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Patient preferences in schizophrenia (SCZ), including identification of key goals and outcomes for treatment and relative importance of certain treatment goals to patients, have been assessed by several studies. However, there continues to be a lack of sufficient evidence on US patient attitudes and perceptions towards treatment goals and pharmacotherapy options in SCZ, especially taking into context long-acting injectable antipsychotics (LAIs) in this disease area. This lack of evidence is further pronounced in caregivers of individuals with SCZ. The objective of this analysis was to characterize patients with SCZ on LAIs vs patients on oral antipsychotics (OAPs) and evaluate the treatment goals of patients in each group.
This was a real-world, cross-sectional survey of US psychiatrists, patients =18 years old with a diagnosis of SCZ, and caregivers. Data was collected using the Disease Specific Programme (DSP) methodology, which has been previously published. Psychiatrists (n=120) completed detailed record forms for next 8 consecutive outpatients and 2 inpatients matching inclusion criteria, including non-interventional clinical and subjective assessments. The same patients and their caregivers, if present, were invited by their psychiatrist to voluntarily complete a separate survey.
Of 1135 patients on treatment where the physician provided survey data; 251 were on an LAI, and 884 were on an OAP. Mean (SD) time to SCZ diagnosis for those on an LAI was 10.3 (12.0) years vs 7.8 (10.5) years for those on OAPs. More patients in the LAI vs OAP group were being treated as an inpatient (27.1% vs 15.7%, respectively; p<0.0001). Patients on an LAI reported being on their current medication regimen for less time (mean 1.7 years) vs those on OAPs (mean 2.5 years) (p=0.0093). More patients on LAIs were unemployed due to disability vs those on OAPs (56.1% vs 39.5%, respectively), and less patients on LAIs were able to work part-time or full-time (21.1% or 4.1%) vs those on OAPs (23.2% or 11.4%). More patients on an LAI had a caregiver vs those on OAPs (37.3% vs 26.1%, respectively; p=0.0011). Regarding the most important treatment goals reported by patients, both groups reported similar preferences for decrease in disease symptoms (62% on LAI vs 65% on OAPs) and thinking more clearly (53% on LAI vs 46% on OAPs); however, a numerically higher proportion of LAI patients reported that the current medication helped decrease hospitalizations due to relapse vs those on OAPs (38% vs 32%, respectively).
Given the characteristics of patients participating in this real-world survey, those on LAIs exhibited qualities which indicate a higher severity of illness vs those on OAPs. Results suggest that treatment with LAIs is still mainly being provided to patients later in the disease course and/or who have adherence problems, despite a growing body of evidence of utility in younger patients earlier in the course of illness.
Otsuka Pharmaceutical Development & Commercialization, Inc. and Lundbeck LLC
Objectives for this survey are to determine similarities or differences in treatment goals reported by psychiatrists, patients with schizophrenia (SCZ) and caregivers in the US, as well as whether goals differed by patients currently on an oral antipsychotic (OAP) or long-acting injectable (LAI), and whether goals differed by age.
This was a real-world, cross-sectional survey of US psychiatrists, patients =18 years old diagnosed with SCZ, and caregivers. Data was collected using the Disease Specific Programme (DSP) methodology. Psychiatrists (n=120) completed detailed record forms for next 8 outpatients and 2 inpatients matching inclusion criteria. The same patients and their caregivers, if present, were invited by their psychiatrist to voluntarily complete a separate survey.
Responses on treatment goals were collected from psychiatrists for all patients included in the analysis (n=1161), patients (n= 542) and caregivers (n=130). Among 3 top goals, psychiatrists, patients and caregivers concurred that “decrease in disease symptoms” is most important (63%, 64%, 68% respectively). For psychiatrists and caregivers, second was “decrease in hospitalization for relapse” (41%, and 38% respectively), whereas for patients, it was “thinking clearly” (47%). Of the 3 least important goals, psychiatrists, patients and caregivers agreed with “sexual problems” (59%, 43%, 44%, respectively) and “weight gain” (38%, 44%, 38%, respectively).
