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Abstract Introduction Frailty is common in critically ill patients and is associated with increased morbidity and mortality. There remains uncertainty as to the optimal method/timing of frailty assessment and the impact of care processes and adverse events on outcomes is unknown. We conducted a pilot study to inform on the conduct, design and feasibility of a multicenter study measuring frailty longitudinally during critical illness, care processes, occurrence of adverse events, and resultant outcomes. Methods Single-center pilot study enrolling patients over the age of 55 admitted to an Intensive Care Unit (ICU) for life-support interventions including mechanical ventilation, vasopressor therapy and/or renal replacement therapy. Frailty was measured on ICU admission and hospital discharge with the Clinical Frailty Scale (CFS), the Frailty Index (FI) and CFS at 6-month follow-up. Frailty was defined as CFS ≥ 5 and a FI ≥ 0.20. Processes of care and adverse events were measured during their ICU and hospital stay including nutritional support, mobility, nosocomial infections and delirium. ICU, hospital and 6 months were determined. Results In 49 patients enrolled, the mean (SD) age was 68.7 ± 7.9 with a 6-month mortality of 29%. Enrollment was 1 patient/per week. Frailty was successfully measured at different time points during the patients stay/follow-up and varied by method/timing of assessment; by CFS and FI, respectively, in 17/49 (36%), 23/49 (47%) on admission, 22/33 (67%), 21/33 (63%) on hospital discharge and 11/30 (37%) had a CFS ≥ 5 at 6 months. Processes of care and adverse events were readily captured during the ICU and ward stay with the exception of ward nutritional data. ICU, hospital outcomes and follow-up outcomes were worse in those who were frail irrespective of ascertainment method. Pre-existing frailty remained static in survivors, but progressed in non-frail survivors. Discussion In this pilot study, we demonstrate that frailty measurement in critically ill patients over the course and recovery of their illness is feasible, that processes of care and adverse events are readily captured, have developed the tools and obtained data necessary for the planning and conduct of a large multicenter trial studying the interaction between frailty and critical illness.

Androgen receptors are expressed in the kidney and serum testosterone is negatively associated with serum phosphate in males, suggesting a role of testosterone in renal phosphate handling. In this cross‐sectional study, we examined the association of serum total and free testosterone with acute phosphate and calcium excretion in males in response to an oral phosphate challenge. Thirty‐five healthy adult males with normal baseline testosterone levels consumed a 500 mg phosphorus drink and the urinary excretion of minerals, as well as levels of relevant circulating parameters, were assessed at baseline and hourly for 4 h. Serum total testosterone was positively associated with overall phosphate excretion (r = 0.35, p = 0.04) and calcium excretion (r = 0.44, p = 0.00) in response to the challenge. Serum free testosterone was positively associated with post‐challenge calcium excretion (r = 0.34, p = 0.048), but significance was not reached for phosphate excretion (r = 0.31, p = 0.07). Serum total and free testosterone were not associated with parathyroid hormone, fibroblast growth factor‐23, or vitamin D—key factors implicated in phosphate and calcium regulation. Overall, higher serum total testosterone levels in healthy middle‐aged males are associated with a greater capacity to acutely excrete phosphate and calcium after a single oral phosphate challenge, suggesting potential ramifications of testosterone deficiency related to mineral homeostasis. [ABSTRACT FROM AUTHOR]

