Suppressed basal melting in the eastern Thwaites Glacier grounding zone.

Thwaites Glacier is one of the fastest-changing ice-ocean systems in Antarctica1-3. Much of the ice sheet within the catchment of Thwaites Glacier is grounded below sea level on bedrock that deepens inland4, making it susceptible to rapid and irreversible ice loss that could raise the global sea level by more than half a metre2,3,5. The rate and extent of ice loss, and whether it proceeds irreversibly, are set by the ocean conditions and basal melting within the grounding-zone region where Thwaites Glacier first goes afloat3,6, both of which are largely unknown. Here we show-using observations from a hot-water-drilled access hole-that the grounding zone of Thwaites Eastern Ice Shelf (TEIS) is characterized by a warm and highly stable water column with temperatures substantially higher than the in situ freezing point. Despite these warm conditions, low current speeds and strong density stratification in the ice-ocean boundary layer actively restrict the vertical mixing of heat towards the ice base7,8, resulting in strongly suppressed basal melting. Our results demonstrate that the canonical model of ice-shelf basal melting used to generate sea-level projections cannot reproduce observed melt rates beneath this critically important glacier, and that rapid and possibly unstable grounding-line retreat may be associated with relatively modest basal melt rates.

Development of a Machine Learning Modelling Tool for Predicting HIV Incidence Using Public Health Data from a County in the Southern United States.

BACKGROUND: Recent advancements in Machine Learning (ML) have significantly improved the accuracy of models predicting HIV incidence. These models typically utilize electronic medical records and patient registries. This study aims to broaden the application of these tools by utilizing de-identified public health datasets for notifiable sexually transmitted infections (STIs) from a southern U.S. County known for high HIV incidence rates. The goal is to assess the feasibility and accuracy of ML in predicting HIV incidence, which could potentially inform and enhance public health interventions. METHODS: We analyzed two de-identified public health datasets, spanning January 2010 to December 2021, focusing on notifiable STIs. Our process involved data processing and feature extraction, including sociodemographic factors, STI cases, and social vulnerability index (SVI) metrics. Various ML algorithms were trained and evaluated for predicting HIV incidence, using metrics such as accuracy, precision, recall, and F1 score. RESULTS: The study included 85,224 individuals, with 2,027 (2.37%) newly diagnosed with HIV during the study period. The ML models demonstrated high performance in predicting HIV incidence among males and females. Influential predictive features for males included age at STI diagnosis, previous STI information, provider type, and SVI. For females, they included age, ethnicity, previous STIs information, overall SVI, and race. CONCLUSIONS: The high accuracy of our ML models in predicting HIV incidence highlights the potential of using public health datasets for public health interventions such as tailored HIV testing and prevention. While these findings are promising, further research is needed to translate these models into practical public health applications.

Monitoring the Evolution of Relative Product Populations at Early Times during a Photochemical Reaction.

Identifying multiple rival reaction products and transient species formed during ultrafast photochemical reactions and determining their time-evolving relative populations are key steps toward understanding and predicting photochemical outcomes. Yet, most contemporary ultrafast studies struggle with clearly identifying and quantifying competing molecular structures/species among the emerging reaction products. Here, we show that mega-electronvolt ultrafast electron diffraction in combination with ab initio molecular dynamics calculations offer a powerful route to determining time-resolved populations of the various isomeric products formed after UV (266 nm) excitation of the five-membered heterocyclic molecule 2(5H)-thiophenone. This strategy provides experimental validation of the predicted high (∼50%) yield of an episulfide isomer containing a strained three-membered ring within ∼1 ps of photoexcitation and highlights the rapidity of interconversion between the rival highly vibrationally excited photoproducts in their ground electronic state.

Deconvolution of the X-ray absorption spectrum of trans-1,3-butadiene with resonant Auger spectroscopy.

High-resolution carbon K-edge X-ray photoelectron, X-ray absorption, non-resonant and resonant Auger spectra are presented of gas phase trans-1,3-butadiene alongside a detailed theoretical analysis utilising nuclear ensemble approaches and vibronic models to simulate the spectroscopic observables. The resonant Auger spectra recorded across the first pre-edge band reveal a complex evolution of different electronic states which remain relatively well-localised on the edge or central carbon sites. The results demonstrate the sensitivity of the resonant Auger observables to the weighted contributions from multiple electronic states. The gradually evolving spectral features can be accurately and feasibly simulated within nuclear ensemble methods and interpreted with the population analysis.

