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The angular distributions of 8Be states in the excitation energy region Ex~(16.5-18.2) MeV produced in the 7Li(³He,d)8Be proton transfer reaction have been measured at the Orsay 14.8-MV tandem accelerator for ³He2+ ion bombarding energy, Elab=20 MeV, and forward angular range, θlab=5°-50°. A high energy resolution detection system composed of a split-pole magnetic spectrometer and a ΔE-E, position-sensitive drift chamber was used to record the energy spectra of outgoing deuterons. The measured cross section data for the direct reaction component have been separated from the compound nucleus one, then analyzed in the framework of the nonlocal, finite-range (FR)-distorted-wave Born approximation (DWBA) theory. New values of the C²S and (Sp1/2,Sp3/2) proton absolute and partial spectroscopic factors and related γ²p(a) proton reduced widths versus the p+7Li channel radius have been extracted for the 2+(16.626) and 2+(16.922),T=0+1 isospin-mixed loosely bound states of astrophysical interest and the 1+(17.640), T=1 unbound state of 8Be. They are compared to sparse earlier experimental values and to shell-model-predicted ones from the literature, and are discussed. In particular, the status of the spectroscopic information on the 2+ isospin-mixed doublet is reviewed and updated. The application in nuclear astrophysics of the DWBA derived results is emphasized. [ABSTRACT FROM AUTHOR]

Objectives: To provide detailed information on the codesign of a digital intervention to support parents with bipolar disorder (BD) who have young children. Each step of this process is reported, as well as a detailed description of the final version of the intervention in line with the TIDieR framework., Methods: Clinical experience and lived experience experts participated in online workshops, meetings, and remote feedback requests, informed by Integrated Knowledge Translation (IKT) principles. The IKT research group responded to each phase of recommendations from the knowledge users., Results: Five clinical experience experts and six lived experience experts engaged with the codesign process. Their recommendations for principles, content, look, and feel, and functionality of the digital intervention were structured over five iterative phases. This led to a final implemented design that was identified by the clinical and lived experience experts (referred to together as the knowledge users group) as genuinely reflecting their input., Conclusions: The IKT principles offer an accessible structure for engaging with clinical and lived experience experts throughout a codesign process, in this case for a digital intervention for parents with BD. The resulting intervention is described in detail for transparency to aid further evaluation and development and to help other teams planning codesign approaches to intervention development., (© 2024 The Author(s). Bipolar Disorders published by John Wiley & Sons Ltd.)

Glioblastoma (GBM) accounts for half of all central nervous system tumors. Once the tumor is removed, many GBM cells remain present near the surgical cavity and infiltrate the brain up to a distance of 20-30 mm, resulting in recurrence a few months later. GBM remains incurable due to the limited efficiency of current treatments, a result of the blood-brain barrier and sensitivity of healthy brain tissues to chemotherapy and radiation. A new therapeutic paradigm under development to treat GBM is to attract and accumulate GBM cells in a cancer cell trap inserted in the surgical cavity after tumor resection. In this work, porous gels were prepared using porous polylactide molds obtained from melt-processed co-continuous polymer blends of polystyrene and polylactide, with an average pore size ranging from 5 μm to over 500 μm. In order to efficiently accumulate and retain GBM brain cancer cells within a macroporous sodium alginate-based hydrogel trap, the pores must have an average diameter superior to 100 μm, with the best results obtained at 225 μm. In that case, the accumulation and retention of F98 GBM cells were more homogeneous, especially when functionalized with RGD adhesion peptides. At an alginate concentration of 1% w/v, the compression modulus reaches 15 kPa, close to the average value of 1-2 kPa reported for brain tissues, while adhesion and retention were also superior compared to 2% w/v gels. Overall, 1% w/v gels with 225 μm pores functionalized with the RGD peptide display the best performances., (Creative Commons Attribution license.)

