Boolean Chaos

We observe deterministic chaos in a simple network of electronic logic gates that are not regulated by a clocking signal. The resulting power spectrum is ultra-wide-band, extending from dc to beyond 2 GHz. The observed behavior is reproduced qualitatively using an autonomously updating Boolean model with signal propagation times that depend on the recent history of the gates and filtering of pulses of short duration, whose presence is confirmed experimentally. Electronic Boolean chaos may find application as an ultra-wide-band source of radio wavesComment: 10 pages and 4 figur

Effect of Seedling Stock on the Early Stand Development and Physiology of Improved Loblolly Pine (Pinus taeda L.) Seedlings

This study assessed the effects of spacing and genotype on the growth and physiology of improved loblolly pine (Pinus taeda L.) seedlings from three distinct genotypes planted in Drew County, Arkansas (USA). Genotype had a significant effect on survival and height. Clone CF Var 1 showed greater height and survival compared to other seedlings. Genotype had significant effects on uniformity in height both years and ground line diameter (GLD) first year. However, genotype had no significant effects on leaf water potential and coefficient variation of leaf water potential. These growth and physiology should be further studied to assess potential genetic differences among seedlings and to determine if they can be identified early for improved growth at later ages

Statin Use and Venous Thromboembolism in Cancer: A Large, Active Comparator, Propensity Score Matched Cohort Study

Background—Statins have been shown to have a protective effect for venous thromboembolism (VTE) in the general population. This study sought to assess the association between statins and the risk for cancer-associated deep vein thrombosis (DVT) and pulmonary embolism (PE). Methods—Patients with newly diagnosed cancer were followed for up to one year in a healthcare claims database (2010–2013). Three treatment groups included statin users, non-statin cholesterol lowering medication users, and an untreated group with pre-existing indications for statin therapy (hyperlipidemia, diabetes, or heart disease). Propensity score matched groups were compared using competing risks survival models for DVT and PE outcomes reporting the hazard ratios (HR) between the treatment groups. Sensitivity analyses assessed the influence of age and individual medications. Results—The total cohort included 170,459 patients, which, after matching, were similar on baseline characteristics. The overall model showed a statistically significant protective effect for statins compared to no treatment attributed only to leukemia for DVT (HR = 0.77, 95% CI 0.61–0.99) and colorectal cancers for PE (HR = 0.80, 95% CI 0.64–0.99) in stratified analyses. There were generally no differences in outcomes between statins and non-statins and no individual statin use showed results different from the class effect. Conclusions—In this propensity score matched sample of patients with cancer, statins were shown to have a small protective effect in some cancers for DVT or PE compared to no treatment and little difference compared to an active control group. The lack of effect was consistent across statins and was also not found for any of the sensitivity analyses included

Heterotic Strings in Two Dimensions and New Stringy Phase Transitions

We discuss heterotic string theories in two dimensions with gauge groups Spin(24) and Spin(8) x E_8. After compactification the theories exhibit a rich spectrum of states with both winding and momentum. At special points some of these stringy states become massless, leading to new first order phase transitions. For example, the thermal theories exhibit standard thermodynamics below the phase transition, but novel and peculiar behavior above it. In particular, when the radius of the Euclidean circle is smaller than the phase transition point the torus partition function is not given by the thermal trace over the spacetime Hilbert space. The full moduli space of compactified theories is 13 dimensional, when Wilson lines are included; the Spin(24) and Spin(8) x E_8 theories correspond to distinct decompactification limits.Comment: 32 pages; v2: references added, minor change

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer’s disease (rg ¼ 0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

Mitotic stress is an integral part of the oncogene-induced senescence program that promotes multinucleation and cell cycle arrest

Oncogene-induced senescence (OIS) is a tumor suppression mechanism that blocks cell proliferation in response to oncogenic signaling. OIS is frequently accompanied by multinucleation; however, the origin of this is unknown. Here, we show that multinucleate OIS cells originate mostly from failed mitosis. Prior to senescence, mutant H-RasV12 activation in primary human fibroblasts compromised mitosis, concordant with abnormal expression of mitotic genes functionally linked to the observed mitotic spindle and chromatin defects. Simultaneously, H-RasV12 activation enhanced survival of cells with damaged mitoses, culminating in extended mitotic arrest and aberrant exit from mitosis via mitotic slippage. ERK-dependent transcriptional upregulation of Mcl1 was, at least in part, responsible for enhanced survival and slippage of cells with mitotic defects. Importantly, mitotic slippage and oncogene signaling cooperatively induced senescence and key senescence effectors p21 and p16. In summary, activated Ras coordinately triggers mitotic disruption and enhanced cell survival to promote formation of multinucleate senescent cells

