Cu-Catalyzed Amination of Base-Sensitive Aryl Bromides and the Chemoselective N- and O-Arylation of Amino Alcohols.

We report a general and functional-group-tolerant method for the Cu-catalyzed amination of base-sensitive aryl bromides including substrates possessing acidic functional groups and small five-membered heteroarenes. The results presented herein substantially expand the scope of Cu-catalyzed C-N coupling reactions. The combination of L8, an anionic N1,N2-diarylbenzene-1,2-diamine ligand, along with the mild base NaOTMS leads to the formation of a stable yet reactive catalyst that resists deactivation from coordination to heterocycles or charged intermediates. This system enables the use of low catalyst and ligand loadings. Exploiting the differences in nucleophile deprotonation in C-O and C-N coupling reactions catalyzed by Cu·L8 we developed a method to chemoselectively N- and O-arylate a variety of amino alcohol substrates. Employing NaOt-Bu as the base resulted exclusively in C-O coupling when the amino alcohols featured primary alcohols and more hindered amines or aniline groups. Utilizing NaOTMS enabled the ability to override the steric-based selectivity of these reactions completely and exclusively promoted C-N coupling regardless of the structure of the amino alcohol. The ability to invert the observed chemoselectivity is distinct from previously described methods that require protecting group manipulations or rely entirely on steric effects to control reactivity. These results substantially improve the scope of Cu-catalyzed C-N coupling reactions using N1,N2-diarylbenzene-1,2-diamine ligands and introduce a new chemoselective method to arylate amino alcohols.

Room-Temperature Copper-Catalyzed Etherification of Aryl Bromides.

We disclose the development of a Cu-catalyzed C-O coupling method utilizing a new N1,N2-diarylbenzene-1,2-diamine ligand, L8. Under optimized reaction conditions, structurally diverse aryl and heteroaryl bromides underwent efficient coupling with a variety of alcohols at room temperature using an L8-based catalyst. Notably, the L8-derived catalyst exhibited enhanced activity when compared to the L4-based system previously disclosed for C-N coupling, namely the ability to functionalize aryl bromides containing acidic functional groups. Mechanistic studies demonstrate that C-O coupling utilizing L8 ⋅ Cu involves rate-limiting alkoxide transmetallation, resulting in a mechanism of C-O bond formation that is distinct from previously described Pd-, Cu-, or Ni-based systems. This lower energy pathway leads to rapid C-O bond formation; a 7-fold increase relative to what is seen with other ligands. The results presented in this report overcome limitations in previously described C-O coupling methods and introduce a new ligand that we anticipate may be useful in other Cu-catalyzed C-heteroatom bond-forming reactions.

Reducing Initial Loss to Follow-up Among People With Bacteriologically Confirmed Tuberculosis: LINKEDin, a Quasi-experimental Study in South Africa.

Every person diagnosed with tuberculosis (TB) needs to initiate treatment. The World Health Organization estimated that 61% of people who developed TB in 2021 were included in a TB treatment registration system. Initial loss to follow-up (ILTFU) is the loss of persons to care between diagnosis and treatment initiation/registration. LINKEDin, a quasi-experimental study, evaluated the effect of 2 interventions (hospital recording and an alert-and-response patient management intervention) in 6 subdistricts across 3 high-TB burden provinces of South Africa. Using integrated electronic reports, we identified all persons diagnosed with TB (Xpert MTB/RIF positive) in the hospital and at primary health care facilities. We prospectively determined linkage to care at 30 days after TB diagnosis. We calculated the risk of ILTFU during the baseline and intervention periods and the relative risk reduction in ILTFU between these periods. We found a relative reduction in ILTFU of 42.4% (95% CI, 28.5%-53.7%) in KwaZulu Natal (KZN) and 22.3% (95% CI, 13.3%-30.4%) in the Western Cape (WC), with no significant change in Gauteng. In KZN and the WC, the relative reduction in ILTFU appeared greater in subdistricts where the alert-and-response patient management intervention was implemented (KZN: 49.3%; 95% CI, 32.4%-62%; vs 32.2%; 95% CI, 5.4%-51.4%; and WC: 34.2%; 95% CI, 20.9%-45.3%; vs 13.4%; 95% CI, 0.7%-24.4%). We reported a notable reduction in ILTFU in 2 provinces using existing routine health service data and applying a simple intervention to trace and recall those not linked to care. TB programs need to consider ILTFU a priority and develop interventions specific to their context to ensure improved linkage to care.