The addition of 2 equiv of the phosphaylide H 2 C═PPh 3 to the dimethyl uranium metallocene Cp* 2 UMe 2 (Cp* = η 5 -C 5 Me 5 ) in toluene with gentle heating at 40 °C generates the phosphorano-stabilized bis(carbene) Cp* 2 U[C(H)PPh 3 ] 2 ( 1 ) in good yield. Characterization of 1 by X-ray crystallographic analysis reveals two short uranium-carbon bonds, ranging from 2.301(5) to 2.322(5) Å, consistent with the presence of U═C carbene-type bonds. Monitoring the reaction by NMR spectroscopy suggests that it proceeds through the intermediate formation of the methyl carbene complex Cp* 2 U[C(H)PPh 3 ](Me) ( 1 Int ); however, prolonged heating of these solutions leads to the ortho -cyclometalated carbene species Cp* 2 U{κ 2 -[C(H)PPh 2 (C 6 H 4 )]} ( 2 ) via intramolecular C-H activation. Rapid conversion from 1 to 2 occurs within hours upon heating its toluene solutions to 100 °C. Preliminary reactivity studies of 1 show that it readily reacts with alcohols, such as HODipp (Dipp = 2,6-diisopropylphenyl) and HOC(CF 3 ) 3 , to give the mixed carbene alkoxide compounds Cp* 2 U[C(H)PPh 3 ](OR) (R = Dipp ( 4 Dipp ), C(CF 3 ) 3 ( 5 CF3 )). In one case, the reaction of 1 with HODipp in the presence of adventitious water led to the formation of a few crystals of the terminal U(IV) oxo complex, [Ph 3 PCH 3 ][Cp* 2 U(O)(ODipp)] ( 3 oxo ). The isolation of 1 marks the first instance of an unchelated, heteroatom-stabilized bis(carbene) complex of uranium that also provides an entryway to the synthesis of its monocarbene derivatives through protonolysis.

The reaction of Fe 2 (mes) 4 with the super-bulky amidines and guanidines HL Ar*-R (L Ar*-R = [(Ar*N) 2 C(R)] - , Ar* = 2,6-bis(diphenylmethyl)-4- tert -butylphenyl), R = Me ( L Ar*-Me ), t Bu ( L Ar*-tBu ), Ph ( L Ar*-Ph ), N i Pr 2 ( L Ar*-iPr2N ), and Pip ( L Ar*-Pip )) gives access to the three-coordinate iron-mesityl complexes (L Ar*-R )Fe(mes) only where L Ar*-R = L Ar*-Me , L Ar*-Ph , or L Ar*-Pip . Subsequent protonolysis with the N-atom transfer reagent Hdbabh (Hdbabh = 2,3:5,6-dibenzo-7-azabicyclo[2.2.1]hepta-2,5-diene) is limited in success, providing in one instance a few crystals of four-coordinate (L Ar*-Me )Fe(dbabh)(Hdbabh) , while three-coordinate (L Ar*-Pip )Fe(dbabh) is synthesized reproducibly. Complexes (L Ar*-Me )Fe(dbabh)(Hdbabh) and (L Ar*-Pip )Fe(dbabh) are thermally insensitive in solution to temperatures of up to 100 °C. On the other hand, both (L Ar*-Me )Fe(dbabh)(Hdbabh) and (L Ar*-Pip )Fe(dbabh) show sensitivity to blue LED light (395 nm), undergoing photochemical transformations. For instance, the photolysis of (L Ar*-Me )Fe(dbabh)(Hdbabh) leads to N-C bond scission and C-C bond coupling across the -dbabh moieties to give four-coordinate (L Ar*-Me )Fe(N=dbabh-dbabhNH 2 ) . Photolyzing pyridine- d 5 (py- d 5 ) solutions of (L Ar*-Pip )Fe(dbabh) at -5 °C produces a new paramagnetic photoproduct, [P] . Due to the thermal sensitivity of compound [P] , it has eluded structural characterization; yet, Evans' method measurements suggest that the iron(II) oxidation state is maintained, thereby pointing to the -dbabh moiety as the locus of chemical change. In line with this assessment, addition of excess Me 3 SiCl to solutions of [P] produces the iron(II) complex (L Ar*-Pip )FeCl(py- d 5 ) as shown by 1 H NMR spectroscopy. Gas chromatography/mass spectrometry analysis of the solutions of [P] shows a peak in the chromatogram with a molecular mass corresponding to a formulation of C 14 H 11 N that cannot be attributed to Hdbabh. This provides evidence for the photochemical-induced isomerization of the -dbabh ligand, revealing a heretofore unknown photochemical sensitivity of this N atom transfer reagent.

