Inert Liquid Exfoliation and Langmuir-Type Thin Film Deposition of Semimetallic Metal Diborides.

Graphite is one of only a few layered materials that can be exfoliated into nanosheets with semimetallic properties, which limits the applications of nanosheet-based electrodes to material combinations compatible with the work function of graphene. It is therefore important to identify additional metallic or semimetallic two-dimensional (2D) nanomaterials that can be processed in solution for scalable fabrication of printed electronic devices. Metal diborides represent a family of layered non-van der Waals crystals with semimetallic properties for all nanosheet thicknesses. While previous reports show that the exfoliated nanomaterial is prone to oxidation, we demonstrate a readily accessible inert exfoliation process to produce quasi-2D nanoplatelets with intrinsic material properties. For this purpose, we demonstrate the exfoliation of three representative metal diborides (MgB2, CrB2, and ZrB2) under inert conditions. Nanomaterial is characterized using a combination of transmission electron microscopy, scanning electron microscopy, atomic force microscopy, IR, and UV-vis measurements, with only minimal oxidation indicated postprocessing. By depositing the pristine metal diboride nanoplatelets as thin films using a Langmuir-type deposition technique, the ohmic behavior of the networks is validated. Furthermore, the material decomposition is studied by using a combination of electrical and optical measurements after controlled exposure to ambient conditions. Finally, we report an efficient, low-cost approach for sample encapsulation to protect the nanomaterials from oxidation. This is used to demonstrate low-gauge factor strain sensors, confirming metal diboride nanosheets as a suitable alternative to graphene for electrode materials in printed electronics.

Tale of quadriceps and hamstring muscle strength after ACL reconstruction: a systematic review with longitudinal and multivariate meta-analysis.

OBJECTIVE: This study aimed to investigate how knee extensor and flexor strength change over time after anterior cruciate ligament reconstruction (ACLR). DESIGN: Systematic review with longitudinal meta-analysis. DATA SOURCES: Medline, Embase, CINAHL, Scopus, Cochrane CENTRAL and SPORTDiscus to 28 February 2023. ELIGIBILITY CRITERIA: Studies of primary ACLR (n≥50), with mean participant age 18-40 years, reporting a quantitative measure of knee extensor or flexor strength were eligible. Muscle strength had to be reported for the ACL limb and compared with: (1) the contralateral limb (within-person); and/or (2) an uninjured control limb (between-person). RESULTS: We included 232 studies of 34 220 participants. Knee extensor and flexor strength showed sharp initial improvement postoperatively before tailing off at approximately 12-18 months post surgery with minimal change thereafter. Knee extensor strength was reduced by more than 10% compared with the contralateral limb and approximately 20% compared with uninjured controls at 1 year for slow concentric, fast concentric and isometric contractions. Knee flexor strength showed smaller deficits but was still 5%-7% lower than the contralateral limb at 1 year for slow concentric, fast concentric and isometric contractions. Between-person comparisons showed larger deficits than within-person comparisons. CONCLUSION: Knee extensor muscle strength is meaningfully reduced (>10%) at 1 year, with limited improvement after this time up to and beyond 5 years post surgery. Many people likely experience persistent and potentially long-term strength deficits after ACLR. Comparison within person (to the contralateral limb) likely underestimates strength deficits in contrast to uninjured controls.

A comparative study of fetal cardiovascular assessment: utilizing Doppler ultrasound gated MRI and echocardiography with detailed analysis using five axial views.

Objectives: To investigate the diagnostic performance of fetal cardiovascular magnetic resonance imaging (MRI) using Doppler ultrasound (DUS) gating for the evaluation of the standardized five axial views in comparison with fetal echocardiography. Methods: In this prospective study 29 pregnant women (median: 34.4 weeks of gestation) underwent fetal cardiovascular MRI using DUS gating at 3 Tesla. The standardized five axial views in prenatal screening (fetal abdomen, four-chamber view, left ventricular outflow tract, right ventricular outflow tract, and three-vessel view) were independently assessed and analysed by both fetal MRI and fetal echocardiography on the same day. Image analysis included qualitative assessment and quantitative measurements of cardiovascular structures. MR image quality was assessed using a 4-point scale (from 1 = low to 4 = excellent). Postnatal echocardiography was performed for validation. Results: 17/28 fetuses (60.7%) had pathological findings [16 congenital heart defect (CHD), one diaphragmatic hernia] in prenatal echocardiography. One fetus was excluded due to severe motion. Overall sensitivity and specificity in detecting fetal cardiac abnormalities was 88% and 100%, respectively, for fetal MRI and 100% and 100% for fetal echocardiography. MR image quality for evaluation of cardiac structures was high with a mean score of 2.8 (±0.8) (score 4: 15.9%, score 3: 53.8%, score 2: 19.3%, score 1: 11%). Quantitative measurements did not differ between fetal cardiovascular MRI and fetal echocardiography (all p > 0.05). Conclusion: Diagnostic performance of fetal cardiovascular MRI using DUS gating was comparable to fetal echocardiography. Fetal cardiovascular MRI using DUS gating might be a valuable diagnostic adjunct for the prenatal evaluation of CHD.

