Long-Range Uniform Deposition of Ag Nanoseed on Cu Current Collector for High-Performance Lithium Metal Batteries.

Uniform lithium deposition is essential to hinder dendritic growth. Achieving this demands even seed material distribution across the electrode, posing challenges in correlating the electrode's surface structure with the uniformity of seed material distribution. In this study, the effect of periodic surface and facet orientation on seed distribution is investigated using a model system consisting of a wrinkled copper (Cu)/graphene structure with a [100] facet orientation. A new methodology is developed for uniformly distributed silver (Ag) nanoparticles over a large area by controlling the surface features of Cu substrates. The regularly arranged Ag nanoparticles, with a diameter of 26.4 nm, are fabricated by controlling the Cu surface condition as [100]-oriented wrinkled Cu. The wrinkled Cu guides a deposition site for spherical Ag nanoparticles, the [100] facet determines the Ag morphology, and the presence of graphene leads to spacings of Ag seeds. This patterned surface and high lithiophilicity, with homogeneously distributed Ag nanoparticles, lead to uniform Li+ flux and reduced nucleation energy barrier, resulting in excellent battery performance. The electrochemical measurements exhibit improved cyclic stability over 260 cycles at 0.5 mA cm-2 and 100 cycles at 1.0 mA cm-2 and enhanced kinetics even under a high current density of 5.0 mA cm-2.

The Genetic Drivers of Juvenile, Young, and Early-Onset Parkinson's Disease in India.

BACKGROUND: Recent studies have advanced our understanding of the genetic drivers of Parkinson's disease (PD). Rare variants in more than 20 genes are considered causal for PD, and the latest PD genome-wide association study (GWAS) identified 90 independent risk loci. However, there remains a gap in our understanding of PD genetics outside of the European populations in which the vast majority of these studies were focused. OBJECTIVE: The aim was to identify genetic risk factors for PD in a South Asian population. METHODS: A total of 674 PD subjects predominantly with age of onset (AoO) ≤50 years (encompassing juvenile, young, or early-onset PD) were recruited from 10 specialty movement disorder centers across India over a 2-year period; 1376 control subjects were selected from the reference population GenomeAsia, Phase 2. We performed various case-only and case-control genetic analyses for PD diagnosis and AoO. RESULTS: A genome-wide significant signal for PD diagnosis was identified in the SNCA region, strongly colocalizing with SNCA region signal from European PD GWAS. PD cases with pathogenic mutations in PD genes exhibited, on average, lower PD polygenic risk scores than PD cases lacking any PD gene mutations. Gene burden studies of rare, predicted deleterious variants identified BSN, encoding the presynaptic protein Bassoon that has been previously associated with neurodegenerative disease. CONCLUSIONS: This study constitutes the largest genetic investigation of PD in a South Asian population to date. Future work should seek to expand sample numbers in this population to enable improved statistical power to detect PD genes in this understudied group. © 2023 Denali Therapeutics and The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

On the Thermodynamic Equivalence of Grand Canonical, Infinite-Size, and Capacitor-Based Models in First-Principle Electrochemistry.

First principles-based computational and theoretical methods are constantly evolving trying to overcome the many obstacles towards a comprehensive understanding of electrochemical processes on an atomistic level. One of the major challenges has been the determination of reaction energetics under a constant potential. Here, a theoretical framework was proposed applying standard electronic structure methods and extrapolating to the infinite-cell size limit where reactions do not alter the potential. Today, electronically grand canonical modifications to electronic structure methods, holding the potential constant by varying the number of electrons in a finite simulation cell, become increasingly popular. In this perspective, we show that these two schemes are thermodynamically equivalent. Further, we link these methods to capacitive models of the interface, in the limit that the capacitance of the charging components (whether continuum or atomistic) are equal and invariant along the reaction pathway. We benchmark the three approaches with an example of alkali cation adsorption on Pt(111) showing that all three approaches converge in the cases of Li, Na and K. For Cs, however, strong deviation from the ideal conditions leads to a spread in the respective results. We discuss the latter by highlighting the cases of broken equivalence and assumptions among the approaches.

Systematic Review of Outcomes for Assessment of Medication Adherence Enhancing Interventions: An ISPOR Special Interest Group Report.

