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In this article, we continue the structural study of factor maps between symbolic dynamical systems and the relative thermodynamic formalism. Here, one is studying a factor map from a shift of finite type X (equipped with a potential function) to a sofic shift Z, equipped with a shift-invariant measure
$\nu $
. We study relative equilibrium states, that is, shift-invariant measures on X that push forward under the factor map to
$\nu $
which maximize the relative pressure: the relative entropy plus the integral of
$\phi $
. In this paper, we establish a new connection to multiplicative ergodic theory by relating these factor triples to a cocycle of Ruelle–Perron–Frobenius operators, and showing that the principal Lyapunov exponent of this cocycle is the relative pressure; and the dimension of the leading Oseledets space is equal to the number of measures of relative maximal entropy, counted with a previously identified concept of multiplicity.
Paramedics received training in point-of-care ultrasound (POCUS) to assess for cardiac contractility during management of medical out-of-hospital cardiac arrest (OHCA). The primary outcome was the percentage of adequate POCUS video acquisition and accurate video interpretation during OHCA resuscitations. Secondary outcomes included POCUS impact on patient management and resuscitation protocol adherence.
Methods:
A prospective, observational cohort study of paramedics was performed following a four-hour training session, which included a didactic lecture and hands-on POCUS instruction. The Prehospital Echocardiogram in Cardiac Arrest (PECA) protocol was developed and integrated into the resuscitation algorithm for medical non-shockable OHCA. The ultrasound (US) images were reviewed by a single POCUS expert investigator to determine the adequacy of the POCUS video acquisition and accuracy of the video interpretation. Change in patient management and resuscitation protocol adherence data, including end-tidal carbon dioxide (EtCO2) monitoring following advanced airway placement, adrenaline administration, and compression pauses under ten seconds, were queried from the prehospital electronic health record (EHR).
Results:
Captured images were deemed adequate in 42/49 (85.7%) scans and paramedic interpretation of sonography was accurate in 43/49 (87.7%) scans. The POCUS results altered patient management in 14/49 (28.6%) cases. Paramedics adhered to EtCO2 monitoring in 36/36 (100.0%) patients with an advanced airway, adrenaline administration for 38/38 (100.0%) patients, and compression pauses under ten seconds for 36/38 (94.7%) patients.
Conclusion:
Paramedics were able to accurately obtain and interpret cardiac POCUS videos during medical OHCA while adhering to a resuscitation protocol. These findings suggest that POCUS can be effectively integrated into paramedic protocols for medical OHCA.
The Middle Mississippian component at Aztalan was a mixed, Late Woodland / Mississippian occupation sited within a heavily fortified habitation and mound center that is located on a tributary of the Rock River in Wisconsin. It represents the northernmost large Cahokian-related village recorded. The Oneota Lake Koshkonong Locality of the Rock River drainage is located approximately 20 km south of Aztalan, and it consists of a 25 km2 area along the northwest shore with a small cluster of habitation settlements. Sixty-eight radiocarbon measurements have been obtained from Aztalan, and 52 from Oneota settlements in the Lake Koshkonong Locality. We discuss how to best interpret this dataset, and we use Bayesian chronological modeling to analyze these dates. The results suggest that (1) Aztalan's Late Woodland (Kekoskee phase) occupation began in the AD 900s or early AD 1000s, (2) Aztalan's Mississippian occupation ceased in the AD 1200s, (3) Oneota occupations at Lake Koshkonong began after AD 1050 and were established by the AD 1200s, and (4) Oneota occupations at Lake Koshkonong continued after Aztalan's Mississippian abandonment until at least the late AD 1300s. Additionally, the results demonstrate that Aztalan was fortified with a palisade with bastions for much of the Mississippian occupation, suggesting a contested presence in a multiethnic landscape.
The police murder of George Floyd in Minneapolis in May 2020 (just twenty-two city blocks from where I write) sparked global demonstrations and renewed long-standing struggles for change. At the southern border, government agents separated migrant children from their families and confined detainees in cages. Politicization of the pandemic made Asian Americans targets of violent racist outbursts. Indigenous women continued to suffer disproportionate harm with little attention to their plight. Finally, the right-wing insurrection at the U.S. Capitol in Washington, DC, in January 2021 marked the moment as especially volatile.
