KineticNet: Deep learning a transferable kinetic energy functional for orbital-free density functional theory.

Orbital-free density functional theory (OF-DFT) holds promise to compute ground state molecular properties at minimal cost. However, it has been held back by our inability to compute the kinetic energy as a functional of electron density alone. Here, we set out to learn the kinetic energy functional from ground truth provided by the more expensive Kohn-Sham density functional theory. Such learning is confronted with two key challenges: Giving the model sufficient expressivity and spatial context while limiting the memory footprint to afford computations on a GPU and creating a sufficiently broad distribution of training data to enable iterative density optimization even when starting from a poor initial guess. In response, we introduce KineticNet, an equivariant deep neural network architecture based on point convolutions adapted to the prediction of quantities on molecular quadrature grids. Important contributions include convolution filters with sufficient spatial resolution in the vicinity of nuclear cusp, an atom-centric sparse but expressive architecture that relays information across multiple bond lengths, and a new strategy to generate varied training data by finding ground state densities in the face of perturbations by a random external potential. KineticNet achieves, for the first time, chemical accuracy of the learned functionals across input densities and geometries of tiny molecules. For two-electron systems, we additionally demonstrate OF-DFT density optimization with chemical accuracy.

Diffuse alveolar hemorrhage: An underreported complication of transplant associated thrombotic microangiopathy.

Hematopoietic stem cell transplantation-associated thrombotic microangiopathy (TA-TMA) and diffuse alveolar hemorrhage (DAH) are well recognized post-transplant complications that carry a high risk of mortality; however, the risk of DAH complicating the course of transplant patients with TA-TMA is not well understood. We conducted a ten-year retrospective study at our institution to determine the incidence of DAH in a cohort of pediatric patients with TA-TMA and described their presentation and outcomes. Additionally, autopsy slides, when available, were reviewed to assess for histological evidence of microvascular injury and alveolar hemorrhages. A total of 58 pediatric patients with TA-TMA were identified. Of these, 14 (24%) had DAH. Majority of DAH cases occurred within a week of TA-TMA diagnosis (n = 8, 57%, range 0-698 days). Mortality was 100% for patients with DAH and TA-TMA. Infections were found to be a significant risk factor for DAH in TA-TMA. Autopsy was performed in 11 of the 14 patients, and pulmonary slides were available for review in ten cases. 70% cases had pathological evidence of microvascular injury, concerning for pulmonary TA-TMA. We conclude that DAH is a potentially fatal complication in patients with TA-TMA and may be a result of pulmonary microangiopathy.

Photocurrent-driven transient symmetry breaking in the Weyl semimetal TaAs.

Symmetry plays a central role in conventional and topological phases of matter, making the ability to optically drive symmetry changes a critical step in developing future technologies that rely on such control. Topological materials, like topological semimetals, are particularly sensitive to a breaking or restoring of time-reversal and crystalline symmetries, which affect both bulk and surface electronic states. While previous studies have focused on controlling symmetry via coupling to the crystal lattice, we demonstrate here an all-electronic mechanism based on photocurrent generation. Using second harmonic generation spectroscopy as a sensitive probe of symmetry changes, we observe an ultrafast breaking of time-reversal and spatial symmetries following femtosecond optical excitation in the prototypical type-I Weyl semimetal TaAs. Our results show that optically driven photocurrents can be tailored to explicitly break electronic symmetry in a generic fashion, opening up the possibility of driving phase transitions between symmetry-protected states on ultrafast timescales.

Clinical characteristics and successful treatment outcomes of children and adolescents with Kaposi sarcoma in Southwestern Tanzania.

The HIV/AIDS epidemic has driven the rise in cases of Kaposi sarcoma (KS) among children and adolescents living with HIV in countries with high Human gammaherpesvirus 8 (HHV-8) seroprevalence, such as Tanzania, where specialized oncology programs are sparse. Consequently, descriptions of successful treatment of KS in children and adolescents by general pediatricians are important. A retrospective analysis was performed of children and adolescents diagnosed with KS and treated with chemotherapy and combination antiretroviral therapy (cART) at the Baylor College of Medicine Children's Foundation Tanzania Center of Excellence - Mbeya between 2011 and 2017. Sixty-one patients were diagnosed with KS with a median age of 12.6 years (interquartile range (IQR) 9.4 - 15.5). Diagnosis was confirmed by histopathology in 36% (22/61). Among HIV positive patients (59/61), 78% (46/59) were on cART at KS diagnosis. Severe immunosuppression was present in 63% (35/56) of those with CD4 data and 44% (27/61) had SAM. Advanced-stage T1 disease was present in 64% (39/61), including 28% (17/61) with visceral/disseminated KS. Two-year estimated overall survival (OS) was 72% (95% Confidence Interval (CI): 58%-82%) and median follow up for survivors was 25.7 months (IQR 14.2-53.8). No patients were lost to follow up. Two-year OS was 63% (95% CI: 44%-77%) in patients with severe immune suppression and 60% (95% CI: 37%-76%) in patients with SAM. Among patients with visceral/disseminated KS, 53% (9/17) survived. This retrospective analysis demonstrated favorable outcomes in a complex cohort of children and adolescents with KS treated with chemotherapy by general pediatricians in Tanzania.

