Extreme climate after massive eruption of Alaska's Okmok volcano in 43 BCE and effects on the late Roman Republic and Ptolemaic Kingdom.

The assassination of Julius Caesar in 44 BCE triggered a power struggle that ultimately ended the Roman Republic and, eventually, the Ptolemaic Kingdom, leading to the rise of the Roman Empire. Climate proxies and written documents indicate that this struggle occurred during a period of unusually inclement weather, famine, and disease in the Mediterranean region; historians have previously speculated that a large volcanic eruption of unknown origin was the most likely cause. Here we show using well-dated volcanic fallout records in six Arctic ice cores that one of the largest volcanic eruptions of the past 2,500 y occurred in early 43 BCE, with distinct geochemistry of tephra deposited during the event identifying the Okmok volcano in Alaska as the source.

Probing the Mineral-Water Interface with Nonlinear Optical Spectroscopy.

The interaction between minerals and water is manifold and complex: the mineral surface can be (de)protonated by water, thereby changing its charge; mineral ions dissolved into the aqueous phase screen the surface charges. Both factors affect the interaction with water. Intrinsically molecular-level processes and interactions govern macroscopic phenomena, such as flow-induced dissolution, wetting, and charging.

Anaerobic guilds responsible for mercury methylation in boreal wetlands of varied trophic status serving as either a methylmercury source or sink.

Wetlands are common sites of active Hg methylation by anaerobic microbes; however, the amount of methylmercury produced varies greatly, as Hg methylation is dependent upon both the availability of Hg and the composition and activity of the microbial community involved. In this study, we identified the major microbial guilds responsible for Hg methylation along a trophic gradient composed of two sites and three different types of wetlands: a bog-fen peatland gradient and a black alder swamp, serving as net sources and a sink for methylmercury respectively. Iron-reducing bacteria in the Geobacteraceae were important Hg methylators across all wetlands and seasons examined, as evidenced by abundant 16S rRNA and hgcA transcripts clustering with this family.

The cirrhosis care Alberta (CCAB) protocol: implementing an evidence-based best practice order set for the management of liver cirrhosis - a hybrid type I effectiveness-implementation trial.

Background: Liver cirrhosis is a leading cause of morbidity, premature mortality and acute care utilization in patients with digestive disease. In the province of Alberta, hospital readmission rates for patients with cirrhosis are estimated at 44% at 90 days. For hospitalized patients, multiple care gaps exist, the most notable stemming from i) the lack of a structured approach to best practice care for cirrhosis complications, ii) the lack of a structured approach to broader health needs and iii) suboptimal preparation for transition of care into the community.

The use of machine learning in rare diseases: a scoping review.

Background: Emerging machine learning technologies are beginning to transform medicine and healthcare and could also improve the diagnosis and treatment of rare diseases. Currently, there are no systematic reviews that investigate, from a general perspective, how machine learning is used in a rare disease context. This scoping review aims to address this gap and explores the use of machine learning in rare diseases, investigating, for example, in which rare diseases machine learning is applied, which types of algorithms and input data are used or which medical applications (e.

Evaluating Behavioral Skills Training as an Evidence-Based Practice When Training Parents to Intervene with Their Children.

The authors of this systematic review identified 20 individual single-subject studies examining the efficacy of Behavior Skills Training (BST) implemented with parents. Findings indicate that researchers have used BST to successfully train parents to implement a range of evidence-based practices (EBP) with their own children. Parents of children with autism or intellectual disability made up the large majority of participants in these studies.

E-vapor aerosols do not compromise bone integrity relative to cigarette smoke after 6-month inhalation in an ApoE mouse model.

Cigarette smoke (CS) exposure is one of the leading risk factors for human health. Nicotine-containing inhalable products, such as e-cigarettes, can effectively support tobacco harm reduction approaches. However, there are limited comparative data on the effects of the aerosols generated from electronic vapor products (e-vapor) and CS on bone.

Twice-Daily Doravirine Overcomes the Interaction Effect from Once-Weekly Rifapentine and Isoniazid in Healthy Volunteers.