In a phenotypical screen of 56 acute myeloid leukemia (AML) patient samples and using a library of 10,000 compounds, we identified a hit with increased sensitivity toward SF3B1 -mutated and adverse risk AMLs. Through structure-activity relationship studies, this hit was optimized into a potent, specific, and nongenotoxic molecule called UM4118. We demonstrated that UM4118 acts as a copper ionophore that initiates a mitochondrial-based noncanonical form of cell death known as cuproptosis. CRISPR-Cas9 loss-of-function screen further revealed that iron-sulfur cluster (ISC) deficiency enhances copper-mediated cell death. Specifically, we found that loss of the mitochondrial ISC transporter ABCB7 is synthetic lethal to UM4118. ABCB7 is misspliced and down-regulated in SF3B1 -mutated leukemia, creating a vulnerability to copper ionophores. Accordingly, ABCB7 overexpression partially rescued SF3B1 -mutated cells to copper overload. Together, our work provides mechanistic insights that link ISC deficiency to cuproptosis, as exemplified by the high sensitivity of SF3B1 -mutated AMLs. We thus propose SF3B1 mutations as a biomarker for future copper ionophore-based therapies.

Background: Comorbidities such as obesity, hypertension, and diabetes are associated with COVID-19 development and severity, probably due to immune dysregulation; however, the mechanisms underlying these associations are not clear. The immune signatures of hypertensive patients with obesity with COVID-19 may provide new insight into the mechanisms of immune dysregulation and progression to severe disease in these patients., Methods: Hypertensive patients were selected prospectively from a multicenter registry of adults hospitalized with COVID-19 and stratified according to obesity (BMI ≥ 30 kg/m²). Clinical data including baseline characteristics, complications, treatment, and 46 immune markers were compared between groups. Logistic regression was performed to identify variables associated with the risk of COVID-19 progression in each group., Results: The sample comprised 213 patients (89 with and 124 without obesity). The clinical profiles of patients with and without obesity differed, suggesting potential interactions with COVID-19 severity. Relative to patients without obesity, patients with obesity were younger and fewer had cardiac disease and myocardial injury. Patients with obesity had higher EGF, GCSF, GMCSF, interleukin (IL)-1ra, IL-5, IL-7, IL-8, IL-15, IL-1β, MCP 1, and VEGF levels, total lymphocyte counts, and CD8 + CD38 + mean fluorescence intensity (MFI), and lower NK-NKG2A MFI and percentage of CD8 + CD38 + T cells. Significant correlations between cytokine and immune cell expression were observed in both groups. Five variables best predicted progression to severe COVID-19 in patients with obesity: diabetes, the EGF, IL-10, and IL-13 levels, and the percentage of CD8 + HLA-DR + CD38 + cells. Three variables were predictive for patients without obesity: myocardial injury and the percentages of B lymphocytes and HLA-DR + CD38 + cells., Conclusion: Our findings suggest that clinical and immune variables and obesity interact synergistically to increase the COVID-19 progression risk. The immune signatures of hypertensive patients with and without obesity severe COVID-19 highlight differences in immune dysregulation mechanisms, with potential therapeutic applications., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Despite decades of efforts, the actinide-carbon triple bond has remained an elusive target, defying synthesis in any isolable compound. Herein, we report the successful synthesis of uranium-carbon triple bonds in carbide-bridged bimetallic [U≡C-Ce] units encapsulated inside the fullerene cages of C 72 and C 78 . The molecular structures of UCCe@C 2 n and the nature of the U≡C triple bond were characterized through X-ray crystallography and various spectroscopic analyses, revealing very short uranium-carbon bonds of 1.921(6) and 1.930(6) Å, with the metals existing in their highest oxidation states of +6 and +4 for uranium and cerium, respectively. Quantum-chemical studies further demonstrate that the C 2 n cages are crucial for stabilizing the [U VI ≡C-Ce IV ] units through covalent and coordinative interactions. This work offers a new fundamental understanding of the elusive uranium-carbon triple bond and informs the design of complexes with similar bonding motifs, opening up new possibilities for creating distinctive molecular compounds and materials.

