Giant Star-shaped meso-substituted Fluorescent Porphyrins with Fluorenyl-containing Arms Designed for Two-photon Oxygen Photosensitization.

In the continuation of previous studies on carbon-rich meso-tetraarylporphyrins featuring 2,7-fluorene units at their periphery, the effect of changing the peripheral dendritic arms for linear arms on their oxygen-photosensitizing ability, their fluorescence and their two-photon absorption (2PA) properties is now analyzed. Thus, starburst porphyrins possessing up to twenty conjugated fluorenyl units were isolated and studied. More precisely, a series of five new free-base porphyrins featuring fully conjugated arms incorporating an increasing number of fluorenyl groups connected via 1,2-alkenyl spacers were synthesized, along with their Zn(II) complexes. Upon excitation in the arm-centred π-π* absorption band, an efficient energy transfer takes place from the peripheral fluorenyl units to the central porphyrin core, leading to intense red-light emission and oxygen photosensitization by the latter. More interestingly, while the linear optical properties of these porphyrins were only slightly improved compared to those of their dendrimer analogues for photodynamic therapy (PDT) or fluorescence imaging, their 2PA cross-sections were much more significantly boosted, evidencing the key role played by different structures on nonlinear optical properties. Finally, by comparison with other porphyrin-based two-photon photosensitizers reported in the literature, we show that these new "semi-disconnected" starburst systems exhibit a remarkable trade-off between intrinsic 2PA, fluorescence and oxygen photosensitization.

Predicting Carcass Weight of Grass-Fed Beef Cattle before Slaughter Using Statistical Modelling.

Gaining insights into the utilization of farm-level data for decision-making within the beef industry is vital for improving production and profitability. In this study, we present a statistical model to predict the carcass weight (CW) of grass-fed beef cattle at different stages before slaughter using historical cattle data. Models were developed using two approaches: boosted regression trees and multiple linear regression. A sample of 2995 grass-fed beef cattle from 3 major properties in Northern Australia was used in the modeling. Four timespans prior to the slaughter, i.e., 1 month, 3 months, 9-10 months, and at weaning, were considered in the predictive modelling. Seven predictors, i.e., weaning weight, weight gain since weaning to each stage before slaughter, time since weaning to each stage before slaughter, breed, sex, weaning season (wet and dry), and property, were used as the potential predictors of the CW. To assess the predictive performance in each scenario, a test set which was not used to train the models was utilized. The results showed that the CW of the cattle was strongly associated with the animal's body weight at each stage before slaughter. The results showed that the CW can be predicted with a mean absolute percentage error (MAPE) of 4% (~12-16 kg) at three months before slaughter. The predictive error increased gradually when moving away from the slaughter date, e.g., the prediction error at weaning was ~8% (~20-25 kg). The overall predictive performances of the two statistical approaches was approximately similar, and neither of the models substantially outperformed each other. Predicting the CW in advance of slaughter may allow farmers to adequately prepare for forthcoming needs at the farm level, such as changing husbandry practices, control inventory, and estimate price return, thus allowing them to maximize the profitability of the industry.

Allegory Analysis from M. Theresa - A Case Study.

In the following article, I will briefly introduce the method of Allegory Analysis (AA) (Guenther, 2020, 2021, in press) and then outline it in its application to the case study of. The goal of this article is to introduce AA and illustrate it using the particularly illustrative case of Theresa. It will be shown how AA can be a new psychotherapeutic method in the therapist's toolbox, with which the human psyche in its individual uniqueness can be understood in the clinical context through creative means. Allegories of patients are defined here as complex linguistic constructs of multiple metaphors and as expressions of complex affective perception and experience. In order to understand a human psyche through its allegories, AA proceeds in four steps: (1) picking up and describing the allegories, (2) summarizing them into a so-called allegory poem, (3) interpreting the allegories on the part of the therapist, and (4) participatory interpretation of the allegories with the patient. The present case of Theresa illustrates the application of the AA method in an outpatient psychotherapeutic context and shows how through AA. In Theresa's case, the client was found to be ideologically guided by values such as autonomy, freedom, honesty, sustainability, charity, and connectedness. Her psychosis represented an autopoietic self-healing attempt to recover these values, which had been inaccessible to her in the antecedent process. The AA showed that Theresa believes that crises in the market economy, interpersonal coexistence, and climate change are at a critical point that threatens the existence of the world and thus her psychological stability. Moreover, in Theresa's allegories, it is evident that she had managed to use her values and beliefs autopoietically to stabilize her crisis through her coping strategy: externalization through poetic-allegorical language.

