Stepwise Introduction Research Articles

Концептуальная модель интродукции дендрофлоры в северных широтах Русской равнины

The increasing of the socio-aesthetic significance of urban green spaces, especially in the formation of a rigid urbanized human habitat, initiates the development of the theoretical foundations of stepwise introduction in the northern direction. The aim of the research has been to generalize the regional features of the introduction of dendroflora species in the conditions of the European North of Russia. The methodological basis has been the works of specialists in the field of forest introduction, including Northern introducers F.B. Orlov, P.M. Malakhovets, V.N. Nilov, N.A. Demidova, O.S. Zalyvskaya, E.B. Karbasnikova et al. The results of the research have both theoretical and practical significance and are an integral part of the general theory of step-by-step introduction in the northern direction. In the process of many years of research and generalization of the experience of spontaneous introduction, an original working hypothesis of the stepwise introduction of woody plants in northern natural and climatic conditions has been formed and developed: for the urban environment, the presence of a special microclimate (heat island) is generally recognized and this microclimatic resource is sufficient for the successful naturalization of some species of dendroflora despite the introduction stress. The results of the work of the oldest introduction centres in the European North are briefly described. An algorithm and a regional strategy for the development of research of the introduction process of dendroflora species in the conditions of the North are presented. A conceptual scheme for the introduction testing of dendroflora species in the conditions of the northern latitudes of the Russian Plain has been proposed. There are 4 stages of acclimatization and 3 stages of naturalization. A number of scales have been developed that contribute to the improvement and optimization of introduction tests, and the assessment of sanitary, hygienic and social functions performed by introduced species of dendroflora. The richness of species diversity of urban dendroflora, new to northern conditions, is a good breeding base for further introduction tests and a scientific basis for predicting the success of the stepwise introduction of many valuable woody and shrub species to northern latitudes.

You cannot have both – Two different ways of change implementation and their effects on adaptive performance and frustration

The dynamics and frequency of change in today's workplaces force organizations to address the question of how to create optimal conditions for facilitating adaptation to change. Identifying critical factors that affect performance and well-being in change situations can help answer this question. Given the need for applied research in this area, the aim of this paper is to investigate whether the way of change implementation has an impact on performance and well-being. Additionally, retentivity and specific self-efficacy as individual factors are exploratorily investigated. In an experimental study, seventy-one participants learned and trained specific manufacturing steps in a simulated production environment. Subsequently, they had to adapt the trained task execution as some of the previously learned manufacturing steps were subject to change. The changes were implemented a) either in a stepwise manner or b) all at once. The executed manufacturing steps were recorded, enabling the calculation of task execution time and classification of adaptation errors. The results of Mann-Whitney-U-tests showed that the stepwise introduction of changes led to significantly faster task execution time than the change introduction all at once. Additionally, descriptive statistics indicated fewer adaptation errors but higher frustration. Our exploratory analysis showed a significant negative relationship between retentivity and task execution time, as well as between specific self-efficacy and frustration. Stepwise change introduction seems to be beneficial for adaptation, even though emotional responses and individual factors must be considered.

Petrochemical Industry for the Future

Petroleum has played a vital role as the major supplier of materials and energy during the evolution of human civilization. Given the change in demand for energy from high to low carbon and ultimately net zero carbon, the energy framework has undergone revolutionary changes. The energy attribute of petroleum will be gradually weakened, while the material and CO2 emission attributes will be gradually strengthened. Thus, the petrochemical processing basis, scientific concepts, and ideas will undergo major adjustments to reshape the petrochemical industry. Hence, it is necessary to reconsider the evolution of the petrochemical industry from a historical perspective and to clarify the historical causes, development contexts, and possible challenges in future development. Herein, we critically reassess the key drivers and rules guiding the development of the petrochemical industry and propose a reconstruction strategy based on simplified engineering thinking, innate nature of energy and material, and CO2 emissions, which can be realized through the integration of gasification with CO as the target product and recent C1 chemistry targeting the precise synthesis of chemicals. The concept of the petrochemical industry will change from the product-based process of selection and transformation of raw material molecules to the process of carbon atom reconfiguration driven by product CO2 emissions. More accurate management of C atoms can be accomplished with greatly improved utilization efficiency and the reduction of separation intensity and CO2 emissions via the stepwise introduction of a new approach in the current petrochemical industry.

