Homoleptic hexa- and penta-coordinated gallium(I) amide complexes of ruthenium and molybdenum.

Reaction of neutral olefin complexes of ruthenium and molybdenum with GaTMP (TMP = 2,2,6,6-tetramethylpiperidinyl) by substitution leads to the formation of respective five- and six-coordinated homoleptic products. [Ru(GaTMP)5] (1) and [Mo(GaTMP)6] (2) were isolated and characterized. Core structure geometries were analyzed using continuous shape measure, and the complexes were subjected to DFT calculations unveiling competing π-interactions between the transition metal center and the amido substituent with the unoccupied pπ orbitals of the gallium.

Evaluating a rehabilitative intervention for substance-dependent patients with and without their accompanying children in Germany (KontextSucht): study protocol for a non-randomised trial.

INTRODUCTION: People suffering from substance use disorders often live in social contexts with children or are parents themselves. Addicted parents show specific substance-related problems while raising their children, which often leads to various lifelong consequences for the children. The German rehabilitative treatment system allows bringing children to inpatient treatment centres. This mixed-methods study evaluates a newly developed intervention, called 'KontextSucht' or 'AddictionContext', for parents in rehabilitation treatment centres concerning the effectiveness of the intervention in parenting and abstinence outcome. METHODS AND ANALYSIS: The study uses a two-stage parallel mixed-methods design. A feasibility study (stage 1) and a benefit assessment (stage 2) will be conducted to evaluate the intervention. Both parts of the study will be carried out with qualitative and quantitative work packages. German-speaking parents of children 0-14 years will be included in this study. Qualitative data will be analysed using qualitative content analyses, whereas quantitative data will be analysed descriptively using regression analysis as well as linear mixed models. ETHICS AND DISSEMINATION: All participants will receive detailed information on the study and sign informed consent before data collection. The research team has obtained the approval of the Ethical Review Committee at the Technical University of Munich in Germany and will follow all legislation rules regarding data protection. The study results will be published in peer-reviewed national and international journals. Furthermore, the study results will be included in an intervention manual distributed to treatment centres. TRIAL REGISTRATION NUMBER: DRKS00030950.

Surgical outcomes of laser in situ keratomileusis (LASIK) in patients with stable systemic disease.

PURPOSE: To evaluate the surgical outcome in terms of safety, efficacy, predictability, and retreatment rate of LASIK surgery in patients with controlled systemic diseases in comparison with healthy individuals. METHODS: The retrospective study included data from 1936 eyes of 976 patients with stable systemic diseases who underwent LASIK surgery between January 2016 and June 2019. The safety, efficacy, predictability of the surgery, and retreatment rate were evaluated in comparison with a control group comprising 1951 patients. The study was approved by the local ethics committee and adhered to the principles of the Declaration of Helsinki. Statistical analysis was performed using R team and the level of statistical significance was set at p < 0.05. RESULTS: All treatment groups demonstrated high safety and efficacy indices after LASIK surgery. Furthermore, the study arms demonstrated comparable predictability and retreatment rates to the control group in nearly all cases. Retreatment rates were significantly higher in the rheumatoid arthritis group (p = 0.03), while safety indices were significantly lower in the hay fever group compared to the control group (p = 0.004). No intra- or postoperative sight-threatening complications were documented. CONCLUSION: Our findings suggest that selected patients with stable systemic conditions can safely undergo LASIK surgery and achieve comparable outcomes to healthy individuals. Further research is needed to better understand the treatment outcomes in this challenging patient population.

All-Hydrocarbon-Ligated Superatomic Gold/Aluminum Clusters.

