TIAMMAt: Leveraging Biodiversity to Revise Protein Domain Models, Evidence from Innate Immunity.

Sequence annotation is fundamental for studying the evolution of protein families, particularly when working with nonmodel species. Given the rapid, ever-increasing number of species receiving high-quality genome sequencing, accurate domain modeling that is representative of species diversity is crucial for understanding protein family sequence evolution and their inferred function(s). Here, we describe a bioinformatic tool called Taxon-Informed Adjustment of Markov Model Attributes (TIAMMAt) which revises domain profile hidden Markov models (HMMs) by incorporating homologous domain sequences from underrepresented and nonmodel species. Using innate immunity pathways as a case study, we show that revising profile HMM parameters to directly account for variation in homologs among underrepresented species provides valuable insight into the evolution of protein families. Following adjustment by TIAMMAt, domain profile HMMs exhibit changes in their per-site amino acid state emission probabilities and insertion/deletion probabilities while maintaining the overall structure of the consensus sequence. Our results show that domain revision can heavily impact evolutionary interpretations for some families (i.e., NLR's NACHT domain), whereas impact on other domains (e.g., rel homology domain and interferon regulatory factor domains) is minimal due to high levels of sequence conservation across the sampled phylogenetic depth (i.e., Metazoa). Importantly, TIAMMAt revises target domain models to reflect homologous sequence variation using the taxonomic distribution under consideration by the user. TIAMMAt's flexibility to revise any subset of the Pfam database using a user-defined taxonomic pool will make it a valuable tool for future protein evolution studies, particularly when incorporating (or focusing) on nonmodel species.

Cool your jets: biological jet propulsion in marine invertebrates.

Pulsatile jet propulsion is a common swimming mode used by a diverse array of aquatic taxa from chordates to cnidarians. This mode of locomotion has interested both biologists and engineers for over a century. A central issue to understanding the important features of jet-propelling animals is to determine how the animal interacts with the surrounding fluid. Much of our knowledge of aquatic jet propulsion has come from simple theoretical approximations of both propulsive and resistive forces. Although these models and basic kinematic measurements have contributed greatly, they alone cannot provide the detailed information needed for a comprehensive, mechanistic overview of how jet propulsion functions across multiple taxa, size scales and through development. However, more recently, novel experimental tools such as high-speed 2D and 3D particle image velocimetry have permitted detailed quantification of the fluid dynamics of aquatic jet propulsion. Here, we provide a comparative analysis of a variety of parameters such as efficiency, kinematics and jet parameters, and review how they can aid our understanding of the principles of aquatic jet propulsion. Research on disparate taxa allows comparison of the similarities and differences between them and contributes to a more robust understanding of aquatic jet propulsion.

Time and Organizational Cost for Facilitating Implementation of Primary Care Mental Health Integration.

BACKGROUND: Integrating mental health services into primary care settings is complex and challenging. Although facilitation strategies have successfully supported implementation of primary care mental health integration and other complex innovations, we know little about the time required or its cost. OBJECTIVE: To examine the time and organizational cost of facilitating implementation of primary care mental health integration. DESIGN: Descriptive analysis. PARTICIPANTS: One expert external facilitator and two internal regional facilitators who helped healthcare system stakeholders, e.g., leaders, managers, clinicians, and non-clinical staff, implement primary care mental health integration at eight clinics. INTERVENTION: Implementation facilitation tailored to the needs and resources of the setting and its stakeholders. MAIN MEASURES: We documented facilitators' and stakeholders' time and types of activities using a structured spreadsheet collected from facilitators on a weekly basis. We obtained travel costs and salary information. We conducted descriptive analysis of time data and estimated organizational cost. KEY RESULTS: The external facilitator devoted 263 h (0.09 FTE), including travel, across all 8 clinics over 28 months. Internal facilitator time varied across networks (1792 h versus 1169 h), as well as clinics. Stakeholder participation time was similar across networks (1280.6 versus 1363.4 person hours) but the number of stakeholders varied (133 versus 199 stakeholders). The organizational cost of providing implementation facilitation also varied across networks ($263,490 versus $258,127). Stakeholder participation accounted for 35% of the cost of facilitation activities in one network and 47% of the cost in the other. CONCLUSIONS: Although facilitation can improve implementation of primary care mental health integration, it requires substantial organizational investments that may vary by site and implementation effort. Furthermore, the cost of using an external expert to transfer facilitation skills and build capacity for implementation efforts appears to be minimal.