Purpose: Myocardial injury is common in hypertensive patients with 2019 coronavirus disease (COVID-19). Immune dysregulation could be associated to cardiac injury in these patients, but the underlying mechanism has not been fully elucidated., Methods: All patients were selected prospectively from a multicenter registry of adults hospitalized with confirmed COVID-19. Cases had hypertension and myocardial injury, defined by troponin levels above the 99th percentile upper reference limit, and controls were hypertensive patients with no myocardial injury. Biomarkers and immune cell subsets were quantified and compared between the two groups. A multiple logistic regression model was used to analyze the associations of clinical and immune variables with myocardial injury., Results: The sample comprised 193 patients divided into two groups: 47 cases and 146 controls. Relative to controls, cases had lower total lymphocyte count, percentage of T lymphocytes, CD8 + CD38 + mean fluorescence intensity (MFI), and percentage of CD8 + human leukocyte antigen DR isotope (HLA-DR) + CD38 - cells and higher percentage of natural killer lymphocytes, natural killer group 2A (NKG2A) + MFI, percentage of CD8 + CD38 + cells, CD8 + HLA-DR + MFI, CD8 + NKG2A + MFI, and percentage of CD8 + HLA-DR - CD38 + cells. On multivariate regression, the CD8 + HLA-DR + MFI, CD8 + CD38 + MFI, and total lymphocyte count were associated significantly with myocardial injury., Conclusion: Our findings suggest that lymphopenia, CD8 + CD38 + MFI, and CD8 + HLA-DR + MFI are immune biomarkers of myocardial injury in hypertensive patients with COVID-19. The immune signature described here may aid in understanding the mechanisms underlying myocardial injury in these patients. The study data might open a new window for improvement in the treatment of hypertensive patients with COVID-19 and myocardial injury., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Organ laterality of vertebrates is specified by accelerated asymmetric decay of Dand5 mRNA mediated by Bicaudal-C1 (Bicc1) on the left side, but whether binding of this or any other mRNA to Bicc1 can be regulated is unknown. Here, we found that a CRISPR-engineered truncation in ankyrin and sterile alpha motif (SAM)-containing 3 (ANKS3) leads to symmetric mRNA decay mediated by the Bicc1-interacting Dand5 3' UTR. AlphaFold structure predictions of protein complexes and their biochemical validation by in vitro reconstitution reveal a novel interaction of the C-terminal coiled coil domain of ANKS3 with Bicc1 that inhibits binding of target mRNAs, depending on the conformation of ANKS3 and its regulation by ANKS6. The dual regulation of RNA binding by mutually opposing structured protein domains in this multivalent protein network emerges as a novel mechanism linking associated laterality defects and possibly other ciliopathies to perturbed dynamics in Bicc1 ribonucleoparticle (RNP) formation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Rothé et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Reaction of the terphenyl bis(anilide) ligand [{K(DME) 2 } 2 L Ar ] (L Ar = {C 6 H 4 [(2,6- i Pr 2 C 6 H 3 )NC 6 H 4 ] 2 } 2- ) with trivalent chloride "MCl 3 " salts (M = Ce, U, Np) yields two distinct products; neutral L Ar M(Cl)(THF) (1 M ) (M = Np, Ce), and the "-ate" complexes [K(DME) 2 ][(L Ar )Np(Cl) 2 ] (2 Np ) or ([L Ar M(Cl) 2 (μ-K(X) 2 )]) ∞ (2 Ce , 2 U ) (M = Ce, U) (X = DME or Et 2 O) (2 M ). Alternatively, analogous reactions with the iodide [MI 3 (THF) 4 ] salts provide access to the neutral compounds L Ar M(I)(THF) (3 M ) (M = Ce, U, Np, Pu). All complexes exhibit close arene contacts suggestive of η 6 -interactions with the central arene ring of the terphenyl backbone, with 3 M comprising the first structurally characterized Pu η 6 -arene moiety. Notably, the metal-arene bond metrics diverge from the predicted trends of metal-carbon interactions based on ionic radii, with the uranium complexes exhibiting the shortest M-C centroid distance in all cases. Overall, the data presents a systematic study of f-element M- η 6 -arene complexes across the early actinides U, Np, Pu, and comparison to cerium congeners., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The growing number of diseases linked to aberrant phase transitioning of ribonucleoproteins highlights the need to uncover how the interplay between multivalent protein and RNA interactions is regulated. Cytoplasmic granules of the RNA binding protein Bicaudal-C (Bicc1) are regulated by the ciliopathy proteins ankyrin (ANK) and sterile alpha motif (SAM) domain-containing ANKS3 and ANKS6, but whether and how target mRNAs are affected is unknown. Here, we show that head-to-tail polymers of Bicc1 nucleated by its SAM domain are interconnected by K homology (KH) domains in a protein meshwork that mediates liquid-to-gel transitioning of client transcripts. Moreover, while the dispersion of these granules by ANKS3 concomitantly released bound mRNAs, co-recruitment of ANKS6 by ANKS3 reinstated Bicc1 condensation and ribonucleoparticle assembly. RNA-independent Bicc1 polymerization and its dual regulation by ANKS3 and ANKS6 represent a new mechanism to couple the reversible immobilization of client mRNAs to controlled protein phase transitioning between distinct metastable states., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)