OBJECTIVES: The lack of universal guidance on outcome measures for evaluating medication adherence enhancing interventions (MAEIs) poses a challenge for assessing their effectiveness. This literature review aimed to provide a systematic overview of outcome measures currently used for the value assessment of MAEIs. METHODS: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and searched MEDLINE, PsycINFO, Scopus, CINAHL, and Academic Search Complete for randomized and nonrandomized clinical trials, prospective cohort studies, model-based economic evaluations, and value frameworks published in English between January 2010 and September 2020. Two independent reviewers screened all titles and abstracts, followed by a full-text review. Due to the large number of relevant studies, data extraction was limited to articles published between January 2018 and September 2020. We collected data on the general characteristics of the study, the type of intervention, and the outcomes measured. RESULTS: We screened 14 685 records and identified 308 articles for data extraction. Behavioral interventions were the most common (n = 143), followed by educational interventions (n = 110) and mixed-method interventions (n = 73). Outcomes were clustered into 7 categories with medication adherence (n = 286) being the most frequently measured, followed by clinical outcomes (n = 155), health-related quality of life (n = 57), resource use (n = 43), patient satisfaction (n = 31), economic outcomes (n = 18), and other outcomes (n = 76). CONCLUSIONS: Various outcomes measures have been used to evaluate MAEIs, with only a small number of studies exploring economic and patient-reported outcomes. Future research is warranted to develop a consensus-based set of criteria for assessing MAEIs to facilitate the comparison of interventions and enable informed decision making.

Retinoic acid from the meninges regulates cortical neuron generation.

Extrinsic signals controlling generation of neocortical neurons during embryonic life have been difficult to identify. In this study we demonstrate that the dorsal forebrain meninges communicate with the adjacent radial glial endfeet and influence cortical development. We took advantage of Foxc1 mutant mice with defects in forebrain meningeal formation. Foxc1 dosage and loss of meninges correlated with a dramatic reduction in both neuron and intermediate progenitor production and elongation of the neuroepithelium. Several types of experiments demonstrate that retinoic acid (RA) is the key component of this secreted activity. In addition, Rdh10- and Raldh2-expressing cells in the dorsal meninges were either reduced or absent in the Foxc1 mutants, and Rdh10 mutants had a cortical phenotype similar to the Foxc1 null mutants. Lastly, in utero RA treatment rescued the cortical phenotype in Foxc1 mutants. These results establish RA as a potent, meningeal-derived cue required for successful corticogenesis.

GPAW: An open Python package for electronic structure calculations.

We review the GPAW open-source Python package for electronic structure calculations. GPAW is based on the projector-augmented wave method and can solve the self-consistent density functional theory (DFT) equations using three different wave-function representations, namely real-space grids, plane waves, and numerical atomic orbitals. The three representations are complementary and mutually independent and can be connected by transformations via the real-space grid. This multi-basis feature renders GPAW highly versatile and unique among similar codes. By virtue of its modular structure, the GPAW code constitutes an ideal platform for the implementation of new features and methodologies. Moreover, it is well integrated with the Atomic Simulation Environment (ASE), providing a flexible and dynamic user interface. In addition to ground-state DFT calculations, GPAW supports many-body GW band structures, optical excitations from the Bethe-Salpeter Equation, variational calculations of excited states in molecules and solids via direct optimization, and real-time propagation of the Kohn-Sham equations within time-dependent DFT. A range of more advanced methods to describe magnetic excitations and non-collinear magnetism in solids are also now available. In addition, GPAW can calculate non-linear optical tensors of solids, charged crystal point defects, and much more. Recently, support for graphics processing unit (GPU) acceleration has been achieved with minor modifications to the GPAW code thanks to the CuPy library. We end the review with an outlook, describing some future plans for GPAW.

Are Psychedelic Experiences Transformative? Can We Consent to Them?

Psychedelic substances have great promise for the treatment of many conditions, and they are the subject of intensive research. As with other medical treatments, both research and clinical use of psychedelics depend on our ability to ensure informed consent by patients and research participants. However, some have argued that informed consent for psychedelic use may be impossible, because psychedelic experiences can be transformative in the sense articulated by L. A. Paul (2014). For Paul, transformative experiences involve either the acquisition of knowledge that cannot be obtained in any other way or changes in the self. Either of these characteristics may appear to undermine informed consent. This article argues, however, that there is limited evidence that psychedelic experiences are transformative in Paul's sense, and that they may not differ in their transformative features from other common medical experiences for which informed consent is clearly possible. Further, even if psychedelic experiences can be transformative, informed consent is still possible. Because psychedelic experiences are importantly different in several respects from other medical experiences, this article closes with recommendations for how these differences should be reflected in informed consent processes.