A measure for assessing the effects of audiovisual speech integration.

We propose a measure of audiovisual speech integration that takes into account accuracy and response times. This measure should prove beneficial for researchers investigating multisensory speech recognition, since it relates to normal-hearing and aging populations. As an example, age-related sensory decline influences both the rate at which one processes information and the ability to utilize cues from different sensory modalities. Our function assesses integration when both auditory and visual information are available, by comparing performance on these audiovisual trials with theoretical predictions for performance under the assumptions of parallel, independent self-terminating processing of single-modality inputs. We provide example data from an audiovisual identification experiment and discuss applications for measuring audiovisual integration skills across the life span.

Systems factorial technology with R.

Systems factorial technology (SFT) comprises a set of powerful nonparametric models and measures, together with a theory-driven experiment methodology termed the double factorial paradigm (DFP), for assessing the cognitive information-processing mechanisms supporting the processing of multiple sources of information in a given task (Townsend and Nozawa, Journal of Mathematical Psychology 39:321-360, 1995). We provide an overview of the model-based measures of SFT, together with a tutorial on designing a DFP experiment to take advantage of all SFT measures in a single experiment. Illustrative examples are given to highlight the breadth of applicability of these techniques across psychology. We further introduce and demonstrate a new package for performing SFT analyses using R for statistical computing.

Making the unbearable, bearable: Qualitative examination of patient, family and nurses' perspectives on the role and value of specialist metastatic breast care nurses.

PURPOSE: To examine the role and value of specialist metastatic breast care nurses in Australia from the perspective of metastatic breast care nurses, patients, and family members. Metastatic breast cancer (mBC) is treatable yet incurable, with distinct supportive care needs, yet many of these needs are unmet. METHOD: Diverse sampling methods were used to recruit 10 people with mBC, 5 family members and 10 metastatic breast care nurses. Semi-structured interviews were conducted online or by telephone during August-December 2020, and analysed thematically. RESULTS: The role of the specialist nurse was strongly valued within and across participant groups, with close alignment regarding what was highly valued. Three themes were identified. First, nurses played a vital role in giving voice and visibility to patients with mBC in a healthcare system in which they often felt invisible. Second, nurses combined their clinical and psychosocial skills with a sense of authentic engagement to create a safe space for those with mBC to discuss their feelings, experiences, and topics, especially those that were unlikely to be discussed in their other social and clinical interactions. Finally, nurses supported patients in living as well as possible while managing symptoms, ongoing treatment, and attendant psychosocial impacts of an incurable and life-limiting condition. CONCLUSIONS: This study underscores the central importance of metastatic breast care nurses in enhancing patient well-being, bridging gaps in care, and offering much-needed support. By addressing patients' emotional, clinical, and social needs, these specialist nurses contribute to a more holistic and compassionate approach to managing mBC.

Impact of Implementation Facilitation on the REACH VET Clinical Program for Veterans at Risk for Suicide.