Key strategies in cluster synthesis include the use of modulating agents (e.g., coordinating additives). We studied the influence of various phosphines exhibiting different steric and electronic properties on the reduction of the Au(I) precursor to Au(0) clusters. We report a synthesis of the bimetallic clusters [Au6(AlCp*)6] = [Au6Al6](Cp*)6 (1) and [HAu7(AlCp*)6] = [HAu7Al6](Cp*)6 (2) (Cp* = pentamethylcyclopentadiene) using Au(I) precursors and AlCp*. The cluster [Au2(AlCp*)5] = [Au2Al5](Cp*)5 (3) was isolated and identified as an intermediate species in the reactions to 1 and 2. The processes of cluster growth and degradation were investigated by in situ 1H NMR and LIFDI-MS techniques. The structures of 1 and 2 were established by DFT geometry optimization. These octahedral clusters can both be described as closed-shell 18-electron superatoms.

Assignment of individual structures from intermetalloid nickel gallium cluster ensembles.

Poorly selective mixed-metal cluster synthesis and separation yield reaction solutions of inseparable intermetalloid cluster mixtures, which are often discarded. High-resolution mass spectrometry, however, can provide precise compositional data of such product mixtures. Structure assignments can be achieved by advanced computational screening and consideration of the complete structural space. Here, we experimentally verify structure and composition of a whole cluster ensemble by combining a set of spectroscopic techniques. Our study case are the very similar nickel/gallium clusters of M12, M13 and M14 core composition Ni6+xGa6+y (x + y ≤ 2). The rationalization of structure, bonding and reactivity is built upon the organometallic superatom cluster [Ni6Ga6](Cp*)6 = [Ga6](NiCp*)6 (1; Cp* = C5Me5). The structural conclusions are validated by reactivity tests using carbon monoxide, which selectively binds to Ni sites, whereas (triisopropylsilyl)acetylene selectively binds to Ga sites.

Development, piloting and evaluation of an app-supported psychosocial prevention intervention to strengthen participation in working life: a study protocol of a mixed-methods approach.

INTRODUCTION: Rates of incapacity to work due to mental disorders have increased in many European countries. The consequences of persistent stress can impact individuals' physical and psychological well-being and gradually develop into chronic stress. Mental disorders or symptoms of burn-out syndrome can have severe consequences. Mental disorders leading to work incapacity significantly burden the health system. Prevention interventions can protect against burn-out, depression, anxiety and other mental health disorders. Digital health is a promising approach to increase the utilisation of effective prevention interventions. This mixed-methods study evaluates a newly developed app-supported psychosocial prevention intervention called 'RV Fit Mental Health' to strengthen participation in working life. METHODS AND ANALYSIS: The study uses a three-stage parallel mixed-methods design. This study accompanies the development (stage 1), piloting (stage 2) and evaluation (stage 3) of the new intervention. Within the stages, there is a quantitative as well as a qualitative research strand. Employed persons with an incipient mental disorder will be included. Additionally, experts within the project or connected areas will be included. Quantitative data will be analysed using multifactorial variance analyses in a pre-post design. Qualitative data will be analysed using qualitative content analysis. The study is a comprehensive research approach to investigate the development, piloting and evaluation of an app-supported psychosocial app-based prevention intervention. The rigour of the study will be achieved through data triangulation. ETHICS AND DISSEMINATION: All participants will receive detailed study information and give written informed consent before data collection. Ethical approval was obtained from the Technical University of Munich Ethics Committee. All data collection will follow all legislative rules regarding data protection, also following the Declaration of Helsinki. The study results will be disseminated in peer-reviewed journals and presented at international conferences. TRIAL REGISTRATION NUMBERS: DRKS00030818 and DRKS00033080.

Photochemically generated reactive sites at ruthenium/gallium complexes: catalysis vs. cluster growth.

Irradiation of [Ru(GaCp*)3(SiEt3)H3] (1) at 350 nm induces reductive elimination of dihydrogen and triethylsilane and generates unsaturated Ru/Ga species. This photochemically induced cascading reductive elimination processes generate the reactive intermediate [Ru(GaCp*)3], which can be trapped by diphosphine coordination to yield the stable complex [(dppe)Ru(GaCp*)3] (4). The photochemically generated RuGa3 species is catalytically active in the hydrogenation of alkynes, which is further investigated by 1H NMR and mass spectrometry. Formation of intermetallic Ru/Ga clusters is observed as a competing and for the catalytic activity of the species limiting side reaction.

