Expanding access to healthcare for people who use drugs and sex workers: hepatitis C elimination implications from a qualitative study of healthcare experiences in British Columbia, Canada.

BACKGROUND: Hepatitis C virus (HCV) is a major health threat in Canada. In British Columbia (BC) province, 1.6% of the population had been exposed to HCV by 2012. Prevalence and incidence of HCV are very high in populations of people who use drugs (PWUD) and sex workers (SW), who may experience unique barriers to healthcare. Consequently, they are less likely to be treated for HCV. Overcoming these barriers is critical for HCV elimination. This research sought to explore the healthcare experiences of PWUD and SW and how these experiences impact their willingness to engage in healthcare in the future, including HCV care. METHODS: Interpretive Description guided this qualitative study of healthcare experiences in BC, underpinned by the Health Stigma and Discrimination framework. The study team included people with living/lived experience of drug use, sex work, and HCV. Twenty-five participants completed in-depth semi-structured interviews on their previous healthcare and HCV-related experiences. Thematic analysis was used to identify common themes. RESULTS: Three major themes were identified in our analysis. First, participants reported common experiences of delay and refusal of care by healthcare providers, with many negative healthcare encounters perceived as rooted in institutional culture reflecting societal stigma. Second, participants discussed their choice to engage in or avoid healthcare. Many avoided all but emergency care following negative experiences in any kind of healthcare. Third, participants described the roles of respect, stigma, dignity, fear, and trust in communication in healthcare relationships. CONCLUSIONS: Healthcare experiences shared by participants pointed to ways that better understanding and communication by healthcare providers could support positive change in healthcare encounters of PWUD and SW, who are at high risk of HCV infection. More positive healthcare encounters could lead to increased healthcare engagement which is essential for HCV elimination.

Chemically Recyclable, High Molar Mass Polyoxazolidinones via Ring-Opening Metathesis Polymerization.

The development of robust methods for the synthesis of chemically recyclable polymers with tunable properties is necessary for the design of next-generation materials. Polyoxazolidinones (POxa), polymers with five-membered urethanes in their backbones, are an attractive target because they are strongly polar and have high thermal stability, but existing step-growth syntheses limit molar masses and methods to chemically recycle POxa to monomer are rare. Herein, we report the synthesis of high molar mass POxa via ring-opening metathesis polymerization of oxazolidinone-fused cyclooctenes. These novel polymers show <5% mass loss up to 382-411 °C and have tunable glass transition temperatures (14-48 °C) controlled by the side chain structure. We demonstrate facile chemical recycling to monomer and repolymerization despite moderately high monomer ring-strain energies, which we hypothesize are facilitated by the conformational restriction introduced by the fused oxazolidinone ring. This method represents the first chain growth synthesis of POxa and provides a versatile platform for the study and application of this emerging subclass of polyurethanes.

Differential Vulnerability and Response to Injury Among Brain Cell Types Comprising the Neurovascular Unit.

The neurovascular unit includes multiple different cell types, including neurons, astrocytes, endothelial cells and pericytes, which respond to insults on very different time or dose scales. We defined differential vulnerability among these cell types, using response to two different insults: oxygen-glucose deprivation and thrombin-mediated cytotoxicity. We found that neurons are most vulnerable, followed by endothelial cells, followed by astrocytes. After temporary focal cerebral ischemia in male rats, we found significantly more injured neurons, compared to astrocytes in the ischemic area, consistent with differential vulnerability in vivo. We sought to illustrate different and shared mechanisms across all cell types during response to insult. We found that gene expression profiles in response to oxygen-glucose deprivation differed among the cell types, with a paucity of gene responses shared by all types. All cell types activated genes relating to autophagy, apoptosis, and necroptosis, but the specific genes differed. Astrocytes and endothelial cells also activated pathways connected to DNA repair and anti-apoptosis. Taken together, the data support the concept of differential vulnerability in the neurovascular unit and suggests that different elements of the unit will evolve from salvageable to irretrievable on different time scales while residing in the same brain region and receiving the same (ischemic) blood flow. Future work will focus on the mechanisms of these differences. These data suggest future stroke therapy development should target different elements of the NVU differently.Significance Statement For decades, stroke treatments proven effective in pre-clinical models have failed in human clinical trials. Experimental, pre-clinical evaluation has focused mostly on protecting neurons, assuming that glia and vascular cells also would be protected. We now define and demonstrate differential vulnerability to insult as well as differential response to treatment among the various brain cell types comprising the neurovascular unit. Neurons, astrocytes, and endothelial cells show markedly different responses to ischemia. Ignoring differential vulnerability and treatment response may explain past clinical trial failures. Future studies should determine the mechanisms that underly differential vulnerability in the neurovascular unit.