Resonant Auger decay of dissociating CH3I near the I 4d threshold.

Resonant Auger processes provide a unique perspective on electronic interactions and excited vibrational and electronic states of molecular ions. Here, new data are presented on the resonant Auger decay of excited CH3I in the region just below the I 4d-1 ionization threshold. The resonances include the Rydberg series converging to the five spin-orbit and ligand-field split CH3I (I 4d-1) thresholds, as well as resonances corresponding to excitation from the I 4d5/2,3/2 orbitals into the σ* lowest unoccupied molecular orbital. This study focuses on participator decay that populates the lowest lying states of CH3I+, in particular, the X̃2E3/2 and 2E1/2 states, and on spectator decay that populates the lowest-lying (CH3I2+)σ* states of CH3I+. The CH3I (I 4d-1)σ* resonances are broad, and dissociation to CH3 + I competes with the autoionization of the core-excited states. Auger decay as the molecule dissociates produces a photoelectron spectrum with a long progression (up to v3+ ∼ 25) in the C-I stretching mode of the X̃2E3/2 and 2E1/2 states, providing insights into the shape of the dissociative core-excited surface. The observed spectator decay processes indicate that CH3I+ is formed on the repulsive wall of the lower-lying (CH3I2+)σ* potentials, and the photon-energy dependence of the processes provides insights into the relative slopes of the (4d-1)σ* and (CH3I2+)σ* potential surfaces. Data are also presented for the spectator decay of higher lying CH3I (I 4d-1)nl Rydberg resonances. Photoelectron angular distributions for the resonant Auger processes provide additional information that helps distinguish these processes from the direct ionization signal.

Resonant Auger decay of iodobenzene below the I 4d edge.

New data are presented on the resonant Auger decay of iodobenzene (C6H5I) in the region of the I 4d-1 ionization threshold. The excited molecules decay by participator and spectator processes to populate single-hole valence states and two-hole, one-particle excited states of the cation, providing new information on the structure of C6H5I+. Excitation of dissociative C6H5I (I 4d5/2,3/2-1)σ* resonances can, in principle, result in ultrafast dissociation to C6H5 + I** and the subsequent autoionization of I**, but no evidence for this process is observed. The results are compared with our recent study of the resonant Auger decay of methyl iodide (CH3I).

Valence shell electronically excited states of norbornadiene and quadricyclane.

The absolute photoabsorption cross sections of norbornadiene (NBD) and quadricyclane (QC), two isomers with chemical formula C7H8 that are attracting much interest for solar energy storage applications, have been measured from threshold up to 10.8 eV using the Fourier transform spectrometer at the SOLEIL synchrotron radiation facility. The absorption spectrum of NBD exhibits some sharp structure associated with transitions into Rydberg states, superimposed on several broad bands attributable to valence excitations. Sharp structure, although less pronounced, also appears in the absorption spectrum of QC. Assignments have been proposed for some of the absorption bands using calculated vertical transition energies and oscillator strengths for the electronically excited states of NBD and QC. Natural transition orbitals indicate that some of the electronically excited states in NBD have a mixed Rydberg/valence character, whereas the first ten excited singlet states in QC are all predominantly Rydberg in the vertical region. In NBD, a comparison between the vibrational structure observed in the experimental 11B1-11A1 (3sa1 ← 5b1) band and that predicted by Franck-Condon and Herzberg-Teller modeling has necessitated a revision of the band origin and of the vibrational assignments proposed previously. Similar comparisons have encouraged a revision of the adiabatic first ionization energy of NBD. Simulations of the vibrational structure due to excitation from the 5b2 orbital in QC into 3p and 3d Rydberg states have allowed tentative assignments to be proposed for the complex structure observed in the absorption bands between ∼5.4 and 7.0 eV.

Catheter Ablation for Atrial Fibrillation-Influence of Modifiable Risk Factors and Ablation Modality on Procedural Efficacy and Safety.