Metal-Metal Bonding in Late Transition-Metal [M2L5] Complexes: Exploring the Limits of the Isolobal Analogy between the CO and AlCp* Ligands.

Late dinuclear transition-metal (especially group 10 and 11) homoleptic carbonyl complexes are elusive species and have so far not been isolated. A typical example is the 30-electron species [Ni2(CO)5], the structure and bonding of which is still debated. We show that, by using the AlCp* ligand (isolobal to CO), it is possible to isolate and fully characterize [Ni2(AlCp*)5] (1), which inspired us to revisit by DFT calculations, the bonding situation within [Ni2L5] (L = CO, AlCp*) and other isoelectronic species. The short Ni-Ni X-ray distance in 1 (2.270 Å) should not be attributed to the existence of a typical localized triple-bond between the metals, but rather to a strong through-bond interaction involving the three bridging ligands via their donating lone pairs and accepting π* orbitals. In contrast, in the isostructural 32-electron [Au2(AlCp*)5] (2) cluster an orbital with M-M antibonding and Al...Al bonding character is occupied, which is in accordance with the particularly long Au-Au distance (3.856 Å) and rather short Al...Al contacts between the bridging ligands (2.843 Å). This work shows that, unlike late transition-metal [M2(CO)x] species, stable [M2(AlCp*)x] complexes can be isolated, owing to the subtle differences between CO and AlCp*. We propose a similar approach for rationalizing the bonding in the emblematic 34 electron species [Fe2(CO)9].

"Dynamical Docking" of Cyclic Dinuclear Au(I) Bis-N-heterocyclic Complexes Facilitates Their Binding to G-Quadruplexes.

With the aim to improve the design of metal complexes as stabilizers of noncanonical DNA secondary structures, namely, G-quadruplexes (G4s), a series of cyclic dinuclear Au(I) N-heterocyclic carbene complexes based on xanthine and benzimidazole ligands has been synthesized and characterized by various methods, including X-ray diffraction. Fluorescence resonance energy transfer (FRET) and CD DNA melting assays unraveled the compounds' stabilization properties toward G4s of different topologies of physiological relevance. Initial structure-activity relationships have been identified and recognize the family of xanthine derivatives as those more selective toward G4s versus duplex DNA. The binding modes and free-energy landscape of the most active xanthine derivative (featuring a propyl linker) with the promoter sequence cKIT1 have been studied by metadynamics. The atomistic simulations evidenced that the Au(I) compound interacts noncovalently with the top G4 tetrad. The theoretical results on the Au(I) complex/DNA Gibbs free energy of binding were experimentally validated by FRET DNA melting assays. The compounds have also been tested for their antiproliferative properties in human cancer cells in vitro, showing generally moderate activity. This study provides further insights into the biological activity of Au(I) organometallics acting via noncovalent interactions and underlines their promise for tunable targeted applications by appropriate chemical modifications.

Continuous Intracorneal Ring Implantation in Keratoconus: Efficacy, Predictive Factors, and Complications.

Purpose: To examine the clinical outcomes, predictors of visual improvement and complications of continuous intracorneal ring (ICCR) implantation in patients with keratoconus and confirmed contact-lens intolerance (CLI). Methods: This nonrandomized, multi-centric, retrospective cohort study examined visual, keratometric and clinical outcomes evaluated after a minimum follow-up of 2 months. Among the inclusion criteria for the standard treatment group (STG) were corrected distance visual acuity (CDVA) <20/25 Snellen, no central corneal scars, minimum corneal thickness >350µm, and central mean keratometry reading (meanK) <55 diopters. All other eyes were classified as non-standard treatment group. Results: A total of 118 eyes of 118 patients with aged 32 ± 11 years were included in this study. At a median follow-up of 161 days (interquartile range: 111-372 days) ICCR implantation improved the CDVA from a mean of 0.38 to 0.15 logMAR (p<0.0001). Our correlation analysis showed lower preoperative CDVA to be the single best predictor of CDVA improvement, with eyes of a CDVA of 20/80 or lower improving by 4.3 ± 2.0 lines on average. Eyes with a meanK >55 diopters gained 9.04±4.83 lines in UDVA and 2.86±3.09 lines in CDVA. However, postoperatively these eyes had a CDVA of 0.32±0.21 logMAR which is significantly inferior to the STG outcome (p=0.001372). Fifteen eyes (12.7%) had to undergo a ring exchange procedure because of refractive under- (9 eyes) or overcorrection (6 eyes). Two eyes (1.7%) experienced medical complications. Conclusion: This study confirms the inclusion criteria of ICCR implantation in KC eyes with CDVA <20/25 and CLI. Particularly in eyes with a preoperative CDVA <20/80 and a meanK <55 diopters, ICCR implantation should be considered due to its reversibility and low rates of serious complications. The main challenge remains in the low predictability of the magnitude of this improvement in eyes with CDVA >20/30.