Examining the uptake of COVID-19 vaccine booster doses among healthcare workers in South Africa: A mixed-methods study.

This study aimed examin the factors associated with the uptake and non-acceptance of COVID-19 vaccine booster doses among healthcare workers (HCWs) in South Africa. We used a mixed-methods design with data from a web-based self-administered survey followed by semi-structured in-depth interviews (IDIs) with selected participants. Of the 6235 HCWs included in our analysis who had fully vaccinated, 3470 (56%) had taken their booster dose with a further 17% intending to get the booster. HCWs aged 35 to 49 years (OR = 1.30 [95% CI: 1.15-1.46]), and those aged 50 years or older (OR = 2.66 [95% CI: 2.32-3.05]) were more likely to get the booster dose. Females were less likely to have received the booster dose (OR = 0.88 [95% CI: 0.79-0.98]) with doctors more likely (OR = 1.58 [95% CI: 1.35-1.84]) than Nurses to have received the booster dose. HCWs in direct contact with patients (OR = 1.17 [95% CI: 1.00-1.38]) and who had previously received a flu vaccine (OR = 1.99 [95% CI: 1.56-2.55]) were more likely to have received the booster dose. Four themes emerged from the qualitative data analysis: (1) Vaccination as routine practice among HCWs; (2) Emergence of new COVID-19 variants necessitating vaccine boosters; (3) Fear of potential side-effects; and (4) Limited value of COVID-19 vaccine boosters. Some HCWs broadly accepted the value of vaccination, and believed that boosters were necessary to effectively combat emergent new virus strains, which contrasted with peers who believed that boosters offered little defence against virus mutations. Fear prohibited some HCWs from getting the booster, with some having experienced adverse side effects from their initial vaccination, whilst others were concerned about future complications. Waning booster uptake rates could be arrested through invigorated communication strategies, while effective evidence-based training can potentially create positive normative vaccination practices amongst HCWs.

Detection of stellar light from quasar host galaxies at redshifts above 6.

The detection of starlight from the host galaxies of quasars during the reionization epoch (z > 6) has been elusive, even with deep Hubble Space Telescope observations1,2. The current highest redshift quasar host detected3, at z = 4.5, required the magnifying effect of a foreground lensing galaxy. Low-luminosity quasars4-6 from the Hyper Suprime-Cam Subaru Strategic Program (HSC-SSP)7 mitigate the challenge of detecting their underlying, previously undetected host galaxies. Here we report rest-frame optical images and spectroscopy of two HSC-SSP quasars at z > 6 with the JWST. Using near-infrared camera imaging at 3.6 and 1.5 µm and subtracting the light from the unresolved quasars, we find that the host galaxies are massive (stellar masses of 13 × and 3.4 × 1010 M☉, respectively), compact and disc-like. Near-infrared spectroscopy at medium resolution shows stellar absorption lines in the more massive quasar, confirming the detection of the host. Velocity-broadened gas in the vicinity of these quasars enables measurements of their black hole masses (1.4 × 109 and 2.0 × 108 M☉, respectively). Their location in the black hole mass-stellar mass plane is consistent with the distribution at low redshift, suggesting that the relation between black holes and their host galaxies was already in place less than a billion years after the Big Bang.

Competition between side-chain interactions dictates 2D polymer stacking order.

Interrogating the stacking of two-dimensional polymers (2DPs) as a function of chemical composition is important to leverage their properties. We explore the dependence of 2DP crystallinity and porosity on variable amounts of zwitterions contained within the pores and find that high zwitterion loadings consistently diminish 2DP materials quality. A competition between disruptive zwitterion electrostatic forces and alkyl stabilization directs the stacking order of each 2DP and demonstrates the contrasting effects of side chain composition on 2DP crystallinity and porosity.