Pre-operative stereotactic radiosurgery and peri-operative dexamethasone for resectable brain metastases: a two-arm pilot study evaluating clinical outcomes and immunological correlates.

Enhancing the efficacy of immunotherapy in brain metastases (BrM) requires an improved understanding of the immune composition of BrM and how this is affected by radiation and dexamethasone. Our two-arm pilot study (NCT04895592) allocated 26 patients with BrM to either low (Arm A) or high (Arm B) dose peri-operative dexamethasone followed by pre-operative stereotactic radiosurgery (pSRS) and resection (n= 13 per arm). The primary endpoint, a safety analysis at 4 months, was met. The secondary clinical endpoints of overall survival, distant brain failure, leptomeningeal disease and local recurrence at 12-months were 66%, 37.3%, 6%, and 0% respectively and were not significantly different between arms (p= 0.7739, p= 0.3884, p= 0.3469). Immunological data from two large retrospective BrM datasets and confirmed by correlates from both arms of this pSRS prospective trial revealed that BrM CD8 T cells were composed of predominantly PD1+ TCF1+ stem-like and PD1+ TCF1-TIM3+ effector-like cells. Clustering of TCF1+ CD8 T cells with antigen presenting cells in immune niches was prognostic for local control, even without pSRS. Following pSRS, CD8 T cell and immune niche density were transiently reduced compared to untreated BrM, followed by a rebound 6+ days post pSRS with an increased frequency of TCF1- effector-like cells. In sum, pSRS is safe and therapeutically beneficial, and these data provide a framework for how pSRS may be leveraged to maximize intracranial CD8 T cell responses.

Noisy knees - knee crepitus prevalence and association with structural pathology: a systematic review and meta-analysis.

OBJECTIVE: Knee crepitus, the audible crackling or grinding noise during knee movement, can be experienced across the lifespan and create concern for underlying pathology. Our systematic review aims to provide a summary estimate of knee crepitus prevalence and its association with structural pathology among the general population and across knee conditions. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline, Embase, CENTRAL, Web of Science, SPORTDiscus and CINAHL. ELIGIBILITY CRITERIA: Studies evaluating knee crepitus prevalence. RESULTS: 103 studies involving 36 439 participants (42 816 knees) were included. Based on very low certainty evidence, the pooled prevalence of knee crepitus in the general population was 41% (7609 knees; 95% CI 36% to 45%; I2=92.6%); in pain-free persons 36% (852 knees; 95% CI 23% to 50%; I2=91.9%), and in those with osteoarthritis (OA) 81% (18 821 knees; 95% CI 75% to 87%; I2=97.9%). Across other musculoskeletal knee conditions, the pooled prevalence of knee crepitus ranged from 35% (ligament injury; 2740 knees; 95% CI 27% to 44%; I2=95.6%) to 61% (cartilage pathology; 1445 knees; 95% CI 40% to 81%; I2=98.2%). There was low to very low certainty evidence of an association between knee crepitus and radiographic OA (OR 3.79, 95% CI 1.99 to 7.24; 1725 knees; I2=53.0%) and several OA-related features on magnetic resonance imaging (MRI). CONCLUSION: In this review, knee crepitus was prevalent in the general population, pain-free persons, those with knee OA and other musculoskeletal knee conditions. Knee crepitus was associated with a more than threefold increased odds of radiographic OA diagnosis and several OA-related MRI features. The low to very low certainty of evidence informing our aggregated prevalence estimates and association outcomes suggest that results should be interpreted with caution.