Topographic, tomographic, and corneal wavefront asymmetry in keratoconus: towards an eye asymmetry index EASIX.

PURPOSE: The study aims to explore the intereye asymmetry in normal and keratoconic individuals and to evaluate the discriminant power of single and combined asymmetry parameters. METHODS: This is a retrospective designed study including 414 patients who had Pentacam Scheimpflug topographic and tomographic imaging in both eyes: 124 subjects with bilateral normal corneas evaluated for refractive surgery and 290 with keratoconus. All elevation-, pachymetric-, and volumetric-based data (56 parameters) were electronically retrieved and analyzed. Intereye asymmetry was determined by subtracting the lowest value from the highest value for each variable. The degree of asymmetry between each subject's eyes was calculated with intraclass correlation coefficients for all the parameters. Receiver operating characteristic curve was used to determine predictive accuracy and to identify optimal cutoffs of these values and combinations thereof. RESULTS: In the normal/keratoconus subjects the median intereye asymmetries were 0.30/3.45 for K2 (flat) meridian, 0.03/0.25 for BFS front, 1.00/15.00 for elevation back BFS apex, and 7.00/29.00 for pachy min. CONCLUSIONS: In addition to Rabinowitz's Kmax intereye asymmetry we propose pachymetric, elevation-based, and high-order corneal wavefront intereye asymmetry parameters to improve the diagnostic armamentarium of keratoconus.

Safety and complications after three different surface ablation techniques with mitomycin C: a retrospective analysis of 2757 eyes.

BACKGROUND: To evaluate the safety and spectrum of complications of three excimer laser surface ablation techniques (SATs) with an intraoperative application of mitomycin C (MMC) 0.02%. A retrospective, non-comparative large case series. METHODS: SATs were performed on 2757 eyes with a preoperative spherical equivalent (SE) of - 4.41 ± 2.44 and a Wavelight Allegretto 200 platform. Ablation zone diameters between 6.0 and 7.0 mm were used according to mesopic pupil size. All patients were treated with an intraoperative application of MMC for 30 to 90 s depending on refractive error. The mean follow-up time was > 3 months (107 ± 24 days). Complication range and incidence were analyzed retrospectively and safety index was calculated. RESULTS: Two thousand seven hundred and fifty-seven eyes met the inclusion criteria for surface ablation. Two thousand five hundred and seventy-three eyes were assigned to alcohol-assisted photorefractive keratectomy (APRK), 135 eyes to transepithelial photorefractive keratectomy (TPRK), and 49 eyes to off-flap epithelial laser in situ keratomileusis (EpiLASIK/EpiK). Overall, the safety index was 1.06 ± 0.28. Haze was graded according to the Fantes scale. Haze incidence rates were highest in the TPRK group (14.81%) and comparably low in APRK (2.95%) and EpiK (4.08%) groups. CONCLUSIONS: Intraoperative topical application of MMC (0.02%) results in good safety and no severe side effects. However, highest incidence of haze was observed after TPRK. The more frequent peripheral localization of haze might be attributed to large ablation zones and the wavefront optimized ablation profile especially in the PTK modus of the laser platform.