Room-Temperature Cu-Catalyzed Amination of Aryl Bromides Enabled by DFT-Guided Ligand Design.

Ullmann-type C-N coupling reactions represent an important alternative to well-established Pd-catalyzed approaches due to the differing reactivity and the lower cost of Cu. While the design of anionic Cu ligands, particularly those by Ma, has enabled the coupling of various classes of aryl halides and alkyl amines, most methods require conditions that can limit their utility on complex substrates. Herein, we disclose the development of anionic N1,N2-diarylbenzene-1,2-diamine ligands that promote the Cu-catalyzed amination of aryl bromides under mild conditions. Guided by DFT calculations, these ligands were designed to (1) increase the electron density on Cu, thereby increasing the rate of oxidative addition of aryl bromides, and (2) stabilize the active anionic CuI complex via a π-interaction. Under optimized conditions, structurally diverse aryl and heteroaryl bromides and a broad range of alkyl amine nucleophiles, including pharmaceuticals bearing multiple functional groups, were efficiently coupled at room temperature. Combined computational and experimental studies support a mechanism of C-N bond formation that follows a catalytic cycle akin to the well-explored Pd-catalyzed variants. Modification of the ligand structure to include a naphthyl residue resulted in a lower energy barrier to oxidative addition, providing a 30-fold rate increase relative to what is seen with other ligands. Collectively, these results establish a new class of anionic ligands for Cu-catalyzed C-N couplings, which we anticipate may be extended to other Cu-catalyzed C-heteroatom and C-C bond-forming reactions.

Understanding COVID-19 Vaccine Hesitancy among Healthcare Workers in South Africa.

Healthcare workers (HCWs) were the first population group offered coronavirus disease 2019 (COVID-19) vaccines in South Africa because they were considered to be at higher risk of infection and required protecting as they were a critical resource to the health system. In some contexts, vaccine uptake among HCWs has been slow, with several studies citing persistent concerns about vaccine safety and effectiveness. This study aimed to determine vaccine uptake among HCWs in South Africa whilst identifying what drives vaccine hesitancy among HCWs. We adopted a multimethod approach, utilising both a survey and in-depth interviews amongst a sample of HCWs in South Africa. In a sample of 7763 HCWS, 89% were vaccinated, with hesitancy highest among younger HCWs, males, and those working in the private sector. Among those who were hesitant, consistent with the literature, HCWs raised concerns about the safety and effectiveness of the vaccine. Examining this further, our data revealed that safety and effectiveness concerns were formed due to first-hand witnessing of patients presenting with side-effects, concern over perceived lack of scientific rigor in developing the vaccine, confidence in the body's immune system to stave off serious illness, and both a general lack of information and distrust in the available sources of information. This study, through discursive narratives, provides evidence elucidating what drives safety and effectiveness concerns raised by HCWs. These concerns will need to be addressed if HCWs are to effectively communicate and influence public behaviour. HCWs are key role players in the national COVID-19 vaccination programme, making it critical for this workforce to be well trained, knowledgeable, and confident if they are going to improve the uptake of vaccines among the general population in South Africa, which currently remains suboptimal.

Electronic Spin Qubit Candidates Arrayed within Layered Two-Dimensional Polymers.

Molecular electronic spin qubits are promising candidates for quantum information science applications because they can be reliably produced and engineered via chemical design. Embedding electronic spin qubits within two-dimensional polymers (2DPs) offers the possibility to systematically engineer inter-qubit interactions while maintaining long coherence times, both of which are prerequisites to their technological utility. Here, we introduce electronic spin qubits into a diamagnetic 2DP by n-doping naphthalene diimide subunits with varying amounts of CoCp2 and analyze their spin densities by quantitative electronic paramagnetic resonance spectroscopy. Low spin densities (e.g., 6.0 × 1012 spins mm-3) enable lengthy spin-lattice (T1) and spin-spin relaxation (T2) times across a range of temperatures, ranging from T1 values of 164 ms at 10 K to 30.2 µs at 296 K and T2 values of 2.36 µs at 10 K to 0.49 µs at 296 K for the lowest spin density sample examined. Higher spin densities and temperatures were both found to diminish T1 times, which we attribute to detrimental cross-relaxation from spin-spin dipolar interactions and spin-phonon coupling, respectively. Higher spin densities decreased T2 times and modulated the T2 temperature dependence. We attribute these differences to the competition between hyperfine and dipolar interactions for electron spin decoherence, with the dominant interaction transitioning from the former to the latter as spin density and temperature increase. Overall, this investigation demonstrates that dispersing electronic spin qubits within layered 2DPs enables chemical control of their inter-qubit interactions and spin decoherence times.