On logistic regression with right censored data, with or without competing risks, and its use for estimating treatment effects.

Simple logistic regression can be adapted to deal with right-censoring by inverse probability of censoring weighting (IPCW). We here compare two such IPCW approaches, one based on weighting the outcome, the other based on weighting the estimating equations. We study the large sample properties of the two approaches and show that which of the two weighting methods is the most efficient depends on the censoring distribution. We show by theoretical computations that the methods can be surprisingly different in realistic settings. We further show how to use the two weighting approaches for logistic regression to estimate causal treatment effects, for both observational studies and randomized clinical trials (RCT). Several estimators for observational studies are compared and we present an application to registry data. We also revisit interesting robustness properties of logistic regression in the context of RCTs, with a particular focus on the IPCW weighting. We find that these robustness properties still hold when the censoring weights are correctly specified, but not necessarily otherwise.

Translation, Cross-Cultural Adaptation and Preliminary Validation of a French Version of the Trauma-Related Nightmare Survey (TRNS-FR) in a PTSD Veteran Population.

INTRODUCTION: In the military population, trauma-related nightmares (TRNs) are highly associated with deployments and combat-related events. Trauma-related nightmares are also correlated with severity, treatment resistance, and chronicity of Post-Traumatic Stress Disorder (PTSD). However, to date, no specific measure of TRNs has been validated for use in the French language. This study aimed to translate and culturally adapt the English version of the Trauma-Related Nightmare Survey into French and to evaluate the psychometric properties of the translation on veterans. MATERIALS AND METHODS: After the translation and cultural adaptation process, we evaluated the reliability and validity of the French version of the questionnaire (TRNS-FR) in a population of veterans suffering from PTSD with nightmare complaints (n = 56 patients for test-retest and n = 60 for internal consistency), recruited from five French military hospitals. RESULTS: Analyses demonstrated that TRNS-FR has good test-retest reliability (r = 0.59) and good internal consistency with PTSD symptoms, insomnia symptoms, and subjective sleep parameters assessed at home. This questionnaire provides a rapid and comprehensive assessment of sleep disturbance and a specific description of TRNs in the population of veterans with severe PTSD. Our results allowed us to propose a valid and reliable French adaptation of the questionnaire. CONCLUSION: Because sleep disturbances and TRNs require specific therapeutic management, the psychometric qualities of TRNS-FR make it a tool of choice for assessing TRNs in future clinical research settings.

Encapsulation of Hydrophobic Porphyrins into Biocompatible Nanoparticles: An Easy Way to Benefit of Their Two-Photon Phototherapeutic Effect without Hydrophilic Functionalization.

Star-shaped hydrophobic porphyrins, acting as powerful fluorescent two-photon photosensitizers for oxygen in organic solvents, can easily be loaded into PMLABe polymeric nanoparticles at various concentrations. In this contribution, the performance of these porphyrin-containing nanoparticles in terms of photodynamic therapy (PDT) is compared to those of the corresponding water-soluble porphyrin analogues when irradiated in MCF-7 cancer cells. While quite promising results are obtained for performing PDT with these nanoparticles, validating this approach as a mean for using more easily accessible and less expensive photosensitizers, from a synthetic perspective, we also show that their luminescence can still be used for bioimaging purposes in spite of their confinement in the nanoparticles, validating also the use of these nano-objects for theranostic purposes.

Synthesis and Photophysical Properties of 1,1,4,4-Tetracyanobutadienes Derived from Ynamides Bearing Fluorophores.

1,1,4,4-Tetracyanobutadienes (TCBDs) bearing a large diversity of fluorophores were prepared following a multi-step synthesis. In a crucial last step, all compounds were obtained from the corresponding ynamides, which were particularly suitable for the formation of the TCBDs in the presence of tetracyanoethylene via a [2+2] cycloaddition/retroelectrocyclization step (CA-RE). Several fluorenyl derivatives in addition to phenanthrenyl and terphenyl ones provided ynamide-based TCBDs affording remarkable emission properties covering a large range of wavelengths. Those compounds emit both in solid state and in solution from the visible region to the NIR range, depending on the molecular structures. Quantum yields in cyclohexane reached unforeseen values for such derivatives, up to 7.8 %. A huge sensitivity to the environment of the TCBDs has also been unraveled for most of the compounds since we observed a dramatic fall of the quantum yields when changing the solvent from cyclohexane to toluene, while they are almost non-emissive in dichloromethane.