Context. Species connectivity mapping is a technically challenging task for conservation practitioners and nongovernment organisations to undertake as it requires experience in geographic information systems and often some computer programming. Aims. We developed a decision support tool to provide spatial information and data on potential habitat connectivity and optimum connectivity pathways for a selection of forest-dependent vertebrate fauna in eastern and south-western Australia. Methods. We systematically searched spatial data repositories for Australian spatial datasets for modelling connectivity. A least cost paths and patch connectivity approach was used to map potential habitat connectivity for (1) a single species - the glossy black cockatoo (Calyptorhynchus lathami) of South East Queensland, and (2) four species guilds - rainforest pigeons, gliding possums, the black cockatoos of south-western Western Australia and a landscape level forest connectivity. Optimum connectivity pathways were assessed for protection status. Key results. In total 71 spatial datasets useful for habitat connectivity mapping were identified. Species and guild modelling found that the protection status for optimum connectivity pathways varied between 24.7% and 53.3%. A decision support mapping tool was then created to enable users to interactively explore the connectivity data and download the spatial datasets for further analysis. Conclusions. The development of a decision support tool for mapping habitat connectivity in eastern and south-western Australia represents a useful platform for conservation practitioners as it provides valuable spatial information on potential connectivity pathways for forest-dependent vertebrate fauna. Implications. The tool can aid in the prioritisation of conservation actions aimed at enhancing habitat connectivity and mitigating the impacts of habitat fragmentation on biodiversity in the two regions. [ABSTRACT FROM AUTHOR]

The world's forests are being increasingly disturbed from exposure to the compounding impacts of land use and climate change, in addition to natural disturbance regimes. Boreal forests have a lower level of deforestation compared to tropical forests, and while they have higher levels of natural disturbances, the accumulated impact of forest management for commodity production coupled with worsening fire weather conditions and other climate-related stressors is resulting in ecosystem degradation and loss of biodiversity. We used satellite-based time-series analysis of two canopy indices—canopy photosynthesis and canopy water stress—to calculate an index that maps the relative stability of forest canopies in the Canadian provinces of Ontario and Quebec. By drawing upon available spatial time-series data on logging, wildfire, and insect infestation impacts, we were able to attribute the causal determinants of areas identified as having unstable forest canopy. The slope of the two indices that comprise the stability index also provided information as to where the forest is recovering from prior disturbances. The stability analyses and associated spatial datasets are available in an interactive web-based mapping app. that can be used to map disturbed forest canopies and the attribution of disturbances to human or natural causes. This information can assist decision-makers in identifying areas that are potentially ecologically degraded and in need of restoration and those stable areas that are a priority for protection. [ABSTRACT FROM AUTHOR]

The Cox regression model or accelerated failure time regression models are often used for describing the relationship between survival outcomes and potential explanatory variables. These models assume the studied covariates are connected to the survival time or its distribution or their transformations through a function of a linear regression form. In this article, we propose nonparametric, nonlinear algorithms (deepAFT methods) based on deep artificial neural networks to model survival outcome data in the broad distribution family of accelerated failure time models. The proposed methods predict survival outcomes directly and tackle the problem of censoring via an imputation algorithm as well as re‐weighting and transformation techniques based on the inverse probabilities of censoring. Through extensive simulation studies, we confirm that the proposed deepAFT methods achieve accurate predictions. They outperform the existing regression models in prediction accuracy, while being flexible and robust in modeling covariate effects of various nonlinear forms. Their prediction performance is comparable to other established deep learning methods such as deepSurv and random survival forest methods. Even though the direct output is the expected survival time, the proposed AFT methods also provide predictions for distributional functions such as the cumulative hazard and survival functions without additional learning efforts. For situations where the popular Cox regression model may not be appropriate, the deepAFT methods provide useful and effective alternatives, as shown in simulations, and demonstrated in applications to a lymphoma clinical trial study. [ABSTRACT FROM AUTHOR]

We present an implementation for the calculation of molecular response properties using the algebraic-diagrammatic construction (ADC)/intermediate state representation approach. For the second-order ADC model [ADC(2)], a memory-efficient ansatz avoiding the storage of double excitation amplitudes is investigated. We compare the performance of different numerical algorithms for the solution of the underlying response equations for ADC(2) and show that our approach also strongly improves the convergence behavior for the investigated algorithms compared with the standard implementation. All routines are implemented in an open-source Python library. [ABSTRACT FROM AUTHOR]