People who use drugs' prioritization of regulation amid decriminalization reforms in British Columbia, Canada: A qualitative study.

BACKGROUND: North America and the province of British Columbia (BC), Canada, is experiencing an unprecedented number of overdose deaths. In BC, overdose has become the leading cause of death for people between the ages of 10-59 years old. In January 2023, BC decriminalized personal possession of a number of illegal substances with one aim being to address overdose deaths through stigma reduction and promoting access to substance use services. METHODS: We conducted a qualitative study to understand people who use drugs' (PWUD) perceptions of the new decriminalization policy, immediately prior to its' implementation (October-December 2022). To contextualize decriminalization within broader drug policy, we also asked PWUD what they perceived as the priority issues drug policy ought to address and the necessary solutions. Our final sample included 38 participants who used illegal drugs in the past month. RESULTS: We identified four themes: 1) The illicit drug supply as the main driver of drug toxicity deaths 2) Concerns about the impact of decriminalization on drug toxicity deaths 3) Views towards decriminalization as a policy response in the context of the drug toxicity crisis 4) Regulation as a symbol of hope for reducing drug toxicity deaths. CONCLUSION: From our data it became clear that many anticipated that decriminalization would have minimal or no impact on the overdose crisis. Regulation was perceived as the necessary policy approach for effectively and candidly addressing the drivers of the ongoing overdose crisis. These findings are important as jurisdictions consider different approaches to moving away from prohibition-based drug policy.

Supported Platinum Nanoparticles Catalyzed Carbon-Carbon Bond Cleavage of Polyolefins: Role of the Oxide Support Acidity.

Supported platinum nanoparticle catalysts are known to convert polyolefins to high-quality liquid hydrocarbons using hydrogen under relatively mild conditions. To date, few studies using platinum grafted onto various metal oxide (MxOy) supports have been undertaken to understand the role of the acidity of the oxide support in the carbon-carbon bond cleavage of polyethylene under consistent catalytic conditions. Specifically, two Pt/MxOy catalysts (MxOy = SrTiO3 and SiO2-Al2O3; Al = 3.0 wt %, target Pt loading 2 wt % Pt ∼1.5 nm), under identical catalytic polyethylene hydrogenolysis conditions (T = 300 °C, P(H2) = 170 psi, t = 24 h; Mw = ∼3,800 g/mol, Mn = ∼1,100 g/mol, D = 3.45, Nbranch/100C = 1.0), yielded a narrow distribution of hydrocarbons with molecular weights in the range of lubricants (Mw = < 600 g/mol; Mn < 400 g/mol; D = 1.5). While Pt/SrTiO3 formed saturated hydrocarbons with negligible branching, Pt/SiO2-Al2O3 formed partially unsaturated hydrocarbons (<1 mol % alkenes and ∼4 mol % alkyl aromatics) with increased branch density (Nbranch/100C = 5.5). Further investigations suggest evidence for a competitive hydrocracking mechanism occurring alongside hydrogenolysis, stemming from the increased acidity of Pt/SiO2-Al2O3 compared to Pt/SrTiO3. Additionally, the products of these polymer deconstruction reactions were found to be independent of the polyethylene feedstock, allowing the potential to upcycle polyethylenes with various properties into a value-added product.

Associations with experience of non-fatal opioid overdose in British Columbia, Canada: a repeated cross sectional survey study.