The germline genetic component of drug sensitivity in cancer cell lines.

Patients with seemingly the same tumour can respond very differently to treatment. There are strong, well-established effects of somatic mutations on drug efficacy, but there is at-most anecdotal evidence of a germline component to drug response. Here, we report a systematic survey of how inherited germline variants affect drug susceptibility in cancer cell lines. We develop a joint analysis approach that leverages both germline and somatic variants, before applying it to screening data from 993 cell lines and 265 drugs. Surprisingly, we find that the germline contribution to variation in drug susceptibility can be as large or larger than effects due to somatic mutations. Several of the associations identified have a direct relationship to the drug target. Finally, using 17-AAG response as an example, we show how germline effects in combination with transcriptomic data can be leveraged for improved patient stratification and to identify new markers for drug sensitivity.

LASIK and PRK in hyperopic astigmatic eyes: is early retreatment advisable?

PURPOSE: To analyze the refractive and keratometric stability in hyperopic astigmatic laser in situ keratomileusis (LASIK) or photorefractive keratectomy (PRK) during the first 6 months after surgery. PATIENTS AND METHODS: This retrospective cross-sectional study included 97 hyperopic eyes; 55 were treated with LASIK and 42 with PRK. Excimer ablation for all eyes was performed using the ALLEGRETTO excimer laser platform using a mitomycin C for PRK and a mechanical microkeratome for LASIK. Keratometric and refractive data were analyzed during three consecutive follow-up intervals (6 weeks, 3 months, and 6 months). The corneal topography was obtained using Scheimpflug topography, and subjective refractions were acquired by expert optometrists according to a standardized protocol. RESULTS: After 3 months, mean keratometry and spherical equivalent were stable after LASIK, whereas PRK-treated eyes presented statistically significant (P<0.001) regression of hyperopia. In eleven cases, hyperopic regression of >1 D occurred. The optical zone diameter did not correlate with the development of regression. CONCLUSION: After corneal laser refractive surgery, keratometric changes are followed by refractive changes and they occur up to 6 months after LASIK and for at least 6 months after PRK, and therefore, caution should be applied when retreatment is planned during the 1st year after surgery because hyperopic refractive regression can lead to suboptimal visual outcome. Keratometric and refractive stability is earlier achieved after LASIK, and therefore, retreatment may be independent of late regression.

A random forest approach to capture genetic effects in the presence of population structure.

The accurate mapping of causal variants in genome-wide association studies requires the consideration of both, confounding factors (for example, population structure) and nonlinear interactions between individual genetic variants. Here, we propose a method termed 'mixed random forest' that simultaneously accounts for population structure and captures nonlinear genetic effects. We test the model in simulation experiments and show that the mixed random forest approach improves detection power compared with established approaches. In an application to data from an outbred mouse population, we find that mixed random forest identifies associations that are more consistent with prior knowledge than competing methods. Further, our approach allows predicting phenotypes from genotypes with greater accuracy than any of the other methods that we tested. Our results show that approaches that simultaneously account for both, confounding due to population structure and epistatic interactions, are important to fully explain the heritable component of complex quantitative traits.

Do outside temperature and sunlight duration influence the outcome of laser refractive surgery? Results from the Hamburg Weather Study.