When asked which goals were met by current medication, patients responded “decrease in disease symptoms” (68%) and “thinking clearly” (39%). However, caregivers responded “thinking clearly” (30%) was not met by current medication. Caregivers most important goals, “decrease in disease symptom” (70%) and “decrease in hospitalization for relapse” (41%), were met. Additional analyses of patients on OAPs and LAIs, did not show differences in goals. However, “decrease in disease symptoms” was numerically more important for patients on LAIs vs OAPs according to psychiatrists (68% vs 62%) and caregivers (77% vs 70% respectively). Caregivers responded “decrease in hospitalization for relapse” was met for 63% patients currently on an LAI and 35% OAP. No major differences in treatment goals were observed by patient age (18–35 vs 36–65 vs >65 years).
There is consensus among US psychiatrists, patients and caregivers on the most important treatment goal “decrease in disease symptoms”, regardless of patients’ current medication or age. For patients, “thinking more clearly” was second, compared with “decrease in hospitalization due to relapse”, for psychiatrists and caregivers. All agreed that least important treatment goals, related to AEs, were “weight gain” and “sexual problems”. More caregivers agreed “decrease in hospitalization for relapse” was met by patients on LAIs vs OAPs. These findings may help with discussions between psychiatrists, patients and caregivers.
Lundbeck LLC and Otsuka Pharmaceutical Development & Commercialization, Inc.
In SETI, when searching for ‘beacons’ – transmissions intended for us and meant to get our attention – one must guess the appropriate frequency to search by considering what frequencies would be universally obvious to other species. This is a well-known concept in game theory, where such solutions to a non-communicative cooperative game (such as a mutual search) are called ‘Schelling points’. It is noteworthy, therefore, that when developing his eponymous units, Planck called them ‘natural’ because they ‘remain meaningful for all times and also for extraterrestrial and non-human cultures’. Here, I apply Planck's suggestion in the context of Schelling points in SETI with a ‘Planck Frequency Comb’, constructed by multiplying the Planck energy by integer powers of the fine structure constant. This comb includes a small number of frequencies in regions of the electromagnetic spectrum where laser and radio SETI typically operates. Searches might proceed and individual teeth in the comb, or at many teeth at once, across the electromagnetic spectrum. Indeed, the latter strategy can be additionally justified by the transmitter's desire to signal at many frequencies at once, to improve the chances that the receiver will guess one of them correctly. There are many arbitrary and anthropocentric choices in this comb's construction, and indeed one can construct several different frequency combs with only minor and arbitrary modifications. This suggests that it may be fruitful to search for signals arriving in frequency combs of arbitrary spacing. And even though the frequencies suggested here are only debatably ‘better’ than others proposed, the addition of the Planck Frequency Comb to the list of ‘magic frequencies’ can only help searches for extraterrestrial beacons.