Racial/ethnic differences in HPV 16/18 genotypes and integration status among women with a history of cytological abnormalities.

OBJECTIVE: HPV genotype distribution varies by race/ethnicity, but is unclear whether there are racial/ethnic variations in HPV 16/18 integration in the host genome. We describe HPV16/18 infection and integration status in a racially/ethnically diverse sample of women with a recent abnormal Pap test. METHODS: Patients (n=640) represent a subset of women participating in a clinical trial. Cervical swabs were tested for HPV16/18 DNA using type-specific polymerase chain reaction assays. Viral integration status was assessed using type-specific integration assays and categorized as fully integrated, fully non-integrated, or mixed. Unconditional logistic regression was used to generate unadjusted (OR) and adjusted odds ratios (aOR) to assess the association between self-reported race/ethnicity and risk of these outcomes. RESULTS: Hispanic and non-Hispanic black women had half the odds of prevalent HPV16 compared to non-Hispanic white women (aORs: 0.43 and 0.45, respectively). The prevalence odds of HPV18 was less than half among Hispanic women (aOR: 0.48), but not significantly different between black and white women (aOR: 0.72). Among women with prevalent HPV16, the odds of fully integrated viral DNA were significantly higher among black women (aORs: 2.78) and marginally higher among Hispanic women (aOR: 1.93). No racial/ethnic differences were observed for HPV18 DNA integration. CONCLUSIONS: While HPV16 and 18 infections were less prevalent among Hispanic and black women compared to whites, their HPV16 DNA was more likely to be present in a fully integrated state. This could potentially contribute to the higher rates of abnormal cytology and cervical dysplasia observed among Hispanic and black women.

Anomalous quantum criticality in an itinerant ferromagnet.

The dynamics of continuous phase transitions is governed by the dynamic scaling exponent relating the correlation length and correlation time. For transitions at finite temperature, thermodynamic critical properties are independent of the dynamic scaling exponent. In contrast, at quantum phase transitions where the transition temperature becomes zero, static and dynamic properties are inherently entangled by virtue of the uncertainty principle. Consequently, thermodynamic scaling equations explicitly contain the dynamic exponent. Here we report on thermodynamic measurements (as a function of temperature and magnetic field) for the itinerant ferromagnet Sr1-xCaxRuO3 where the transition temperature becomes zero for x=0.7. We find dynamic scaling of the magnetization and specific heat with highly unusual quantum critical dynamics. We observe a small dynamic scaling exponent of 1.76 strongly deviating from current models of ferromagnetic quantum criticality and likely being governed by strong disorder in conjunction with strong electron-electron coupling.

The interaction between smoking status and highly active antiretroviral therapy (HAART) use on the risk of Kaposi's sarcoma (KS) in a cohort of HIV-infected men.

BACKGROUND: Although the independent effects of smoking status and HAART are reported as lower risks against KS, their combined effects have not been explored. We examined whether there is an interaction between smoking status and HAART use on the risk of KS development in an on-going US cohort of HIV-infected men. METHODS: Cox proportional hazards regression was used to analyse a total sample of 2736 participants of the Multicenter AIDS Cohort Study (MACS). RESULTS: We identified 530 incident KS cases with a total follow-up time of 26 594 person-years (incidence rate: 2.00 out of 100 person-years). Current smoking status and HAART use were independently associated with a lower risk of KS development (hazard ratio - HR=0.56, 95% CI: 0.35-0.90, P=0.02 and HR=0.27, 95% CI: 0.16-0.48, P<0.0001, respectively). There was no evidence of multiplicative interaction between current smoking status and HAART use on KS risk (HR=2.14, 95% CI: 0.97-4.73, Pinteraction=0.06). Lower effect of smoking was only present among those not on HAART (HR=0.57, 95% CI: 0.35-0.92, P=0.02). CONCLUSION: The inverse association of cigarette smoking on KS risk may be limited to those not on HAART. The biological mechanism of smoking in KS carcinogenesis should be elucidated.

HHV-6 encephalitis in umbilical cord blood transplantation: a systematic review and meta-analysis.