Preferences, beliefs, and attitudes about oral fluid and blood-based HIV self-testing among truck drivers in Kenya choosing not to test for HIV.

Introduction: Clinical trials in sub-Saharan Africa support that HIV self-testing (HIVST) can increase testing rates in difficult-to-reach populations. However, trials mostly evaluate oral fluid HIVST only. We describe preferences for oral fluid vs. blood-based HIVST to elucidate prior trial results and inform testing programs. Methods: Participants were recruited from a HIVST randomized controlled trial in Nakuru County, Kenya, which aimed to test the effect of choice between oral HIVST and facility-based testing compared to standard-of-care on HIV testing among truck drivers. We conducted in-depth interviews (IDIs) with purposively sampled trial participants who declined HIV testing at baseline or who were offered access to oral fluid HIVST and chose not to pick up the kit during follow-up. IDIs were conducted with all consenting participants. We first describe IDI participants compared to the other study participants, assessing the statistical significance of differences in characteristics between the two samples and then describe preferences, beliefs, and attitudes about HIVST biospecimen type expressed in the IDIs. Results: The final sample consisted of 16 men who refused HIV testing at baseline and 8 men who did not test during follow-up. All IDI participants had tested prior to study participation; mean number of years since last HIV test was 1.55, vs. 0.98 among non-IDI participants (p = 0.093). Of the 14 participants who answered the question about preferred type of HIVST, nine preferred blood-based HIVST, and five, oral HIVST. Preference varied by study arm with four of five participants who answered this question in the Choice arm and five of nine in the SOC arm preferring blood-based HIVST. Six key themes characterized truckers' views about test type: (1) Rapidity of return of test results. (2) Pain and fear associated with finger prick. (3) Ease of use. (4) Trust in test results; (5) fear of infection by contamination; and (6) Concerns about HIVST kit storage and disposal. Conclusion: We found no general pattern in the themes for preference for oral or blood-based HIVST, but if blood-based HIVST had been offered, some participants in the Choice arm might have chosen to self-test. Offering choices for HIVST could increase testing uptake.

Single-Crystalline Imine-Linked Two-Dimensional Covalent Organic Frameworks Separate Benzene and Cyclohexane Efficiently.

Two-dimensional (2D) covalent organic frameworks (COFs) are composed of structurally precise, permanently porous, layered macromolecular sheets, which are traditionally synthesized as polycrystalline solids with crystalline domain lengths smaller than 100 nm. Here, we polymerize imine-linked 2D COFs as suspensions of faceted single crystals in as little as 5 min at moderate temperature and ambient pressure. Single crystals of two imine-linked 2D COFs were prepared, consisting of a rhombic 2D COF (TAPPy-PDA) and a hexagonal 2D COF (TAPB-DMPDA). The sizes of TAPPy-PDA and TAPB-DMPDA crystals were tuned from 720 nm to 4 µm and 450 nm to 20 µm in width, respectively. High-resolution transmission electron microscopy revealed that the COF crystals consist of layered, 2D polymers comprising single-crystalline domains. Continuous rotation electron diffraction resolved the unit cell and crystal structure of both COFs, which are single-crystalline in the a-b plane but disordered in the stacking c dimension. Single crystals of both COFs were incorporated into gas chromatography separation columns and exhibited unusual selective retention of cyclohexane over benzene, with single-crystalline TAPPy-PDA significantly outperforming single-crystalline TAPB-DMPDA. Polycrystalline TAPPy-PDA exhibited no separation, while polycrystalline TAPB-DMPDA exhibited poor separation and the opposite order of elution, retaining benzene more than cyclohexane, indicating the importance of improved material quality for COFs to exhibit properties that derive from their precise, crystalline structures. This work represents the first example of synthesizing imine-linked 2D COF single crystals at ambient pressure and short reaction times and demonstrates the promise of high-quality COFs for molecular separations.