Building Quality Control for Molecular Assays in the Global Measles and Rubella Laboratory Network.

More than 100 laboratories in the World Health Organization Global Measles and Rubella Laboratory Network (GMRLN) perform nucleic acid-based methods for case confirmation of measles or rubella infections and/or strain surveillance (genotyping). The quality of laboratory data is critical to ensure that diagnostic results and country reports to regional verification committees are based on accurate data. A molecular External Quality Assurance (mEQA) program was initiated by the US-CDC in 2014 to evaluate the performance of laboratories in the network. The inclusion of testing for measles and rubella viruses, with a focus on detection and genotyping, plus the diversity of assays and platforms employed required a flexible and comprehensive proficiency testing program. A stepwise introduction of new evaluation criteria gradually increased the stringency of the proficiency testing program, while giving laboratories time to implement the required changes. The mEQA program plays an important role in many processes in the GMRLN, including informing plans for the training of laboratory staff, access to reagents, and the submission of sequence data to global databases. The EQA program for Local Public Health Institutes in Japan is described as an example for national mEQA programs. As more laboratories initiate molecular testing, the mEQA will need to continue to expand and to adapt to the changing landscape for molecular testing.

Strategy for an early simultaneous introduction of four-pillars of heart failure therapy: results from a single center experience.

The 2021 European Society of Cardiology (ESC) Guidelines recommend the use of four different classes of drugs for heart failure with reduced ejection fraction (HFrEF): beta blockers (BB), sodium-glucose cotransporter-2 inhibitors (SGLT2i), angiotensin receptor/neprilysin inhibitor (ARNI), and mineralocorticoid receptor antagonists (MRAs). Moreover, the 2023 ESC updated Guidelines suggest an intensive strategy of initiation and rapid up-titration of evidence-based treatment before discharge, based on trials not using the four-pillars. We hypothesized that an early concomitantly administration and up-titration of four-pillars, compared with a conventional stepwise approach, may impact the vulnerable phase after hospitalization owing to HF. This prospective, single center, observational study included consecutive in-hospital patients with HFrEF. After performing propensity score matching, they were divided according to treatment strategy into group 1 (G1), with predischarge start of all four-pillars, with their up-titration within 1 month, and group 2 (G2) with the pre Guidelines update stepwise four-pillars introduction. HF hospitalization, cardiovascular (CV) death, and the composite of both were evaluated between the two groups at 6-month follow-up. The study included a total of 278 patients who completed 6-month follow-up (139 for both groups). There were no differences in terms of baseline features between the two groups. At survival analysis, HF hospitalization risk was significantly lower in G1 compared with G2 (p < 0.001), while no significant differences were observed regarding CV death (p = 0.642) or the composite of CV death and HF hospitalization (p = 0.135). In our real-world population, patients with HF treated with a predischarge and simultaneous use of four-pillars showed a reduced risk of HF hospitalizationduring the vulnerable phase after discharge, compared with a conventional stepwise approach.

Dietary Advancement Therapy Using Milk and Egg Ladders Among Children With a History of Anaphylaxis

BackgroundAnaphylaxis is increasing in recent years, with common triggers in infants being milk and eggs. Currently the mainstay of treatment for milk and/or egg allergy is strict avoidance. Recently new therapies have emerged including stepwise introduction of allergens via a ladder approach. The suitability of infants for the ladders is debated. ObjectiveThis study aims to focus on the use of food ladders in children with anaphylaxis to egg or milk. MethodsRetrospective review of paediatric patients diagnosed with IgE-mediated milk and/or egg allergy between 2011-2021. Inclusion and exclusion criteria applied. Anaphylaxis defined as per the World Allergy Organisation amended criteria 2020. Data analysis utilised SPSS Version 28. Results1552 patient charts reviewed, 1094 excluded (n=458). 70 infants had anaphylaxis at diagnosis (milk n=36, egg n=34). 77.8%-85.2% with anaphylaxis successfully completed the ladder, 88.9-92.9% without anaphylaxis were successful. Children who successfully completed the ladder did so at similar rates. 20.6-50% children presenting with anaphylaxis at diagnosis experienced allergic symptoms during treatment, compared to 17.3-40.7% without anaphylaxis. Reactions were mild, mostly cutaneous and not requiring medical attention. Patients experiencing allergic symptoms while on the ladder were less likely to successfully complete treatment. ConclusionMilk and egg ladders are a safe and effective way of inducing tolerance in infants, including those with a history of anaphylaxis at diagnosis. There are no obvious predictors for who will experience allergic reactions while on the ladder, however these children are less likely to complete the ladder so parents should be educated in management of mild allergic reactions at home.