A chloroacetamide herbicide by application timing factorial experiment was conducted in 2017 and 2018 in Mississippi to investigate chloroacetamide use in a dicamba-based Palmer amaranth management program in cotton production. Herbicides used were S-metolachlor or acetochlor, and application timings were preemergence, preemergence followed by (fb) early postemergence, preemergence fb late postemergence, early postemergence alone, late postemergence alone, and early postemergence fb late postemergence. Dicamba was included in all preemergence applications, and dicamba plus glyphosate was included with all postemergence applications. Differences in cotton and weed response due to chloroacetamide type were minimal, and cotton injury at 14 d after late postemergence application was less than 10% for all application timings. Late-season weed control was reduced up to 30% and 53% if chloroacetamide application occurred preemergence or late postemergence only, respectively. Late-season weed densities were minimized if multiple applications were used instead of a single application. Cotton height was reduced by up to 23% if a single application was made late postemergence relative to other application timings. Chloroacetamide application at any timing except preemergence alone minimized late-season weed biomass. Yield was maximized by any treatment involving multiple applications or early postemergence alone, whereas applications preemergence or late postemergence alone resulted in up to 56% and 27% yield losses, respectively. While no yield loss was reported by delaying the first of sequential applications until early postemergence, forgoing a preemergence application is not advisable given the multiple factors that may delay timely postemergence applications such as inclement weather.
John McGuckin examines early writings of Christian theologians about conscience. These relied upon the Scriptures and upon Plato, Aristotle, and others, and they regularly grappled with the positive and negative possibilities of conscience. But Christian writers made religious inquiries. St. Paul wrote about conscience in connection with a law “written on the heart,” a guide to everyone, but fallible and in need of the grace of Christ. The Greek fathers, led by Origen, emphasized conscience as an awareness of divine things, albeit impaired by man’s fall, yet still oriented to God and to obedience to moral norms. The Latin fathers, led by Augustine, emphasized humanity’s corruption after the fall and need for divine grace. Thus, conscience may convict, but might not provoke a person to goodness. Only loving God could do this. In both Latin and Greek thought, therefore, conscience was more than an inner voice instructing about right and wrong. It was a set of reflections on the spiritual identity of human beings.
Individuals with treatment-resistant depression (TRD) experience a high burden of illness. Current guidelines recommend a stepped care approach for treating depression, but the extent to which best-practice care pathways are adhered to is unclear.
Aims
To explore the extent and nature of ‘treatment gaps’ (non-adherence to stepped care pathways) experienced by a sample of patients with established TRD (non-response to two or more adequate treatments in the current depressive episode) across three cities in the UK.
Method
Five treatment gaps were considered and compared with guidelines, in a cross-sectional retrospective analysis: delay to receiving treatment, lack of access to psychological therapies, delays to medication changes, delays to adjunctive (pharmacological augmentation) treatment and lack of access to secondary care. We additionally explored participant characteristics associated with the extent of treatment gaps experienced.
Results
Of 178 patients with TRD, 47% had been in the current depressive episode for >1 year before initiating antidepressants; 53% had received adequate psychological therapy. A total of 47 and 51% had remained on an unsuccessful first and second antidepressant trial respectively for >16 weeks, and 24 and 27% for >1 year before medication switch, respectively. Further, 54% had tried three or more antidepressant medications within their episode, and only 11% had received adjunctive treatment.
Conclusions
There appears to be a considerable difference between treatment guidelines for depression and the reality of care received by people with TRD. Future research examining representative samples of patients could determine recommendations for optimising care pathways, and ultimately outcomes, for individuals with this illness.
San Francisco (California USA) is a relatively compact city with a population of 884,000 and nine stroke centers within a 47 square mile area. Emergency Medical Services (EMS) transport distances and times are short and there are currently no Mobile Stroke Units (MSUs).
Methods:
This study evaluated EMS activation to computed tomography (CT [EMS-CT]) and EMS activation to thrombolysis (EMS-TPA) times for acute stroke in the first two years after implementation of an emergency department (ED) focused, direct EMS-to-CT protocol entitled “Mission Protocol” (MP) at a safety net hospital in San Francisco and compared performance to published reports from MSUs. The EMS times were abstracted from ambulance records. Geometric means were calculated for MP data and pooled means were similarly calculated from published MSU data.
Results:
From July 2017 through June 2019, a total of 423 patients with suspected stroke were evaluated under the MP, and 166 of these patients were either ultimately diagnosed with ischemic stroke or were treated as a stroke but later diagnosed as a stroke mimic. The EMS and treatment time data were available for 134 of these patients with 61 patients (45.5%) receiving thrombolysis, with mean EMS-CT and EMS-TPA times of 41 minutes (95% CI, 39-43) and 63 minutes (95% CI, 57-70), respectively. The pooled estimates for MSUs suggested a mean EMS-CT time of 35 minutes (95% CI, 27-45) and a mean EMS-TPA time of 48 minutes (95% CI, 39-60). The MSUs achieved faster EMS-CT and EMS-TPA times (P <.0001 for each).
