by which selection continuously favors both maintenance of the duplicate copy and divergence of that copy from the parent gene. Before duplication, the original gene has a trace side activity (the innovation) in addition to its original function. When an altered ecological niche makes the minor innovation valuable, selection favors increases in its level (the amplification), which is most frequently conferred by increased dosage of the parent gene. Selection for the amplified minor function maintains the extra copies and raises the frequency of the amplification in the population. The same selection favors mutational improvement of any of the extra copies, which are not constrained to maintain their original function (the divergence). The rate of mutations (per genome) that improve the new function is increased by the multiplicity of target copies within a genome. Improvement of some copies relaxes selection on others and allows their loss by mutation (becoming pseudogenes). Ultimately one of the extra copies is able to provide all of the new activity. [ABSTRACT FROM AUTHOR]

For many bird species, growth is negative or equivocal during development. Traditional, parametric growth curves assume growth follows a sigmoidal form with prescribed inflection points and is positive until asymptotic size. Accordingly, these curves will not accurately capture the variable, sometimes considerable, fluctuations in avian growth over the course of the trajectory. We evaluated the fit of three traditional growth curves (logistic, Gompertz, and von Bertalanffy) and a nonparametric spline estimator to simulated growth data of six different specified forms over a range of sample sizes. For all sample sizes, the spline best fit the simulated model that exhibited negative growth during a portion of the trajectory. The Gompertz curve was the most flexible for fitting simulated models that were strictly sigmoidal in form, yet the fit of the spline was comparable to that of the Gompertz curve as sample size increased. Importantly, confidence intervals for all of the fitted, traditional growth curves were wholly inaccurate, negating the apparent robustness of the Gompertz curve, while confidence intervals of the spline were acceptable. We further evaluated the fit of traditional growth curves and the spline to a large data set of wood thrush Hylocichla mustelina mass and wing chord observations. The spline fit the wood thrush data better than the traditional growth curves, produced estimates that did not differ from known observations, and described negative growth rates at relevant life history stages that were not detected by the growth curves. The common rationale for using parametric growth curves, which compress growth information into a few parameters, is to predict an expected size or growth rate at some age or to compare estimated growth with other published estimates. The suitability of these traditional growth curves may be compromised by several factors, however, including variability in the true growth trajectory. Nonparametric methods, such as the spline, provide a precise description of empirical growth yet do not produce such parameter estimates. Selection of a growth descriptor is best determined by the question being asked but may be constrained by inherent patterns in the growth data. [ABSTRACT FROM AUTHOR]

The aim of the study was to determine the effects of a specific epithelial growth factor Receptor kinase inhibitor (EGFR-KI) and Taxol on tumor growth in a novel tumor model. Material & methods: A genetically engineered tumor model which uses "transgenic" organs in immune competent mice was used. NeuT-transfected immortalized HC11 epithelial cells and primary mouse mammary epithelial cells have been transplanted into the gland-free mammary fat pad of female BALB/c mice. Mammary tumors developed after a latency period of three to four weeks. The mice were thereafter daily orally treated over a 19 or 22-day period with 0, 38, 75, 2 × 75 mg/kg body weight (b.w.) EGFR-KI (n: 7-9 per group) or intravenously with 10 mg/kg b.w. Taxol. After necropsy the histopathological evaluation of the tumors was performed in a coded manner. The proliferation activity of tumor cells was analyzed by laser scanning cytometry (LSC) using anti-Ki67-antibodies. Results: Oral Treatment with EGFR-KI in this transgenic organ model showed clear antitumor efficacy in a dose-dependent manner in the range between 38 and 75 mg/kg b.w. This antiproliferative effect appears to be minimally increased at 75 mg/kg/day twice per day. For all treatments a strong correlation between the biological behavior of the tumor, histopathology and cell proliferation could be established. In contrast, treatment with Taxol showed no significant reduction of tumor growth or cell proliferation in this model. This new transgenic organ model comprising histopathological evaluation and cell proliferation analysis appears to be a suitable test system for drug candidates that affect specific biochemical pathways. It may have greater predictive nature for clinical effects in humans as compared to conventional tumor models because of its c-erb B2 gene overexpression. [ABSTRACT FROM AUTHOR]