BACKGROUND: Modifiable lifestyle risk factors, in particular obesity and related conditions, are important drivers of atrial fibrillation (AF), impacting the severity of symptoms and influence the efficacy and safety of treatment. OBJECTIVE: The study aimed to assess the impact of modifiable lifestyle factors on the effectiveness and safety of AF ablation, and examine the procedural characteristics, efficacy, safety and cost outcomes of cryoballoon vs radiofrequency ablation, in a real-world clinical setting. METHOD: Patients undergoing catheter ablation for AF (June 2017 to December 2020) were included in this retrospective analysis. Efficacy and safety outcomes were obtained from electronic medical records and state-wide databases. The primary outcome was successful isolation of the pulmonary veins and freedom from AF without repeat ablation or ongoing antiarrhythmic therapy at 12 months. RESULTS: The study included 141 patients (mean age 60±11 years, 57% male). The average body mass index (BMI) was 29.2±5.6 kg/m2. Ablation by cryoballoon was undertaken in 59% (radiofrequency 41%). Acutely successful pulmonary vein isolation was achieved in 92%, however, only 52% (n=74) met the primary outcome (successful isolation of the pulmonary veins and freedom from AF without repeat ablation or ongoing antiarrhythmic therapy) at 12 months. Successful management of AF was more likely in patients with lower BMI (p=0.006; particularly with BMI <27 kg/m2; p=0.004) and weight (p=0.003), and in those without obstructive sleep apnoea (p=0.032). The only independent predictor of the primary outcome was BMI (ß=0.25, p=0.004). Over 75% of complications occurred in those with BMI ≥27 kg/m2. CONCLUSIONS: Catheter ablation for AF is more likely to be unsuccessful in patients with uncontrolled risk factors, particularly obesity. Risk factor optimisation may improve procedural success and reduce the risk of procedural complications.

Symptoms and Systemic Drug Reactions in Persons Receiving Weekly Rifapentine Plus Isoniazid (3HP) Treatment for Latent Tuberculosis Infection.

BACKGROUND: Three months of weekly rifapentine plus isoniazid (3HP) therapy for latent tuberculosis infection (LTBI) is recommended worldwide. The development of symptoms and systemic drug reactions (SDRs) on 3HP have not been fully characterized. We aimed to determine the patterns of symptom development and identify SDRs and associated factors in patients taking 3HP. METHODS: We analyzed symptoms data in participants receiving 3HP in the Tuberculosis Trials Consortium's iAdhere study (Study 33). We examined the patterns of symptom reporting across participants from baseline and 4 monthly visits. Bivariate analyses and multivariable regression models were used to identify factors associated with SDRs. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated. RESULTS: Among 1002 participants receiving 3HP, 768 (77%) reported at least 1 symptom; 97% of these symptoms were grade 1 (79%) or grade 2 (18%). Most symptoms developed in the first month and resolved. A total of 111 (11%) participants had symptoms that met criteria for SDRs; however, 53 (48%) of these participants completed therapy. Factors associated with SDRs and discontinuation included female sex (RR: 2.05; 95% CI: 1.19-3.54), age ≥45 years (RR: 1.99; 95% CI: 1.19-3.31), and use of concomitant medications (RR: 2.26; 95% CI: 1.15-4.42). CONCLUSIONS: Although most patients receiving 3HP reported symptoms, most were mild, occurred early, and resolved without stopping treatment. Among patients experiencing SDRs, nearly half were able to complete therapy. Patient and provider education should focus on differentiating severe reactions where 3HP should be stopped from minor symptoms that will resolve. Clinical Trials Registration. NCT01582711.

An evolutionarily distinct ringed seal in the Ilulissat Icefjord.

The Earth's polar regions are low rates of inter- and intraspecific diversification. An extreme mammalian example is the Arctic ringed seal (Pusa hispida hispida), which is assumed to be panmictic across its circumpolar Arctic range. Yet, local Inuit communities in Greenland and Canada recognize several regional variants; a finding supported by scientific studies of body size variation. It is however unclear whether this phenotypic variation reflects plasticity, morphs or distinct ecotypes. Here, we combine genomic, biologging and survey data, to document the existence of a unique ringed seal ecotype in the Ilulissat Icefjord (locally 'Kangia'), Greenland; a UNESCO World Heritage site, which is home to the most productive marine-terminating glacier in the Arctic. Genomic analyses reveal a divergence of Kangia ringed seals from other Arctic ringed seals about 240 kya, followed by secondary contact since the Last Glacial Maximum. Despite ongoing gene flow, multiple genomic regions appear under strong selection in Kangia ringed seals, including candidate genes associated with pelage coloration, growth and osmoregulation, potentially explaining the Kangia seal's phenotypic and behavioural uniqueness. The description of 'hidden' diversity and adaptations in yet another Arctic species merits a reassessment of the evolutionary processes that have shaped Arctic diversity and the traditional view of this region as an evolutionary freezer. Our study highlights the value of indigenous knowledge in guiding science and calls for efforts to identify distinct populations or ecotypes to understand how these might respond differently to environmental change.