Two-photon absorption properties of multipolar triarylamino/tosylamido 1,1,4,4-tetracyanobutadienes.

The synthesis and characterization of four new tetracyanobutadiene (TCBD) derivatives (1, 3c and 4b-c) incorporating tosylamido and 4-triphenylamino moieties are reported. Along with those of five closely related or differently branched TCBDs derivatives (2, 3a-b, 4c and 5), their linear and (third-order) nonlinear optical properties were investigated by electronic absorption spectroscopy and Z-scan measurements. Among these compounds, the tri-branched compounds 3c and 5 are the most active two-photon absorbers, with effective cross-sections of 275 and 350 GM at 900 nm, respectively. These properties are briefly discussed with the help of DFT calculations, focussing on structural and electronic factors, and contextualized with results obtained previously for related compounds.

1,1,4,4-Tetracyanobutadiene-Functionalized Anthracenes: Regioselectivity of Cycloadditions in the Synthesis of Small Near-IR Dyes.

Two small 1,1,4,4-tetracyanobutadiene-functionalized chromophores were obtained by careful leverage of the regioselectivity of the cycloaddition reaction of tetracyanoethylene with anthracene-ynamide derivatives, inducing either a [2 + 2] or a [4 + 2] Diels-Alder process. DFT calculations unraveled the mechanism of the [2 + 2] cycloaddition-retroelectrocyclization reaction sequence with ynamides and elucidated the differing mechanisms in the two substrates. The synthesized dyes presented panchromatic absorption extending into the near-IR and far-red/near-IR photoluminescence in the solid state up to 1550 nm.

Comparison of outcomes between Aurolab aqueous drainage implant placed in the superotemporal versus inferonasal quadrant.

AIM: To determine the outcomes of Aurolab aqueous drainage implant (AADI) placed in the superotemporal versus the inferonasal quadrant in adult eyes with refractory glaucoma. METHODS: This was a retrospective study of eyes that had AADI placement and completed a minimum of 2-year follow-up. The choice of the quadrant was at the surgeon's discretion and mainly depended on the amount of scarring and conjunctival mobility. The cumulative failure rate of the AADI was defined as intraocular pressure (IOP) >21 mm Hg or not reduced by 20% below baseline on two consecutive follow-up visits after 3 months, IOP ≤5 mm Hg on two consecutive follow-up visits after 3 months, reoperation for glaucoma or a complication, or loss of light perception vision. RESULTS: We included 84 eyes with AADI in the inferonasal quadrant versus 69 eyes in the superotemporal quadrant. A significant drop in IOP was seen in both groups (18.4±10.4 mm Hg in the inferonasal group vs 17.7±11.1 mm Hg in the superotemporal group; p=0.63) at 3-month follow-up and this was maintained until last follow-up. Best-corrected visual acuity, IOP, number of IOP-lowering medications and complications were similar between the two groups at all time points. The cumulative success rate at 2-year follow-up without IOP-lowering medications was 57.1% (47.1%-68.1%) in the inferonasal group and 50.7% (39.8%-63.1%) in the superotemporal group (p=0.47). CONCLUSIONS: Inferonasal AADI placement appears to be an equally safe and effective surgical option compared with superotemporal AADI placement and may be helpful in certain clinical situations.

1,3,5-Triaryl-1,3,5-Triazinane-2,4,6-Trithiones: Synthesis, Electronic Structure and Linear Optical Properties.

The synthesis of four new 1,3,5-triaryl-1,3,5-triazinane-2,4,6-trithione derivatives (thioisocyanurates) and two new partially thionated analogues from the corresponding 1,3,5-triaryl-1,3,5-triazinane-2,4,6-triones (isocyanurates) is reported, together with their spectroscopic properties. DFT calculations and comparison with the corresponding isocyanurates evidence the impact of the oxygen-for-sulfur replacement on the electronic structure and linear optical properties of these heterocycles. A bathochromic shift of the absorption bands and more efficient quenching of the fluorescence was observed.

Triarylisocyanurate-Based Fluorescent Two-Photon Absorbers.