Conclusions:
In a moderate-sized, urban setting with high population density, MP was able to achieve EMS activation to treatment times for stroke thrombolysis that were approximately 15 minutes slower than the published performance of MSUs.
Linoleic acid (LA), an essential n-6 fatty acid (FA), is critical for fetal development. We investigated the effects of maternal high LA (HLA) diet on offspring cardiac development and its relationship to circulating FA and cardiovascular function in adolescent offspring, and the ability of the postnatal diet to reverse any adverse effects. Female Wistar Kyoto rats were fed low LA (LLA; 1·44 % energy from LA) or high LA (HLA; 6·21 % energy from LA) diets for 10 weeks before pregnancy and during gestation/lactation. Offspring, weaned at postnatal day 25, were fed LLA or HLA diets and euthanised at postnatal day 40 (n 6–8). Maternal HLA diet decreased circulating total cholesterol and HDL-cholesterol in females and decreased total plasma n-3 FA in males, while maternal and postnatal HLA diets decreased total plasma n-3 FA in females. α-Linolenic acid (ALA) and EPA were decreased by postnatal but not maternal HLA diets in both sexes. Maternal and postnatal HLA diets increased total plasma n-6 and LA, and a maternal HLA diet increased circulating leptin, in both male and female offspring. Maternal HLA decreased slopes of systolic and diastolic pressure–volume relationship (PVR), and increased cardiac Col1a1, Col3a1, Atp2a1 and Notch1 in males. Maternal and postnatal HLA diets left-shifted the diastolic PVR in female offspring. Coronary reactivity was altered in females, with differential effects on flow repayment after occlusion. Thus, maternal HLA diets impact lipids, FA and cardiac function in offspring, with postnatal diet modifying FA and cardiac function in the female offspring.
Pharmacogenomic testing has emerged to aid medication selection for patients with major depressive disorder (MDD) by identifying potential gene-drug interactions (GDI). Many pharmacogenomic tests are available with varying levels of supporting evidence, including direct-to-consumer and physician-ordered tests. We retrospectively evaluated the safety of using a physician-ordered combinatorial pharmacogenomic test (GeneSight) to guide medication selection for patients with MDD in a large, randomized, controlled trial (GUIDED).
Materials and Methods
Patients diagnosed with MDD who had an inadequate response to ≥1 psychotropic medication were randomized to treatment as usual (TAU) or combinatorial pharmacogenomic test-guided care (guided-care). All received combinatorial pharmacogenomic testing and medications were categorized by predicted GDI (no, moderate, or significant GDI). Patients and raters were blinded to study arm, and physicians were blinded to test results for patients in TAU, through week 8. Measures included adverse events (AEs, present/absent), worsening suicidal ideation (increase of ≥1 on the corresponding HAM-D17 question), or symptom worsening (HAM-D17 increase of ≥1). These measures were evaluated based on medication changes [add only, drop only, switch (add and drop), any, and none] and study arm, as well as baseline medication GDI.
Results
Most patients had a medication change between baseline and week 8 (938/1,166; 80.5%), including 269 (23.1%) who added only, 80 (6.9%) who dropped only, and 589 (50.5%) who switched medications. In the full cohort, changing medications resulted in an increased relative risk (RR) of experiencing AEs at both week 4 and 8 [RR 2.00 (95% CI 1.41–2.83) and RR 2.25 (95% CI 1.39–3.65), respectively]. This was true regardless of arm, with no significant difference observed between guided-care and TAU, though the RRs for guided-care were lower than for TAU. Medication change was not associated with increased suicidal ideation or symptom worsening, regardless of study arm or type of medication change. Special attention was focused on patients who entered the study taking medications identified by pharmacogenomic testing as likely having significant GDI; those who were only taking medications subject to no or moderate GDI at week 8 were significantly less likely to experience AEs than those who were still taking at least one medication subject to significant GDI (RR 0.39, 95% CI 0.15–0.99, p=0.048). No other significant differences in risk were observed at week 8.
Conclusion
These data indicate that patient safety in the combinatorial pharmacogenomic test-guided care arm was no worse than TAU in the GUIDED trial. Moreover, combinatorial pharmacogenomic-guided medication selection may reduce some safety concerns. Collectively, these data demonstrate that combinatorial pharmacogenomic testing can be adopted safely into clinical practice without risking symptom degradation among patients.