Reduction of the diamagnetic Ti(III)/Ti(III) dimer [Cl 2 Ti(μ-NIm Dipp )] 2 ( 1 ) (NIm Dipp = [1,3-bis(Dipp)imidazolin-2-iminato] - , Dipp = C 6 H 3 -2,6- i Pr 2 ) with 4 and 6 equiv of KC 8 generates the intramolecularly arene-masked, dinuclear titanium compounds [(μ-N-η 6 -Im Dipp )Ti] 2 ( 2 ) and {[(Et 2 O) 2 K](μ-N-μ -η 6 :η 6 -Im Dipp )Ti} 2 ( 3 ), respectively, in modest yields. The compounds have been structurally characterized by X-ray crystallographic analysis, and inspection of the bond metrics within the η 6 -coordinated aryl substituent of the bridging imidazolin-2-iminato ligand shows perturbation of the aromatic system most consistent with two-electron reduction of the ring. As such, 2 and 3 can be assigned respectively as possessing metal centers in formal Ti(III)/Ti(III) and Ti(II)/Ti(II) oxidation states. Exploration of their redox chemistry reveal the ability to reduce several substrate equivalents. For instance, treatment of 2 with excess C 8 H 8 (COT) forms the novel COT-bridged complex [(Im Dipp N)(η 8 -COT)Ti](μ-η 2 :η 3 -COT)[Ti(η 4 -COT)(NIm Dipp )] ( 4 ) that dissociates in THF solutions to give mononuclear (Im Dipp N)Ti(η 8 -COT)(THF) ( 5 ). Addition of COT to 3 yields heterometallic [(Im Dipp N)(η 4 -COT)Ti(μ-η 4 :η 5 -COT)K(THF)(μ-η 6 :η 4 -COT)Ti(NIm Dipp )(μ-η 4 :η 4 -COT)K(THF) 2 ] n ( 6 ). Compounds 4 and 5 are the products of the 4-electron oxidation of 2 , while 6 stands as the 8-electron oxidation product of 3 . Reduction of organozides was also explored. Low temperature reaction of 2 with 4 equiv of AdN 3 gives the terminal and bridged imido complex [(Im Dipp N)Ti(═NAd)](μ-NAd) 2 [Ti(NIm Dipp )(N 3 Ad)] ( 7 ) that undergoes intermolecular C-H activation of toluene at room temperature to afford the amido compound [(Im Dipp N)Ti(NHAd)](μ-NAd) 2 [Ti(C 6 H 4 Me)(NIm Dipp )] ( 8-tol ). These complexes are the 6-electron oxidation products of the reaction of 2 with AdN 3 . Furthermore, treatment of 3 with 4 equiv of AdN 3 produces the thermally stable Ti(III)/Ti(III) terminal and bridged imido [K(18-crown-6)(THF) 2 ]{[(Im Dipp N)Ti(NAd)](μ-NAd) 2 K[Ti(NIm Dipp )]} ( 10 ). Altogether, these reactions firmly establish 2 and 3 as unprecedented Ti(I)/Ti(I) and Ti(0)/Ti(0) synthons with the clear capacity to effect multielectron reductions ranging from 4 to 8 electrons.