What to do with foundation therapies for heart failure for patients with end-stage kidney disease on haemodialysis.

There is a significant burden of cardiovascular disease morbidity and mortality in the end-stage kidney disease population, driven by traditional and non-traditional risk factors. Despite its prevalence, heart failure is difficult to diagnose in the dialysis population due to overlapping clinical presentations, limitations of investigations, and the impact on the cardiorenal axis. 'Foundation therapies' are the key medications which improve patient outcomes in heart failure with reduced ejection fraction and include beta-blockers, renin-angiotensin-aldosterone system inhibitors and sodium-glucose cotransporter-2 inhibitors. They are underutilised in the dialysis population due to the exclusion of chronic kidney disease patients from major trials and legitimate clinical concerns e.g. hyperkalaemia, intradialytic hypotension and residual kidney function preservation. A coordinated cardiorenal multidisciplinary approach can guide appropriate diagnostic considerations (biomarkers interpretation, imaging, addressing unique complications of kidney disease), optimise dialysis management (prescription length, frequency and ultrafiltration targets) and when at euvolaemia facilitate the stepwise introduction of appropriate foundation therapies.

Stepwise introduction of stabilizing mutations reveals nonlinear additive effects in de novo TIM barrels.

Over the past decades, the TIM-barrel fold has served as a model system for the exploration of how changes in protein sequences affect their structural, stability, and functional characteristics, and moreover, how this information can be leveraged to design proteins from the ground up. After numerous attempts to design de novo proteins with this specific fold, sTIM11 was the first validated de novo design of an idealized four-fold symmetric TIM barrel. Subsequent efforts to enhance the stability of this initial design resulted in the development of DeNovoTIMs, a family of de novo TIM barrels with various stabilizing mutations. In this study, we present an investigation into the biophysical and thermodynamic effects upon introducing a varying number of stabilizing mutations per quarter along the sequence of a four-fold symmetric TIM barrel. We compared the base design DeNovoTIM0 without any stabilizing mutations with variants containing mutations in one, two, three, and all four quarters-designated TIM1q, TIM2q, TIM3q, and DeNovoTIM6, respectively. This analysis revealed a stepwise and nonlinear change in the thermodynamic properties that correlated with the number of mutated quarters, suggesting positive nonadditive effects. To shed light on the significance of the location of stabilized quarters, we engineered two variants of TIM2q which contain the same number of mutations but positioned in different quarter locations. Characterization of these TIM2q variants revealed that the mutations exhibit varying effects on the overall protein stability, contingent upon the specific region in which they are introduced. These findings emphasize that the amount and location of stabilized interfaces among the four quarters play a crucial role in shaping the conformational stability of these four-fold symmetric TIM barrels. Analysis of de novo proteins, as described in this study, enhances our understanding of how sequence variations can finely modulate stability in both naturally occurring and computationally designed proteins.

The influence of the da Vinci surgical robot on electromagnetic tracking in a clinical environment

Robot-assisted surgery is increasingly used in surgery for cancer. Reduced overview and loss of anatomical orientation are challenges that might be solved with image-guided surgical navigation using electromagnetic tracking (EMT). However, the robot’s presence may distort the electromagnetic field, affecting EMT accuracy. The aim of this study was to evaluate the robot’s influence on EMT accuracy. For this purpose, two different electromagnetic field generators were used inside a clinical surgical environment: a table top field generator (TTFG) and a planar field generator (PFG). The position and orientation of sensors within the electromagnetic field were measured using an accurate in-house developed 3D board. Baseline accuracy was measured without the robot, followed by stepwise introduction of potential distortion sources (robot and robotic instruments). The absolute accuracy was determined within the entire 3D board and in the clinical working volume. For the baseline setup, median errors in the entire tracking volume within the 3D board were 0.9 mm and 0.3° (TTFG), and 1.1 mm and 0.4° (PFG). Adding the robot and instruments did not affect the TTFG’s position accuracy (p = 0.60), while the PFG’s accuracies decreased to 1.5 mm and 0.7° (p < 0.001). For both field generators, when adding robot and instruments, accuracies inside the clinical working volume were higher compared to the entire tracking 3D board volume, 0.7 mm and 0.3° (TTFG), and 1.1 mm and 0.7° (PFG). Introduction of a surgical robot and robotic instruments shows limited distortion of the EMT field, allowing sufficient accuracy for surgical navigation in robotic procedures.