OBJECTIVE: In 2017, the Veterans Health Administration (VHA) implemented a national suicide prevention program, called Recovery Engagement and Coordination for Health-Veterans Enhanced Treatment (REACH VET), that uses a predictive algorithm to identify, attempt to reach, assess, and care for patients at the highest risk for suicide. The authors aimed to evaluate whether facilitation enhanced implementation of REACH VET at VHA facilities not meeting target completion rates. METHODS: In this hybrid effectiveness-implementation type 2 program evaluation, a quasi-experimental pre-post design was used to assess changes in implementation outcome measures evaluated 6 months before and 6 months after onset of facilitation of REACH VET implementation at 23 VHA facilities. Measures included percentages of patients with documented coordinator and provider acknowledgment of receipt, care evaluation, and outreach attempt. Generalized estimating equations were used to compare differences in REACH VET outcome measures before and after facilitation. Qualitative interviews were conducted with personnel and were explored via template analysis. RESULTS: Time had a significant effect in all outcomes models (p<0.001). An effect of facilitation was significant only for the outcome of attempted outreach. Patients identified by REACH VET had significantly higher odds of having a documented outreach attempt after facilitation of REACH VET implementation, compared with before facilitation. Site personnel felt supported and reported that the external facilitators were helpful and responsive. CONCLUSIONS: Facilitation of REACH VET implementation was associated with an improvement in outreach attempts to veterans identified as being at increased risk for suicide. Outreach is critical for engaging veterans in care.

Functional principal components analysis of workload capacity functions.

Workload capacity, an important concept in many areas of psychology, describes processing efficiency across changes in workload. The capacity coefficient is a function across time that provides a useful measure of this construct. Until now, most analyses of the capacity coefficient have focused on the magnitude of this function, and often only in terms of a qualitative comparison (greater than or less than one). This work explains how a functional extension of principal components analysis can capture the time-extended information of these functional data, using a small number of scalar values chosen to emphasize the variance between participants and conditions. This approach provides many possibilities for a more fine-grained study of differences in workload capacity across tasks and individuals.

Don't be a Square: The processing mechanisms characterising the elemental dimensions of width and height.

What are the geometric and information processing characteristics of elementary figures composed of simple physical dimensions? There have been a number of investigations of perception of rectangles, including debate about configurality (e.g., integrality and gestalt properties) as well as the prime perceptual dimensions. Yet, because of ambiguity even in the "right" definition of configurality and an absence of penetrating methodologies, there is still little known concerning the information processing of these patterns. To this end, the present study brings together two separate theory-driven methodologies, general recognition theory (GRT) and systems factorial technology (SFT). The first attacks the problem of dimensional interactions while the latter seeks to uncover process characteristics such as architecture, decisional stopping rules, and workload capacity. The same observers and as much as possible, the same stimuli were used in both approaches. Through our GRT analyses, we found strong evidence for dependencies between the percepts of height and width on both within-stimulus and cross-stimulus bases. Height perception was better with narrow widths and width perception was superior with short heights. In addition, a significant positive within-trial correlation of dimensions was evidenced within squares but not with rectangles. Our SFT initiative uncovered consistent signatures of parallelism paired with super capacity, the latter appearing both through the traditional conditioning on being correct and still present when modest speed accuracy trade-off was accounted for. Thus, the SFT and GRT inferences were quite compatible with a plausible cause of the positive correlations being across-channel facilitatory interactions which led to super capacity processing.

Characteristics and Context of Veterans Experiencing Serious Suicidal Ideation or Suicide Attempt by Firearm which led to Hospitalization.

OBJECTIVE: Suicide by former United States military service members is of great public health concern, and one area, veterans' suicide attempts involving firearms, is understudied. One group that has a unique perspective on this are veterans with a psychiatric admission following a firearm-related suicide crisis, such as making a suicide plan or a suicide rehearsal with a firearm within the preceding 72 hours. This study seeks to address this gap in the literature by describing the characteristics and context of non-fatal suicide events involving firearms among veterans. METHOD: This convergent parallel mixed-methods design study collected both quantitative and qualitative data from male veterans (N = 15) who were hospitalized due to a suicide attempt or serious ideation using a firearm. Veterans admitted to a Veterans Affairs Medical Center (VAMC) were interviewed and asked to complete a survey. Qualitative data on characteristics and context were analyzed using a thematic analysis. RESULTS: The fifteen male U.S. military veterans described their personal characteristics, such as their beliefs, family beliefs and structure, emotions, and employment status. Most participants were unemployed (n = 10; 67%), divorced (n = 7; 47%) or married (n = 5; 33%). Seven themes related to context emerged from qualitative interviews to include: combat trauma, non-combat trauma and negative life event(s), current and past suicide attempt(s), firearms, substance use, known deaths by suicide, and protective factors for suicide. CONCLUSION: Results suggest that engaging support networks and communities is essential when developing programs to promote identification of early warning signs and implementation of interventions or programs for reducing veteran suicide.