INTRODUCTION: Lives lost in North America due to the unregulated drug poisoning emergency are preventable and those who survive an opioid overdose may suffer long-term disability. Rates of opioid overdose more than doubled following the onset of the COVID-19 pandemic in British Columbia, Canada. MATERIALS AND METHODS: Our analytical sample was comprised of 1447 participants from the 2018, 2019, and 2021 Harm Reduction Client Survey who responded yes or no to having experienced an opioid overdose in the past 6 months. Participants were recruited from harm reduction sites from across British Columbia. We used logistic regression to explore associations of experiencing an opioid overdose. RESULTS: Overall, 21.8% of participants reported experiencing an opioid overdose in the last six months (18.2% in 2019 and 26.6% in 2021). The following factors were positively associated with increased adjusted odds of experiencing a non-fatal opioid overdose: cis men relative to cis women (AOR 1.49, 95% CI 1.10-2.02), unstably housed compared to people with stable housing (AOR 1.87, 95% CI 1.40-2.50), and participants from 2021 compared to those from 2019 (AOR 3.06, 95% CI 1.57-5.97). The effects of both previous experience of a stimulant overdose and having witnessed an opioid overdose depended on the year of study, with both effects decreasing over subsequent years. CONCLUSIONS: Overdoses have increased over time; in 2021 more than one in four participants experienced an overdose. There is an urgent need for policy and program development to meaningfully address the unregulated drug poisoning emergency through acceptable life-saving interventions and services to prevent overdoses and support overdose survivors.

Two-step conversion of polyethylene into recombinant proteins using a microbial platform.

BACKGROUND: The increasing prevalence of plastic waste combined with the inefficiencies of mechanical recycling has inspired interest in processes that can convert these waste streams into value-added biomaterials. To date, the microbial conversion of plastic substrates into biomaterials has been predominantly limited to polyhydroxyalkanoates production. Expanding the capabilities of these microbial conversion platforms to include a greater diversity of products generated from plastic waste streams can serve to promote the adoption of these technologies at a larger scale and encourage a more sustainable materials economy. RESULTS: Herein, we report the development of a new strain of Pseudomonas bacteria capable of converting depolymerized polyethylene into high value bespoke recombinant protein products. Using hexadecane, a proxy for depolymerized polyethylene, as a sole carbon nutrient source, we optimized media compositions that facilitate robust biomass growth above 1 × 109 cfu/ml, with results suggesting the benefits of lower hydrocarbon concentrations and the use of NH4Cl as a nitrogen source. We genomically integrated recombinant genes for green fluorescent protein and spider dragline-inspired silk protein, and we showed their expression in Pseudomonas aeruginosa, reaching titers of approximately 10 mg/L when hexadecane was used as the sole carbon source. Lastly, we demonstrated that chemically depolymerized polyethylene, comprised of a mixture of branched and unbranched alkanes, could be converted into silk protein by Pseudomonas aeruginosa at titers of 11.3 ± 1.1 mg/L. CONCLUSION: This work demonstrates a microbial platform for the conversion of a both alkanes and plastic-derived substrates to recombinant, protein-based materials. The findings in this work can serve as a basis for future endeavors seeking to upcycle recalcitrant plastic wastes into value-added recombinant proteins.

Switchable Organocatalysis from N-heterocyclic Carbene-Carbodiimide Adducts with Tunable Release Temperature.

N-Heterocyclic carbenes (NHCs) are powerful organocatalysts, but practical applications often require in situ generation from stable precursors that "mask" the NHC reactivity via reversible binding. Previously established "masks" are often simple small molecules, such that the NHC structure is used to control both catalytic activity and activation temperature, leading to undesirable tradeoffs. Herein, we show that NHC-carbodiimide (CDI) adducts can be masked precursors for switchable organocatalysis and that the CDI substituents can control the reaction profile without changing the NHC structure. Large electronic variations on the CDI (e.g., alkyl versus aryl) drastically change the catalytically active temperature, whereas smaller perturbations (e.g., different para-substituted phenyls) tune the catalyst release within a narrower window. This control was demonstrated for three classic NHC-catalyzed reactions, each influencing the NHC-CDI equilibrium in different ways. Our results introduce a new paradigm for controlling NHC organocatalysis as well as present practical considerations for designing appropriate masks for various reactions.

A multi-laboratory preclinical trial in rodents to assess treatment candidates for acute ischemic stroke.

Human diseases may be modeled in animals to allow preclinical assessment of putative new clinical interventions. Recent, highly publicized failures of large clinical trials called into question the rigor, design, and value of preclinical assessment. We established the Stroke Preclinical Assessment Network (SPAN) to design and implement a randomized, controlled, blinded, multi-laboratory trial for the rigorous assessment of candidate stroke treatments combined with intravascular thrombectomy. Efficacy and futility boundaries in a multi-arm multi-stage statistical design aimed to exclude from further study highly effective or futile interventions after each of four sequential stages. Six independent research laboratories performed a standard focal cerebral ischemic insult in five animal models that included equal numbers of males and females: young mice, young rats, aging mice, mice with diet-induced obesity, and spontaneously hypertensive rats. The laboratories adhered to a common protocol and efficiently enrolled 2615 animals with full data completion and comprehensive animal tracking. SPAN successfully implemented treatment masking, randomization, prerandomization inclusion and exclusion criteria, and blinded assessment of outcomes. The SPAN design and infrastructure provide an effective approach that could be used in similar preclinical, multi-laboratory studies in other disease areas and should help improve reproducibility in translational science.