Adequate cardiorespiratory fitness is critical for firefighters since an insufficient level of fitness threatens the integrity of their operations and could be dangerous for their lives. In fact, the leading cause of mortality for on-duty firefighters is not injury but sudden cardiac death. Therefore, to mitigate these risks, potential firefighter recruits are often required to perform a graded exercise test to determine their cardiorespiratory fitness as part of the recruitment process. However, there are currently limited data available to prospective firefighters on the amounts and types of exercises needed to be successful in the graded exercise test, commonly known as a V̇O 2max test. Physiological parameters for the current secondary analysis were collected on firefighter applicants who performed the graded exercise test where 72% were successful and 28% were unsuccessful to meet the minimum standard set at 42.5 ml kg -1 min -1 . Prior to their test, applicants were asked to describe their exercise training routine by indicating the number of minutes per week spent exercising. Activities were then divided into one of two categories: endurance exercise or strength and power exercise training. The total exercise training describes the sum of all activities performed each week. The sum of endurance exercise activities and the sum of strength and power exercise activities were compared between the successful and the unsuccessful groups and results showed that successful applicants had a higher training volume and performed more endurance exercise training as compared to unsuccessful applicants. Therefore, practical recommendations related to exercise training regime are presented for firefighter applicants to embrace as guidance to prepare for their graded exercise test as part of their recruitment process., Competing Interests: The authors declare there are no competing interests., (©2022 Fortier et al.)

An unprecedented sandwich complex of the actinides is synthesized from the treatment of [UI 2 (HMPA) 4 ]I (HMPA = OP(NMe 2 ) 3 ) (2) with 3 equiv. of K(C 14 H 10 ) to give the neutral, bis(arenide) species U(η 6 -C 14 H 10 )(η 4 -C 14 H 10 )(HMPA) 2 (1). Solid-state X-ray, SQUID magnetometry, and XANES analyses are consistent with tetravalent uranium supported by [C 14 H 10 ] 2- ligands. In one case, treatment of 1 with an equiv. of AgOTf led to the isolation of U(η 6 -C 14 H 10 ) 2 (HMPA)(THF) (3), formed from ring migration and haptotropic rearrangement. Complete active space (CASSCF) calculations indicate the U-C bonding to solely consist of π-interactions, presenting a unique electronic structure distinct from classic actinide sandwich compounds.

Glioblastoma multiforme is a type of brain cancer associated with a very low survival rate since a large number of cancer cells remain infiltrated in the brain despite the treatments currently available. This work presents a macroporous hydrogel trap, destined to be implanted in the surgical cavity following tumor resection and designed to attract and retain cancer cells, in order to eliminate them afterward with a lethal dose of stereotactic radiotherapy. The biocompatible hydrogel formulation comprises sodium alginate (SA) and chitosan (CHI) bearing complementary electrostatic charges and stabilizing the gels in saline and cell culture media, as compared to pristine SA gels. The highly controlled and interconnected porosity, characterized by X-ray microCT, yields mechanical properties comparable to those of brain tissues and allows F98 glioblastoma cells to penetrate the gels within the entire volume, as confirmed by fluorescence microscopy. The addition of a grafted -RGD peptide on SA, combined with CHI, significantly enhances the adhesion and retention of F98 cells within the gels. Overall, the best compromise between low proliferation and a high level of accumulation and retention of F98 cells was obtained with the hydrogel formulated with 1% SA and 0.2% CHI, without the -RGD adhesion peptide.