The synthesis and characterization of six triarylisocyanurates, featuring 2,7-fluorenyl or 9,10-anthracenyl groups incorporated in their peripheral arms are reported. Photophysical studies reveal that these new octupolar derivatives are more fluorescent (ΦF ≥0.60 for all new compounds except for 1,3,5-tri(9H-fluoren-2-yl)-1,3,5-triazinane-2,4,6-trione 3) and present a red-shifted lowest absorption and emission compared to their known phenyl analogues of comparable size. Depending on the nature of the terminal substituent, fast intramolecular energy transfer among the three arms or localization of the excitation on a single branch occurs after population of their first singlet excited state. The latter effect was only observed in the presence of strongly electron-releasing substituents in polar media. These new chromophores are also better two-photon absorbers than the 1,4-phenylene-based isocyanurates reported so far, with cross sections σ2 ≥500 GM at 770 nm for 4-NPh2 the fluorenyl group containing (13) and the anthracenyl group containing (14) chromophores. All these spectroscopic features, analyzed with the help of quantum chemical calculations, are crucial for the design of new biphotonic fluorescent dyes.

Synthesis, characterization and unusual near-infrared luminescence of 1,1,4,4-tetracyanobutadiene derivatives.

Two 1,1,4,4-tetracyanobutadiene (TCBD) derivatives were prepared by [2+2]cycloaddition-retroelectrocyclization from ynamides bearing either a pyrene (1) or a perylene unit (2). In addition to panchromatic absorptions in 2, in the solid state, both compounds unexpectedly display NIR photoluminescence that could be detected up to about 1350 nm.

Phthalocyanine-Cored Fluorophores with Fluorene-Containing Peripheral Two-Photon Antennae as Photosensitizers for Singlet Oxygen Generation.

: A series of free base and Zn(II) phthalocyanines featuring fluorenyl antennae linked by methoxy or oxo bridges to the phthalocyanine core (Pc) were synthesized and characterized. Selected linear and nonlinear (two-photon absorption) optical properties of these new compounds were subsequently studied. As previously observed for related porphyrin dendrimers bearing 2-fluorenyl peripheral dendrons, an efficient energy transfer occurs from the peripheral antennae to the central phthalocyanine core following excitation in the fluorenyl-based π-π* absorption band of these chromophores. Once excited, these compounds relax to the ground state, mostly by emitting intense red light or by undergoing intersystem crossing. As a result, the tetrafunctionalized Zn(II) phthalocyanines are fluorescent, but can also efficiently photosensitize molecular oxygen in tetrahydrofurane (THF), forming singlet oxygen with nearly comparable yields to bare Zn(II) phthalocyanine (ZnPc). In comparison with the latter complex, the positive role of the fluorenyl-containing antennae on one- and two-photon brightness (2PA) is presently demonstrated when appended in peripheral (ß) position to the phthalocyanine core. Furthermore, when compared to known porphyrin analogues, the interest in replacing the porphyrin by a phthalocyanine as the central core to obtain more fluorescent two-photon oxygen photosensitizers is clearly established. As such, this contribution paves the way for the future development of innovative biphotonic photosensitizers usable in theranostics.

Intermediate-term outcomes of Aurolab aqueous drainage implant in refractory paediatric glaucoma.

AIM: To report the intermediate-term outcomes of Aurolab aqueous drainage implant (AADI) surgery in paediatric eyes with refractory glaucoma. METHODS: Case records of patients below 18 years, who underwent AADI surgery between 2012 and 2015 with >2 years follow-up, were analysed. The intraocular pressure (IOP), visual acuity, number of antiglaucoma medications, complications and resurgery if any were recorded at baseline, day 1and then at months 1, 3, 6, 9, 12, 18, 24 and at the last visit. Failure was defined as IOP >18 mm Hg or not reduced by at least 30% below baseline, IOP ≤5 mm Hg on two consecutive follow-up visits after 3 months, reoperation for a complication or loss of light perception vision. RESULTS: 101 eyes of 101 patients were included with a mean age of 10.4±4.7 years at the time of surgery and a mean follow-up of 40.9±15.1 months. Glaucoma following cataract surgery was the most common type of glaucoma (n=31, 30%), followed by primary congenital glaucoma (n=29, 29%). The cumulative probability of failure was 15.8% (95% CI 10.1% to 24.5%) at 1 year, 22.7% (95% CI 15.7% to 32.2%) at 2 years, 42.5% (95% CI 32.6% to 53.9%) at 3 years and 62.1% (95% CI 49.5% to 74.8%) at the 4 years time point. CONCLUSION: The AADI showed excellent success until 2 years after surgery in paediatric eyes after which failure rates increased. Further prospective studies with longer follow-up are required to evaluate the long-term success of the AADI for paediatric glaucomas.

Biocompatible conjugated fluorenylporphyrins for two-photon photodynamic therapy and fluorescence imaging.