Two Mesoporous Domains Are Better Than One for Catalytic Deconstruction of Polyolefins.

Catalytic hydrogenolysis of polyolefins into valuable liquid, oil, or wax-like hydrocarbon chains for second-life applications is typically accompanied by the hydrogen-wasting co-formation of low value volatiles, notably methane, that increase greenhouse gas emissions. Catalytic sites confined at the bottom of mesoporous wells, under conditions in which the pore exerts the greatest influence over the mechanism, are capable of producing less gases than unconfined sites. A new architecture was designed to emphasize this pore effect, with the active platinum nanoparticles embedded between linear, hexagonal mesoporous silica and gyroidal cubic MCM-48 silica (mSiO2/Pt/MCM-48). This catalyst deconstructs polyolefins selectively into ∼C20-C40 paraffins and cleaves C-C bonds at a rate (TOF = 4.2 ± 0.3 s-1) exceeding that of materials lacking these combined features while generating negligible volatile side products including methane. The time-independent product distribution is consistent with a processive mechanism for polymer deconstruction. In contrast to time- and polymer length-dependent products obtained from non-porous catalysts, mSiO2/Pt/MCM-48 yields a C28-centered Gaussian distribution of waxy hydrocarbons from polyolefins of varying molecular weight, composition, and physical properties, including low-density polyethylene, isotactic polypropylene, ultrahigh-molecular-weight polyethylene, and mixtures of multiple, post-industrial polyolefins. Coarse-grained simulation reveals that the porous-core architecture enables the paraffins to diffuse away from the active platinum site, preventing secondary reactions that produce gases.

Awareness, predictors and outcomes of drug alerts among people who access harm reduction services in British Columbia, Canada: findings from a 2021 cross-sectional survey.

OBJECTIVES: To assess the awareness and predictors of seeing/hearing a drug alert in British Columbia (BC) and subsequent drug use behaviour after seeing/hearing an alert. METHODS: This study analysed the 2021 BC harm reduction client survey (HRCS)-a cross-sectional self-reported survey administered at harm reduction sites throughout the province and completed by participants using the services. RESULTS: In total, n=537 respondents participated and n=482 (89.8%) responded to the question asking if they saw/heard a drug alert. Of those, n=300 (62.2%) stated that they saw/heard a drug alert and almost half reported hearing from a friend or peer network; the majority (67.4%) reported altering their drug use behaviour to be safer after seeing/hearing a drug alert. The proportion of individuals who saw/heard a drug alert increased with each ascending age category. Among health authorities, there were significant differences in the odds of seeing/hearing an alert. In the past 6 months, the odds of participants who attended harm reduction sites a few times per month seeing/hearing an alert were 2.73 (95% CI: 1.17 to 6.52) times the odds of those who did not. Those who attended more frequently were less likely to report seeing/hearing a drug alert. The odds of those who witnessed an opioid-related overdose in the past 6 months seeing/hearing an alert were 1.96 (95% CI: 0.86 to 4.50) times the odds of those who had not. CONCLUSION: We found that drug alerts were mostly disseminated through communication with friends or peers and that most participants altered their drug use behaviour after seeing/hearing a drug alert. Therefore, drug alerts can play a role in reducing harms from substance use and more work is needed to reach diverse populations, such as younger people, those in differing geographical locations, and those who attend harm reduction sites more frequently.

"It's just a perfect storm": Exploring the consequences of the COVID-19 pandemic on overdose risk in British Columbia from the perspectives of people who use substances.