Online Plain Language Tool and Health Information Quality: A Randomized Clinical Trial.

Importance: Complex and ineffective health communication is a critical source of health inequity and occurs despite repeated policy directives to provide health information that is easy to understand and applies health literacy principles. Objective: To evaluate the effectiveness of the Sydney Health Literacy Lab Health Literacy Editor, an easy-to-use online plain language tool that supports health information providers to apply health literacy guidelines to written health information. Design, Setting, and Participants: This randomized clinical trial, conducted online in Australia from May 2023 to February 2024, included a convenience sample of health information providers with no previous experience using the Health Literacy Editor. Analysts were blinded to study group. Intervention: Participants were randomized 1:1 to the intervention or control group. Participants in the intervention group were provided access to the Health Literacy Editor and a 30-minute online training program prior to editing 3 prespecified health texts. The Health Literacy Editor gives objective, real-time feedback on words and sentences. Control participants revised the texts using their own standard health information development processes. Main Outcomes and Measures: The preregistered primary outcome was the text school grade reading score (using a validated instrument, the Simple Measure of Gobbledygook). Secondary outcomes were text complexity (percentage of text using complex language), use of passive voice (number of instances), and subjective expert ratings (5-point Likert scale corresponding to items on the Patient Education Materials Assessment Tool). Results: A total of 211 participants were randomized, with 105 in the intervention group and 106 in the control group. Of 181 participants in the intention-to-treat analysis (mean [SD] age, 41.0 [11.6] years; 154 women [85.1%]), 86 were in the intervention group and 95 in the control group. Texts revised in the intervention group had significantly improved grade reading scores (mean difference [MD], 2.48 grades; 95% CI, 1.84-3.12 grades; P < .001; Cohen d, 0.99), lower text complexity scores (MD, 6.86; 95% CI, 4.99-8.74; P < .001; Cohen d, 0.95), and less use of passive voice (MD, 0.95 instances; 95% CI, 0.44-1.47 instances; P < .001; Cohen d, 0.53) compared with texts revised in the control group in intention-to-treat analyses. Experts rated texts in the intervention group more favorably for word choice and style than those in the control group (MD, 0.44; 95% CI, 0.25-0.63; P < .001; Cohen d, 0.63), with no loss of meaning or content. Conclusions and Relevance: In this randomized clinical trial, the Health Literacy Editor helped users simplify health information and apply health literacy guidelines to written text. The findings suggest the tool has high potential to improve development of health information for people who have low health literacy. As an online tool, the Health Literacy Editor is also easy to access and implement at scale. Trial Registration: ANZCTR Identifier: ACTRN12623000386639.

Few-shot Algorithms for Consistent Neural Decoding (FALCON) Benchmark.

Intracortical brain-computer interfaces (iBCIs) can restore movement and communication abilities to individuals with paralysis by decoding their intended behavior from neural activity recorded with an implanted device. While this activity yields high-performance decoding over short timescales, neural data are often nonstationary, which can lead to decoder failure if not accounted for. To maintain performance, users must frequently recalibrate decoders, which requires the arduous collection of new neural and behavioral data. Aiming to reduce this burden, several approaches have been developed that either limit recalibration data requirements (few-shot approaches) or eliminate explicit recalibration entirely (zero-shot approaches). However, progress is limited by a lack of standardized datasets and comparison metrics, causing methods to be compared in an ad hoc manner. Here we introduce the FALCON benchmark suite (Few-shot Algorithms for COnsistent Neural decoding) to standardize evaluation of iBCI robustness. FALCON curates five datasets of neural and behavioral data that span movement and communication tasks to focus on behaviors of interest to modern-day iBCIs. Each dataset includes calibration data, optional few-shot recalibration data, and private evaluation data. We implement a flexible evaluation platform which only requires user-submitted code to return behavioral predictions on unseen data. We also seed the benchmark by applying baseline methods spanning several classes of possible approaches. FALCON aims to provide rigorous selection criteria for robust iBCI decoders, easing their translation to real-world devices. https://snel-repo.github.io/falcon/.

Virtual stimulation of the interictal EEG network localizes the EZ as a measure of cortical excitability.

