Time to Cancer Treatment and Chemotherapy Relative Dose Intensity for Patients With Breast Cancer Living With HIV.

Importance: Patients with breast cancer and comorbid HIV experience higher mortality than other patients with breast cancer. Objective: To compare time to cancer treatment initiation and relative dose intensity (RDI) of neoadjuvant and adjuvant chemotherapy among patients with breast cancer with vs without HIV. Design, Setting, and Participants: A retrospective, matched cohort study enrolled women who received a diagnosis of breast cancer from January 1, 2000, through December 31, 2018. The electronic medical records of 3 urban, academic cancer centers were searched for women with confirmed HIV infection prior to or simultaneous with diagnosis of stage I to III breast cancer. Tumor registry data were used to identify 2 control patients with breast cancer without HIV for each participant with HIV, matching for study site, stage, and year of cancer diagnosis. Statistical analysis was performed from December 2022 to October 2023. Exposure: HIV infection detected before or within 90 days of participants' breast cancer diagnosis. Main Outcomes and Measures: The primary outcome was time to breast cancer treatment initiation, defined as the number of days between cancer diagnosis and first treatment. The secondary outcome was overall RDI for patients who received chemotherapy. These outcomes were compared by HIV status using Cox proportional hazards regression and linear regression modeling, respectively, adjusting for confounding demographic and clinical factors. Exploratory outcomes included instances of anemia, neutropenia, thrombocytopenia, and liver function test result abnormalities during chemotherapy, which were compared using Fisher exact tests. Results: The study enrolled 66 women with comorbid breast cancer and HIV (median age, 51.1 years [IQR, 45.7-58.2 years]) and 132 with breast cancer alone (median age, 53.9 years [IQR, 47.0-62.5 years]). The median time to first cancer treatment was not significantly higher among patients with HIV than those without (48.5 days [IQR, 32.0-67.0 days] vs 42.5 days [IQR, 25.0-59.0 days]; adjusted hazard ratio, 0.78, 95% CI, 0.55-1.12). Among the 36 women with HIV and 62 women without HIV who received chemotherapy, the median overall RDI was lower for those with HIV vs without HIV (0.87 [IQR, 0.74-0.97] vs 0.96 [IQR, 0.88-1.00]; adjusted P = .01). Grade 3 or higher neutropenia during chemotherapy occurred among more women with HIV than those without HIV (13 of 36 [36.1%] vs 5 of 58 [8.6%]). Conclusions and Relevance: This matched cohort study suggests that patients with breast cancer and HIV may have experienced reduced adjuvant chemotherapy RDI, reflecting greater dose reductions, delays, or discontinuation. Strategies for supporting this vulnerable population during chemotherapy treatment are necessary.

Identification and targeting of treatment resistant progenitor populations in T-cell Acute Lymphoblastic Leukemia.

Refractoriness to initial chemotherapy and relapse after remission are the main obstacles to cure in T-cell Acute Lymphoblastic Leukemia (T-ALL). Biomarker guided risk stratification and targeted therapy have the potential to improve outcomes in high-risk T-ALL; however, cellular and genetic factors contributing to treatment resistance remain unknown. Previous bulk genomic studies in T-ALL have implicated tumor heterogeneity as an unexplored mechanism for treatment failure. To link tumor subpopulations with clinical outcome, we created an atlas of healthy pediatric hematopoiesis and applied single-cell multiomic (CITE-seq/snATAC-seq) analysis to a cohort of 40 cases of T-ALL treated on the Children's Oncology Group AALL0434 clinical trial. The cohort was carefully selected to capture the immunophenotypic diversity of T-ALL, with early T-cell precursor (ETP) and Near/Non-ETP subtypes represented, as well as enriched with both relapsed and treatment refractory cases. Integrated analyses of T-ALL blasts and normal T-cell precursors identified a bone-marrow progenitor-like (BMP-like) leukemia sub-population associated with treatment failure and poor overall survival. The single-cell-derived molecular signature of BMP-like blasts predicted poor outcome across multiple subtypes of T-ALL within two independent patient cohorts using bulk RNA-sequencing data from over 1300 patients. We defined the mutational landscape of BMP-like T-ALL, finding that NOTCH1 mutations additively drive T-ALL blasts away from the BMP-like state. We transcriptionally matched BMP-like blasts to early thymic seeding progenitors that have low NR3C1 expression and high stem cell gene expression, corresponding to a corticosteroid and conventional cytotoxic resistant phenotype we observed in ex vivo drug screening. To identify novel targets for BMP-like blasts, we performed in silico and in vitro drug screening against the BMP-like signature and prioritized BMP-like overexpressed cell-surface (CD44, ITGA4, LGALS1) and intracellular proteins (BCL-2, MCL-1, BTK, NF-κB) as candidates for precision targeted therapy. We established patient derived xenograft models of BMP-high and BMP-low leukemias, which revealed vulnerability of BMP-like blasts to apoptosis-inducing agents, TEC-kinase inhibitors, and proteasome inhibitors. Our study establishes the first multi-omic signatures for rapid risk-stratification and targeted treatment of high-risk T-ALL.