Switching Product Selectivity in Immobilized Tungstate Catalysts by Control of Hydrophobicity of Mesoporous Silicate Supports

AbstractNovel mesoporous silicates modified with imidazolium cation were applied as the support for peroxotungstate. Stepwise introduction of multiple functional groups to SBA‐15 was achieved by the combination of the direct and post‐synthesis procedures. The co‐condensation of tetraethoxysilane and 3‐(imidazolyl‐1‐yl)‐propyltriethoxysilane in the presence of the micelles of an amphiphilic surfactant yields the hydrophilic SBA‐15 type silicate support with the imidazole modifier locating into the mesopores. The hydrophobic environment of the supports was imparted by capping the residual silanols on the silicate surface with trimethylsilyl groups. The fluoroalkyl‐ or alkyl‐imidazolium cation‐anchored supports were derived from the corresponding imidazole‐functionalized precursors. The anion‐exchanging reaction between peroxytungstate and the imidazolium cation‐anchored supports yielded the corresponding tungstate‐immobilized catalysts. The hydrophilic catalyst with the fluoroalkyl‐imidazolium mediated alkene epoxidation with H2O2 in less polar solvents. The hydrophobic one, in contrast, produced diol through the epoxidation and following hydration in an aqueous solvent by the action of the highly Lewis acidic tungsten. The hydrophobic catalysts had the advantage of being more tolerant than hydrophilic catalysts, as evidenced by reusability tests. The activities of the alkyl‐imidazolium catalysts were lower than those of the corresponding fluoroalkyl‐imidazolium catalysts, indicating that the local structures surrounding the tungstate site affected the catalytic performance.

From Development to Place in Therapy of Lorlatinib for the Treatment of ALK and ROS1 Rearranged Non-Small Cell Lung Cancer (NSCLC).

Following the results of the CROWN phase III trial, the third-generation macrocyclic ALK inhibitor lorlatinib has been introduced as a salvage option after the failure of a first-line TKI in ALK-rearranged NSCLC, while its precise role in the therapeutic algorithm of ROS1 positive disease is still to be completely defined. The ability to overcome acquired resistance to prior generation TKIs (alectinib, brigatinib, ceritinib, and crizotinib) and the high intracranial activity in brain metastatic disease thanks to increased blood-brain barrier penetration are the reasons for the growing popularity and interest in this molecule. Nevertheless, the major vulnerability of this drug resides in a peculiar profile of related collateral events, with neurological impairment being the most conflicting and debated clinical issue. The cognitive safety concern, the susceptibility to heterogeneous resistance pathways, and the absence of a valid alternative in the second line are strongly jeopardizing a potential paradigm shift in this oncogene-addicted disease. So, when prescribing lorlatinib, clinicians must face two diametrically opposed characteristics: a great therapeutic potential without the intrinsic limitations of its precursor TKIs, a cytotoxic activity threatened by suboptimal tolerability, and the unavoidable onset of resistance mechanisms we cannot properly manage yet. In this paper, we give a critical point of view on the stepwise introduction of this promising drug into clinical practice, starting from its innovative molecular and biochemical properties to intriguing future developments, without forgetting its weaknesses.