BACKGROUND: Despite the implementation and expansion of public health and harm reduction strategies aimed at preventing and reversing overdoses, rates of overdose-related events and fatalities continue to rise in British Columbia. The COVID-19 pandemic created a second, concurrent public health emergency that further exacerbated the illicit drug toxicity crisis, reinforced existing social inequities and vulnerabilities, and highlighted the precariousness of systems in place that are meant to protect the health of communities. By exploring the perspectives of people with recent experience of illicit substance use, this study sought to characterize how the COVID-19 pandemic and associated public health measures influenced risk and protective factors related to unintentional overdose by altering the environment in which people live and use substances, influencing the ability of people who use substances to be safe and well. METHODS: One-on-one semi-structured interviews were conducted by phone or in-person with people who use illicit substances (n = 62) across the province. Thematic analysis was performed to identify factors shaping the overdose risk environment. RESULTS: Participants pointed to factors that increased risk of overdose, including: [1] physical distancing measures that created social and physical isolation and led to more substance use alone without bystanders nearby able to respond in the event of an emergency; [2] early drug price spikes and supply chain issues that created inconsistencies in drug availability; [3] increasing toxicity and impurities in unregulated substances; [4] restriction of harm reduction services and supply distribution sites; and [5] additional burden placed on peer workers on the frontlines of the illicit drug toxicity crisis. Despite these challenges, participants highlighted factors that protected against overdose and substance-related harm, including the emergence of new programs, the resiliency of communities of people who use substances who expanded their outreach efforts, the existence of established social relationships, and the ways that individuals consistently prioritized overdose response over concerns about COVID-19 transmission to care for one another. CONCLUSIONS: The findings from this study illustrate the complex contextual factors that shape overdose risk and highlight the importance of ensuring that the needs of people who use substances are addressed in future public health emergency responses.

Double-resonance 17O NMR experiments reveal unique configurational information for surface organometallic complexes.

Obtaining three-dimensional (3D) configurational information of surface organometallic complexes is a persistent challenge due to the low spatial sensitivity of most spectroscopic methods. We show that employing 17O-enriched supports enables highly informative multidimensional NMR experiments, including radial and vertical distance measurements, that can be used to elucidate site geometry.

Embracing Heterogeneity in The Multicenter Stroke Preclinical Assessment Network (SPAN) Trial.

The Stroke Preclinical Assessment Network (SPAN) is a multicenter preclinical trial platform using rodent models of transient focal cerebral ischemia to address translational failure in experimental stroke. In addition to centralized randomization and blinding and large samples, SPAN aimed to introduce heterogeneity to simulate the heterogeneity embodied in clinical trials for robust conclusions. Here, we report the heterogeneity introduced by allowing the 6 SPAN laboratories to vary most of the biological and experimental model variables and the impact of this heterogeneity on middle cerebral artery occlusion (MCAo) performance. We included the modified intention-to-treat population of the control mouse cohort of the first SPAN trial (n=421) and examined the biological and procedural independent variables and their covariance. We then determined their impact on the dependent variables cerebral blood flow drop during MCAo, time to achieve MCAo, and total anesthesia duration using multivariable analyses. We found heterogeneity in biological and procedural independent variables introduced mainly by the site. Consequently, all dependent variables also showed heterogeneity among the sites. Multivariable analyses with the site as a random effect variable revealed filament choice as an independent predictor of cerebral blood flow drop after MCAo. Comorbidity, sex, use of laser Doppler flow to monitor cerebral blood flow, days after trial onset, and maintaining anesthesia throughout the MCAo emerged as independent predictors of time to MCAo. Total anesthesia duration was predicted by most independent variables. We present with high granularity the heterogeneity introduced by the biological and model selections by the testing sites in the first trial of cerebroprotection in rodent transient filament MCAo by SPAN. Rather than trying to homogenize all variables across all sites, we embraced the heterogeneity to better approximate clinical trials. Awareness of the heterogeneity, its sources, and how it impacts the study performance may further improve the study design and statistical modeling for future multicenter preclinical trials.

Endohedrally Functionalized Metal-Organic Cage-Cross-Linked Polymer Gels as Modular Heterogeneous Catalysts.