The photophysical properties of a new series of fluorenyl porphyrins bearing water-solubilising oligoethyleneglycol chains are described. These biocompatible compounds present very good two-photon absorption and singlet oxygen generation properties, while retaining some fluorescence in water. After testing in vitro on breast cancer cells, some of them were shown to be efficient non-toxic two-photon photosensitisers allowing for fluorescence imaging, thus demonstrating their theranostic potential.

Fluorenylporphyrins functionalized by electrochromic ruthenium units as redox-triggered fluorescence switches.

Two dyads containing tris- and tetrakis-meso-fluorenyl-substituted porphyrin and ethynylruthenium units, 1 and 2, were investigated by emission spectro-electrochemical (SEC) methods for their potential use as fluorescence switches. The ruthenium group as a potential electron donor and the porphyrin as a potential electron acceptor are connected by a phenylene bridge in 1 and by a fluorenylene bridge in 2. The new fluorenyl-linked dyad 2 was probed by UV-visible, near-infrared (NIR) and infrared (IR) absorption SEC methods, and the properties interpreted with the aid of hybrid-DFT computations, for comparison with reported data for 1. The porphyrin-based fluorescence of 1 decreased in intensity upon oxidation to 1+ and decreased further on oxidising 1+ to 12+. A much weaker change in the fluorescence intensity of 2 was observed upon oxidation to 2+ but the intensity decreased upon subsequent oxidation of 2+ to 22+. These findings contrast with data reported for some other porphyrins appended with redox-active ruthenium or iron units, where fluorescence intensities increase upon oxidation of the peripheral metal centers, but they match data reported more recently for closely related arrays. A rationale for these apparently contrasting observations is proposed.

Differential Impact According to Mission's Operational Intensity on Psychoactive Substance Use: A Retrospective Cohort of French Male Army Service Members.

BACKGROUND: Stressful deployments in combat areas are known to increase the risk of substance abuse in military personnel. OBJECTIVES: The aim of the study was to compare deployment on stressful, high-intensity missions (HIMs) to deployment on low-intensity missions (LIMs) in order to understand factors associated with substance use variations across the mission. METHODS: A retrospective cohort study based on a one-shot self-questionnaire was performed four months after their return on two samples of male French Army service members: one returning from an HIM and one from an LIM. The questionnaire focused on tobacco, alcohol, cannabis, cocaine, and psychoactive medication use at three times: before, during, and after the mission. RESULTS: During an HIM, the frequency of tobacco use increased, alcohol use remained stable - although 38% declared a decrease in consumption - and illicit drug use decreased. During an LIM, tobacco and alcohol use increased, cannabis use remained stable, and only cocaine and medication use decreased. After their return, use levels among both samples reverted to values similar to those reported before the mission, except for a decrease in tobacco use observed at return from an HIM. The main factors perceived as related to variations were stress in an HIM and low cost in an LIM. Conclusions/importance: The study suggests a differential impact of deployment on substance use according to the operational intensity of the mission. Variations in use are predominant during the mission with a washout effect after returning home.

Synthesis, characterization and third-order nonlinear optical properties of a dodecaruthenium organometallic dendrimer with a zinc(ii) tetraphenylporphyrin core.

A new Zn(ii) porphyrin-based dendrimer (52) containing twelve Ru(ii) alkynyl fragments, has been prepared following a convergent approach in two steps from 5,10,15,20-tetra(4-ethynylphenyl)porphyrinatozinc(ii) (6). The cubic nonlinear optical (NLO) properties of 52 and other derivatives of 6 have been measured by third-harmonic generation (THG) at 1907 nm and by Z-scan over the spectral range 500-1700 nm, revealing the remarkable NLO response of 52 in the near-IR range. These results highlight the beneficial role of the extended "cross fourchée"-like polymetallic structure of 52 on its third-order NLO properties.

Linear and Third-Order Nonlinear Optical Properties of Triazobenzene-1,3,5-triazinane-2,4,6-trione (Isocyanurate) Derivatives.

The synthesis of three new isocyanurate derivatives 2-X (X=NO2 , H, NMe2 ) with azobenzene arms terminated by various X substituents is reported, and their linear and nonlinear absorption properties are studied. It is shown that mixtures that contain increased contents of cis-azo isomers can be reversibly generated upon photoirradiation at specific wavelengths from the most stable all-trans isomers with X=NO2 and H. In addition, we show that 2-X derivatives are two-photon absorbers with cross-section maxima around 120 GM for 2-NO2 , thus indicating that trans-to-cis isomerization might be achievable by two-photon excitation, whereas the photoinduced structural changes should have only a modest influence on these nonlinear absorption properties.