Introduction: Vitamin D insufficiency is common in patients who receive hemodialysis, yet there is no clear guidance regarding surveillance or treatment. We hypothesized that increasing 25(OH)D3 levels is associated with lower phosphate, parathyroid hormone (PTH), and alkaline phosphatase (ALP). Methods: Baseline 25(OH)D3 level was measured in all patients receiving in-center hemodialysis in June 2017. Laboratory parameters were measured every 6 (phosphate, calcium) or 12 weeks (25(OH)D3, PTH, ALP) until February 2021. In September 2018, a treatment algorithm of 50,000 IU weekly until sufficient followed by 50,000 IU monthly was suggested. Generalized linear mixed regression models including linear spline effects, a log link function, and random effects were used to examine the impact of increasing 25(OH)D3 levels on calcium, phosphate, ALP, and PTH. Results: Of 697 participants, 15% and 57% had vitamin D deficiency (25(OH)D3 <25 nmol/L) and insufficiency (between 25 and 74 nmol/L). Incorporating up to 7,272 observations, increasing 25(OH)D3 was associated with significantly decreasing PTH for 25(OH)D3 levels between 25 and 75 nmol/L regardless of vitamin D treatment. In an interaction model, the negative slope between 25(OH)D3 and PTH remained significant beyond 75 nmol/L in the absence of calcitriol. Increasing 25(OH)D3 was associated with significantly decreasing phosphate for 25(OH)D3 levels between 25 and 75 nmol/L regardless of vitamin D treatment and below 25 nmol/L in values of untreated patients. Calcium increased across the spectrum of 25(OH)D3 regardless of vitamin D treatment. Overall, 0.2% of 25(OH)D3 levels exceeded 250 nmol/L and 2.1% of calcium levels exceeded the normal range. Conclusions: Vitamin D treatment in a real-world setting was safe and associated with lower PTH levels. Whether improved biochemical markers translate to a reduction in clinical endpoints warrants further study. [ABSTRACT FROM AUTHOR]

Context: The southern and central greater glider (Petauroides volans) is a nationally listed endangered species in Australia. The species depends upon mature native forest providing critical habitat resources including tree hollows. Aims: This study aimed to map and evaluate the tenure of patches of potential high-quality (core) habitat and corridors for the southern greater glider in Queensland. Methods: Within greater glider habitat, we mapped 10 ranked classes of relative forest maturity using a model comprising remotely sensed metrics of canopy height, above-ground living biomass and canopy cover at a 30 m resolution. We also modelled the optimum movement corridors within and between habitat patches. Key results: Results showed that 35% (4.943 million ha) of habitat was found in the more mature classes (Classes 7–9), which represent a proxy for associated limiting habitat resources, especially tree hollows. Mean patch size above a 1.6 ha threshold was found to be 122 ha and most patches (71%) were ≤10 ha, with 14 patches ≥100 000 ha. Freehold and leasehold lands hold 63.4% of the more mature habitat, multiple-use public forest 21.4% and nature conservation areas 12.8%. About half of the potential habitat is located on formally recognised Indigenous lands that represent different categories of Aboriginal ownership, management and other special rights. Conclusions: The protection of mature forest patches and movement corridors is necessary for the conservation of the greater glider, a nationally listed threatened species. Implications: Conservation interventions are needed, using a whole-of-landscape approach to protect core habitat and corridors from inappropriate land use. With increasing pressures on Australian forests, identifying old growth and mature habitats for threatened species is vital. We evaluated greater glider habitats and found that mature areas are vulnerable to human impacts. Protecting areas containing mature forests and hollow-bearing trees is crucial for the species' survival. [ABSTRACT FROM AUTHOR]