We investigate giant resonances of spherical nuclei on the basis of the Argonne V18 potential after unitary transformation within the similarity renormalization group or the unitary correlation operator method supplemented by a phenomenological three-body contact interaction. Such Hamiltonians can provide a good description of ground-state energies and radii within Hartree–Fock plus low-order many-body perturbation theory. The standard random phase approximation is applied here to calculate the isoscalar monopole, isovector dipole, and isoscalar quadrupole excitation modes of the , , and nuclei. Thanks to the inclusion of the three-nucleon interaction and despite the minimal optimization effort, a reasonable agreement with experimental centroid energies of all three modes has been achieved. The role and scope of the Hartree–Fock reference state in RPA methods are discussed. [ABSTRACT FROM AUTHOR]

Abstract Background When a new guideline is published there is a need to understand how its recommendations can best be implemented in real-world practice. Yet, guidelines are often published with little to no roadmap for organizations to follow to promote adherence to their recommendations. The purpose of this study was to evaluate the impact of using a common process model to implement a single clinical practice guideline across multiple physical therapy clinical settings. Methods Five organizationally distinct sites with physical therapy services for patients with peripheral vestibular hypofunction participated. The Knowledge to Action model served as the foundation for implementation of a newly published guideline. Site leaders conducted preliminary gap surveys and face-to-face meetings to guide physical therapist stakeholders’ identification of target-behaviors for improved guideline adherence. A 6-month multimodal implementation intervention included local opinion leaders, audit and feedback, fatigue-resistant reminders, and communities of practice. Therapist adherence to target-behaviors for the 6 months before and after the intervention was the primary outcome for behavior change. Results Therapist participants at all sites indicated readiness for change and commitment to the project. Four sites with more experienced therapists selected similar target behaviors while the fifth, with more inexperienced therapists, identified different goals. Adherence to target behaviors was mixed. Among four sites with similar target behaviors, three had multiple areas of statistically significantly improved adherence and one site had limited improvement. Success was most common with behaviors related to documentation and offering patients low technology resources to support home exercise. A fifth site showed a trend toward improved therapist self-efficacy and therapist behavior change in one provider location. Conclusions The Knowledge to Action model provided a common process model for sites with diverse structures and needs to implement a guideline in practice. Multimodal, active interventions, with a focus on auditing adherence to therapist-selected target behaviors, feedback in collaborative monthly meetings, fatigue-resistant reminders, and developing communities of practice was associated with long-term improvement in adherence. Local rather than external opinion leaders, therapist availability for community building meetings, and rate of provider turnover likely impacted success in this model. Trial registration This study does not report the results of a health care intervention on human participants.

Atrial septal defects (ASD) caused by traumatic events, specifically blunt cardiac trauma, are considered an infrequent occurrence, yet their true prevalence has been difficult to ascertain. The general lack of knowledge is likely due to the pathology being severely understudied. We present the case of a 21-year-old male who was diagnosed with ASD following a motor vehicle accident. Initial assessment utilizing the point-of-care ultrasound (POCUS) technique - focused assessment with sonography for trauma (FAST) was found to be negative for free intraperitoneal or pericardial fluid. Subsequent computed tomography displayed multiple injuries but agreed with the FAST exam findings of no fluid within the abdomen or pericardium. Later in the patient's care a dedicated POCUS transthoracic echocardiogram was performed which identified right sided heart dilatation. The patient was managed in the intensive care unit (ICU) for an extensive period but recovered sufficiently to be discharged. The plan was to repair the ASD on a non-emergent basis. This case highlights the importance and diagnostic utility of bedside POCUS. Categories: Emergency Medicine