Many factors such as environment, herbicide rate, growth stage at application, and days between sequential applications can influence the response of a crop to herbicides. Florpyrauxifen-benzyl is a new broad-spectrum, POST herbicide that was commercialized for use in U.S. rice production in 2018. Field experiments were conducted in 2018 at the Pine Tree Research Station (PTRS) near Colt, AR, and the Rice Research and Extension Center (RREC), near Stuttgart, AR, to evaluate crop injury and yield response of three rice cultivars to sequential applications of florpyrauxifen-benzyl. Greenhouse and growth chamber experiments were conducted at the Altheimer Laboratory in Fayetteville, AR, to evaluate cultivar responses when florpyrauxifen-benzyl was applied at 30 or 60 g ae ha−1 to rice exposed to different temperature regimes or at various growth stages. Three rice cultivars were used in all experiments: long-grain variety ‘CL111’, medium-grain variety ‘CL272’, and long-grain hybrid cultivar ‘CLXL745’. CL111 exhibited sufficient tolerance to florpyrauxifen-benzyl with only 10% visible injury and no effect on yield. CL272 showed 15% injury 3 wk after the second application in the field experiment when applications were made 14 d apart. Additionally, 12% injury was observed in greenhouse studies when florpyrauxifen-benzyl was applied at 30 g ae ha−1, averaged over various growth stages at application. Florpyrauxifen-benzyl did not reduce the yield of CL272 in field experiments, indicating that CL272 can recover from florpyrauxifen-benzyl injury. As much as 64% injury was observed for CLXL745 at 3 wk after application (WAA) when sequential herbicide applications were made 4 d apart. High levels of injury occurred in the growth chamber and greenhouse studies for this cultivar as well. Sequential applications of florpyrauxifen-benzyl reduced yields of CLXL745 in nearly all treatments. Data from these experiments suggest that CL272 and CLXL745 are sensitive to sequential applications of florpyrauxifen-benzyl. Growers must follow the prescribed guidelines for using florpyrauxifen-benzyl in these cultivars and others like it.
OBJECTIVES/GOALS: We use a tissue engineered, biomimetic, 3D model to study the pathogenesis of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) by comparing the effect of silicone implant shell on proliferation of patient-derived BIA-ALCL to its precursor T cells within the breast microenvironment. METHODS/STUDY POPULATION: Patient-derived breast tissue was processed for component adipocytes, ductal organoids, and stromal vascular fraction. These were suspended within 50 µl of 0.3% type I collagen matrix to which was added 200,000 cells/mL of either patient-derived BIA-ALCL cells or T progenitor cells. These were then plated into 6mm wells. As a control, both BIA-ALCL cells and T progenitor cells were suspended within type I collagen alone at the same seeding density without breast components. Before plating, wells were lined circumferentially with either textured, smooth, or no implant shell. These were 1cm by 2cm pieces dissected from the whole implant. Wells were imaged using confocal microscopy over 8 days. RESULTS/ANTICIPATED RESULTS: Unstimulated T progenitor cell count showed no significant increase in any of the conditions tested. The change in cell count over 8 days was 3.85% in each condition (p = 0.3352). A Tukey’s multiple comparison test comparing each condition revealed no significant increase in cell count over 8 days for all six conditions. Notably, our previous studies have shown proliferation of BIA-ALCL cells to be significantly more robust in the biomimetic platform compared to collagen-only groups, regardless of implant shell type (p < 0.01). BIA-ALCL cells grew nearly 30% faster in textured and smooth shell biomimetic groups compared to biomimetic wells lacking implant shell. DISCUSSION/SIGNIFICANCE OF IMPACT: Towards elucidating BIA-ALCL’s etiopathology, we show that silicone implant shell has a significant effect on proliferation of BIA-ALCL cells, but not their precursor T cells. If breast implant silicone shell is not a sufficient stimulus for T cell proliferation, co-stimulatory factors are required.
The Rio scale is a tool for communicating the significance of a signal to the general public. It assigns scores to signals detected in searches for extraterrestrial intelligence (SETI), which characterizes both the consequences of a signal and the probability the signal is truly from ETI, in an easily digestible format for laypeople to interpret. In the 17 years since its construction, the number of groups actively conducting searches for evidence of intelligent life beyond the Earth has increased significantly, and theoretical work has established a new suite of observables that are capable of revealing the presence of ETI in a range of astronomical observations. In this paper, we revise the Rio scale, with the aim of (i) achieving consensus across academic disciplines on a scheme for classifying signals potentially indicating the existence of advanced extraterrestrial life, (ii) supplying a pedagogical tool to help inform the public about the process scientists go through to develop an understanding of a signal and (iii) providing a means of calibrating the expectations of the world at large when signals are discussed in the media. We also present (and encourage the SETI community to adopt) a single set of consistent terminology for discussing signals.