The immobilization of homogeneous catalysts onto supports to improve recyclability while maintaining catalytic efficiency is often a trial-and-error process limited by poor control of the local catalyst environment and few strategies to append catalysts to support materials. Here, we introduce a modular heterogenous catalysis platform that addresses these challenges. Our approach leverages the well-defined interiors of self-assembled Pd12L24 metal-organic cages/polyhedra (MOCs): simple mixing of a catalyst-ligand of choice with a polymeric ligand, spacer ligands, and a Pd salt induces self-assembly of Pd12L24-cross-linked polymer gels featuring endohedrally catalyst-functionalized junctions. Semi-empirical calculations show that catalyst incorporation into the MOC junctions of these materials has minimal affect on the MOC geometry, giving rise to well-defined nanoconfined catalyst domains as confirmed experimentally using several techniques. Given the unique network topology of these freestanding gels, they are mechanically robust regardless of their endohedral catalyst composition, allowing them to be physically manipulated and transferred from one reaction to another to achieve multiple rounds of catalysis. Moreover, by decoupling the catalyst environment (interior of MOC junctions) from the physical properties of the support (the polymer matrix), this strategy enables catalysis in environments where homogeneous catalyst analogues are not viable, as demonstrated for the Au(I)-catalyzed cyclization of 4-pentynoic acid in aqueous media.

The Stroke Preclinical Assessment Network: Rationale, Design, Feasibility, and Stage 1 Results.

Cerebral ischemia and reperfusion initiate cellular events in brain that lead to neurological disability. Investigating these cellular events provides ample targets for developing new treatments. Despite considerable work, no such therapy has translated into successful stroke treatment. Among other issues-such as incomplete mechanistic knowledge and faulty clinical trial design-a key contributor to prior translational failures may be insufficient scientific rigor during preclinical assessment: nonblinded outcome assessment; missing randomization; inappropriate sample sizes; and preclinical assessments in young male animals that ignore relevant biological variables, such as age, sex, and relevant comorbid diseases. Promising results are rarely replicated in multiple laboratories. We sought to address some of these issues with rigorous assessment of candidate treatments across 6 independent research laboratories. The Stroke Preclinical Assessment Network (SPAN) implements state-of-the-art experimental design to test the hypothesis that rigorous preclinical assessment can successfully reduce or eliminate common sources of bias in choosing treatments for evaluation in clinical studies. SPAN is a randomized, placebo-controlled, blinded, multilaboratory trial using a multi-arm multi-stage protocol to select one or more putative stroke treatments with an implied high likelihood of success in human clinical stroke trials. The first stage of SPAN implemented procedural standardization and experimental rigor. All participating research laboratories performed middle cerebral artery occlusion surgery adhering to a common protocol and rapidly enrolled 913 mice in the first of 4 planned stages with excellent protocol adherence, remarkable data completion and low rates of subject loss. SPAN stage 1 successfully implemented treatment masking, randomization, prerandomization inclusion/exclusion criteria, and blinded assessment to exclude bias. Our data suggest that a large, multilaboratory, preclinical assessment effort to reduce known sources of bias is feasible and practical. Subsequent SPAN stages will evaluate candidate treatments for potential success in future stroke clinical trials using aged animals and animals with comorbid conditions.

N-Heterocyclic carbene-carbodiimide (NHC-CDI) betaine adducts: synthesis, characterization, properties, and applications.

N-Heterocyclic carbenes (NHCs) are an important class of reactive organic molecules used as ligands, organocatalysts, and σ-donors in a variety of electroneutral ylide or betaine adducts with main-group compounds. An emerging class of betaine adducts made from the reaction of NHCs with carbodiimides (CDIs) form zwitterionic amidinate-like structures with tunable properties based on the highly modular NHC and CDI scaffolds. The adduct stability is controlled by the substituents on the CDI nitrogens, while the NHC substituents greatly affect the configuration of the adduct in the solid state. This Perspective is intended as a primer to these adducts, touching on their history, synthesis, characterization, and general properties. Despite the infancy of the field, NHC-CDI adducts have been applied as amidinate-type ligands for transition metals and nanoparticles, as junctions in zwitterionic polymers, and to stabilize distonic radical cations. These applications and potential future directions are discussed.

Survival of Single-Unit Porcelain-Fused-to-Metal (PFM) and Metal Crowns Placed by Students at an Australian University Dental Clinic over a Five-Year Period.