Signal recovery in single cell batch integration.

Data integration to align cells across batches has become a cornerstone of single cell data analysis, critically affecting downstream results. Yet, how much biological signal is erased during integration? Currently, there are no guidelines for when the biological differences between samples are separable from batch effects, and thus, data integration usually involve a lot of guesswork: Cells across batches should be aligned to be "appropriately" mixed, while preserving "main cell type clusters". We show evidence that current paradigms for single cell data integration are unnecessarily aggressive, removing biologically meaningful variation. To remedy this, we present a novel statistical model and computationally scalable algorithm, CellANOVA, to recover biological signal that is lost during single cell data integration. CellANOVA utilizes a "pool-of-controls" design concept, applicable across diverse settings, to separate unwanted variation from biological variation of interest. When applied with existing integration methods, CellANOVA allows the recovery of subtle biological signals and corrects, to a large extent, the data distortion introduced by integration. Further, CellANOVA explicitly estimates cell- and gene-specific batch effect terms which can be used to identify the cell types and pathways exhibiting the largest batch variations, providing clarity as to which biological signals can be recovered. These concepts are illustrated on studies of diverse designs, where the biological signals that are recovered by CellANOVA are shown to be validated by orthogonal assays. In particular, we show that CellANOVA is effective in the challenging case of single-cell and single-nuclei data integration, where the recovered biological signals are replicated in an independent study.

Clinical Characteristics and Outcomes of COVID-19 Acute Respiratory Distress Syndrome (ARDS) Survivors in Early Pandemic: A Single Healthcare System Retrospective Study.

INTRODUCTION:  Acute respiratory distress syndrome (ARDS) management in the intensive care unit (ICU) has attracted strong interest since the start of the COVID-19 pandemic. Our retrospective study aims to describe the outcomes and predictors of mortality of ARDS associated with COVID-19 within one university-based healthcare system. METHODS:  We identified 165 patients within our healthcare system during the months of April 2020 through July 2020, who were admitted to our medical ICUs and eligible for our study. Baseline patient characteristics, ICU and hospital course information, ICU interventions, ventilator settings, and hospital complications were collected and analyzed using descriptive statistical techniques. RESULTS:  Our cohort had an average age of 64. No significant difference in mortality was identified with male vs. female gender or BMI. Most of the patient cohort was identified as black (68.2%). The overall mortality of our cohort was 38.2%. Hyperlipidemia, coronary artery disease, and chronic obstructive pulmonary disease were all associated with higher mortality. There was a significant difference in mortality between those with higher observed ventilator plateau pressures at 24 hours and higher driving pressures at 24 hours. CONCLUSION:  COVID-19-associated ARDS is associated with significant mortality. Physicians should be aware of pre-existing conditions potentially related to worse outcomes so that they receive an appropriate level of care in a timely manner. Ventilator management should focus on maintaining low intra-thoracic pressure changes. Prospective studies are needed to guide COVID-19-associated ARDS management.

Combining natural and artificial intelligence for robust automatic anatomy segmentation: Application in neck and thorax auto-contouring.