Reversing Inequity in Mpox Vaccine Distribution, Fulton County, Georgia, June-September 2022.

Racial/ethnic disparities in the administration of mpox vaccine in Fulton County, Georgia, threatened to undermine the effectiveness of the response. To counteract this inequity, the Fulton County Board of Health partnered with local agencies serving Black and Latino men who have sex with men to coordinate efforts and reserve blocks of time for clients of these agencies to receive a vaccine. The disparities were reversed and approached equity with case rates. (Am J Public Health. 2023;113(12):1263-1266. https://doi.org/10.2105/AJPH.2023.307416).

Public Health Response to Clusters of Rapid HIV Transmission Among Hispanic or Latino Gay, Bisexual, and Other Men Who Have Sex with Men - Metropolitan Atlanta, Georgia, 2021-2022.

During February 2021-June 2022, the Georgia Department of Public Health (GDPH) detected five clusters of rapid HIV transmission concentrated among Hispanic or Latino (Hispanic) gay, bisexual, and other men who have sex with men (MSM) in metropolitan Atlanta. The clusters were detected through routine analysis of HIV-1 nucleotide sequence data obtained through public health surveillance (1,2). Beginning in spring 2021, GDPH partnered with health districts with jurisdiction in four metropolitan Atlanta counties (Cobb, DeKalb, Fulton, and Gwinnett) and CDC to investigate factors contributing to HIV spread, epidemiologic characteristics, and transmission patterns. Activities included review of surveillance and partner services interview data,† medical chart reviews, and qualitative interviews with service providers and Hispanic MSM community members. By June 2022, these clusters included 75 persons, including 56% who identified as Hispanic, 96% who reported male sex at birth, 81% who reported male-to-male sexual contact, and 84% of whom resided in the four metropolitan Atlanta counties. Qualitative interviews identified barriers to accessing HIV prevention and care services, including language barriers, immigration- and deportation-related concerns, and cultural norms regarding sexuality-related stigma. GDPH and the health districts expanded coordination, initiated culturally concordant HIV prevention marketing and educational activities, developed partnerships with organizations serving Hispanic communities to enhance outreach and services, and obtained funding for a bilingual patient navigation program with academic partners to provide staff members to help persons overcome barriers and understand the health care system. HIV molecular cluster detection can identify rapid HIV transmission among sexual networks involving ethnic and sexual minority groups, draw attention to the needs of affected populations, and advance health equity through tailored responses that address those needs.

Characterization and clustering of kinase isoform expression in metastatic melanoma.

Mutations to the human kinome are known to play causal roles in cancer. The kinome regulates numerous cell processes including growth, proliferation, differentiation, and apoptosis. In addition to aberrant expression, aberrant alternative splicing of cancer-driver genes is receiving increased attention as it could lead to loss or gain of functional domains, altering a kinase's downstream impact. The present study quantifies changes in gene expression and isoform ratios in the kinome of metastatic melanoma cells relative to primary tumors. We contrast 538 total kinases and 3,040 known kinase isoforms between 103 primary tumor and 367 metastatic samples from The Cancer Genome Atlas (TCGA). We find strong evidence of differential expression (DE) at the gene level in 123 kinases (23%). Additionally, of the 468 kinases with alternative isoforms, 60 (13%) had significant difference in isoform ratios (DIR). Notably, DE and DIR have little correlation; for instance, although DE highlights enrichment in receptor tyrosine kinases (RTKs), DIR identifies altered splicing in non-receptor tyrosine kinases (nRTKs). Using exon junction mapping, we identify five examples of splicing events favored in metastatic samples. We demonstrate differential apoptosis and protein localization between SLK isoforms in metastatic melanoma. We cluster isoform expression data and identify subgroups that correlate with genomic subtypes and anatomic tumor locations. Notably, distinct DE and DIR patterns separate samples with BRAF hotspot mutations and (N/K/H)RAS hotspot mutations, the latter of which lacks effective kinase inhibitor treatments. DE in RAS mutants concentrates in CMGC kinases (a group including cell cycle and splicing regulators) rather than RTKs as in BRAF mutants. Furthermore, isoforms in the RAS kinase subgroup show enrichment for cancer-related processes such as angiogenesis and cell migration. Our results reveal a new approach to therapeutic target identification and demonstrate how different mutational subtypes may respond differently to treatments highlighting possible new driver events in cancer.