The Canadian boreal forest biome has been subjected to a long history of management for wood production. Here, we examined the cumulative impacts of logging on older forests in terms of area, distribution and patch configuration in the managed forest zones of the Eastern Canadian provinces of Ontario and Quebec. We also examined the consequences of these cumulative impacts on a once widely distributed and now threatened species, the woodland caribou (Rangifer tarandus caribou). The cumulative area of recently logged forest (since ~1976) was 14,024,619 ha, with 8,210,617 ha in Quebec and 5,814,002 ha in Ontario. The total area of older forests was 21,249,341 ha, with 11,840,474 ha in Quebec and 9,408,867 ha in Ontario. Patch statistics revealed that there were 1,085,822 older forests with core patches < 0.25 ha and an additional 603,052 < 1.0 ha. There were 52 > 10,00–50,000 ha and 8 < 50,000 ha. Older forest patches (critical caribou habitat) in the 21 local population ranges totalled 6,103,534 ha, distributed among ~387,102 patches with 362,933 < 10 ha and 14 > 50,000 ha. The median percentage of local population ranges that was disturbed was 53.5%, with Charlevoix having the maximum (90.3%) and Basse Côte-Nord the least (34.9%). Woodland caribou local population ranges with disturbed suitable habitats >35% are considered unable to support self-sustaining populations. We found that for the 21 caribou local population ranges examined, 3 were at very high risk (>75% area disturbed), 16 at high risk (>45 ≤ 75% area disturbed), and 2 at low risk (≤35% area disturbed). Major changes are needed in boreal forest management in Ontario and Quebec for it to be ecologically sustainable, including a greater emphasis on protection and restoration for older forests, and to lower the risks for caribou populations. [ABSTRACT FROM AUTHOR]

Expressions for analytical molecular gradients of core-excited states have been derived and implemented for the hierarchy of algebraic diagrammatic construction (ADC) methods up to extended second-order within the core–valence separation (CVS) approximation. We illustrate the use of CVS-ADC gradients by determining relaxed core-excited state potential energy surfaces and optimized geometries for water, formic acid, and benzene. For water, our results show that in the dissociative lowest core-excited state, a linear configuration is preferred. For formic acid, we find that the O K-edge lowest core-excited state is non-planar, a fact that is not captured by the equivalent core approximation where the core-excited atom with its hole is replaced by the "Z + 1" neighboring atom in the periodic table. For benzene, the core-excited state gradients are presented along the Jahn–Teller distorted geometry of the 1s → π* excited state. Our development may pave a new path to studying the dynamics of molecules in their core-excited states. [ABSTRACT FROM AUTHOR]

Distinct aggregated proteins are correlated with numerous neurodegenerative diseases and the development of ligands that selectively detect these pathological hallmarks is vital. Recently, the synthesis of thiophene‐based optical ligands, denoted bi‐thiophene‐vinyl‐benzothiazoles (bTVBTs), that could be utilized for selective assignment of tau pathology in brain tissue with Alzheimer's disease (AD) pathology, was reported. Herein, we investigate the ability of these ligands to selectively distinguish tau deposits from aggregated amyloid‐β (Aβ), the second AD associated pathological hallmark, when replacing the terminal thiophene moiety with other heterocyclic motifs. The selectivity for tau pathology was reduced when introducing specific heterocyclic motifs, verifying that specific molecular interactions between the ligands and the aggregates are necessary for selective detection of tau deposits. In addition, ligands having certain heterocyclic moieties attached to the central thiophene‐vinylene building block displayed selectivity to aggregated Aβ pathology. Our findings provide chemical insights for the development of ligands that can distinguish between aggregated proteinaceous species consisting of different proteins and might also aid in creating novel agents for clinical imaging of tau pathology in AD. [ABSTRACT FROM AUTHOR]

We describe a concise synthetic strategy for the preparation of heterocyclic [9]helicenes and a simple preparative‐scale protocol for the optical resolution of the resulting M‐ and P‐enantiomers. The helicenes were characterized by single‐crystal X‐ray diffraction along with a range of spectroscopic and computational techniques. A fluorescence quantum yield of up to 65 % was observed, and the chiroptical properties of both M‐ and P‐helicenes revealed large dissymmetry factors. The circularly polarized luminescence brightness reaches up to 17 M−1 cm−1, as measured experimentally and verified computationally, which makes this the highest circularly polarized luminescence brightness among heterocyclic helicenes. We describe how chiroptical properties (both circular dichroism and circularly polarized luminescence) can be described and predicted using quantum chemical calculations. The synthetic approach also reveals by‐products that originate from internal oxidation reactions, presumably mediated by the close proximity of the π‐surfaces in the helicene structure. [ABSTRACT FROM AUTHOR]