The aim of this retrospective study was to determine the survival rate of single-unit porcelain-fused-to-metal (PFM) and metal crowns placed by dental students at an Australian university undergraduate dental clinic over a five-year period. Complications and the incidences of crown failures were recorded. Clinical records pertaining to single-unit PFM and metal crowns inserted over a five-year period were reviewed, including patient-related, tooth-related, and procedural factors for each crown. Crowns were evaluated as surviving, surviving with complications, or failed. Kaplan-Meier statistical analysis was used to estimate survival rate., This study is based on a sample of 232 (78.4%) PFM crowns and 64 (21.6%) metal crowns inserted between 2014 and 2018. Cumulatively, 224 (75.7%) were surviving, 48 (16.2%) were surviving but previously had complications, and 24 (8.1%) failed. The 5-year cumulative survival rate of all PFM and metal crowns was 83.9% (0.839 ± 0.038, Kaplan-Meier). The average survival time for all crowns was 4.432 ± 0.089 years. Comparatively, PFM crowns had a higher survival rate at 1 year (0.972 ± 0.010) and 2 years (0.919 ± 0.017), compared to metal crowns at 1 year (0.964 ± 0.011) and 2 years (0.894± 0.018). The survival rate of metal crowns remained constant from 2 years to 4 years and thereafter, whereas there was a continued decline in the survival rate of PFM crowns to 83.2% (0.832 ± 0.038) at 4 years and thereafter. Crowns placed on premolars had the highest cumulative survival rate whereas those placed on molars exhibited the lowest survival rate for the duration of the study period. Despite single-unit PFM crowns having a higher 1- and 2-year survival rate compared to metal crowns, metal crowns had a higher survival rate at 4 years and thereafter. Survival rates are comparable to previous studies.

Ring-opening polymerisation of l- and rac-lactide using group 4 permethylpentalene aryloxides and alkoxides.

A new family of group 4 permethylpentalene (C8Me62-; Pn*) aryloxide and alkoxide complexes have been synthesised and fully characterised by multinuclear NMR spectroscopy and single-crystal X-ray diffraction; (η8-C8Me6)Zr(OR)2 (R = tBu (1), 2,6-Me-C6H3 (2), 2,6-iPr-C6H3 (3) and 4-OMe-C6H4 (4)), (η8-C8Me6)Zr (OR) (R = 2,6-tBu-C6H3 (5) and 2,6-tBu-4-Me-C6H2 (6)), (η8-C8Me6)ZrCp(OR) (R = tBu (7), 2,6-Me-C6H3 (8) and 2,6-iPr-C6H3 (9)), (η8-C8Me6)TiCp(O-2,6-Me-C6H3) (10) and (η8-C8Me6)ZrCpMe(OR) (R = 2,6-Me-C6H3 (11), 2,6-iPr-C6H3 (12) and 2,4-tBu-C6H3 (13)). 2, 3, 6, 7, 9, 10 and 12 were studied as initiators for the ring-opening polymerisation (ROP) of l-lactide, and 2, 3, 6, 7 and 10 were studied as initiators for the ROP of rac-lactide. 3 was found to be the most active initiator for the ROP of l-lactide (kobs = 0.35 h-1) and 2 for the ROP of rac-lactide (kobs = 0.21 h-1). These initiators produced isotactic PLA for the ROP of l-lactide and moderately heterotactic enriched (maximum Pr of 0.69) or atactic PLA for the ROP of rac-lactide with polymer chains consisting of polylactic acid repeat units with -OR and -OH end groups.

Synthesis of ultra-high molecular weight poly(ethylene)-co-(1-hexene) copolymers through high-throughput catalyst screening.

A family of permethylindenyl titanium constrained geometry complexes, Me2SB(R'N,3-RI*)TiX2 ((3-R-η5-C9Me5)Me2Si(R'TiX2)), supported on solid polymethylaluminoxane (sMAO) are investigated as slurry-phase catalysts for ethylene/H2 homopolymerisation and ethylene/1-hexene copolymerisation by high-throughput catalyst screening. Me2SB( tBuN,I*)TiCl2 supported on sMAO [sMAO-Me2SB( tBuN,I*)TiCl2] is responsive to small quantities of H2 (<1.6%), maintaining high polymerisation activities (up to 4900 kgPE molTi -1 h-1 bar-1) and yielding polyethylenes with significantly decreased molecular weight (M w) (from 2700 to 41 kDa with 1.6% H2). In slurry-phase ethylene/1-hexene copolymerisation studies, a decrease in polymerisation activity and polymer molecular weights compared to ethylene homopolymerisation is observed. Compared to many solid supported system, these complexes all display high 1-hexene incorporation levels up to a maximum incorporation of 14.2 mol% for sMAO-Me2SB(iPrN,I*)TiCl2). We observe a proportionate increase in 1-hexene incorporation with concentration, highlighting the ability of these catalysts to controllably tune the amount of 1-hexene incorporated into the polymer chain to produce linear low-density polyethylene (LLDPE) materials.