Outcomes of adults with invasive meningococcal disease with reduced penicillin susceptibility in Auckland 2004-2017.

PURPOSE: The purpose of this study was to assess the clinical outcomes of adults with invasive meningococcal disease (IMD) and to compare the outcomes of patients with IMD caused by a penicillin susceptible isolate (minimum inhibitory concentration (MIC) ≤ 0.06 mg/L) with patients with IMD caused by an isolate with reduced penicillin susceptibility (MIC > 0.06 mg/L). We also assessed the outcomes of patients with IMD caused by an isolate with reduced penicillin susceptibility who were treated exclusively with intravenous (IV) benzylpenicillin. METHODS: Retrospective study of all culture positive IMD in adult patients (age ≥ 15 years) in the Auckland region from 2004 to 2017. RESULTS: One hundred and thirty-nine patients were included; 94 had penicillin susceptible isolates (88 cured, 6 died), and 45 had an isolate with reduced penicillin susceptibility (41 cured, 1 possible relapse, 3 died). The median benzylpenicillin/ceftriaxone treatment duration was 3 days for both groups. There was no difference in the patient outcomes of both groups. Eighteen patients with IMD caused by an isolate with reduced penicillin susceptibility received benzylpenicillin alone and were cured. CONCLUSIONS: This study provides further support to existing data that has shown that short duration IV beta-lactam treatment is effective for IMD in adults. Only a small number of patients with meningitis caused by an isolate with reduced penicillin susceptibility received benzylpenicillin alone, limiting its evaluation. For Neisseria meningitidis meningitis, we recommend ceftriaxone as empiric treatment and as definitive treatment when this is caused by an isolate with reduced penicillin susceptibility.

Comparing open-ended question methods to vignette methods to explore willingness to obtain pre-exposure prophylaxis access in pharmacies among black men who have sex with men.

Black men who have sex with men (BMSM) are at higher risk of HIV transmission than any other group; however, their uptake of the highly effective HIV prevention medication, pre-exposure prophylaxis (PrEP), is low. In collaboration with a communitybased organization in Atlanta, Georgia, we explored ten HIV-negative BMSM's willingness to obtain PrEP in pharmacies using standard open-ended and vignette qualitative methods. Three overarching themes were identified: privacy, patient-pharmacist interactions, and HIV/STI screening. While open-ended questions allowed participants to provide broad answers on their willingness to receive prevention services at a pharmacy, the vignette drew out specific responses to facilitate in-pharmacy PrEP delivery. Using both openended questions and vignette data collection strategies, BMSM reported high willingness to screen for and uptake PrEP in pharmacies. However, the vignette method allowed for greater depth. Open-ended questions elicited responses that highlighted general barriers and facilitators of PrEP dispensing in pharmacies. However, the vignette allowed participants to customize a plan of action that would best fit their needs. Vignette methods are underutilized in HIV research and may be helpful in supplementing standard open-ended interview questions to uncovering unknown challenges about health behaviors and obtain more robust data on highly sensitive research topics in HIV research.

Barriers and Facilitators to HIV Service Access among Hispanic/Latino Gay, Bisexual, and Other Men Who Have Sex with Men in Metropolitan Atlanta-a Qualitative Analysis.

Hispanic/Latino persons are disproportionately impacted by HIV in the US, and HIV diagnoses among Hispanic/Latino men in Georgia have increased over the past decade, particularly in metropolitan Atlanta. In 2022, the Georgia Department of Public Health detected five clusters of rapid HIV transmission centered among Hispanic/Latino gay, bisexual, and other men who have sex with men (HLMSM) in metropolitan Atlanta. We conducted in-depth interviews with 65 service providers and 29 HLMSM to identify barriers and facilitators to HIV service access for HLMSM. Interviews were audio recorded, transcribed, and translated, if needed. Initial data analyses were conducted rapidly in the field to inform public health actions. We then conducted additional analyses including line-by-line coding of the interview transcripts using a thematic analytic approach. We identified four main themes. First, inequity in language access was a predominant barrier. Second, multiple social and structural barriers existed. Third, HLMSM encountered intersectional stigma. Finally, the HLMSM community is characterized by its diversity, and there is not a one-size-fits-all approach to providing appropriate care to this population. The collection of qualitative data during an HIV cluster investigation allowed us to quickly identity barriers experienced by HLMSM when accessing HIV and other medical care, to optimize public health response and action. Well-designed program evaluation and implementation research may help elucidate specific strategies and tools to reduce health disparities, ensure equitable service access for HLMSM, and reduce HIV transmission in this population.