Purpose: The use of a standardized geriatric assessment (GA) to inform treatment decisions in older adults with cancer improves quality of life, reduces treatment-related toxicity, and is guideline-recommended. This study aimed to assess community oncologists' knowledge and utilization of GAs., Methods: Between September 2019 and February 2020, practicing US-based oncologists were invited to attend live meetings and complete web-based surveys designed to collect information on treatment decision making and various practice-based challenges in oncology care., Results: Among the 349 oncologists surveyed, 74% practiced in a community setting. Sixty percent did not use a formal GA to inform treatment decisions for any of their older patients; the most common reasons for not using a GA were "Too cumbersome to incorporate into routine practice" (44%) and "Adds no value beyond the comprehensive history and physical exam" (36%). Validated GA instruments used in routine clinical practice included: Mini-Mental State Exam (54%), Comprehensive Geriatric Assessment (23%), Cancer and Aging Research Group toxicity tool (12%), and Chemotherapy Risk Assessment Scale for High-Age Patients tool (9%). Nineteen percent of oncologists were not aware of any validated GA instruments. Eastern Cooperative Oncology Group performance status and comorbidities were the most frequently used assessment factors to inform treatment decisions (88% and 73%, respectively)., Conclusion: Many oncologists have not incorporated GA tools because of perceptions that GAs are difficult to implement or do not add any value. Increasing education of the benefits of GA-directed therapy could help to increase GA utilization among community oncologists.

This clinical consensus document addresses the assessment, selection, and fitting considerations for non-surgical bone conduction hearing devices (BCHD) for children under the age of 5 years identified as having unilateral or bilateral, permanent conductive or mixed hearing losses. Children with profound unilateral sensorineural hearing losses are not addressed. The document was developed based on evidence review and consensus by The Paediatric Bone Conduction Working Group, which is composed of audiologists from North America who have experience working with BCHDs in children. The document aims to provide clinical direction for an area of paediatric audiology practice that is under development and is therefore lacking in standard protocols or guidelines. This work may serve as a basis for future research and clinical contributions to support prospective paediatric audiology practices.

Chronic lymphocytic leukaemia (CLL) has a highly variable clinical course. In addition to biological factors, socioeconomic factors and health system characteristics may influence CLL outcome. Data from the Brazilian Registry of CLL were analyzed to compare clinical and treatment-related characteristics in patients with CLL, from public or private institutions. A total of 3326 patients from 43 centres met the eligibility criteria, of whom 81% were followed up at public hospitals and 19% at private hospitals. The majority were male (57%), with a median age of 65 years. Comparing public and private hospitals, patients in public hospitals were older, had more advanced disease at diagnosis, and more frequently had elevated creatinine levels. All investigated prognostic markers were evaluated more often in private hospitals. First-line treatment was predominantly based on chlorambucil in 41% of the cases and fludarabine in 38%. Anti-CD20 monoclonal antibody was used in only 36% of cases. In public hospitals, significantly fewer patients received fludarabine-based regimens and anti-CD20 monoclonal antibodies. Patients from public hospitals had significantly worse overall survival (71% vs. 90% for private hospitals, p  < 0.0001) and treatment-free survival (32% vs. 40%, for private hospitals, p  < 0.0001) at seven years. Our data indicate striking differences between patients followed in public and private hospitals in Brazil. A worse clinical condition and lack of accessibility to basic laboratory tests and adequate therapies may explain the worse outcomes of patients treated in public institutions., Competing Interests: The authors declare they have no conflicts of interest., (© 2022 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)

Titanium is a versatile metal that has important applications in practical synthesis, though this is typically limited to stoichiometric reactions or Lewis acid catalysis. Recently, interest has grown in using titanium and other early-metals for redox catalysis; however, notable limitations exist due to the thermodynamic preference of these metals to adopt high oxidation states. Nonetheless, discrete low-valent titanium (LVT) complexes and their synthons (titanium complexes which chemically behave as LVT sources) are known. Here, we detail the various ligand platforms that are capable of stabilizing LVT compounds and present the redox chemistry of these systems. This includes a discussion of recent developments in the use of LVT synthons for accessing fully reversible oxidative-addition/reductive-elimination reactions.