Doravirine (DOR) is a non-nucleoside reverse transcriptase inhibitor indicated for the treatment of HIV-1. Its use in combination with rifapentine (RPT), an antituberculosis (TB) antibiotic, may reduce the exposure of DOR compromising viral suppression in those living with HIV-1 co-infected with TB. We conducted a prospective, phase I, open label, two-period, fixed sequence, drug interaction study to evaluate the effect of once-weekly RPT and isoniazid (INH) on the pharmacokinetics (PKs) of DOR in healthy volunteers.

Single-Spin Magnetomechanics with Levitated Micromagnets.

We demonstrate a new mechanical transduction platform for individual spin qubits. In our approach, single micromagnets are trapped using a type-II superconductor in proximity of spin qubits, enabling direct magnetic coupling between the two systems. Controlling the distance between the magnet and the superconductor during cooldown, we demonstrate three-dimensional trapping with quality factors around 1×10^{6} and kHz trapping frequencies.

The Role of Reconstructive Surgery and Brachytherapy in Pediatric Bladder/Prostate Rhabdomyosarcoma.

Purpose: The surgical approach to localized bladder/prostate rhabdomyosarcoma in children may change due to a new radiotherapeutic modality. We assessed the impact of brachytherapy following surgery for local tumor control, and report surgical techniques and outcomes.

Materials And Methods: We retrospectively analyzed the records of all children who underwent surgery for bladder/prostate rhabdomyosarcoma, including tumor relapse, at our institution from 2009 onward.

Primary care experiences of veterans with opioid use disorder in the Veterans Health Administration.

Background: While patients with substance use disorders (SUDs) are thought to encounter poor primary care experiences, the perspectives of patients with opioid use disorder (OUD), specifically, are unknown. This study compares the primary care experiences of patients with OUD, other SUDs and no SUD in the Veterans Health Administration.

Methods: The sample included Veterans who responded to the national Patient-Centered Medical Home Survey of Healthcare Experiences of Patients, 2013-2015.

A provider's guide to primary myelofibrosis: pathophysiology, diagnosis, and management.

Although understanding of the pathogenesis and molecular biology of primary myelofibrosis continues to improve, treatment options are limited, and several biological features remain unexplained. With an appropriate clinical history, exam, laboratory evaluation, and bone marrow biopsy, the diagnosis can often be established. Recent studies have better characterized prognostic factors and driver mutations in myelofibrosis, facilitated by use of next-generation sequencing.

Measurement of Platelet Function in an Experimental Stroke Model With Aspirin and Clopidogrel Treatment.

Dual antiplatelet treatment (DAPT) increases the risk of tPA-associated hemorrhagic transformation (HT) in ischemic stroke. To investigate the effects of DAPT in rodents, reliable indicators of platelet function utilizing a minimally invasive procedure are required. We here established a fluorescence-based assay to monitor DAPT efficiency in a mouse model of ischemic stroke with HT.

Use of GMI-1271, an E-selectin antagonist, in healthy subjects and in 2 patients with calf vein thrombosis.

Background: There is an unmet need for antithrombotic treatments for venous thromboembolic disease that do not increase bleeding risk. Selectins are cell adhesion molecules that augment thrombosis by activating immune cells to initiate the coagulation cascade. GMI-1271, a potent small-molecule E-selectin antagonist, has been shown in mouse models to decrease thrombus burden with a low risk of bleeding.

Diagnostic Accuracy of Glial Fibrillary Acidic Protein and Ubiquitin Carboxy-Terminal Hydrolase-L1 Serum Concentrations for Differentiating Acute Intracerebral Hemorrhage from Ischemic Stroke.

Background: Biomarkers indicative of intracerebral hemorrhage (ICH) may help triage acute stroke patients in the pre-hospital phase. We hypothesized that serum concentration of glial fibrillary acidic protein (GFAP) in combination with ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1), measured by a rapid bio-assay, could be used to distinguish ICH from ischemic stroke.

Methods: This prospective two-center study recruited patients with a clinical diagnosis of acute stroke both in the pre-hospital phase and at hospital admission (within 4 and 6 h after symptom onset, respectively).