ABSTRACT IMPACT: This work has begun to provide the foundation for better ensuring that translational research funded and supported by our IDeA-CTR grant is more directly addressing community- and stakeholder-authored health priorities. OBJECTIVES/GOALS: In order to effectively engage diverse, societal perspectives, we aimed to determine the relevance and feasibility of purposefully aligning translational research with health priorities adopted by the RI Department of Health, health-focused organizations, and community leaders. METHODS/STUDY POPULATION: Individuals from 27 community organizations in RI were asked, ‘What are your health related goals for your community’ and submitted responses online for 2 weeks. Participants generated 71 goals which they sorted into meaningful clusters and rated for importance and feasibility. Clusters were contrasted with RI health priorities to gauge alignment and saturation. In the next phase of this project, researchers and service users funded by Advance-CTR will be asked in routinely administered surveys how their current work may align with RI health goals and whether their future work can feasibly be connected to those priorities. RESULTS/ANTICIPATED RESULTS: Using Group Concept Mapping software, the 71 health goals identified by community organization representatives were fit into an 8-cluster model. Results suggested highest importance placed on Accessible & Healthy Housing (M=4.12, SD=0.29), Community (M=4.08, SD=0.28), Youth (M=4.04, SD=0.49) and Mental Health (M=4.03, SD=0.46). State agency priorities were found to overlap substantially with clusters defined by community leaders. We expect researchers will rate clusters differently, and find some community-endorsed health goals more relevant to their work than others. Perceived feasibility of tailoring future research to state health goals is expected to vary widely by item and researcher. DISCUSSION/SIGNIFICANCE OF FINDINGS: We intend to: 1) facilitate discussions about successes and challenges of translating community-authored priorities into research, and 2) foster better understanding between researchers and the communities they aim to serve on the role of CTR for addressing health challenges in the state.
ABSTRACT IMPACT: Identifying the causative antigen in membranous glomerulopathy cohorts enables the development of serum assays to detect and monitor disease progression without the need for invasive kidney biopsies. OBJECTIVES/GOALS: Primary membranous glomerulopathy is caused by the formation of autoantibody immune complexes which deposit in the glomerulus and obstruct kidney function. Causative antigens remain to be identified in roughly 20% of cases. Our goal is to identify the antigen in these cohorts, so that non-invasive assays can be developed for disease monitoring. METHODS/STUDY POPULATION: Renal biopsy tissue from known antigen cases (PLA2R, THSD7A), and unknown cases were included in the analysis. Renal biopsy tissue from formalin fixed paraffin embedded tissue was cut at a thickness of 10 µm onto Leica PET-membrane frame slides. These slides were then stained with hematoxylin. The glomeruli were microdissected into microcentrifuge tubes using a Leica DM6000B microscope. The microdissected glomeruli were lysed in 2% SDS and 0.1M DTT at 99 degrees Celsius for 1 hour and processed by filter assisted sample preparation (FASP). Digested peptides were analyzed by liquid chromatography-mass spectrometry using an Orbitrap Fusion Lumos using data-dependent acquisition. RESULTS/ANTICIPATED RESULTS: Mass spectrometry data collected from the laser captured glomeruli was searched against the human proteome fasta database from Uniprot using MaxQuant. IBAQ values were used for quantitation and statistical analysis. Null hypothesis significance testing was performed for each protein by comparing each sample group to the rest of the samples in the data set. In the control groups, the causative antigens PLA2R and THSD7A were detected and quantified with the largest magnitude fold change in their respective category, validating the experimental design. Using this approach, the proteins SAP, NELL1, and NCAM1 were identified and subsequently validated as causative antigens in distinct patient cohorts. DISCUSSION/SIGNIFICANCE OF FINDINGS: Here, we share the results of our efforts to comprehensively identify the spectrum of causative antigens in membranous glomerulopathy. In this context, antigen discovery is an essential first step for the development of non-invasive assays to inform prognosis, monitor response to treatment, and better understand disease etiology.