BACKGROUND: Automatic segmentation of 3D objects in computed tomography (CT) is challenging. Current methods, based mainly on artificial intelligence (AI) and end-to-end deep learning (DL) networks, are weak in garnering high-level anatomic information, which leads to compromised efficiency and robustness. This can be overcome by incorporating natural intelligence (NI) into AI methods via computational models of human anatomic knowledge. PURPOSE: We formulate a hybrid intelligence (HI) approach that integrates the complementary strengths of NI and AI for organ segmentation in CT images and illustrate performance in the application of radiation therapy (RT) planning via multisite clinical evaluation. METHODS: The system employs five modules: (i) body region recognition, which automatically trims a given image to a precisely defined target body region; (ii) NI-based automatic anatomy recognition object recognition (AAR-R), which performs object recognition in the trimmed image without DL and outputs a localized fuzzy model for each object; (iii) DL-based recognition (DL-R), which refines the coarse recognition results of AAR-R and outputs a stack of 2D bounding boxes (BBs) for each object; (iv) model morphing (MM), which deforms the AAR-R fuzzy model of each object guided by the BBs output by DL-R; and (v) DL-based delineation (DL-D), which employs the object containment information provided by MM to delineate each object. NI from (ii), AI from (i), (iii), and (v), and their combination from (iv) facilitate the HI system. RESULTS: The HI system was tested on 26 organs in neck and thorax body regions on CT images obtained prospectively from 464 patients in a study involving four RT centers. Data sets from one separate independent institution involving 125 patients were employed in training/model building for each of the two body regions, whereas 104 and 110 data sets from the 4 RT centers were utilized for testing on neck and thorax, respectively. In the testing data sets, 83% of the images had limitations such as streak artifacts, poor contrast, shape distortion, pathology, or implants. The contours output by the HI system were compared to contours drawn in clinical practice at the four RT centers by utilizing an independently established ground-truth set of contours as reference. Three sets of measures were employed: accuracy via Dice coefficient (DC) and Hausdorff boundary distance (HD), subjective clinical acceptability via a blinded reader study, and efficiency by measuring human time saved in contouring by the HI system. Overall, the HI system achieved a mean DC of 0.78 and 0.87 and a mean HD of 2.22 and 4.53 mm for neck and thorax, respectively. It significantly outperformed clinical contouring in accuracy and saved overall 70% of human time over clinical contouring time, whereas acceptability scores varied significantly from site to site for both auto-contours and clinically drawn contours. CONCLUSIONS: The HI system is observed to behave like an expert human in robustness in the contouring task but vastly more efficiently. It seems to use NI help where image information alone will not suffice to decide, first for the correct localization of the object and then for the precise delineation of the boundary.

Phase II Trial of Flaxseed to Prevent Acute Complications After Chemoradiation for Lung Cancer.

Background: Thoracic radiotherapy is complicated by acute radiation-induced adverse events such as radiation pneumonitis (RP) and radiation esophagitis (RE). Based on preclinical work and a randomized pilot trial from our laboratory, this single-arm phase II trial investigated administering flaxseed as a radioprotector in patients receiving definitive chemoradiation for nonsmall cell lung cancer (NSCLC). Methods: Between June 2015 and February 2018, 33 patients with locally advanced or metastatic NSCLC with planned definitive chemoradiation were enrolled. Finely-ground Linum usitatissimum L. (Linaceae; flaxseed or linseed) in 40-g packets were provided for daily consumption in any patient-desired formulation 1 week before radiotherapy and throughout radiotherapy as tolerated. The primary outcomes were overall adverse events, with particular focus on Grade ≥3 RP, and flaxseed tolerability. Adverse events were graded according to CTCAE v4.0. Results: Of the 33 patients enrolled, 5 patients (15%) did not receive chemoradiation, 4 (12%) withdrew promptly after enrollment, 4 (12%) did not return a flaxseed consumption log, and 1 patient had irritable bowel syndrome (3%). The remaining 19 patients (57%) had chemoradiation and flaxseed ingestion with a mean completion and standard deviation of the intended flaxseed course of 62% ± 8.3%. Nine (50%) of these 19 patients reported difficulties with flaxseed consumption, citing nausea, constipation, odynophagia, or poor taste or texture. One patient (5%), with unverifiable flaxseed consumption, developed Grade 3 RP. There were no cases of Grade 2 RP. Six patients (32%) developed Grade 2 RE, but no patients developed Grade ≥3 RE. Median overall and progression-free survival were 31 and 12 months, respectively. Conclusions: Despite the low incidence of acute radiation-induced complications reported, significant treatment-related gastrointestinal toxicities and subsequently low flaxseed tolerability inhibit accurate determination of flaxseed effect in patients receiving concurrent thoracic chemoradiation. Thus, further investigations should focus on optimizing flaxseed formulation for improved tolerability and evaluation. ClinicalTrials.gov ID: NCT02475330.