Quantifying the feeding behavior and trophic impact of a widespread oceanic ctenophore.

Oceanic ctenophores are widespread predators on pelagic zooplankton. While data on coastal ctenophores often show strong top-down predatory impacts in their ecosystems, differing morphologies, prey capture mechanisms and behaviors of oceanic species preclude the use of coastal data to draw conclusion on oceanic species. We used high-resolution imaging methods both in situ and in the laboratory to quantify interactions of Ocyropsis spp. with natural copepod prey. We confirmed that Ocyropsis spp. uses muscular lobe contraction and a prehensile mouth to capture prey, which is unique amongst ctenophores. This feeding mechanism results in high overall capture success whether encountering single or multiple prey between the lobes (71 and 81% respectively). However, multiple prey require several attempts for successful capture whereas single prey are often captured on the first attempt. Digestion of adult copepods takes 44 min at 25 °C and does not vary with ctenophore size. At high natural densities, we estimate that Ocyropsis spp. consume up to 40% of the daily copepod standing stock. This suggests that, when numerous, Ocyropsis spp. can exert strong top-down control on oceanic copepod populations. At more common densities, these animals consume only a small proportion of the daily copepod standing stock. However, compared to data from pelagic fishes and oceanic medusae, Ocyropsis spp. appears to be the dominant copepod predator in this habitat.

The Mycobacterium tuberculosis early secreted antigenic target of 6 kDa inhibits T cell interferon-γ production through the p38 mitogen-activated protein kinase pathway.

We reported previously that the early secreted antigenic target of 6 kDa (ESAT-6) from Mycobacterium tuberculosis directly inhibits human T cell IFN-γ production and proliferation in response to stimulation with anti-CD3 and anti-CD28. To determine the mechanism of this effect, we treated T cells with kinase inhibitors before stimulation with ESAT-6. Only the p38 MAPK inhibitor, SB203580, abrogated ESAT-6-mediated inhibition of IFN-γ production in a dose-dependent manner. SB203580 did not reverse ESAT-6-mediated inhibition of IL-17 and IL-10 production, suggesting a specific effect of SB203580 on IFN-γ production. SB203580 did not act through inhibition of AKT (PKB) as an AKT inhibitor did not affect ESAT-6 inhibition of T cell IFN-γ production and proliferation. ESAT-6 did not reduce IFN-γ production by expanding FoxP3(+) T regulatory cells. Incubation of T cells with ESAT-6 induced phosphorylation and increased functional p38 MAPK activity, but not activation of ERK or JNK. Incubation of peripheral blood mononuclear cells with ESAT-6 induced activation of p38 MAPK, and inhibition of p38 MAPK with SB203580 reversed ESAT-6 inhibition of M. tuberculosis-stimulated IFN-γ production by peripheral blood mononuclear cells from subjects with latent tuberculosis infection. Silencing of p38α MAPK with siRNA rendered T cells resistant to ESAT-6 inhibition of IFN-γ production. Taken together, our results demonstrate that ESAT-6 inhibits T cell IFN-γ production in a p38 MAPK-dependent manner.

Diaqua-[(1R,2S,4R,8R,9S,11R)-2,9-di-methyl-1,4,8,11-tetra-aza-cyclo-tetra-decane]nickel(II) dichloride dihydrate.

The crystal structure of the title complex, [Ni(C(12)H(28)N(4))(H(2)O)(2)]Cl(2)·2H(2)O, displays O-H⋯Cl and O-H⋯O hydrogen bonding. The tetra-aza-cyclo-tetra-decane ligand inter-acts with the Ni(II) atom in the cis V configuration and the final two ligand binding sites are occupied by water.