Bladder Neck Contractures Stabilize After Placement of the Artificial Urinary Sphincter.

PURPOSE: For male cancer survivors, the combination of stress urinary incontinence and recurrent bladder neck contracture presents a management dilemma with poor consensus. Our objective was to assess the impact of artificial urinary sphincter placement on bladder neck contracture recurrence among prostate cancer survivors with stress urinary incontinence and bladder neck contracture. MATERIALS AND METHODS: Men electing artificial urinary sphincter placement at our institution undergo synchronous bladder neck contracture treatment if indicated. An institutional database was queried for men with stress urinary incontinence and ≥1 intervention for bladder neck contracture. Records were divided according to whether an artificial urinary sphincter was ever placed. The impact of artificial urinary sphincter placement on bladder neck contracture recurrence was assessed using a multivariable conditional survival analysis, with survival defined as the recurrence-free interval following bladder neck contracture intervention. The proportional hazards assumption was assessed on the basis of Schoenfeld residuals. RESULTS: The analytic cohort consisted of 118 in the artificial urinary sphincter group and 88 in the non-artificial urinary sphincter group. Patients in both groups underwent a median of 2 (range 1-8) bladder neck contracture interventions over the entire course of their care, encompassing 445 total bladder neck contracture interventions. The artificial urinary sphincter group was on average 2.6 years younger (P = .02) and had a higher pack-year smoking history (P < .01). The presence of an artificial urinary sphincter was associated with a 61% lower bladder neck contracture re-intervention rate (HR 0.39, P < .01, CI 0.30-0.50) at any time when accounting for number of prior bladder neck contracture interventions and bladder neck contracture risk factors. CONCLUSIONS: Artificial urinary sphincter placement is associated with a lower rate of bladder neck contracture re-intervention. Artificial urinary sphincter placement should not be delayed or avoided due to the presence of bladder neck contracture.

Artificial Urinary Sphincter Cuff Downsizing Improves Continence and Patient Satisfaction in Cases of Sub-cuff Atrophy.

PURPOSE: The management of artificial urinary sphincter sub-cuff atrophy remains controversial, and clinical outcomes are underreported. We intend to examine the impact of cuff downsizing in cases of isolated sub-cuff atrophy. MATERIALS AND METHODS: We reviewed our prospectively collected, institutionally approved quality improvement database for this study from 2011 to 2022. Institutional Review Board approval was obtained for the analysis. Sub-cuff atrophy in patients with post-prostatectomy incontinence was diagnosed with a clinical presentation of recurrent urinary leakage, serial pelvic films, cystoscopy, and patient evaluation. Outcomes were assessed with pad use, subjective measures, and American Urological Association Symptom Score scores. RESULTS: During the study interval, 871 encounters for artificial urinary sphincter placement were identified, 229 for revision or replacement, of which cuff downsizing for isolated cases of sub-cuff atrophy occurred in 34. Downsizing took place after a median of 6.5 years after initial artificial urinary sphincter placement. Of the patients, 97% reported subjective improvement and 93% experienced a decrease in daily incontinence pad use, with a mean±SD decrease of 2.2±1.45 pads (P < .01). American Urological Association Symptom Score bother scores decreased from pre-downsizing values by a mean±SD of 1.5±1.4 (P = .01). After a median follow-up of 1.8 years after downsizing, 24 (70.6%) of downsized cuffs remained in place, 2 (5.9%) were further downsized, 2 (5.9%) required replacement for mechanical failure, 4 (11.8%) underwent removal for erosion, and 2 (5.9%) underwent replacement for a herniated pressure regulating balloon. CONCLUSIONS: When diagnosed using objective criteria, cuff downsizing improves continence and patient satisfaction in cases of sub-cuff atrophy.

Urethral Stricture Formation After Artificial Urinary Sphincter Cuff Erosion Is Uncommon in the Absence of Pelvic Radiation.