South African University Staff and Students' Perspectives, Preferences, and Drivers of Hesitancy Regarding COVID-19 Vaccines: A Multi-Methods Study.

COVID-19 vaccine hesitancy poses a threat to the success of vaccination programmes currently being implemented. Concerns regarding vaccine effectiveness and vaccine-related adverse events are potential barriers to vaccination; however, it remains unclear whether tailored messaging and vaccination programmes can influence uptake. Understanding the preferences of key groups, including students, could guide the implementation of youth-targeted COVID-19 vaccination programmes, ensuring optimal uptake. This study examined university staff and students' perspectives, preferences, and drivers of hesitancy regarding COVID-19 vaccines. A multi-methods approach was used-an online convenience sample survey and discrete choice experiment (DCE)-targeting staff and students at the University of KwaZulu-Natal, South Africa. The survey and DCE were available for staff and students, and data were collected from 18 November to 24 December 2021. The survey captured demographic characteristics as well as attitudes and perspectives of COVID-19 and available vaccines using modified Likert rating questions adapted from previously used tools. The DCE was embedded within the survey tool and varied critical COVID-19 vaccine programme characteristics to calculate relative utilities (preferences) and determine trade-offs. A total of 1836 staff and students participated in the study (541 staff, 1262 students, 33 undisclosed). A total of 1145 (62%) respondents reported that they had been vaccinated against COVID-19. Vaccination against COVID-19 was less prevalent among students compared with staff (79% of staff vs. 57% of students). The vaccine's effectiveness (22%), and its safety (21%), ranked as the two dominant reasons for not getting vaccinated. These concerns were also evident from the DCE, with staff and students being significantly influenced by vaccine effectiveness, with participants preferring highly effective vaccines (90% effective) as compared with those listed as being 70% or 50% effective (ß = -3.72, 95% CI = -4.39 to -3.04); this characteristic had the strongest effect on preferences of any attribute. The frequency of vaccination doses was also found to have a significant effect on preferences with participants deriving less utility from choice alternatives requiring two initial vaccine doses compared with one dose (ß = -1.00, 95% CI = -1.42 to -0.58) or annual boosters compared with none (ß = -2.35, 95% CI = -2.85 to -1.86). Notably, an incentive of ZAR 350 (USD 23.28) did have a positive utility (ß = 1.14, 95% CI = 0.76 to 1.53) as compared with no incentive. Given the slow take-up of vaccination among youth in South Africa, this study offers valuable insights into the factors that drive hesitancy among this population. Concerns have been raised around the safety and effectiveness of vaccines, although there remains a predilection for efficient services. Respondents were not enthusiastic about the prospect of having to take boosters, and this has played out in the roll-out data. Financial incentives may increase both the uptake of the initial dose of vaccines and see a more favourable response to subsequent boosters. Universities should consider tailored messaging regarding vaccine effectiveness and facilitate access to vaccines, to align services with the stated preferences of staff and students.

Delayed recognition of Type II decompression sickness in a diver with chronic atrial fibrillation.