Dyspnea is a common complaint in patients who present to the emergency department and can be due to numerous etiologies. This case report details a 90-year-old female with a history significant for hypertension, hyperlipidemia, and new diagnosis of ovarian malignancy whose symptoms increased over the past three days. Point-of-care Ultrasonography showed multiple B-lines, a plethoric IVC without respiratory variation, a markedly low EF and a lack of RV dilation. There was also no evidence of effusion which led the emergency medicine team to the diagnosis of acute decompensated heart failure. This quick diagnosis was possible due to using the standardized POCUS approach guided by the BEE FIRST algorithm. BEE FIRST can help physicians remember: B-lines are indicative of interstitial thickening, Effusion such as pericardial or pleural should be checked for, Ejection Fraction is useful in assessing for heart failure, IVC/Infection/Infarct correlates with central venous pressure, and can be used to assess volume status, check for enlargement, evidence of pneumonia, subpleural consolidation “shred sign”, hepatization of lung, and/or pulmonary infarction related to pulmonary embolism, Right Heart Strain can indicate pulmonary embolism or pulmonary hypertension, Sliding Lung can assess for pneumothorax and pleural characteristics, and lastly, Thrombosis/Tumor can assess for myxoma and interrogation of lower extremities for deep vein thrombosis can aid in dyspnea differentiation. In this report, we demonstrate how the framework BEE FIRST offers a standardized stepwise approach to the utilization of POCUS in a patient with acute dyspnea in the ED setting.

Ion channels are fundamental biological devices that act as gates in order to ensure selective ion transport across cellular membranes; their operation constitutes the molecular mechanism through which basic biological functions, such as nerve signal transmission and muscle contraction, are carried out. Here, we review recent results in the field of computational research on ion channels, covering theoretical advances, state-of-the-art simulation approaches, and frontline modeling techniques. We also report on few selected applications of continuum and atomistic methods to characterize the mechanisms of permeation, selectivity, and gating in biological and model channels.

Television sitcoms frequently invoke social network concepts to highlight specific jokes or scenes. In this visualization, the author draws on data from NBC’s The Office to explore how show creator Greg Daniels and his writing staff leveraged a well-known social network concept in the overall development of their show. By identifying the presence of structural holes (i.e., the absence of ties between two or more network members), The Office produced multiple novel storylines in which different sets of characters who did not routinely interact were jointly forced into comedic situations. As evidenced through a network visualization—and interviews with the show’s writers—Greg Daniels was clearly thinking like a social network theorist in his careful development of one of the most successful sitcoms in television history.

Syncope is a common emergency department (ED) chief complaint. Rarely, syncope can be the result of right ventricular outflow obstruction from an intracardiac tumor, such as an intracardiac extension of intravenous leiomyomatosis (IVL). Typically, this type of tumor is confined to the pelvic veins, but in very rare cases, it can extend through the inferior vena cava into the right atrium. Point-of-care ultrasound (POCUS) can be a crucial tool in the ED for identifying intracardiac tumors presenting as syncope and expediting clinical management.We present the case of a 39-year-old female with no prior medical history that presented to the ED having experienced dyspnea on exertion and two syncopal episodes prior to ED admission. POCUS use in the ED elucidated the presence of a right atrial mass and further imaging showed a mass on the patient's uterus. After surgical removal of a portion of the atrial mass, a subsequent biopsy revealed it had leiomyoma-like features; as such, the patient was diagnosed with IVL. This case illustrates the importance of using POCUS in the ED to help determine the etiology of syncope. Although intracardiac extensions of IVL are rare, it is important for emergency physicians to keep this diagnosis in the differential in patients with symptoms or risk factors suggestive of IVL with intracardiac extension.

Medical image annotation is a major hurdle for developing precise and robust machine-learning models. Annotation is expensive, time-consuming, and often requires expert knowledge, particularly in the medical field. Here, we suggest using minimal user interaction in the form of extreme point clicks to train a segmentation model which, in effect, can be used to speed up medical image annotation. An initial segmentation is generated based on the extreme points using the random walker algorithm. This initial segmentation is then used as a noisy supervision signal to train a fully convolutional network that can segment the organ of interest, based on the provided user clicks. Through experimentation on several medical imaging datasets, we show that the predictions of the network can be refined using several rounds of training with the prediction from the same weakly annotated data. Further improvements are shown using the clicked points within a custom-designed loss and attention mechanism. Our approach has the potential to speed up the process of generating new training datasets for the development of new machine-learning and deep-learning-based models for, but not exclusively, medical image analysis.