Introduction: For patients with drug-resistant epilepsy, successful localization and surgical treatment of the epileptogenic zone (EZ) can bring seizure freedom. However, surgical success rates vary widely because there are currently no clinically validated biomarkers of the EZ. Highly epileptogenic regions often display increased levels of cortical excitability, which can be probed using single-pulse electrical stimulation (SPES), where brief pulses of electrical current are delivered to brain tissue. It has been shown that high-amplitude responses to SPES can localize EZ regions, indicating a decreased threshold of excitability. However, performing extensive SPES in the epilepsy monitoring unit (EMU) is time-consuming. Thus, we built patient-specific in silico dynamical network models from interictal intracranial EEG (iEEG) to test whether virtual stimulation could reveal information about the underlying network to identify highly excitable brain regions similar to physical stimulation of the brain. Methods: We performed virtual stimulation in 69 patients that were evaluated at five centers and assessed for clinical outcome 1 year post surgery. We further investigated differences in observed SPES iEEG responses of 14 patients stratified by surgical outcome. Results: Clinically-labeled EZ cortical regions exhibited higher excitability from virtual stimulation than non-EZ regions with most significant differences in successful patients and little difference in failure patients. These trends were also observed in responses to extensive SPES performed in the EMU. Finally, when excitability was used to predict whether a channel is in the EZ or not, the classifier achieved an accuracy of 91%. Discussion: This study demonstrates how excitability determined via virtual stimulation can capture valuable information about the EZ from interictal intracranial EEG.

Effectiveness of whole-body electromyostimulation on knee pain and physical function in knee osteoarthritis: a randomized controlled trial.

In a randomized, controlled study, whole-body electromyostimulation (WB-EMS) was investigated as a promising alternative treatment technique compared to conventional strength training for the management of knee osteoarthritis (OA). Seventy-two overweight participants with symptomatic knee OA were randomly assigned to WB-EMS (n = 36) or a usual care group (UCG, n = 36). For seven months, the WB-EMS group received three times per fortnight a WB-EMS training, while the UCG was prescribed six-times physiotherapeutic treatments. We observed significant effects for the primary outcome "pain", as determined by the Knee injury and Osteoarthritis Outcome Score (KOOS), with more favourable changes in the WB-EMS group vs UCG (between-group difference 9.0 points, 95%CI 2.9-15.1, p = 0.004). Secondary outcomes, including the other KOOS subscales (symptoms, function in daily living, function in sports/recreational activities and quality of life), 7 day pain diary, hip/leg extensor strength and lower limb function (30s sit-to-stand test), were also statistically significant in favour of the WB-EMS group. Overall, WB-EMS was found to be effective in relieving knee pain symptoms and improving physical function in individuals with symptomatic knee OA compared to usual care treatment. WB-EMS could be used as an alternative therapy in the management of knee OA; particularly for patients that cannot be motivated for conventional training.

Defect-engineering of liquid-phase exfoliated 2D semiconductors: stepwise covalent growth of electronic lateral hetero-networks.

Two-dimensional (2D) in-plane heterostructures display exceptional optical and electrical properties well beyond those of their pristine components. However, they are usually produced by tedious and energy-intensive bottom-up growth approaches, not compatible with scalable solution-processing technologies. Here, we report a new stepwise microfluidic approach, based on defect engineering of liquid-phase exfoliated transition metal dichalcogenides (TMDs), to synthesize 2D hetero-networks. The healing of sulfur vacancies in MoS2 and WS2 is exploited to controllably bridge adjacent nanosheets of different chemical nature with dithiolated conjugated molecular linkers, yielding solution-processed nm-scale thick networks with enhanced percolation pathways for charge transport. In-plane growth and molecular-driven assembly synergistically lead to molecularly engineered heterojunctions suppressing the formation of tightly bound interlayer excitons that are typical of conventional TMD blends, promoting faster charge separation. Our strategy offers an unprecedented route to chemically assemble solution-processed heterostructures with functional complexity that can be further enhanced by exploiting stimuli-responsive molecular linkers.

The Impact of Area Deprivation Index, Geography, and Mechanism on Incidence of Ballistic Injury to the Upper Extremity.