Introduction: This case report describes an initially overlooked Type II decompression sickness (DCS) occurrence that was confused with a cerebral vascular accident in a patient with chronic atrial fibrillation (AF). The purpose of this case report is to reinforce the maxim that DCS needs to be suspected anytime a scuba diver experiences signs or symptoms compatible with DCS after completing a scuba dive. Methods: A 71-year-old scuba diver with a history of AF and who was taking warfarin made four dives, all with maximum depths less than 60 fsw (20 msw) over a 10-hour interval. Shoulder pain developed before entering the water on the fourth dive and was worse after exiting from the fourth dive. Twenty minutes later the diver collapsed while standing and was unable to make a grip using his left hand. A literature review failed to locate any case reports of divers with AF presenting with strokelike symptoms only to find the cause was Type II DCS.. Findings: Initially the patient's findings were reviewed with a diving medicine team. The recommendation was for the patient to be managed for a stroke. The patient was transferred to a hospital for a computed tomography scan, but no recommendation was made for a hyperbaric oxygen recompression treatment. The scan showed no brain bleed or infarct. The attending neurologist (not diving medicine-trained) was concerned that the patient's findings were diving-related and arranged for transferring the patient to a hyperbaric medicine facility 25 hours later. With hyperbaric oxygen (HBO2) therapy the patient's symptoms remitted over several weeks. Conclusion: The presence of symptoms attributed to a stroke immediately after a scuba dive should not deter a trial of HBO2 therapy. The delay in starting HBO2 therapy is concerning and perhaps the reason recovery was delayed and the need for repetitive HBO2 therapies.

The role of hyperbaric oxygen for acute traumatic ischemias.

Acute traumatic ischemias are an array of disorders that range from crush injuries to compartment syndromes, from burns to frostbite and from threatened flaps to compromised reimplantations. Two unifying components common to these conditions are a history of trauma be it physical, thermal, or surgical coupled with ischemia to the traumatized tissues. Their pathophysiology resolves around the self-perpetuating cycle of edema and ischemia, and their severity represents a spectrum from mild, almost non-existent, to tissue death. Since ischemia is a fundamental component of the traumatic ischemias and hypoxia is a consequence of ischemia, hyperbaric oxygen is a logical intervention for those conditions where tissue survival, infection control and healing is at risk. Unfortunately, even with mechanisms of hyperbaric oxygen that strongly support its usefulness in traumatic ischemias coupled with supportive clinical data, clinicians are disinclined to utilize it for these conditions. This focuses on the orthopedic aspects of the traumatic ischemias, namely crush injury and compartment syndrome, and show how hyperbaric oxygen treatments can mitigate their severity.

Arene-perfluoroarene interactions confer enhanced mechanical properties to synthetic nanotubes.

Supramolecular nanotubes prepared through macrocycle assembly offer unique properties that stem from their long-range order, structural predictability, and tunable microenvironments. However, assemblies that rely on weak non-covalent interactions often have limited aspect ratios and poor mechanical integrity, which diminish their utility. Here pentagonal imine-linked macrocycles are prepared by condensing a pyridine-containing diamine and either terephthalaldehyde or 2,3,5,6-tetrafluoroterephthalaldehyde. Atomic force microscopy and synchrotron in solvo X-ray diffraction demonstrate that protonation of the pyridine groups drives assembly into high-aspect ratio nanotube assemblies. A 1 : 1 mixture of each macrocycle yielded nanotubes with enhanced crystallinity upon protonation. UV-Vis and fluorescence spectroscopy indicate that nanotubes containing both arene and perfluoroarene subunits display spectroscopic signatures of arene-perfluoroarene interactions. Touch-spun polymeric fibers containing assembled nanotubes prepared from the perhydro- or perfluorinated macrocycles exhibited Young's moduli of 1.09 and 0.49 GPa, respectively. Fibers containing nanotube assemblies reinforced by arene-perfluoroarene interactions yielded a 93% increase in the Young's modulus over the perhydro derivative, up to 2.1 GPa. These findings demonstrate that tuning the chemical composition of the monomeric macrocycles can have profound effects on the mechanical strength of the resulting assemblies. More broadly, these results will inspire future studies into tuning orthogonal non-covalent interactions between macrocycles to yield nanotubes with emergent functions and technological potential.

Controlled n-Doping of Naphthalene-Diimide-Based 2D Polymers.