PURPOSE: Reported rates of urethral stricture development after artificial urinary sphincter erosion are highly variable. We hypothesized that the risk of stricture is commensurate with the degree of erosion. MATERIALS AND METHODS: We reviewed our prospectively maintained quality improvement database for all patients with artificial urinary sphincter erosion from 2011 to 2022. The incidence of postoperative stricture development was compared to the severity of erosion using a graded scale: 1, <25% circumference; 2, 25%-50% circumference; 3, >50% and <100% circumference; and 4, 100% circumference. From 862 artificial urinary sphincter surgeries, 102 erosion cases were identified, and 63 with documented erosion severity were included for analysis. Additional analysis was performed on 28 cases without documented erosion severity for validation. RESULTS: Within the main cohort, urethral stricture developed in 22 (34.9%) patients. The incidence of stricture did not vary by grade of erosion (P = .73) and was not significantly higher in men with grade 4 erosion vs lower-grade erosions (32.7% vs 50.0%, P = .34). Radiation exposure was associated with a 41.1% higher incidence of stricture (P < .01) and nearly every stricture occurred in the setting of prior radiation (21 of 22; 95.5%). In the validation group, 10 (35.7%) developed stricture, mostly in the setting of radiation (8 of 10; 80%). Overall, 29 of 32 (90.6%) cases of stricture involved a history of radiation. CONCLUSIONS: Artificial urinary sphincter erosion does not lead to urethral stricture formation in most cases and is not associated with degree of erosion. Those who develop strictures nearly always have a history of pelvic radiation.

A Contemporary Analysis of Combat-related Urological Injuries: Data From the Department of Defense Trauma Registry.

PURPOSE: There has been little to no literature published on combat-related genitourinary injuries beyond 2013. With the goal of enhancing medical readiness prior to deployment and making recommendations to improve the long-term rehabilitation of service members as they become civilians, we sought to describe the incidence of combat-related genitourinary injuries and interventions from January 1, 2007, to March 17, 2020. MATERIALS AND METHODS: We conducted a retrospective analysis of the Department of Defense Trauma Registry, which is a prospectively maintained database, for the time between 2007 and 2020. We used predefined search criteria to primarily identify any casualties that arrived at a military treatment facility with urological-based injuries. RESULTS: The registry contained 25,897 adult casualties, of which 7.2% sustained urological injuries. The median age was 25. Explosive injuries (64%) and firearms (27%) predominated. The median injury severity score was 18 (IQR 10-29). Most patients survived until hospital discharge (94%). The most frequently injured organs were the scrotum (60%), testes (53%), penis (30%), and kidneys (30%). Massive transfusion protocols were activated in 35% of all patients who sustained a urological injury and accounted for 28% of all protocols between 2007 and 2020. CONCLUSIONS: The incidence of genitourinary trauma persistently increased for both military and civilian personnel as the U.S. remained actively engaged in major military conflicts during this period. Patients with genitourinary trauma in this data set were often associated with high injury severity scores and required an increased number of immediate and long-term resources for survival and rehabilitation.

Fundamental Drivers of Electrochemical Barriers.

We find that ion creation and destruction dominate the behavior of electrochemical reaction barriers, through grand-canonical electronic structure calculations of proton deposition on transition metal surfaces. We show that barriers respond to potential in a nonlinear manner and trace this to the continuous degree of electron transfer as an ion is created or destroyed. This explains both Marcus-like curvature and Hammond-like shifts. Across materials, we find the barrier energy to be driven primarily by the charge presented on the surface, which, in turn, is dictated by the native work function, a fundamentally different driving force than in nonelectrochemical systems.

Outcomes of an Algorithmic, Multidisciplinary Approach to Rectourethral Fistula Repair: A Pre- and Postintervention Quasi-Experimental Study.