Intrauterine devices (IUDs) are used worldwide. The 2 types that are used are the levonorgestrel IUD and a copper containing IUD. This is a case study of a 30-year-old female with a levonorgestrel IUD who was diagnosed with a ruptured ectopic pregnancy in the emergency department (ED). Point-of-care urine pregnancy test and point-of-care ultrasound (POCUS) were vital in making this diagnosis and should be utilized in patients assigned female at birth who present with abdominal pain.

It is generally recognized that lives are saved by administering high-quality cardiopulmonary resuscitation (CPR) to patients in cardiac arrest. A focused assessment with sonography for trauma (FAST) examination is an effective and non–invasive method for detecting rare complications of CPR, such as hemorrhage from abdominal visceral injury. We report the case of a 56-year-old female suffering from intra-abdominal hemorrhage caused by a liver laceration following CPR. The hemoperitoneum was diagnosed by a FAST examination. Although severe complications of CPR are rare, they can be easily detected with the use of a FAST examination. A FAST examination should be considered as a post-resuscitation approach to assess for life-threatening complications in all patients following cardiopulmonary resuscitation.

Emergency physicians often rely on heuristics to facilitate clinical decisions due to the large volume of patients they see daily. Consequently, they are vulnerable to error and bias. We report the case of a 69-year-old male that presented to the emergency department (ED) with shortness of breath, productive cough, and dyspnea on exertion. One day prior to ED admission, he was diagnosed with bronchitis; however, point-of-care ultrasound (POCUS) in the ED identified acute pulmonary embolism. This case illustrates the potential dangers of anchoring bias and shows the benefits of using point-of-care ultrasound of the lungs and heart to assist in the diagnosis of acute pulmonary embolism.

The World Health Organization categorized coronavirus disease 2019 (COVID-19) as a pandemic due to its high contagion rate and widespread infectivity in February 2020. In the United States, one of the public health concerns is the adequacy of resources to treat infected cases. We describe a case of a previously well, 9-year-old obese boy who presented to the emergency department with shortness of breath, fever, abdominal pain, and cough with chest pain. He was diagnosed with COVID-19 through significant family contact, confirmed by polymerase chain reaction and found to be at high risk of venous thromboembolism due to abnormal d-dimer. Lung point-of-care ultrasound (POCUS) in the emergency department observed significant lung pathology, including pleural thickening, consolidation, and B lines. A chest X-ray found bilateral ground glass opacities and interstitial prominences consistent with viral pneumonia. Our case suggests that lung POCUS can provide adequate and rapid imaging to assess lung pathology of COVID-19 in a pediatric patient. As there is limited literature on use of lung POCUS in pediatric patients infected with SARS-CoV-2, our case emphasizes its function as a potentially efficient modality in bedside assessment.

Abstract Data-driven machine learning (ML) has emerged as a promising approach for building accurate and robust statistical models from medical data, which is collected in huge volumes by modern healthcare systems. Existing medical data is not fully exploited by ML primarily because it sits in data silos and privacy concerns restrict access to this data. However, without access to sufficient data, ML will be prevented from reaching its full potential and, ultimately, from making the transition from research to clinical practice. This paper considers key factors contributing to this issue, explores how federated learning (FL) may provide a solution for the future of digital health and highlights the challenges and considerations that need to be addressed.