Merging the Psychophysical Function With Response Times for Auditory Detection of One vs. Two Tones.

The purpose of this study is to take preliminary steps to unify psychoacoustic techniques with reaction-time methodologies to address the perceptual mechanisms responsible for the detection of one vs. multiple sounds. We measured auditory redundancy gains for auditory detection of pure tones widely spaced in frequency using the tools of Systems Factorial Technology to evince the system architecture and workload capacity in two different scenarios (SOFT and LOUD). We adopted an experimental design in which the presence or absence of a target at each of two frequencies was combined factorially with two stimulus levels. Replicating previous work, results did not allow an assessment of system architecture due to a failure to observe factor influence at the level of distribution ordering for dual-target stimuli for both SOFT and LOUD scenarios. All subjects demonstrated very modest redundancy gains for the dual-target compared to the single-target stimuli, and results were similar for both LOUD and SOFT. We propose that these results can be predicted by a mental architecture that falls into the class of integrated subadditive parallel systems, using a well-supported assumption that reaction time is driven by loudness. We demonstrate that modeled loudness of the experimental sounds (which ranged between about 0.2 and 14 sones) is highly correlated with mean reaction time (r = -0.87), and we provide a proof-of-concept model based on Steven's Power law that predicts both a failure of distributional ordering for dual-target stimuli and very modest redundancy gains.

Extending systems factorial technology to errored responses.

Systems factorial technology (SFT) is a theoretically derived methodology that allows for strong inferences to be made about underlying processing architectures (e.g., whether processing occurs in a pooled, coactive fashion or in serial or in parallel). Measures of mental architecture using SFT have been restricted to the use of error-free response times (RTs). In this article, through formal proofs and demonstrations, we extended the measure of architecture, the survivor interaction contrast (SIC), to RTs conditioned on whether they are correct or incorrect. We show that so long as an ordering relation (between stimulus conditions of different difficulty) is preserved, we learn that the canonical SIC predictions result when exhaustive processing is necessary and sufficient for a response. We further prove that this ordering relation holds for the popular Wiener diffusion model for both correct and error RTs but fails under some classes of a Poisson counter model, which affords a strong potential experimental test of the latter class versus the others. Our exploration also serves to point to the importance of detailed studies of how errors are made in perceptual and cognitive tasks. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Effects of shifts in response preferences on characteristics of representation and real-time processing: An application to the Hering illusion.

The multidimensional generalization of signal detection theory known as General Recognition Theory (GRT, Ashby & Townsend, Psychological Review, 93, 154-179 1986) has been used to model and characterize the ways in which changes in encoded perceptual information and the application of decisional operators can produce patterns in behavior that are consistent with notions such as configural processing and representation. In particular, a set of studies (e.g., Cornes et al.,, 2011; Wenger & Ingvalson; 2002, 2003) have shown how decisional influences might exert themselves in situations of configural perception, such that effects such as the Thatcher illusion can be obtained by way of shifts in decisional criteria. The present investigation brought to bear the combined tools of GRT and Systems Factorial Technology (SFT, Little et al.,, 2017; Townsend & Nozawa, 1995) with a classical illusion, to show that it is possible to induce a shift in a decisional criterion by way of varying payoffs and that this shift is accompanied by regular changes in the workload capacity statistic. The combined sets of analyses on the same stimuli reveal orderly effects on the decisional criteria (i.e., the signal detection parameter c), report independence (suggesting perceptual independence), invariant measures of sensitivity (i.e., the signal detection parameter [Formula: see text]),and exhaustive parallel processing accompanied by super capacity. We therefore propose wider use of the combined sets of tools, further exploration of the ability of decisional alterations to affect processing times while leaving accuracy largely unscathed, and reaching out to explore more of the information processing mechanisms of classical illusions.

Unmet supportive care needs of people with advanced cancer and their caregivers: A systematic scoping review.