2D polymers (2DPs) are promising as structurally well-defined, permanently porous, organic semiconductors. However, 2DPs are nearly always isolated as closed shell organic species with limited charge carriers, which leads to low bulk conductivities. Here, the bulk conductivity of two naphthalene diimide (NDI)-containing 2DP semiconductors is enhanced by controllably n-doping the NDI units using cobaltocene (CoCp2 ). Optical and transient microwave spectroscopy reveal that both as-prepared NDI-containing 2DPs are semiconducting with sub-2 eV optical bandgaps and photoexcited charge-carrier lifetimes of tens of nanoseconds. Following reduction with CoCp2 , both 2DPs largely retain their periodic structures and exhibit optical and electron-spin resonance spectroscopic features consistent with the presence of NDI-radical anions. While the native NDI-based 2DPs are electronically insulating, maximum bulk conductivities of >10-4  S cm-1 are achieved by substoichiometric levels of n-doping. Density functional theory calculations show that the strongest electronic couplings in these 2DPs exist in the out-of-plane (π-stacking) crystallographic directions, which indicates that cross-plane electronic transport through NDI stacks is primarily responsible for the observed electronic conductivity. Taken together, the controlled molecular doping is a useful approach to access structurally well-defined, paramagnetic, 2DP n-type semiconductors with measurable bulk electronic conductivities of interest for electronic or spintronic devices.

Two-Dimensional Polymers and Polymerizations.

Synthetic chemists have developed robust methods to synthesize discrete molecules, linear and branched polymers, and disordered cross-linked networks. However, two-dimensional polymers (2DPs) prepared from designed monomers have been long missing from these capabilities, both as objects of chemical synthesis and in nature. Recently, new polymerization strategies and characterization methods have enabled the unambiguous realization of covalently linked macromolecular sheets. Here we review 2DPs and 2D polymerization methods. Three predominant 2D polymerization strategies have emerged to date, which produce 2DPs either as monolayers or multilayer assemblies. We discuss the fundamental understanding and scope of each of these approaches, including: the bond-forming reactions used, the synthetic diversity of 2DPs prepared, their multilayer stacking behaviors, nanoscale and mesoscale structures, and macroscale morphologies. Additionally, we describe the analytical tools currently available to characterize 2DPs in their various isolated forms. Finally, we review emergent 2DP properties and the potential applications of planar macromolecules. Throughout, we highlight achievements in 2D polymerization and identify opportunities for continued study.

Paediatric tuberculosis preventive treatment preferences among HIV-positive children, caregivers and healthcare providers in Eswatini: a discrete choice experiment.

OBJECTIVE: Isoniazid preventive therapy initiation and completion rates are suboptimal among children. Shorter tuberculosis (TB) preventive treatment (TPT) regimens have demonstrated safety and efficacy in children and may improve adherence but are not widely used in high TB burden countries. Understanding preferences regarding TPT regimens' characteristics and service delivery models is key to designing services to improve TPT initiation and completion rates. We examined paediatric TPT preferences in Eswatini, a high TB burden country. DESIGN: We conducted a sequential mixed-methods study utilising qualitative methods to inform the design of a discrete choice experiment (DCE) among HIV-positive children, caregivers and healthcare providers (HCP). Drug regimen and service delivery characteristics included pill size and formulation, dosing frequency, medication taste, treatment duration and visit frequency, visit cost, clinic wait time, and clinic operating hours. An unlabelled, binary choice design was used; data were analysed using fixed and mixed effects logistic regression models, with stratified models for children, caregivers and HCP. SETTING: The study was conducted in 20 healthcare facilities providing TB/HIV care in Manzini, Eswatini, from November 2018 to December 2019. PARTICIPANTS: Ninety-one stakeholders completed in-depth interviews to inform the DCE design; 150 children 10-14 years, 150 caregivers and 150 HCP completed the DCE. RESULTS: Despite some heterogeneity, the results were fairly consistent among participants, with palatability of medications viewed as the most important TPT attribute; fewer and smaller pills were also preferred. Additionally, shorter waiting times and cost of visit were found to be significant drivers of choices. CONCLUSION: Palatable medication, smaller/fewer pills, low visit costs and shorter clinic wait times are important factors when designing TPT services for children and should be considered as new paediatric TPT regimens in Eswatini are rolled out. More research is needed to determine the extent to which preferences drive TPT initiation, adherence and completion rates.