Herbicide resistance, and in particular multiple-herbicide resistance, poses an ever-increasing threat to food security. A biotype of junglerice [Echinochloa colona (L.) Link] with resistance to four herbicides, imazamox, fenoxaprop-P-ethyl, quinclorac, and propanil, each representing a different mechanism of action, was identified in Sunflower County, MS. Dose responses were performed on the resistant biotype and a biotype sensitive to all four herbicides to determine the level of resistance. Application of a cytochrome P450 inhibitor, malathion, with the herbicides imazamox and quinclorac resulted in increased susceptibility in the resistant biotype. Differential gene expression analysis of resistant and sensitive plants revealed that 170 transcripts were upregulated in resistant plants relative to sensitive plants and 160 transcripts were upregulated in sensitive plants. In addition, 507 transcripts were only expressed in resistant plants and 562 only in sensitive plants. A subset of these transcripts were investigated further using quantitative PCR (qPCR) to compare gene expression in resistant plants with expression in additional sensitive biotypes. The qPCR analysis identified two transcripts, a kinase and a glutathione S-transferase that were significantly upregulated in resistant plants compared with the sensitive plants. A third transcript, encoding an F-box protein, was downregulated in the resistant plants relative to the sensitive plants. As no cytochrome P450s were differentially expressed between the resistant and sensitive plants, a single-nucleotide polymorphism analysis was performed, revealing several nonsynonymous point mutations of interest. These candidate genes will require further study to elucidate the resistance mechanisms present in the resistant biotype.
Background: Evidence for the efficacy of computer-based psychological interventions is growing. A number of such interventions have been found to be effective, especially for mild to moderate cases. They largely rely on psychoeducation and ‘homework tasks’, and are specific to certain diagnoses (e.g. depression). Aims: This paper presents the results of a web-based randomized controlled trial of Manage Your Life Online (MYLO), a program that uses artificial intelligence to engage the participant in a conversation across any problem topic. Method: Healthy volunteers (n = 213) completed a baseline questionnaire and were randomized to the MYLO program or to an active control condition where they used the program ELIZA, which emulates a Rogerian psychotherapist. Participants completed a single session before completing post-study and 2-week follow-up measures. Results: Analyses were per protocol with intent to follow-up. Both programs were associated with improvements in problem distress, anxiety and depression post-intervention, and again 2 weeks later, but MYLO was not found to be more effective than ELIZA. MYLO was rated as significantly more helpful than ELIZA, but there was no main effect of intervention on problem resolution. Conclusions: Findings are consistent with those of a previous smaller, laboratory-based trial and provide support for the acceptability and effectiveness of MYLO delivered over the internet for a non-clinical sample. The lack of a no-treatment control condition means that the effect of spontaneous recovery cannot be ruled out.
We discuss how visions for the futures of humanity in space and SETI are intertwined, and are shaped by prior work in the fields and by science fiction. This appears in the language used in the fields, and in the sometimes implicit assumptions made in discussions of them. We give examples from articulations of the so-called Fermi Paradox, discussions of the settlement of the Solar System (in the near future) and the Galaxy (in the far future), and METI. We argue that science fiction, especially the campy variety, is a significant contributor to the ‘giggle factor’ that hinders serious discussion and funding for SETI and Solar System settlement projects. We argue that humanity's long-term future in space will be shaped by our short-term visions for who goes there and how. Because of the way they entered the fields, we recommend avoiding the term ‘colony’ and its cognates when discussing the settlement of space, as well as other terms with similar pedigrees. We offer examples of science fiction and other writing that broaden and challenge our visions of human futures in space and SETI. In an appendix, we use an analogy with the well-funded and relatively uncontroversial searches for the dark matter particle to argue that SETI's lack of funding in the national science portfolio is primarily a problem of perception, not inherent merit.