Validation of coding algorithms for the identification of herpes zoster among children.

PURPOSE: To examine the validity of International Classification of Diseases, 10th Revision, (ICD-10) code-based algorithms for herpes zoster (HZ) in the electronic medical record (EMR) of a large, integrated pediatric healthcare network and to examine baseline demographics and chronic comorbidities associated with HZ in a representative pediatric population. METHODS: We reviewed the electronic charts of all patients with a single ICD-10 for HZ (B02.xx) as their primary or secondary diagnosis in the EMR of the Children's Hospital of Philadelphia (CHOP) healthcare network from January 2010-March 2019. The positive predictive value (PPV) for a single code for HZ was calculated and alternative algorithms were examined to determine which method resulted in the highest PPV. RESULTS: The PPV for a single ICD-10 code was 91.7% (95% CI 80.8-95.4) for definitive and/or probable cases of HZ and 63.9% (95% CI 53.4%-75.5%) for definitive cases alone. Adding a prescription for an antiviral did not improve the PPV. However, adding a new code for rash entered within 1 week of the HZ code increased the PPV to 100% for definitive and/or probable cases but with substantial loss of sensitivity. A high proportion of children with HZ who required inpatient hospitalization had chronic disease (70%) and were on systemic immunomodulatory therapy (50%). CONCLUSIONS: HZ can be identified with a high PPV in electronic medical records of children using ICD-10 code alone. These findings lay the foundation for future pharmacoepidemiologic research to better understand risk factors for HZ infection.

Transcranial Photoacoustic Detection of Blood-Brain Barrier Disruption Following Focused Ultrasound-Mediated Nanoparticle Delivery.

PURPOSE: Blood-brain barrier disruption (BBBD) is of interest for treating neurodegenerative diseases and tumors by enhancing drug delivery. Focused ultrasound (FUS) is a powerful method to alleviate BBB challenges; however, the detection of BBB opening by non-invasive methods remains limited. The purpose of this work is to demonstrate that 3D transcranial color Doppler (3DCD) and photoacoustic imaging (PAI) combined with custom-made nanoparticle (NP)-mediated FUS delivery can detect BBBD in mice. PROCEDURES: We use MRI and stereotactic ultrasound-mediated BBBD to create and confirm four openings in the left hemisphere and inject intravenously indocyanine green (ICG) and three sizes (40 nm, 100 nm, and 240 nm in diameter) of fluorophore-labeled NPs. We use PAI and fluorescent imaging (FI) to assess the spatial distribution of ICG/NPs in tissues. RESULTS: A reversible 41 ± 12 % (n = 8) decrease in diameter of the left posterior cerebral artery (PCA) relative to the right after FUS treatment is found using CD images. The spectral unmixing of photoacoustic images of the in vivo (2 h post FUS), perfused, and ex vivo brain reveals a consistent distribution pattern of ICG and NPs at *FUS locations. Ex vivo spectrally unmixed photoacoustic images show that the opening width is, on average, 1.18 ± 0.12 mm and spread laterally 0.49 ± 0.05 mm which correlated well with the BBB opening locations on MR images. In vivo PAI confirms a deposit of NPs in tissues for hours and potentially days, is less sensitive to NPs of lower absorbance at a depth greater than 3 mm and too noisy with NPs above an absorbance of 85.4. FI correlates well with ex vivo PAI to a depth of 3 mm in tissues for small NPs and 4.74 mm for large NPs. CONCLUSIONS: 3DCD can monitor BBBD over time by detecting reversible anatomical changes in the PCA. In vivo 3DPAI at 15 MHz combined with circulating ICG and/or NPs with suitable properties can assess BBB opening 2 h post FUS.

Binary small molecule organic nanoparticles exhibit both direct and diffusion-limited ultrafast charge transfer with NIR excitation.

Here we describe a facile, one-step synthesis of a binary organic nanoparticle composed completely of NIR-absorbing small molecules, a quatterylene diimide and a vanadyl napthalocyanine, using Flash Nanoprecipitation. We show that the molecules are co-encapsulated within an amphiphilic block copolymer shell by observing distinct ultrafast dynamics in the binary nanoparticles compared to nanoparticles of their individual components, which we rationalize as a photoinduced charge transfer. We then draw similarities between the charge transfer dynamics studied in our system and the charge dissociation process in macroscale organic bulk heterojunction blends for OPV applications by assigning the ultrafast time component (∼10 ps) to direct interfacial charge transfer and the slow component (70-200 ps) to diffusion limited charge transfer. This discovery can inspire the development of mixed-composition nanoparticles with new functionality for optoelectronic and theranostic applications.