INTRODUCTION: This study investigates the intersection of ballistic injuries, geography, and Area Deprivation Index (ADI). We hypothesized that both ADI and geography are correlated with incidence of upper extremity ballistic injuries. Further, we characterize and compare 2 distinct upper extremity gunshot injury populations presenting to our institution: those sustaining violent ballistic injuries and those who suffer an accidental, self-inflicted injury. Our purpose is to evaluate the impact of geography and ADI on the pattern of upper extremity gunshot injuries in Illinois and Missouri. MATERIALS AND METHODS: This was a retrospective review of adult patients sustaining ballistic injury to the upper extremity at a single urban level I trauma center over 10 years (n = 797). Seven hundred thirty patients had home addresses in Illinois or Missouri; these addresses were geocoded and included for analysis. Mechanism of injury was self-reported. ADI was measured from the 2019 Neighborhood Atlas, in which deprivation increases from 1 to 100. Comparisons between groups were conducted with unpaired t tests, Fisher exact test, or χ2 testing, where appropriate. RESULTS: Addresses constituted 259 unique census tracts, and the average number of upper extremity gunshot wound incidents per tract was 3, with a maximum of 22; 15.4% of census block tracts made up almost half (48.4%) of the total ballistic injuries in the study period; 97.7% of violent injuries occurred in Urban areas, as compared with only 60% of accidental injuries (P < 0.05). ADI and incidence of upper extremity ballistic injury were positively correlated. ADI varied significantly between patients sustaining violent (median, 94; mean, 86.1) versus accidental self-inflicted (median, 79; mean, 70.9) injuries (P < 0.05). Fifty percent of violent injuries in our data set occurred in block groups from the 2 most deprived quintiles. CONCLUSIONS: Upper extremity gunshot wounds in general are concentrated in census blocks with high ADI. Violent injuries in particular are more likely to occur in urban areas with high ADI, whereas patients with accidental, self-inflicted injuries are more geographically and socioeconomically diverse. These differing populations require unique approaches to reduce incidence and morbidity.

Representative honey bee viruses do not replicate in the small hive beetle, Aethina tumida Murray.

The small hive beetle (SHB), Aethina tumida Murray, is an invasive pest of the honey bee and causes significant damage through the consumption of colony resources and brood. Two assumptions related to honey bee virus transmission have been made about SHB: first, that SHB vectors honey bee viruses and second, that these viruses replicate in SHB based on the detection of both positive and negative strand viral genomic RNA within SHB. To clarify the role of SHB in virus transmission, we sought to address whether selected honey bee viruses replicate in SHB. Sequences derived from five honey bee viruses were identified in the transcriptomes of field-caught SHB from the U.S., but not in those of lab-reared SHB, suggesting that these viruses do not replicate in SHB. To elucidate whether the representative viruses, Israeli acute paralysis virus (IAPV; Dicistroviridae) and Deformed wing virus (DWV; Iflaviridae) replicate in SHB, we tested for replication in vitro in an SHB-derived cell line (BCIRL-AtumEN-1129-D6). Following treatment of the cell line with viral particles or viral RNA, the number of virus genomes was monitored by reverse transcription quantitative PCR (RT-qPCR). In contrast to the positive control, IAPV and DWV RNA levels steadily decreased over a period of 8 days. Collectively, these results from bioinformatic observations and in vitro experiments indicate that IAPV and DWV do not replicate in SHB. These results are consistent with the host specificity of most insect viruses within a single insect order and indicate that while SHB may serve as a mechanical vector of honey bee viruses within and between hives, this insect does not serve as a biological vector for these honey bee viruses.

Rigid crosslinking of the CD3 complex leads to superior T cell stimulation.

Functionally bivalent non-covalent Fab dimers (Bi-Fabs) specific for the TCR/CD3 complex promote CD3 signaling on T cells. While comparing functional responses to stimulation with Bi-Fab, F(ab')2 or mAb specific for the same CD3 epitope, we observed fratricide requiring anti-CD3 bridging of adjacent T cells. Surprisingly, anti-CD3 Bi-Fab ranked first in fratricide potency, followed by anti-CD3 F(ab')2 and anti-CD3 mAb. Low resolution structural studies revealed anti-CD3 Bi-Fabs and F(ab')2 adopt similar global shapes with CD3-binding sites oriented outward. However, under molecular dynamic simulations, anti-CD3 Bi-Fabs crosslinked CD3 more rigidly than F(ab')2. Furthermore, molecular modelling of Bi-Fab and F(ab')2 binding to CD3 predicted crosslinking of T cell antigen receptors located in opposing plasma membrane domains, a feature fitting with T cell fratricide observed. Thus, increasing rigidity of Fab-CD3 crosslinking between opposing effector-target pairs may result in stronger T cell effector function. These findings could guide improving clinical performance of bi-specific anti-CD3 drugs.