One of the primary open questions of astrobiology is whether there is extant or extinct life elsewhere the solar system. Implicit in much of this work is that we are looking for microbial or, at best, unintelligent life, even though technological artefacts might be much easier to find. Search for Extraterrestrial Intelligence (SETI) work on searches for alien artefacts in the solar system typically presumes that such artefacts would be of extrasolar origin, even though life is known to have existed in the solar system, on Earth, for eons. But if a prior technological, perhaps spacefaring, species ever arose in the solar system, it might have produced artefacts or other technosignatures that have survived to present day, meaning solar system artefact SETI provides a potential path to resolving astrobiology's question. Here, I discuss the origins and possible locations for technosignatures of such a prior indigenous technological species, which might have arisen on ancient Earth or another body, such as a pre-greenhouse Venus or a wet Mars. In the case of Venus, the arrival of its global greenhouse and potential resurfacing might have erased all evidence of its existence on the Venusian surface. In the case of Earth, erosion and, ultimately, plate tectonics may have erased most such evidence if the species lived Gyr ago. Remaining indigenous technosignatures might be expected to be extremely old, limiting the places they might still be found to beneath the surfaces of Mars and the Moon, or in the outer solar system.
A population of junglerice from Sunflower County, MS, exhibited resistance to fenoxaprop-P-ethyl. An 11-fold difference in ED50 (the effective dose needed to reduce growth by 50%) values was observed when comparing the resistant population (249 g ae ha–1) with susceptible plants (20 g ae ha–1) collected from a different field. The resistant population was controlled by clethodim and sethoxydim at the field rate. Sequencing of the acetyl coenzyme A carboxylase, which encodes the enzyme targeted by fenoxaprop-P-ethyl, did not reveal the presence of any known resistance-conferring point mutations. An enzyme assay confirmed that the acetyl coenzyme A carboxylase in the resistant population is herbicide sensitive. Further investigations with two cytochrome P450 inhibitors, malathion and piperonyl butoxide, and a glutathione-S-transferase inhibitor, 4-chloro-7-nitrobenzofurazan, did not indicate involvement of any metabolic enzymes inhibited by these compounds. The absence of a known target-site point mutation and the sensitivity of the ACCase enzyme to herbicide show that fenoxaprop-P-ethyl resistance in this population is due to a non–target-site mechanism or mechanisms.
Transfer of herbicide resistance among closely related weed species is a
topic of growing concern. A spiny amaranth × Palmer amaranth hybrid was
confirmed resistant to several acetolactate synthase (ALS) inhibitors
including imazethapyr, nicosulfuron, pyrithiobac, and trifloxysulfuron.
Enzyme assays indicated that the ALS enzyme was insensitive to pyrithiobac
and sequencing revealed the presence of a known resistance conferring point
mutation, Trp574Leu. Alignment of the ALS gene for Palmer amaranth, spiny
amaranth, and putative hybrids revealed the presence of Palmer amaranth ALS
sequence in the hybrids rather than spiny amaranth ALS sequences. In
addition, sequence upstream of the ALS in the hybrids matched Palmer
amaranth and not spiny amaranth. The potential for transfer of ALS inhibitor
resistance by hybridization has been demonstrated in the greenhouse and in
field experiments. This is the first report of gene transfer for ALS
inhibitor resistance documented to occur in the field without
artificial/human intervention. These results highlight the need to control
related species in both field and surrounding noncrop areas to avoid
interspecific transfer of resistance genes.
The magnetic activity levels of planet host stars may differ from that of stars not known to host planets in several ways. Hot Jupiters may induce activity in their hosts through magnetic interactions, or through tidal interactions by affecting their host's rotation or convection. Measurements of photospheric, chromospheric, or coronal activity might then be abnormally high or low compared to control stars that do not host hot Jupiters, or might be modulated at the planet's orbital period. Such detections are complicated by the small amplitude of the expected signal, by the fact that the signals may be transient, and by the difficulty of constructing control samples due to exoplanet detection biases and the uncertainty of field star ages. We review these issues, and discuss avenues for future progress in the field.