BACKGROUND: Rectourethral fistulas are a rare yet severe complication of prostate surgery, pelvic irradiation therapy, or both. Multiple surgical repairs exist with widely varying success rates. OBJECTIVE: This study aimed to present our institutional multidisciplinary algorithm for rectourethral fistula repair and its outcomes. DESIGN: This was a retrospective, pre- and postintervention, quasi-experimental design, comparing the frequency of fistula healing and reversal of urinary and fecal diversion before and after implementation of our algorithm. SETTING: All patients who presented to the Duke University with rectourethral fistula between 2002 and 2019 were included. PATIENTS: This study included 79 patients treated for rectourethral fistula: 36 prealgorithm and 43 postalgorithm. INTERVENTIONS: Our multidisciplinary algorithm was implemented in 2012. Patients with fistulas <2 cm and without history of radiation therapy underwent York-Mason repair, whereas those with fistulas 2-3 cm or with prior irradiation underwent transperineal repair with gracilis flap interposition. Those with nonrepairable fistulas (>3 cm or fixed tissues) underwent pelvic exenteration. Before repair, the algorithm recommended all patients to undergo urinary and bowel diversion. MAIN OUTCOME MEASURES: The 2 primary outcomes were rectourethral fistula healing, defined as both radiographic and clinical resolutions, and reversal of urinary and fecal diversions. RESULTS: Frequency of fistula healing improved in the post- versus prealgorithm subgroups (93.1% vs 71.9%; p = 0.04). The relative risk of fistula healing pre- versus postintervention was 0.77 (0.61-0.98; p = 0.04) among the overall cohort. Eighteen patients (22.8%) underwent pelvic exenteration for nonrepairable fistulas and were not included in primary outcome measures. LIMITATIONS: Limitations include the study's retrospective nature, possible selection bias because of algorithmic patient selection, and small sample size. CONCLUSIONS: Implementation of a multidisciplinary institutional algorithm improved rectourethral fistula repair success with high rates of ostomy reversal. Proper patient selection and multidisciplinary involvement are paramount to this success. See Video Abstract at http://links.lww.com/DCR/B955 . RESULTADOS DE UN ABORDAJE ALGORTMICO Y MULTIDISCIPLINARIO PARA LA REPARACIN DE FSTULAS RECTOURETRALES UN ESTUDIO CUASIEXPERIMENTAL PREVIO Y POSTERIOR A LA INTERVENCIN: ANTECEDENTES:Las fístulas rectouretrales son una complicación rara pero grave de la cirugía de próstata, la radiación pélvica o ambas. Existen múltiples reparaciones quirúrgicas con tasas de éxito muy variables.OBJETIVO:Presentar el algoritmo multidisciplinario de nuestra institución para la reparación de fístulas rectouretrales y sus resultados.DISEÑO:Este fue un diseño retrospectivo, previo y posterior a la intervención, cuasiexperimental, que comparó la frecuencia de curación de la fístula y la reversión de la derivación urinaria y fecal antes y después de la implementación de nuestro algoritmo.ESCENARIO:Se incluyeron todos los pacientes que acudieron a Duke con fístula rectouretral entre 2002 y 2019.PACIENTES:Setenta y nueve pacientes fueron tratados por fístula rectouretral; 36 pre-algoritmo y 43 post-algoritmo.INTERVENCIONES:Nuestro algoritmo multidisciplinario se implementó en 2012. Los pacientes con fístulas <2 cm y sin antecedentes de radiación se sometieron a reparación de York-Mason, mientras que aquellos con fístulas de 2-3 cm o radiación pélvica previa se sometieron a reparación transperineal con interposición de colgajo de gracilis. Aquellos con fístulas no reparables (> 3 cm o tejidos fijos) fueron sometidos a exenteración pélvica. Antes de la reparación, el algoritmo recomomendó que todos los pacientes se sometieran a una derivación urinaria y fecal.PRINCIPALES MEDIDAS DE RESULTADO:Los dos resultados primarios fueron la curación de la fístula rectouretral, definida como la resolución radiográfica y clínica, y la reversión de las derivaciones urinaria y fecale.RESULTADOS:La frecuencia de curación de la fístula mejoró en el subgrupo post-algoritmo vs. pre-algoritmo (93.1% vs. 71.9%, p = 0.04). El riesgo relativo de curación de la fístula antes de la intervención en comparación con después de la intervención fue de 0.77 (0.61-0.98, p = 0.04) entre la cohorte general. Dieciocho pacientes (22.8%) se sometieron a exenteración pélvica por fístulas no reparables y, por lo tanto, no se incluyeron en las medidas de resultado primarias.LIMITACIONES:Las limitaciones de este estudio incluyen su naturaleza retrospectiva, posible sesgo de selección debido a la selección algorítmica de pacientes y un tamaño de muestra pequeño.CONCLUSIONES:La implementación de un algoritmo institucional multidisciplinario mejoró el éxito en la reparación de la fístula rectouretral con altas tasas de reversión de la ostomía. La selección adecuada de pacientes y la participación multidisciplinaria son fundamentales para este éxito. Consulte Video Resumen en http://links.lww.com/DCR/B955 . (Traducción-Dr. Jorge Silva Velazco ).