Simulated cost-effectiveness and long-term clinical outcomes of addiction care and antibiotic therapy strategies for patients with injection drug use-associated infective endocarditis

Importance: Emerging evidence supports the use of outpatient parenteral antimicrobial therapy (OPAT) and, in many cases, partial oral antibiotic therapy for the treatment of injection drug use-associated infective endocarditis (IDU-IE); however, long-term outcomes and cost-effectiveness remain unknown. Objective: To compare the added value of inpatient addiction care services and the cost-effectiveness and clinical outcomes of alternative antibiotic treatment strategies for patients with IDU-IE. Design, Setting, and Participants: This decision analytical modeling study used a validated microsimulation model to compare antibiotic treatment strategies for patients with IDU-IE. Model inputs were derived from clinical trials and observational cohort studies. The model included all patients with injection opioid drug use (N = 5 million) in the US who were eligible to receive OPAT either in the home or at a postacute care facility. Costs were annually discounted at 3%. Cost-effectiveness was evaluated from a health care sector perspective over a lifetime starting in 2020. Probabilistic sensitivity, scenario, and threshold analyses were performed to address uncertainty. Interventions: The model simulated 4 treatment strategies: (1) 4 to 6 weeks of inpatient intravenous (IV) antibiotic therapy along with opioid detoxification (usual care strategy), (2) 4 to 6 weeks of inpatient IV antibiotic therapy along with inpatient addiction care services that offered medication for opioid use disorder (usual care/addiction care strategy), (3) 3 weeks of inpatient IV antibiotic therapy along with addiction care services followed by OPAT (OPAT strategy), and (4) 3 weeks of inpatient IV antibiotic therapy along with addiction care services followed by partial oral antibiotic therapy (partial oral antibiotic strategy). Main Outcomes and Measures: Mean percentage of patients completing treatment for IDU-IE, deaths associated with IDU-IE, life expectancy (measured in life-years [LYs]), mean cost per person, and incremental cost-effectiveness ratios (ICERs). Results: All modeled scenarios were initialized with 5 million individuals (mean age, 42 years; range, 18-64 years; 70% male) who had a history of injection opioid drug use. The usual care strategy resulted in 18.63 LYs at a cost of $416 570 per person, with 77.6$412 150 per person. Compared with the OPAT strategy, the partial oral antibiotic strategy had an ICER of $163 370 per LY. Increasing IDU-IE treatment uptake and decreasing treatment discontinuation made the partial oral antibiotic strategy more cost-effective compared with the OPAT strategy. When assuming that all patients with IDU-IE were eligible to receive partial oral antibiotic therapy, the strategy was cost-saving and resulted in 0.0247 additional discounted LYs. When treatment discontinuation was decreased from 3.30$100 000 per LY threshold. Conclusions and Relevance: In this decision analytical modeling study, incorporation of OPAT or partial oral antibiotic approaches along with addiction care services for the treatment of patients with IDU-IE was associated with increases in the number of people completing treatment, decreases in mortality, and savings in cost compared with the usual care strategy of providing inpatient IV antibiotic therapy alone

Combining remote sensing techniques and field surveys for post‑earthquake reconnaissance missions

Remote reconnaissance missions are promising solutions for the assessment of earthquake induced structural damage and cascading geological hazards. Space-borne remote sensing can complement in-field missions when safety and accessibility concerns limit post-earthquake operations on the ground. However, the implementation of remote sensing techniques in post-disaster missions is limited by the lack of methods that combine different techniques and integrate them with field survey data. This paper presents a new approach for rapid post-earthquake building damage assessment and landslide mapping, based on Synthetic Aperture Radar (SAR) data. The proposed texture-based building damage classification approach exploits very high resolution post-earthquake SAR data integrated with building survey data. For landslide mapping, a backscatter intensity-based landslide detection approach, which also includes the separation between landslides and flooded areas, is combined with optical-based manual inventories. The approach was implemented during the joint Structural Extreme Event Reconnaissance, GeoHazards International and Earthquake Engineering Field Investigation Team mission that followed the 2021 Haiti Earthquake and Tropical Cyclone Grace