People Are More Variable Than Their Hop Test Would Suggest: Hop Performance and Self-Reported Outcomes Over 11 Years Following ACL Reconstruction.

We aimed to report the trajectory of self-reported outcomes up to 11 years post-ACLR. We also explored the relationship between hop performance at 1 year and: (i) future self-reported knee outcomes; and (ii) risk of subsequent knee events. 124 participants (43 women, mean age 31 ± 8 years) were recruited at 1 year following hamstring-autograft ACLR. Hop performance was assessed with single-forward and side-hop tests. Follow-up was completed at 3 (n = 114), 5 (n = 89) and 11 years (n = 72) post-ACLR. Self-reported outcomes were assessed at each follow-up with the Knee injury Osteoarthritis Outcome Score (KOOS) pain and quality of life (QOL) subscales. Generalized linear mixed models estimated the relationship between hop performance and self-reported outcomes. Subsequent knee events (new injury/surgery) to either knee were recorded, with the relationship between hop performance and risk of subsequent knee events analyzed with Cox proportional hazards. Self-reported knee outcomes were stable (mean change < 10 points) across all timepoints but with major within-sample variability. There was a modest relationship between greater hop performance at 1 year and better future KOOS-pain (average marginal effect [AME] % improvement with + 1 cm single forward hop = 0.06% [95% CI 0.02-0.10]). A nonlinear spline relationship showed better single-forward hop performance was associated with better KOOS-QOL for scores < 108 cm, not present for higher hop scores > 108 cm. There were 21 index and 11 contralateral subsequent knee events. Hop performance was not related to risk of a subsequent knee event (hazard ratio index knee 0.99 [95% CI 0.98-1.02]). In conclusion, self-reported knee pain and quality of life were generally stable across the 11-year follow-up period. Greater hop performance at 1-year post-ACLR was related to better self-reported knee outcomes up to 11-year follow-up (of questionable clinical importance), but not associated with the risk of subsequent knee injury/surgery.

The use of oral benzodiazepines for patient anxiety associated with Mohs micrographic surgery: An Australian survey.

A survey of Mohs surgery specialists in Australia showed diazepam was the preferred agent and felt to be the safest oral benzodiazepine for perioperative anxiolysis.

Optogenetic control of kinesin-1, -2, -3 and dynein reveals their specific roles in vesicular transport.

Each cargo in a cell employs a unique set of motor proteins for its transport. To dissect the roles of each type of motor, we developed optogenetic inhibitors of endogenous kinesin-1, -2, -3 and dynein motors and examined their effect on the transport of early endosomes, late endosomes, and lysosomes. While kinesin-1, -3, and dynein transport vesicles at all stages of endocytosis, kinesin-2 primarily drives late endosomes and lysosomes. Transient optogenetic inhibition of kinesin-1 or dynein causes both early and late endosomes to move more processively by relieving competition with opposing motors. Kinesin-2 and -3 support long-range transport, and optogenetic inhibition reduces the distances that their cargoes move. These results suggest that the directionality of transport is controlled through regulating kinesin-1 and dynein activity. On vesicles transported by several kinesin and dynein motors, modulating the activity of a single type of motor on the cargo is sufficient to direct motility.

Structure-Activity Relationship Studies of the Peptide Antibiotic Clovibactin.

Our laboratory reported the chemical synthesis and stereochemical assignment of the recently discovered peptide antibiotic clovibactin. The current paper reports an improved, gram-scale synthesis of the amino acid building block Fmoc-(2R,3R)-3-hydroxyasparagine-OH that enables structure-activity relationship studies of clovibactin. An alanine scan reveals that residues Phe1, d-Leu2, Ser4, Leu7, and Leu8 are important for antibiotic activity. The side-chain amide group of the rare d-Hyn5 residue is not essential to activity and can be replaced with a methyl group with a moderate loss of activity. An acyclic clovibactin analogue reveals that the macrolactone ring is essential to antibiotic activity. The enantiomer of clovibactin is active, albeit somewhat less so than clovibactin. A conformationally constrained clovibactin analogue retains moderate antibiotic activity, while a backbone N-methylated analogue is almost completely inactive. X-ray crystallography of these two analogues reveals that the macrolactone ring adopts a crown-like conformation that binds anions.