Reactivation of human herpesvirus-6 (HHV-6) frequently occurs following hematopoietic SCT (HSCT), and has been associated with clinical consequences in many patient populations. HHV-6 reactivation and HHV-6 encephalitis seem to occur more frequently in patients undergoing HSCT with cord blood (CB) as the stem cell source. We have conducted a systematic literature review and meta-analysis to investigate the clinical significance of this correlation. A systematic review of publications indexed in PubMed was performed for HSCT studies published over the past 10 years that fit inclusion criteria. Data on prevalences of HHV-6 reactivation and HHV-6 encephalitis post HSCT were abstracted from 19 papers. Meta-analyses were conducted to calculate combined prevalence estimates. The prevalences of HHV-6 reactivation and encephalitis were compared among CB vs non-CB HSCT. Prevalences of HHV-6 reactivation and HHV-6 encephalitis were significantly higher in patients receiving CB as the stem cell source than in patients receiving another stem cell source (72.0% vs 37.4%, P<0.0001; 8.3% vs 0.50%, P<0.0001, respectively). HHV-6 reactivation and HHV-6 encephalitis are significant complications in the post-HSCT setting, particularly in patients receiving CB as the stem cell source. Thus, patients undergoing umbilical CB transplantation should be closely monitored for HHV-6 reactivation.

Association between smoking and size of anal warts in HIV-infected women.

While the association between smoking and human papillomavirus infection, cervical cancer, and anal cancer has been well studied, evidence on the association between cigarette smoking and anal warts is limited. The purpose of this study was to investigate if cigarette smoking status influences the size of anal warts over time in HIV-infected women in a sample of 976 HIV-infected women from the Women's Interagency HIV Study (WIHS). A linear mixed model was used to determine the effect of smoking on anal wart size. Even though women who were currently smokers had larger anal warts at baseline and slower growth rate of anal wart size after each visit than women who were not current smokers, there was no association between size of anal wart and current smoking status over time. Further studies on the role of smoking and interaction between smoking and other risk factors, however, should be explored.

Simplified pulmonary vasodilatory testing in the cardiac catheterization laboratory with nasal cannula nitric oxide.

In patients with pulmonary hypertension, pulmonary vasodilator testing with inhaled nitric oxide (NO) during cardiac catheterization provides valuable data for defining future care plans. Previously, the use of delivery systems for spontaneously breathing individuals required a tight-fitting seal by face mask and an approved delivery and dilution device. We hypothesized that a simplified delivery system using nasal cannula could be utilized to effectively deliver NO during cardiac catheterization. We developed a simple delivery system to deliver through a nasal cannula a concentration of NO at 50 ppm at the nares along with supplemental oxygen (O2) via face tent. We prospectively employed this system for 10-minute intervals on 11 patients (age range, 7 months to 41 years) with pulmonary hypertension undergoing scheduled cardiac catheterization. Mean pulmonary artery pressure (PAp) decreased from 62 mmHg (range, 38-99) at room air testing to 45 mmHg (range, 36-91) with the addition of NO plus O2 (p = 0.014). Pulmonary vascular resistance (PVR) decreased from 11.6 U.m2 (range, 4.5-43.4) to 6.3 U.m2 (range, 2.0-34.2) (p = 0.001). A response of 20% or more reduction in PVR was seen in all 11 patients. The initial ratio of pulmonary to systemic vascular resistance (Rp:Rs) was 0.49 (range, 0.25-3.5) and decreased to 0.35 (range 0.1-2.6) (p = 0.002). No adverse side effects were noted. We found this NO delivery system to be a simple and effective method of pulmonary vasodilatory testing that may have wide applicability in the cardiac catheterization laboratory.

Human papillomavirus infection: biology, epidemiology, and prevention.

Over the past several decades, knowledge of the biology and epidemiology of human papillomavirus (HPV) infection has increased tremendously. However, there are still many unanswered questions concerning the interaction of the virus with its host. The virus has been identified as a necessary causal agent for cervical squamous neoplasia and has been linked to the development of neoplasia in several other mucosal sites. The viral oncogenes E6 and E7 are the major players in the virus' scheme to evade the immune system and use the host cell replication machinery to survive. Many risk factors for infection with HPV have been identified; however, the focus now centers on identifying risk factors for persistence of the infection as it is likely that transient infections play a very small role in the overall development of clinical disease. Prevention measures to date have centered around screening programs, mostly for cervical cancer, including the perfection of screening techniques and inclusion of molecular testing for HPV into screening regimens. The development of prophylactic and therapeutic vaccines has also increased as primary prevention measures appear to have the best hope for long-term effects on cancer incidence.