Urethroscopic Findings following Urethroplasty Predict the Need for Secondary Intervention in the Long Term: A Multi-Institutional Study from Trauma and Urologic Reconstructive Network of Surgeons.

PURPOSE: Postoperative surveillance urethroscopy has been shown to be an effective tool to predict reoperation within 1 year after urethroplasty. We aimed to evaluate early surveillance urethroscopy findings and long-term outcomes among urethroplasty patients in order to define the value of surveillance urethroscopy to predict failure. MATERIALS AND METHODS: We evaluated 304 patients with at least 4 years of followup after urethroplasty performed at 10 institutions across the United States and Canada. All patients were surveilled using a flexible 17Fr cystoscope and were categorized into 3 groups: 1) normal lumen, 2) large-caliber stricture (≥17Fr) defined as the ability of the cystoscope to easily pass the narrowing and 3) small-caliber stricture (<17Fr) that the cystoscope could not be passed. Failure was stricture recurrence requiring a secondary intervention. RESULTS: The median followup time was 64.4 months (range 55.3-80.6) and the time to initial surveillance urethroscopy was 3.7 months (range 3.1-4.8) following urethroplasty. Secondary interventions were performed in 29 of 194 (15%) with normal lumens, 11 of 60 (18.3%) with ≥17Fr strictures and 32 of 50 (64%) with <17Fr strictures (p <0.001). The 1-, 3- and 9-year cumulative probability of intervention was 0.01, 0.06 and 0.23 for normal, 0.05, 0.17 and 0.18 for ≥17Fr, and 0.32, 0.50 and 0.73 for <17Fr lumen groups, respectively. Patient-reported outcome measures performed poorly to differentiate the 3 groups. CONCLUSIONS: Early cystoscopic visualization of scar recurrence that narrows the lumen to <17Fr following urethroplasty is a significant long-term predictor for patients who will eventually undergo a secondary intervention.

Neuroethics across the Disorders of Consciousness Care Continuum.

This review provides an ethical analysis of disorders of consciousness (DoC) along the care continuum, from preinjury to injury, acute care to subacute care and early rehabilitation, and finally transitioning to chronic rehabilitation and societal reintegration. We provide an actionable, chronological assessment of ethical issues related to DoC care. This expands upon established ethics literature, which focuses almost exclusively on the clinical encounter for DoC. Our goal is to broaden the aperture of ethical analysis to address how social and environmental conditions predispose some persons to brain injury, and how such conditions might also pose barriers to meaningful societal reintegration after recovery.

A nearsighted force-training approach to systematically generate training data for the machine learning of large atomic structures.

A challenge of atomistic machine-learning (ML) methods is ensuring that the training data are suitable for the system being simulated, which is particularly challenging for systems with large numbers of atoms. Most atomistic ML approaches rely on the nearsightedness principle ("all chemistry is local"), using information about the position of an atom's neighbors to predict a per-atom energy. In this work, we develop a framework that exploits the nearsighted nature of ML models to systematically produce an appropriate training set for large structures. We use a per-atom uncertainty estimate to identify the most uncertain atoms and extract chunks centered around these atoms. It is crucial that these small chunks are both large enough to satisfy the ML's nearsighted principle (that is, filling the cutoff radius) and are large enough to be converged with respect to the electronic structure calculation. We present data indicating when the electronic structure calculations are converged with respect to the structure size, which fundamentally limits the accuracy of any nearsighted ML calculator. These new atomic chunks are calculated in electronic structures, and crucially, only a single force-that of the central atom-is added to the growing training set, preventing the noisy and irrelevant information from the piece's boundary from interfering with ML training. The resulting ML potentials are robust, despite requiring single-point calculations on only small reference structures and never seeing large training structures. We demonstrated our approach via structure optimization of a 260-atom structure and extended the approach to clusters with up to 1415 atoms.

Electrochemistry from the atomic scale, in the electronically grand-canonical ensemble.