PURPOSE: To examine the impact of temperature and sunlight duration on refractive and visual outcome of laser-assisted in situ keratomileusis (LASIK) in myopic eyes. SETTING: University Medical Center Hamburg-Eppendorf, Germany, and Care Vision Refractive Centers, Germany. DESIGN: Retrospective, cross-sectional data analysis. METHODS: This study comprised 1,052 eyes of 1,052 consecutive myopic patients (419 males, 633 females; mean age at surgery 35.0±9.0 years) with a mean preoperative refractive spherical equivalent (SE) of -3.88±1.85 diopters (D). Two subgroups were defined, comprising patients undergoing surgery during either meteorological winter or summer. Manifest refraction, uncorrected, and corrected distant visual acuity (UDVA and CDVA) were assessed pre- and postoperatively. We applied robust regression analysis with efficiency index (EI), safety index (SI), and postoperative SE (in D) as dependent variables. RESULTS: At the 1-month (33.0±5.0 days) follow-up, the mean postoperative SE was -0.18±0.44 D. Bivariate comparisons showed that statistically significant better EI was related to days with lower temperature. We obtained a significant difference for SI which suggested that low temperature had a positive influence on SI. No change by more than one line on LogMAR scale was obtained. CONCLUSION: Although being statistically significant, there was no clinically relevant difference in the outcome of LASIK, which demonstrates its highly standardized quality. Prospective, longitudinal studies are warranted to address meteorotropic reactions through evaluating defined meteorological parameters.

Variation in the effectiveness of refractive surgery during the year: results from the Hamburg Weather Study.

PURPOSE: To examine the impact of seasonality on the refractive and visual outcomes of laser in situ keratomileusis (LASIK) in myopic eyes. SETTING: Department of Ophthalmology and Care Vision Refractive Centers, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. DESIGN: Retrospective cross-sectional data analysis. METHODS: Two subgroups were defined. The first comprised patients having surgery during meteorological winter and the second, patients having surgery during meteorological summer. The manifest refraction and uncorrected and corrected visual acuities were assessed preoperatively and postoperatively. Robust regression analysis was applied with the efficacy index, safety index, and postoperative SE as dependent variables. RESULTS: This study comprised 1052 eyes of 1052 consecutive myopic patients (419 men, 633 women; mean age at surgery 35.0 years ± 9.0 [SD]) with a mean preoperative refractive spherical equivalent (SE) of -3.88 ± 1.85 diopters (D). At the 1-month follow-up (mean 33.0 ± 5.0 days), the mean postoperative SE was -0.18 ± 0.44 D. The efficacy index was 0.023 higher in eyes with refractive surgery during summer than in eyes treated during winter (P=.032), indicating less efficacy during winter. The differences in the safety index and postoperative SE between summer and winter were not statistically significant. No eye had a change of more than 1 line on the logMAR scale (corrected distance visual acuity). CONCLUSIONS: Although the difference in the efficacy index was statistically significant, the difference in the outcomes of LASIK was not clinically relevant, which shows the procedure's highly standardized reliability. Prospective longitudinal studies are warranted to address meteorotropic reactions by evaluating defined meteorological parameters. FINANCIAL DISCLOSURE(S): No author has a financial or proprietary interest in any material or method mentioned.

Do air pressure and wind speed influence the outcome of myopic laser refractive surgery? Results from the Hamburg Weather Study.

Laser in situ keratomileusis (LASIK) is one of the dominant procedures for the surgical correction of refractive errors. Meteorotropic reaction has been described regarding the field of ophthalmology. This study was thus initiated to assess the impact of air pressure and wind speed on the refractive and visual outcome of LASIK in myopic eyes. Our study comprised 1,052 eyes of 1,052 consecutive myopic patients (419 males, 633 females; mean age at surgery 35.0 ± 9.0 years) with mean preoperative refractive spherical equivalent (SE) of -3.88 ± 1.85 diopters (D). Two subgroups were defined, which had undergone surgery either during meteorological winter or summer. Manifest refraction, uncorrected and corrected visual acuity were assessed pre- and post-operatively. We applied robust regression analysis with efficiency index (EI), safety index, and postoperative SE (D) as dependent variables. At the 1-month (33.0 ± 5.0 days) follow-up, the mean postoperative SE was -0.18 ± 0.44 D. Bivariate comparisons showed that statistically significant better EI was related to days with low to moderate air-pressure. This was confirmed by robust regression analysis. Moderate to high wind speed was related to more appropriate postoperative SE. No change by more than one line on logMar scale was obtained. Although being statistically significant, there is no clinically relevant difference in outcome of LASIK, which demonstrates its highly standardized quality. Prospective, longitudinal studies are warranted to address meteorotropic reactions through evaluating individual risk profiles.