Jahn-Teller effects in initial and final states: high-resolution X-ray absorption, photoelectron and Auger spectroscopy of allene.

Carbon K-edge resonant Auger spectra of gas-phase allene following excitation of the pre-edge 1s → π* transitions are presented and analysed with the support of EOM-CCSD/cc-pVTZ calculations. X-Ray absorption (XAS), X-ray photoelectron (XPS), valence band and non-resonant Auger spectra are also reanalysed with a series of computational approaches. The results presented demonstrate the importance of including nuclear ensemble effects for simulating X-ray observables and as an effective strategy for capturing Jahn-Teller effects in spectra.

Effectiveness of a digital medication event reminder and monitor device for patients with tuberculosis (SELFTB): a multicenter randomized controlled trial.

BACKGROUND: Tuberculosis remains the leading cause of death from a single infectious disease worldwide. Trials evaluating digital adherence technologies for tuberculosis in low- and middle-income countries are urgently needed. We aimed to assess whether a digital medication event reminder and monitor (MERM) device-observed self-administered therapy improves adherence and treatment outcomes in patients with tuberculosis compared with the standard in-person directly observed therapy (DOT). METHODS: We did a two-arm, attention-controlled, effectiveness-implementation type 2 hybrid, randomized controlled trial in ten healthcare facilities in Addis Ababa, Ethiopia. We included adults with new or previously treated, bacteriologically confirmed, drug-sensitive pulmonary tuberculosis who were eligible to start anti-tuberculosis therapy. Participants were randomly assigned (1:1) to receive a 15-day tuberculosis medication supply in the evriMED500® MERM device to self-administer and return every 15 days (intervention arm) or visit the healthcare facilities each day to swallow their daily dose with DOT by healthcare providers (control arm). Both arms were followed throughout the standard two-month intensive treatment phase (2RHZE). For control participants, some provider-approved take-home doses might be allowed for extenuating circumstances in real-world practice. Data were collected on patient information (demographic, socioeconomic, behavioral, social, and clinical information), medication adherence measures (MERM vs. DOT records, IsoScreenTM urine colorimetric isoniazid test, and adherence self-report), and clinical measures (pre-post treatment sputum Xpert MTB/RIF assay or microscopy, and adverse treatment outcomes). The intention-to-treat (ITT) primary endpoints were (1) individual-level percentage adherence over the two-month intensive phase measured by adherence records compiled from MERM device vs. DOT records that also considered all take-home doses as having been ingested and (2) sputum smear conversion following the standard two-month intensive phase treatment. Secondary endpoints were (1) individual-level percentage adherence over the two-month intensive phase measured by adherence records compiled from the MERM device vs. DOT records that considered all take-home doses as not ingested, (2) negative IsoScreen urine isoniazid test, (3) adverse treatment outcome (having at least one of the three events: treatment not completed; death; or loss to follow-up), and (4) self-reported adherence. The MERM device has an electronic module and a medication container that records adherence, stores medication, emits audible and visual on-board alarms to remind patients to take their medications on time and refill, and enables providers to download the data and monitor adherence. RESULTS: Participants were enrolled into the study between 02 June 2020 and 15 June 2021, with the last participant completing follow-up on 15 August 2021. A total of 337 patients were screened for eligibility, of whom 114 were randomly assigned and included in the final analysis [57 control and 57 intervention participants]. Participants were 64.9% male, 15% with HIV, 10.5% retreatment, and 5.3% homeless. Adherence to TB medication was comparable between the intervention arm [geometric mean percentage (GM%) 99.01%, geometric standard deviation (GSD) 1.02] and the control arm [GM% 98.97%, GSD 1.04] and was within the prespecified margin for non-inferiority [mean ratio (MR) 1.00 (95% CI 0.99-1.01); p = 0.954]. The intervention arm was significantly superior to the control arm in the secondary analysis that considered all take-home doses in the control were not ingested [control GM% 77.71 (GSD 1.57), MR 1.27 (95% CI 1.33-1.43)]. Urine isoniazid testing was done on 443 (97%) samples from 114 participants; 13 participants had at least one negative result; a negative test was significantly more common among the control group compared with the intervention group [11/57 (19.3%) vs 2/57 (3.5%); p = 0.008]. There was no significant difference between the control and intervention arms for smear conversion [55 (98.2%) vs 52 (100%); p>0.999], adverse treatment outcomes [0 vs 1 (1.9%); p = 0.48], and self-report non-adherence [5 (8.9%) vs 1 (1.9%); p = 0.21]. CONCLUSIONS: In this randomized trial of patients with drug-sensitive pulmonary tuberculosis, medication adherence among participants assigned to MERM-observed self-administered therapy was non-inferior and superior by some measures when compared with the standard in-person DOT. Further research is needed to understand whether adherence in the intervention is primarily driven by allowing self-administered therapy which reduced challenges of repeated clinic visits or by the adherence support provided by the MERM system. To avoid contributing to patient barriers with DOT, tuberculosis medical programs should consider alternatives such as medication event monitors. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04216420.