A theoretical and experimental study of the gas phase and liquid acetic acid based on resonant inelastic x-ray scattering (RIXS) spectroscopy is presented. We combine and compare different levels of theory for an isolated molecule for a comprehensive analysis, including electronic and vibrational degrees of freedom. The excitation energy scan over the oxygen K-edge absorption reveals nuclear dynamic effects in the core-excited and final electronic states. The theoretical simulations for the monomer and two different forms of the dimer are compared against high-resolution experimental data for pure liquid acetic acid. We show that the theoretical model based on a dimer describes the hydrogen bond formation in the liquid phase well and that this bond formation sufficiently alters the RIXS spectra, allowing us to trace these effects directly from the experiment. Multimode vibrational dynamics is accounted for in our simulations by using a hybrid time-dependent stationary approach for the quantum nuclear wave packet simulations, showing the important role it plays in RIXS. [ABSTRACT FROM AUTHOR]

While the anomalous non-additive size-dependencies of static dipole polarizabilities and van der Waals C6 dispersion coefficients of carbon fullerenes are well established, the widespread reported scalings for the latter (ranging from N2.2 to N2.8) call for a comprehensive first-principles investigation. With a highly efficient implementation of the linear complex polarization propagator, we have performed Hartree–Fock and Kohn–Sham density functional theory calculations of the frequency-dependent polarizabilities for fullerenes consisting of up to 540 carbon atoms. Our results for the static polarizabilities and C6 coefficients show scalings of N1.2 and N2.2, respectively, thereby deviating significantly from the previously reported values obtained with the use of semi-classical/empirical methods. Arguably, our reported values are the most accurate to date as they represent the first ab initio or first-principles treatment of fullerenes up to a convincing system size. [ABSTRACT FROM AUTHOR]

Expressions for the calculation of rotatory strengths using the algebraic diagrammatic construction (ADC) scheme of the polarization propagator in both length and velocity gauges have been implemented. This enables the simulation of electronic circular dichroism (ECD) spectra at the ADC level up to third order of perturbation theory. The ADC(n) methods produce rotatory strengths of comparable accuracy to those obtained with coupled cluster methods of corresponding approximation levels, as evaluated for methyloxirane, methylthiirane, dimethyloxirane, dimethylthiirane, hydrogen peroxide, and dihydrogen disulfide. ECD spectra of (1R)-camphor, (1R)-norcamphor, and (1R)-fenchone computed at the third order ADC(3) level of theory are shown to agree very favorably with experimental gas phase spectra, demonstrating the usefulness of ADC for the calculation of chiro-optical properties of organic molecules. ADC(2) in combination with the polarizable continuum model is shown to successfully reproduce the ECD spectrum of the L-epinephrine enantiomer in water, further demonstrating the applicability of this approach. [ABSTRACT FROM AUTHOR]

Within the self-consistent field approximation, computationally tractable expressions for the isotropic second-order hyperpolarizability have been derived and implemented for the calculation of two-photon absorption cross sections. The novel tensor average formulation presented in this work allows for the evaluation of isotropic damped cubic response functions using only ∼3.3% (one-photon off-resonance regions) and ∼10% (one-photon resonance regions) of the number of auxiliary Fock matrices required when explicitly calculating all the needed individual tensor components. Numerical examples of the two-photon absorption cross section in the one-photon off-resonance and resonance regions are provided for alanine–tryptophan and 2,5-dibromo-1,4-bis(2-(4-diphenylaminophenyl)vinyl)-benzene. Furthermore, a benchmark set of 22 additional small- and medium-sized organic molecules is considered. In all these calculations, a quantitative assessment is made of the reduced and approximate forms of the cubic response function in the one-photon off-resonance regions and results demonstrate a relative error of less than ∼5% when using the reduced expression as compared to the full form of the isotropic cubic response function. [ABSTRACT FROM AUTHOR]