Altered goblet cell function in Hirschsprung's disease.

AIMS AND OBJECTIVES: Hirschsprung's disease-associated enterocolitis (HAEC) is the most serious complication of Hirschsprung's disease (HSCR). HAEC occurs in 17-50% of patients with HSCR and may occur before or after a properly performed pull-through operation. The pathogenesis of HAEC is poorly understood. It is well recognized that a complex mucosal barrier protects, as the first line of defense, the surface of healthy intestinal tract from adhesion and invasion by luminal micro-organisms. Within the intestinal epithelium, goblet cells secrete gel-forming mucins, the major component of mucus, which block the direct attachment of commensal bacteria to the epithelial layer. Mucin 2 (MUC2) is the predominant mucin expressed in humans. Trefoil factor 3 (TFF3) synergizes with mucin and enhances the protective barrier properties of the mucus layer. SAM pointed domain-containing ETS transcription factor (SPDEF) drives terminal differentiation and maturation of secretory progenitors into goblet cells. Krueppel-like factor 4 (KLF4) is a goblet cell-specific differentiation factor in the colon and controls goblet cell differentiation and activates mucin synthesis. We hypothesized that the goblet cell function in the ganglionic pulled-through bowel in HSCR is abnormal and, therefore, we investigated the changes in goblet cell differentiation and functional expression of mucin in the bowel specimens from patients with HSCR. MATERIAL AND METHODS: We investigated MUC2, TFF3, SPDEF and KLF4 expression, and the goblet cell population in the ganglionic and aganglionic bowel of HSCR patients (n = 10) and controls (n = 10) by qPCR, Western blotting, confocal immunofluorescence, and alcian blue staining. RESULTS: The qPCR and Western blotting analysis revealed that TFF3, SPDEF and KLF4 expressions were significantly downregulated in the aganglionic and ganglionic colon of patients with HSCR as compared to controls (p < 0.05). Alcian blue staining revealed that the goblet cell population was significantly decreased in aganglionic and ganglionic colon as compared to controls (p < 0.05). Confocal microscopy revealed a markedly decreased expression of TFF3, SPDEF and KLF4 in colonic epithelium of patients with HSCR as compared to controls. CONCLUSION: This is, to our knowledge, the first report of decreased expression of TFF3, SPDEF, KLF4, and goblet cell population in the colon of patients with HSCR. Altered goblet cell function may result in intestinal barrier dysfunction contributing to the development of HAEC.

Increased CaSR and TRPC6 pulmonary vascular expression in the nitrofen-induced model of congenital diaphragmatic hernia.

AIMS AND OBJECTIVES: The high morbidity and mortality rates in congenital diaphragmatic hernia (CDH) are attributed primarily to severe lung hypoplasia and/or persistent pulmonary hypertension (PPH). PPH in CDH is characterized by abnormal vascular remodeling with thickening of medial and adventitial layers and extension of smooth muscle into previously nonmuscularized arteries. Excessive proliferation of pulmonary arterial smooth muscle cells (PASMC) is an important contributor to the concentric pulmonary arterial remodeling. An increase in cytosolic-free Ca2+ concentration in PASMC is a major trigger for pulmonary vasoconstriction and a key stimulus for PASMC proliferation and migration. Calcium-sensing receptor (CaSR), a member of the G-protein coupled receptor family, is activated by cations (e.g., Ca2+, Mg2+) and polyamines. Under normal physiological conditions, the expression levels of CaSR in the pulmonary vasculature are very low. Canonical transient receptor potential channels (TRPCs) constitute a series of nonselective cation channels with variable degree of Ca2+ selectivity. TRPC6 has been reported to play a crucial role in the regulation of neo-muscularization, vasoreactivity, and vasomotor tone in the pulmonary vasculature. We hypothesized that CaSR and TRPC6 expression is upregulated in the pulmonary vasculature of nitrofen-induced CDH rats. MATERIALS AND METHODS: Following ethical approval (REC1103), time-pregnant Sprague Dawley rats received nitrofen or vehicle on gestational day (D) 9. D21 fetuses were divided into CDH and control (n = 12). Quantitative real-time polymerase chain reaction (QRT-PCR), western blotting, and confocal-immunofluorescence microscopy were performed to detect lung gene and protein expression of CaSR and TRPC6. RESULTS: QRT-PCR and western blot analysis revealed that CaSR and TPRC6 expression was significantly increased in the CDH group compared to controls (p < 0.05). Confocal-immunofluorescence microscopy revealed that CaSR and TRPC6 lung expression was markedly increased in CDH group compared to controls. CONCLUSION: Increased CaSR and TRPC6 expression in CDH lung suggests that CaSR interacting with TRPC6 may contribute to abnormal vascular remodeling resulting in pulmonary vasoconstriction and development of PPH.