Abstract Background Stroke is a major cause of disability and stroke incidence increases with age. Stroke frequently results in permanent limitations of mobility, and, consequently, the need for the help of others in activities of daily living. In order to optimize rehabilitative efforts and their functional outcomes, detailed knowledge of the functional recovery process, regarding mobility, is needed. Objectives of the MOBITEC-Stroke study are: 1.) To characterize mobility, including lower extremity physical function (LEPF) and life space (the geospatial extent of all of a person’s movements), and changes in mobility within the first year after stroke. 2.) To identify and characterize subgroups with different mobility trajectories. 3.) To evaluate whether changes in LEPF are associated with changes in life-space. 4.) To evaluate participants’ reasons for going outdoors, transportation use, and assistance needed for outdoor movement. Methods Patients with incident first stroke who live in their own homes (target N = 59, based on sample size calculation) will be included in this cohort study. At 3, 6, 9, and 12 months after stroke a battery of mobility tests will be performed at the study centre, including laboratory-based tests of balance and strength, and quantitative gait analysis. Life-space assessment (including 1-week GPS measurements) will be performed in participants’ real life. Semantic information on visited locations (reasons for going outdoors, transportation use, assistance needed) will be collected by using interactive digital maps. Linear mixed effects models will be used to model the trajectories of mobility measures for the total sample and for predefined subgroups. As an exploratory analysis, growth mixture models (GMMs) will be used to identify relevant subgroups with different trajectories. Linear mixed effect models will be used to test whether changes in LEPF parameters are associated with changes in life-space. Participants’ motivation for going outdoors, transportation use, and assistance needed for outdoor mobility will be analysed descriptively. Discussion A comprehensive and detailed knowledge of recovery patterns will enable the planning of targeted and adaptively tailored rehabilitation measures. Information about patients’ reasons for outdoor mobility will provide the opportunity to define individualized and patient-oriented rehabilitation goals. Trial registration ISRCTN85999967 (on 13 August 2020; retrospectively).

Desmoglein 1 (Dsg1) is a cadherin restricted to stratified tissues of terrestrial vertebrates, which serve as essential physical and immune barriers. Dsg1 loss-of-function mutations in humans result in skin lesions and multiple allergies, and isolated patient keratinocytes exhibit increased proallergic cytokine expression. However, the mechanism by which genetic deficiency of Dsg1 causes chronic inflammation is unknown. To determine the systemic response to Dsg1 loss, we deleted the 3 tandem Dsg1 genes in mice. Whole transcriptome analysis of embryonic Dsg1–/– skin showed a delay in expression of adhesion/differentiation/keratinization genes at E17.5, a subset of which recovered or increased by E18.5. Comparing epidermal transcriptomes from Dsg1-deficient mice and humans revealed a shared IL-17–skewed inflammatory signature. Although the impaired intercellular adhesion observed in Dsg1–/– mice resembles that resulting from anti-Dsg1 pemphigus foliaceus antibodies, pemphigus skin lesions exhibit a weaker IL-17 signature. Consistent with the clinical importance of these findings, treatment of 2 Dsg1-deficient patients with an IL-12/IL-23 antagonist originally developed for psoriasis resulted in improvement of skin lesions. Thus, beyond impairing the physical barrier, loss of Dsg1 function through gene mutation results in a psoriatic-like inflammatory signature before birth, and treatment with a targeted therapy significantly improved skin lesions in patients.

The continued proliferation of superbugs in hospitals and the coronavirus disease 2019 (COVID-19) has created an acute worldwide demand for sustained broadband pathogen suppression in households, hospitals, and public spaces. In response, we have created a highly active, self-sterilizing copper configuration capable of inactivating a wide range of bacteria and viruses in 30-60 seconds. The highly active material destroys pathogens faster than any conventional copper configuration and acts as quickly as alcohol wipes and hand sanitizers. Unlike the latter, our copper material does not release volatile compounds or leave harmful chemical residues and maintains its antimicrobial efficacy over sustained use; it is shelf stable for years. We have performed rigorous testing in accordance with guidelines from U.S. regulatory agencies and believe that the material could offer broad spectrum, non-selective defense against most microbes via integration into masks, protective equipment, and various forms of surface coatings.

Numerous studies highlight the value of spouses spending quality time together. Although it is undoubtedly important to make sufficient time for each other, minimal research considers the degree to which married individuals socialize with others outside the presence of their spouses. These latter interactions provide an opportunity to practice social autonomy (i.e., time during which one’s actions are not directly influenced by their spouse). Drawing on data from the American Time Use Survey, the author finds that (1) the number of minutes married women engage in nonspousal interactions peaks in midlife and declines in later life, (2) married men spend more time engaging in nonspousal interactions at work than married women, and (3) the number of minutes married men engage in nonspousal interactions in nonwork settings steadily decreases as they age. These findings suggest that age and gender play central roles in the social lives of married couples.