Native tungsten (IMA2011-004), W, is officially described as a new mineral from gold placers in the Bol'shaya Pol'ya river valley, Prepolar Urals, Russia, associated with yttriaite-(Y) and from quartz veins in the Mt Neroyka rock-crystal field, Ust–Puiva, Tyumenskaya Oblast', Russia. Tungsten forms polycrystalline grains and masses, and rarely cubo-octahedra. It is silver white to steel grey in colour, with metallic lustre and grey streak. The calculated density is 19.226 g/cm3. The Vickers hardness (VHN25) is 571.45 kg/mm2. In plane polarised light, tungsten is white with a pale-yellow tint and optically isotropic. Electron microprobe analyses of Bol'shaya Pol'ya river valley material provided W 99.27, Mo 0.06, Mn 0.04, Fe 0.01, total 99.38 wt.%. The five strongest powder X-ray diffraction lines are [dobs Å(I)(hkl)]: 2.2422(100)(110), 1.5835(25)(200), 1.2929(48)(211), 1.0010(23)(310) and 0.8457(24)(321). Tungsten is cubic, Im$\bar{3}$m, a = 3.1648(4) Å, V = 31.69(4) Å3 and Z = 2. Some additional occurrences of native tungsten and technogenic tungsten found in Nature are also described.
Advance Clinical and Translational Research (Advance-CTR) serves as a central hub to support and educate clinical and translational researchers in Rhode Island. Understanding barriers to clinical research in the state is the key to setting project aims and priorities.
Methods:
We implemented a Group Concept Mapping exercise to characterize the views of researchers and administrators regarding how to increase the quality and quantity of clinical and translational research in their settings. Participants generated ideas in response to this prompt and rated each unique idea in terms of how important it was and feasible it seemed to them.
Results:
Participants generated 78 unique ideas, from which 9 key themes emerged (e.g., Building connections between researchers). Items rated highest in perceived importance and feasibility included providing seed grants for pilot projects, connecting researchers with common interests and networking opportunities. Implications of results are discussed.
Conclusions:
The Group Concept Mapping exercise enabled our project leadership to better understand stakeholder-perceived priorities and to act on ideas and aims most relevant to researchers in the state. This method is well suited to translational research enterprises beyond Rhode Island when a participatory evaluation stance is desired.
The first demonstration of laser action in ruby was made in 1960 by T. H. Maiman of Hughes Research Laboratories, USA. Many laboratories worldwide began the search for lasers using different materials, operating at different wavelengths. In the UK, academia, industry and the central laboratories took up the challenge from the earliest days to develop these systems for a broad range of applications. This historical review looks at the contribution the UK has made to the advancement of the technology, the development of systems and components and their exploitation over the last 60 years.
Jeankempite, Ca5(AsO4)2(AsO3OH)2(H2O)7, is a new mineral species (IMA2018-090) discovered amongst coatings of arsenate minerals on oxidised copper arsenides from the Mohawk No. 2 mine, Mohawk, Keweenaw County, Michigan, USA. The new mineral occurs as lamellar bundles of colourless to white plates up to 1 mm wide and is visually indistinguishable from guérinite, with which it forms intergrowths. Jeankempite is transparent to translucent with a waxy lustre and white streak, is non-fluorescent under longwave and shortwave ultraviolet illumination, has a Mohs hardness of ~1.5 and brittle tenacity with uneven fracture. Crystals are flattened on {01$\bar{1}$} and exhibit perfect cleavage on {01$\bar{1}$}. Optically, jeankempite is biaxial (+), α = 1.601(2), β = 1.607(2), γ = 1.619(2) (white light); 2Vmeas. = 72(2)° and 2Vcalc. = 71.0°. The empirical formula is (Ca4.97Na0.013Mg0.017)(As3.99S0.01)4O23H16, based on 23 O and 16 H atoms per formula unit. Thermogravimetric analysis indicates that jeankempite undergoes four weight losses totalling 16.82%, close to the expected loss of 16.30%, corresponding to eight H2O. Jeankempite is triclinic, P$\bar{1}$, a = 6.710(6), b = 14.901(14), c = 15.940(15) Å, α = 73.583(12)°, β = 81.984(12)°, γ = 82.754(12)°, V = 1507(2) Å3 and Z = 3. The final structure was refined to R1 = 0.0591 for 2781 reflections with Iobs > 3σI. The crystal structure of jeankempite is built from a network of edge- and vertex-sharing CaO6, CaO7 and AsO4 polyhedra, and we hypothesise that the new mineral has formed due to a topotactic reaction brought on by dehydration of preexisting guérinite.
The global community needs to be aware of the potential psychosocial consequences that may be experienced by health care workers who are actively managing patients with coronavirus disease (COVID-19). These health care workers are at increased risk for experiencing mood and trauma-related disorders, including posttraumatic stress disorder (PTSD). In this concept article, strategies are recommended for individual health care workers and hospital leadership to aid in mitigating the risk of PTSD, as well as to build resilience in light of a potential second surge of COVID-19.