Assessing aneuploidy with repetitive element sequencing.

We report a sensitive PCR-based assay called Repetitive Element AneupLoidy Sequencing System (RealSeqS) that can detect aneuploidy in samples containing as little as 3 pg of DNA. Using a single primer pair, we amplified ∼350,000 amplicons distributed throughout the genome. Aneuploidy was detected in 49% of liquid biopsies from a total of 883 nonmetastatic, clinically detected cancers of the colorectum, esophagus, liver, lung, ovary, pancreas, breast, or stomach.

Availability and Quality of Assessment Instruments on Patient-Centredness in the Multimorbid Elderly (AQuA-PCE): a study protocol of a systematic review.

Introduction: Elderly, multimorbid patients are a primary target group for patient-centred care, and fostering patient-centredness (PC) in this group has been associated with different healthcare aims such as safety and quality of healthcare. However, evidence on effects of patient-centred interventions is still limited and mixed. In part, the lack of consistent evidence has its roots in a conceptual uncertainty of the term 'PC', which also hampers the development of assessment tools for PC.

Differing Pulmonary Structural Abnormalities Detected on Pulmonary MR Imaging in Cystic Fibrosis Patients with Varying Pancreatic Function.

Purpose:  In cystic fibrosis (CF) the phenotypic expression of complaints varies widely. Genotypes with sufficient pancreatic function (PS) exhibit milder lung disease compared to CF patients with insufficient pancreatic function (PI). The purpose of this study was to evaluate structural lung disease (SLD) in CF patients with differing pancreatic status but similar results on pulmonary function testing using a pulmonary magnetic resonance imaging score (MR-CF score).

Long-term blood pressure lowering and cGMP-activating actions of the novel ANP analog MANP.

Based on the cardiac hormone atrial natriuretic peptide (ANP) and its seminal role in blood pressure (BP) homeostasis, we investigated the chronic BP lowering actions of a novel ANP analog currently entering clinical trials for hypertension. Previous reports demonstrate that this analog MANP activates the guanylyl cyclase A receptor (GC-A) and results in more potent biological actions compared with ANP; thus, it may represent a new therapeutic drug for hypertension. A major goal of this study was to establish that chronic subcutaneous delivery of MANP is feasible and hypotensive together with cGMP effects.

Cost-effectiveness analysis of low-dose direct oral anticoagulant (DOAC) for the prevention of cancer-associated thrombosis in the United States.

Background: Randomized controlled trials (RCTs) have demonstrated that low-dose direct oral anticoagulants (DOACs), including rivaroxaban and apixaban, may help reduce the incidence of cancer-associated venous thromboembolism (VTE).

Methods: A cost-utility analysis was performed from the health sector perspective using a Markov state-transition model in patients with cancer who are at intermediate-to-high risk for VTE. Transition probability, relative risk, cost, and utility inputs were obtained from a meta-analysis of the RCTs and relevant epidemiology studies.

Left ventricle assist device pulsatility index at the time of implantation is associated with follow-up pulmonary hemodynamics.

HeartMate II left ventricular assist device controllers provide data including pulsatility index, reflecting the relationship between pump function and hemodynamics. We propose that a higher pulsatility index at hospital discharge following implant may be associated with less vascular congestion and improved clinical outcomes. A retrospective analysis of 40 patients (age 59.

Uterine aquaporin expression is dynamically regulated by estradiol and progesterone and ovarian stimulation disrupts embryo implantation without affecting luminal closure.

The study investigated the effect of normal and supraphysiological (resulting from gonadotropin-dependent ovarian stimulation) levels of estradiol (E2) and progesterone (P4) on mouse uterine aquaporin gene/protein (Aqp/AQP) expression on Day 1 (D1) and D4 of pregnancy. The study also examined the effect of ovarian stimulation on uterine luminal closure and uterine receptivity on D4 of pregnancy and embryo implantation on D5 and D7 of pregnancy. These analyses revealed that the expression of Aqp3, Aqp4, Aqp5 and Aqp8 is induced by E2 while the expression of Aqp1 and Aqp11 is induced by P4.