Stepwise Introduction of Elexacaftor-Tezacaftor-Ivacaftor in Patients With Cystic Fibrosis and Liver Cirrhosis Child-Pugh A or B Using Clinical and Therapeutic Drug Monitoring: A Case Series

Cystic fibrosis (CF) is a monogenetic disease caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein and affecting multiple organs, including the lungs and liver. Almost 90% of people affected carry at least 1 Phe508del CFTR mutation. Medical treatment with the CFTR-modulating drug elexacaftor-tezacaftor-ivacaftor (ETI) has been proven to be efficacious in carriers of at least 1 Phe508del CFTR mutation. Use of ETI in patients with CF (pwCF) and liver cirrhosis is still controversial. Therefore, stepwise introduction of ETI in pwCF and liver cirrhosis Child-Pugh A or B was evaluated using clinical and therapeutic drug monitoring. Seven consecutive pwCF received ETI. Four dosing steps were defined, at each of which the patients underwent clinical examination, routine blood tests, and therapeutic drug monitoring. Exposure of elexacaftor, tezacaftor, and ivacaftor was assessed by means of determination of AUC. ETI was successfully introduced and maintained in all pwCF. In those with Child-Pugh B cirrhosis (n = 2), diminishment of the dose as recommended by the label resulted in AUC values that were lower than the mean AUC values in pwCF without hepatic impairment, as reported previously. Despite the limitations of this small case series, stepwise elevation of ETI dose did not induce clinical adverse effects or increases in serum liver test results under strict clinical follow-up and therapeutic drug monitoring, and may allow tolerable introduction of this therapy in pwCF and cirrhosis Child-Pugh A and possibly B.

OGC O05 Linear stapled technique for robotic assisted minimally invasive oesophagectomy and gastrectomy: technique, stepwise introduction, reproducibility and outcomes

Abstract Background Robotic-assisted surgery (RAS) for oesophagectomy and gastrectomy is gaining in popularity. Compared to open oesophagectomy and conventional minimally invasive techniques, RAS is associated with decreased rates of complications, increased harvested lymph nodes and shorter length-of-stay. However, high anastomotic leak rates (20-27%) have been seen within randomised trials and case series, with up to 50% early in some published series. We present our technique for a linear anastomosis and the results of its staged introduction. Methods Initially developed by a single surgeon at open surgery, it was adapted to thoracoscopic procedures and then reproduced during RAS by several surgeons across two centres. Using a prospectively maintained database we reviewed the first sixty-three cases utilising a modified linear anastomosis technique for oesophageal anastomosis. Outcomes, with particular focus on the anastomosis were reviewed. We also describe in detail the technical steps involved in our technique for a side-to-side linear semi-mechanical stapled anastomosis using a tri-stapler with a 2-layer V-lock closure of the common enterotomy, during robotic surgery (video). Results Sixty-one patients had a two-stage oesophagectomy (one for benign disease), one with colonic reconstruction and two total gastrectomy. Median age was 63 (range 47-85). 89% (55/62) were adenocarcinomas, the remainder squamous cell carcinomas. The anastomosis was performed via an open approach initially in 11, thoracoscopically in 4, then robotically in 48 (including the gastrectomies). The first 20 anastomoses were performed by one surgeon, who then proctored four others. Two Type I anastomotic leaks (3.2%) and two Type I conduit necrosis occurred. There was no in hospital mortality. Non-anastomotic complications occurred in 28/63 (44.4%) of patients, most commonly respiratory (15/63, 23.8%). Conclusions We report a reproducible technique for semi-mechanical linear stapled anastomosis and its safe introduction into oesophageal and gastric resections including RAS, with anastomotic leak rates below the internationally reported rates, even in the early phase of its introduction in open, thoracoscopic and RAS. This technique, combined with training and mentorship may help more centres safely introduce a RAS oesophago-gastric programme, and improve patient outcomes.

Nexus Evaluation Primary Trident II UNcemented shEll (NEPTUNE).

The primary aim of this study is to assess the survival of the uncemented hydroxyapatite (HA) coated Trident II acetabular component as part of a hybrid total hip arthroplasty (THA) using a cemented Exeter stem. The secondary aims are to assess the complications, joint-specific function, health-related quality of life, and radiological signs of loosening of the acetabular component. A single-centre, prospective cohort study of 125 implants will be undertaken. Patients undergoing hybrid THA at the study centre will be recruited. Inclusion criteria are patients suitable for the use of the uncemented acetabular component, aged 18 to 75 years, willing and able to comply with the study protocol, and provide informed consent. Exclusion criteria includes patients not meeting study inclusion criteria, inadequate bone stock to support fixation of the prosthesis, a BMI > 40 kg/m2, or THA performed for pain relief in those with severely restricted mobility. Implant survival, complications, functional outcomes and radiological assessment up to ten years following index THA (one, two, five, seven, and ten years) will be performed. Functional assessment will include the Oxford Hip Score, Forgotten Joint Score, 12-Item Short Form Health Survey, EuroQol five-dimension health questionnaire, and pain and patient satisfaction. Radiological assessment with assess for acetabula lucent lines, lysis, and loosening according to DeLee and Charnley zones. This study is part of a stepwise introduction of a new device to orthopaedic practice, and careful monitoring of implants should be carried out as part of the Beyond Compliance principles. The results of this study will provide functional, radiological, and survival data to either support the ongoing use of the HA acetabulum or highlight potential limitations of this new implant before wide adoption.