Assembly of Macrocycle Dye Derivatives into Particles for Fluorescence and Photoacoustic Applications.

Optical imaging is a rapidly progressing medical technique that can benefit from the development of new and improved optical imaging agents suitable for use in vivo. However, the molecular rules detailing what optical agents can be processed and encapsulated into in vivo presentable forms are not known. We here present the screening of series of highly hydrophobic porphyrin, phthalocyanine, and naphthalocyanine dye macrocycles through a self-assembling Flash NanoPrecipitation process to form a series of water dispersible dye nanoparticles (NPs). Ten out of 19 tested dyes could be formed into poly(ethylene glycol) coated nanoparticles 60-150 nm in size, and these results shed insight on dye structural criteria that are required to permit dye assembly into NPs. Dye NPs display a diverse range of absorbance profiles with absorbance maxima within the NIR region, and have absorbance that can be tuned by varying dye choice or by doping bulking materials in the NP core. Particle properties such as dye core load and the compositions of co-core dopants were varied, and subsequent effects on photoacoustic and fluorescence signal intensities were measured. These results provide guidelines for designing NPs optimized for photoacoustic imaging and NPs optimized for fluorescence imaging. This work provides important details for dye NP engineering, and expands the optical imaging tools available for use.

Real-Time and Multiplexed Photoacoustic Imaging of Internally Normalized Mixed-Targeted Nanoparticles.

Photoacoustic (PA) imaging is a developing diagnostic technique where multiple species can be simultaneously imaged with high spatial resolution in 3D if the absorbance spectrum of each species is distinct and separable. However, multiplexed PA imaging has been greatly limited by the availability of spectrally separable contrast agents that can be used in vivo. Toward this end, we present the formation and application of a series of poly ethylene glycol (PEG)-coated nanoparticles (NPs) with unique separable absorbance profiles suitable for simultaneous multiplexed imaging. As a proof-of-concept, we demonstrate this form of mixed-sample multiplexed imaging, using cRGD peptide surface-modified NPs with nonmodified NPs in a murine subcutaneous Lewis lung carcinoma tumor model. The simultaneous imaging of nonmodified NPs provides an "internal standard", to deconvolute the contributions of active-ligand and passive-NP targeting effects. Particles with 25% surface cRGD modification display 52 ± 22 fold higher liver to tumor ratio accumulation levels, while the same set of particles display only 9.8 ± 4 fold accumulation levels when internally normalized. The pharmacokinetic profiles of targeted and nontargeted NPs can be simultaneously tracked in real-time to study how biodistribtions of particles are affected by ligand modification. The internal normalization of control particles greatly enhances the precision and decreases the number of animals needed in studies of nanoparticle targeting. These new dyes are an enabling technology for PA imaging of NP fate and targeting. This is the first demonstration of real-time multiplexed PA imaging of mixed-targeted samples in vivo.

Hylleraas hydride binding energy: diatomic electron affinities.

Theoretical adiabatic electron affinities are often considered inaccurate because they are referenced to only a single value. Ground state electron affinities for all the main group elements and homonuclear diatomics were identified recently using the normalized binding energy of the hydrogen atom: [0.75420375(3)/2 = 0.37710187(1) eV]. Here we revisit experimental values and extend the identifications to diatomics in the G2-1 set. We assign new ground state electron affinities: (eV) Cl2, 3.2(2); Br2, 2.87(14); CH, 2.1(2); H2, 0.6 ; NH, 1.1, SiH, 1.90. Anion Morse potentials are calculated for H2 and N2 from positive electron affinities and for hyperfine superoxide states for the first time.