Addition of [UI 2 (THF) 3 (μ-OMe)] 2 ·THF ( 2 ·THF) to THF solutions containing 6 equiv. of K[C 14 H 10 ] generates the heteroleptic dimeric complexes [K(18-crown-6)(THF) 2 ] 2 [U(η 6 -C 14 H 10 )(η 4 -C 14 H 10 )(μ-OMe)] 2 ·4THF ( 118C6 ·4THF) and {[K(THF) 3 ][U(η 6 -C 14 H 10 )(η 4 -C 14 H 10 )(μ-OMe)]} 2 ( 1THF ) upon crystallization of the products in THF in the presence or absence of 18-crown-6, respectively. Both 118C6 ·4THF and 1THF are thermally stable in the solid-state at room temperature; however, after crystallization, they become insoluble in THF or DME solutions and instead gradually decompose upon standing. X-ray diffraction analysis reveals 118C6 ·4THF and 1THF to be structurally similar, possessing uranium centres sandwiched between bent anthracenide ligands of mixed tetrahapto and hexahapto ligation modes. Yet, the two complexes are distinguished by the close contact potassium-arenide ion pairing that is seen in 1THF but absent in 118C6 ·4THF, which is observed to have a significant effect on the electronic characteristics of the two complexes. Structural analysis, SQUID magnetometry data, XANES spectral characterization, and computational analyses are generally consistent with U(iv) formal assignments for the metal centres in both 118C6 ·4THF and 1THF , though noticeable differences are detected between the two species. For instance, the effective magnetic moment of 1THF (3.74 μ B ) is significantly lower than that of 118C6 ·4THF (4.40 μ B ) at 300 K. Furthermore, the XANES data shows the U L III -edge absorption energy for 1THF to be 0.9 eV higher than that of 118C6 ·4THF, suggestive of more oxidized metal centres in the former. Of note, CASSCF calculations on the model complex {[U(η 6 -C 14 H 10 )(η 4 -C 14 H 10 )(μ-OMe)] 2 } 2- ( 1* ) shows highly polarized uranium-arenide interactions defined by π-type bonds where the metal contributions are primarily comprised by the 6d-orbitals (7.3 ± 0.6%) with minor participation from the 5f-orbitals (1.5 ± 0.5%). These unique complexes provide new insights into actinide-arenide bonding interactions and show the sensitivity of the electronic structures of the uranium atoms to coordination sphere effects., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Introduction Socio-professional reintegration is an objective that is regularly sought-after by people in the early stages of a psychotic disorder. Despite this, employment rates are low for this population and high school dropout rates remind at a high level. Objectives and method This literature synthesis based on recent meta-analyses and studies aims at presenting the determinants of vocational and school integration for people in the early stages of a psychotic disorder. This will be followed by the presentation of the most studied supported employment and education programs, as well as by complementary interventions to support existing programs. In addition, key concepts are illustrated through clinical vignettes for this clientele. Results. Several barriers to socio-professional reintegration in this population could help explain the lower success rates when compared to the general population, including individual factors (e.g., past employment history, length of absence from the labour market, negative and cognitive symptoms, motivation) and environmental factors (e.g., availability of supported employment or education programs, competence of the employment specialist, social assistance benefits, employer attitude). The program that shows the most accumulated evidence is called Individual Placement and Support (IPS) and is frequently used in Quebec. IPS focuses on competitive job search, rapid placement in the labour market and collaboration between an employment specialist, the client, and the employer. Mowbray's supported education programs, as well as IPS adapted for education, help respond more specifically to the needs of people in the early stages of a psychotic disorder, who often wish to return to school. This article describes two clinical examples of programs offered in Quebec. Despite the interesting results provided by supported programs, socio-professional reintegration and maintaining employment remain difficult for people who are in the early stages of a psychotic disorder. Considering this, several researchers suggest that interventions for people with psychotic disorders should be more individualized, given the great heterogeneity associated with this condition. Combining interventions that are specific to each candidate's pre-existing individual deficits (e.g., cognitive remediation, cognitive-behavioural therapy, social skills training) appears to be an effective solution for optimizing the therapeutic response in supported employment or education programs. Conclusion This article highlights the issues related to the professional or academic reintegration of people in the early stages of a psychotic disorder, in order to guide practitioners in the field and to offer possible solutions to the current limitations of these programs in Quebec, including access to certain interventions.