Large-scale template-based structural modeling of T-cell receptors with known antigen specificity reveals complementarity features.

T-cell receptor (TCR) recognition of foreign peptides presented by the major histocompatibility complex (MHC) initiates the adaptive immune response against pathogens. While a large number of TCR sequences specific to different antigenic peptides are known to date, the structural data describing the conformation and contacting residues for TCR-peptide-MHC complexes is relatively limited. In the present study we aim to extend and analyze the set of available structures by performing highly accurate template-based modeling of these complexes using TCR sequences with known specificity. Identification of CDR3 sequences and their further clustering, based on available spatial structures, V- and J-genes of corresponding T-cell receptors, and epitopes, was performed using the VDJdb database. Modeling of the selected CDR3 loops was conducted using a stepwise introduction of single amino acid substitutions to the template PDB structures, followed by optimization of the TCR-peptide-MHC contacting interface using the Rosetta package applications. Statistical analysis and recursive feature elimination procedures were carried out on computed energy values and properties of contacting amino acid residues between CDR3 loops and peptides, using R. Using the set of 29 complex templates (including a template with SARS-CoV-2 antigen) and 732 specificity records, we built a database of 1585 model structures carrying substitutions in either TCRα or TCRβ chains with some models representing the result of different mutation pathways for the same final structure. This database allowed us to analyze features of amino acid contacts in TCR - peptide interfaces that govern antigen recognition preferences and interpret these interactions in terms of physicochemical properties of interacting residues. Our results provide a methodology for creating high-quality TCR-peptide-MHC models for antigens of interest that can be utilized to predict TCR specificity.

Baked Milk and Baked Egg Survey: A Work Group Report of the AAAAI Adverse Reactions to Foods Committee.

Most milk- and egg-allergic children can tolerate milk and egg in baked forms. Some allergists have extended the use of baked milk (BM) and baked egg (BE) to advocating for the stepwise introduction of small amounts of BM and BE to children who are reactive to larger amounts of BM and BE. Little is known about the practice of introducing BM and BE and existing barriers to this approach. The purpose of this study was to gather a current assessment of the implementation of BM and BE oral food challenges and diets for milk- and egg-allergic children. We conducted an electronic survey of North American Academy of Allergy, Asthma & Immunology members offering BM and BE introduction in 2021. The response rate was 10.1% of distributed surveys (72 of 711). Surveyed allergists had a similar approach to both BM and BE introduction. Demographic features of time in practice and region of practice were significantly associated with the odds of introducing BM and BE. A wide variety of tests and clinical features guided decisions. Some allergists determined BM and BE to be appropriate for home introduction and offered this for BM and BE more often than other foods. The use of BM and BE as a food for oral immunotherapy was endorsed by almost half of respondents. Less time in practice was the most significant factor associated with offering this approach. Published recipes were used and written information was widely provided to patients by most allergists. The wide practice variabilities reveal a need for more structured guidance about oral food challenges, in-office versus home procedures, and patient education.

Heterometallic lanthanide complexes with site-specific binding that enable simultaneous visible and NIR-emission.

Macrocyclic lanthanide complexes have become widely developed due to their distinctive luminescence characteristics and wide range of applications in biological imaging. However, systems with sufficient brightness and metal selectivity can be difficult to produce on a molecular scale. Presented herein is the stepwise introduction of differing lanthanide ions in a bis-DO3A/DTPA scaffold to afford three trinuclear bimetallic [Ln2Ln'] lanthanide complexes with site-specific, controlled binding [(Yb2Tb), (Eu2Tb), (Yb2Eu)]. The complexes display simultaneous emission from all LnIII centers across the visible (TbIII, EuIII) and near infra-red (YbIII) spectrum when excited via phenyl ligand sensitization at a wide range of temperatures and are consequently of interest for exploiting imaging in the near infra-red II biological window. Analysis of lifetime data over a range of excitation regimes reveals intermetallic communication between TbIII and EuIII centers and further develops the understanding of multimetallic lanthanide complexes.