Clinical prediction scores and the utility of time to blood culture positivity in stratifying the risk of infective endocarditis in Staphylococcus aureus bacteraemia.

BACKGROUND: Infective endocarditis (IE) complicates up to a quarter of Staphylococcus aureus bacteraemia (SAB) cases. Risk scores predict IE complicating SAB but have undergone limited external validation, especially in community-acquired infections and those who use IV drugs. Addition of the time to positive culture (TTP) may provide incremental risk prognostication. OBJECTIVES: To externally validate risk scores for predicting IE in SAB and assess the incremental value of TTP. METHODS: The modified Duke score was calculated for adults hospitalized with SAB at a major tertiary institution. All patients underwent echocardiography. Sensitivity and specificity of the risk scores for predicting IE were calculated, and the incremental value of TTP was assessed. RESULTS: One hundred and six cases were analysed and 18 (17%) met definite IE criteria. The optimal TTP to predict IE was 11.5 h (sensitivity 88.9%; specificity 71.6%). The sensitivity of VIRSTA and PREDICT (Predicting risk of endocarditis using a clinical tool) were similar (94.4% for both) and higher than POSITIVE (Prediction Of Staphylococcus aureus Infective endocarditis Time to positivity, IV drug use, Vascular phenomena, pre-Existing heart condition; 77.8%). The receiver-operator characteristic AUCs were VIRSTA 0.83, PREDICT 0.75, POSITIVE 0.89 and TTP 0.85. Adding TTP to VIRSTA (i.e. VIRSTA+) resulted in the highest AUC (0.90), sensitivity (100%) and negative predictive value (100%), albeit with a low specificity (33%). CONCLUSIONS: The VIRSTA and POSITIVE scores were the strongest predictors for IE complicating SAB. The addition of TTP to VIRSTA (VIRSTA+) significantly improved discriminatory value and may be safely used to rationalize echocardiography strategies.

The Role of Staff in Transmission of SARS-CoV-2 in Long-term Care Facilities.

BACKGROUND: US long-term care facilities (LTCFs) have experienced a disproportionate burden of COVID-19 morbidity and mortality. METHODS: We examined SARS-CoV-2 transmission among residents and staff in 60 LTCFs in Fulton County, Georgia, from March 2020 to September 2021. Using the Wallinga-Teunis method to estimate the time-varying reproduction number, R(t), and linear-mixed regression models, we examined associations between case characteristics and R(t). RESULTS: Case counts, outbreak size and duration, and R(t) declined rapidly and remained low after vaccines were first distributed to LTCFs in December 2020, despite increases in community incidence in summer 2021. Staff cases were more infectious than resident cases (average individual reproduction number, R i = 0.6 [95% confidence intervals [CI] = 0.4, 0.7] and 0.1 [95% CI = 0.1, 0.2], respectively). Unvaccinated resident cases were more infectious than vaccinated resident cases (R i = 0.5 [95% CI = 0.4, 0.6] and 0.2 [95% CI = 0.0, 0.8], respectively), but estimates were imprecise. CONCLUSIONS: COVID-19 vaccines slowed transmission and contributed to reduced caseload in LTCFs. However, due to data limitations, we were unable to determine whether breakthrough vaccinated cases were less infectious than unvaccinated cases. Staff cases were six times more infectious than resident cases, consistent with the hypothesis that staff were the primary drivers of SARS-CoV-2 transmission in LTCFs.