The ability to simulate electrochemical reactions from first-principles has advanced significantly in recent years. Here, we discuss the atomistic interpretation of electrochemistry at three scales: from the electronic structure to elementary processes to constant-potential reactions. At each scale, we highlight the importance of the grand-canonical nature of the process and show that the grand-canonical energy is the natural thermodynamic state variable, which has the additional benefit of simplifying calculations. We show that atomic forces are the derivative of the grand-potential energy when the potential is fixed. We further examine the meaning of potential at the atomic scale and its link to the chemical potential and discuss the link between charge transfer and potential in several situations.

Genetics of adaptation in modern chicken.

We carried out whole genome resequencing of 127 chicken including red jungle fowl and multiple populations of commercial broilers and layers to perform a systematic screening of adaptive changes in modern chicken (Gallus gallus domesticus). We uncovered >21 million high quality SNPs of which 34% are newly detected variants. This panel comprises >115,000 predicted amino-acid altering substitutions as well as 1,100 SNPs predicted to be stop-gain or -loss, several of which reach high frequencies. Signatures of selection were investigated both through analyses of fixation and differentiation to reveal selective sweeps that may have had prominent roles during domestication and breed development. Contrasting wild and domestic chicken we confirmed selection at the BCO2 and TSHR loci and identified 34 putative sweeps co-localized with ALX1, KITLG, EPGR, IGF1, DLK1, JPT2, CRAMP1, and GLI3, among others. Analysis of enrichment between groups of wild vs. commercials and broilers vs. layers revealed a further panel of candidate genes including CORIN, SKIV2L2 implicated in pigmentation and LEPR, MEGF10 and SPEF2, suggestive of production-oriented selection. SNPs with marked allele frequency differences between wild and domestic chicken showed a highly significant deficiency in the proportion of amino-acid altering mutations (P<2.5×10-6). The results contribute to the understanding of major genetic changes that took place during the evolution of modern chickens and in poultry breeding.

Smell Changes and Efficacy of Nasal Theophylline (SCENT) irrigation: A randomized controlled trial for treatment of post-viral olfactory dysfunction.

OBJECTIVE: To evaluate the efficacy and safety of intranasal theophylline saline irrigation on olfactory recovery in patients with post-viral olfactory dysfunction (PVOD). METHODS: Between May 2019 and April 2020, we conducted a double-blinded, placebo-controlled randomized clinical trial of adults with 6-36 months of PVOD. Patients were randomized to nasal theophylline saline irrigation or placebo saline irrigation twice a day for 6 weeks. The primary outcome was the Global Rating of Smell Change. Secondary outcomes were changes in the University of Pennsylvania Smell Identification Test (UPSIT) and Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS). RESULTS: Twenty-two patients (n = 12, theophylline; n = 10, placebo) completed the study. Slightly more patients in the theophylline group (33%) reported improved smell compared to the placebo group (30%, difference 3.3%, 95% CI -35.6% to 42.3%). The median differences in pre- and post-treatment UPSIT and QOD-NS change between the two groups were 1 (95% CI -3 to 5) and -10 (95% CI -15 to -4), respectively in favor of theophylline. Three patients receiving theophylline and 2 receiving placebo had clinically meaningful improvements on the UPSIT (difference 5%, 95% CI -30% to 40%). There were no adverse events, and serum theophylline levels were undetectable in 10/10 patients. CONCLUSIONS: While safe, there were no clinically meaningful differences in olfactory change between the two groups except for olfaction-related quality of life, which was better with theophylline. The imprecise estimates suggest future trials will need substantially larger sample sizes or treatment modifications, such as increasing the theophylline dose, to observe larger treatment effects.

What is paradoxical lucidity? The answer begins with its definition.

Paradoxical lucidity in dementia is a clinically significant but understudied phenomenon. A provisional definition was proposed by the 2018 National Institute on Aging expert workshop and published in Alzheimer's and Dementia. However, several conceptual features of this definition remain vague, creating barriers to robust clinical research. Here, we critically analyze the provisional definition and present a refined definition that can be applied in clinical research. The refined definition is based on an analytic process our research group recently undertook to operationalize paradoxical lucidity for our own study protocol. Our goal is to facilitate debate and potentially harmonize interpretations of paradoxical lucidity among research groups.