Precarious Manhood Beliefs Are Positively Associated with Erectile Dysfunction in Cisgender Men.

The notions that manhood is hard to attain, easy to lose, and needs to be proven via public action constitute precarious manhood beliefs (PMB). PMB is a new concept and it remains unclear whether and how PMB relate to erectile dysfunction (ED) in cisgender men. The ability to achieve an erection remains considered as a cornerstone of masculinity and sexual performance can be conceived as a proof of one's masculinity. In this context, ED can be received as sexual failure and a threat to a man's masculinity and sense of adequacy. For these reasons, the hypothesis that PMB are associated with ED warranted empirical testing. In an anonymous online survey focusing on men's mental health conducted in German-speaking countries of Europe, 507 cisgender men (Mage = 44.2, SDage = 15.2) completed measures on PMB, sexual function, self-stigma, social desirability, and conformity to traditional masculinity ideology (TMI). Multilinear regression analysis with stepwise introduction of relevant covariates evaluated potential associations between PMB and ED. Of a 507 cisgendered male sample, 63.1% reported an increased risk for ED based on previously established cutoff points. Elevated levels of PMB endorsement among the men predicted reduced sexual and erectile function in all models, even when accounting for relevant control variables such as age, education, self-stigma, social desirability, or conformity to TMI. Group comparisons revealed that the men suffering from ED showed higher levels of PMB endorsement but not self-stigma nor TMI relative to men without ED. PMB are significantly associated with ED. While determining causality will require further study, our results may support the hypothesis that higher levels of PMB endorsement may lead to increased tension to perform sexually, resulting in increased psychological pressure and a higher risk to develop ED.

P301 Step-wise introduction of elexacaftor/tezacaftor/ivacaftor in patients with cystic fibrosis and liver cirrhosis Child-Pugh A or B using clinical- and therapeutic drug monitoring: a case series

Serum liver test abnormalities are described as a common adverse effect of elexacaftor-tezacaftor-ivacator (ETI) in patients with Cystic Fibrosis (pwCF). In the phase I registration studies the PK of ETI have been compared between non-CF people with hepatic impairment and healthy individuals. In the former group exposure of ETI was increased and therefore a reduced dose in pwCF and cirrhosis Child-Pugh B is recommended. To our knowledge, there are no data on the exposure of ETI in pwCF and cirrhosis Child-Pugh A or B. In this case series we describe seven pwCF and cirrhosis Child-Pugh A or B where ETI was gradually introduced using clinical and therapeutic drug monitoring (TDM).

Effective strategy of incorporating Co3O4 as a co-catalyst onto an innovative BiVO4/Fe2TiO5 core-shell heterojunction for effective photoelectrochemical water-splitting application

In the realm of photoelectrochemical (PEC) water splitting, core-shell heterojunction followed by catalyst loading over the photoelectrodes are known to speed up both separation and injection of photogenerated charge carriers. In this work we have reported the fabrication of BiVO4/Fe2TiO5/Co3O4 photoelectrodes through simple chemical routes. The fabricated photoelectrodes have been confirmed through different structural, morphological and optical analysis. Stepwise introduction of Fe2TiO5 as shell loaded with catalyst Co3O4 enhance the parameters like separation and injection efficiency of BiVO4 based photoanodes respectively. The effect of formation of the heterojunction followed by immobilization of loaded catalysts results in 5.3 folded highest photocurrent density with remarkable cathodic shift than bare BiVO4 photoanodes in a neutral electrolytic condition. Along with this it has been found that apart from heterojunction formation there in the creation of the oxygen vacancies which is also responsible to produce cumulative effect of the charge separation and injection of the photoanodes. Finally different PEC characterizations such as (a) flat band estimation, (b) study of charge transfer resistances and capacitances along with band structure analysis proved that proposed BiVO4/Fe2TiO5 core-shell heterojunction loaded with the catalyst Co3O4 possess n-n-p staggered type-II configuration.