Examining and addressing unmet care needs is integral to improving the provision and quality of cancer services. This review explored the prevalence of unmet supportive care needs, and factors associated with unmet need, in adults with advanced cancers (solid and hematological malignancies) and their caregivers. Electronic databases (PubMed, CINAHL, EMBASE) were searched, producing 85 papers representing 81 included studies. People with advanced cancer reported the highest unmet needs in financial, health system and information, psychological, and physical and daily living domains, whereas caregivers reported the highest unmet needs in psychological, and patient care and support domains. Distress, depression, and anxiety were associated with higher unmet needs across all unmet need domains for people with advanced cancer and their caregivers. Substantial heterogeneity in study populations and methods was observed. Findings from this review can inform targeted strategies and interventions to address these unmet needs in people with advanced cancer.

ESAT-6 inhibits production of IFN-gamma by Mycobacterium tuberculosis-responsive human T cells.

The Mycobacterium tuberculosis early secreted Ag of 6 kDa (ESAT-6) is a potent Ag for human T cells and is a putative vaccine candidate. However, ESAT-6 also contributes to virulence in animal models, mediates cellular cytolysis, and inhibits IL-12 production by mononuclear phagocytes. We evaluated the effects of ESAT-6 and its molecular chaperone, culture filtrate protein of 10 kDa (CFP10), on the capacity of human T cells to produce IFN-gamma and proliferate in response to TCR activation. Recombinant ESAT-6, but not CFP10, markedly inhibited IFN-gamma production by T cells stimulated with M. tuberculosis or with the combination of anti-CD3 and anti-CD28, in a dose-dependent manner. ESAT-6 also inhibited T cell production of IL-17 and TNF-alpha but not IL-2. Preincubation of ESAT-6 with CFP10 under conditions that favor dimer formation did not affect inhibition of IFN-gamma. ESAT-6 decreased IFN-gamma transcription and reduced expression of the transcription factors, ATF-2 and c-Jun, which normally bind to the IFN-gamma proximal promoter and stimulate mRNA expression. ESAT-6 inhibited T cell IFN-gamma secretion through mechanisms that did not involve cellular cytotoxicity or apoptosis. ESAT-6, but not CFP10, bound to T cells and inhibited expression of early activation markers without reducing activation of ZAP70. We conclude that ESAT-6 directly inhibits human T cell responses to mycobacterial Ags by affecting TCR signaling pathways downstream of ZAP70.

Some normative data on lip-reading skills (L).

The ability to obtain reliable phonetic information from a talker's face during speech perception is an important skill. However, lip-reading abilities vary considerably across individuals. There is currently a lack of normative data on lip-reading abilities in young normal-hearing listeners. This letter describes results obtained from a visual-only sentence recognition experiment using CUNY sentences and provides the mean number of words correct and the standard deviation for different sentence lengths. Additionally, the method for calculating T-scores is provided to facilitate the conversion between raw and standardized scores. This metric can be utilized by clinicians and researchers in lip-reading studies. This statistic provides a useful benchmark for determining whether an individual's lip-reading score falls within the normal range, or whether it is above or below this range.

A beginning quantitative taxonomy of cognitive activation systems and application to continuous flow processes.

Much progress has been made in the investigation of perceptual, cognitive, and action mechanisms under the assumption that when one subprocess precedes another, the first one starts and finishes before the other begins. We call such processes "Dondersian" after the Dutch physiologist who first formulated this concept. Serial systems obey this precept (e.g., Townsend, 1974). However, most dynamic systems in nature do not: instead, each subprocess communicates its state to its immediate successors continuously. Although the mathematics for physical systems has received extensive treatment over the last three centuries, applications to human cognition have been exiguous. Therefore, the pioneering papers by Charles Eriksen and colleagues on continuous flow dynamics (e.g., Eriksen & Schulz, Perception & Psychophysics, 25, 249-263, 1979; Coles et al.,, Journal of Experimental Psychology: Human Perception and Performance, 11(5), 529, 1985) must be viewed as truly revolutionary. Surprisingly, there has been almost no advancement on this front since. With the goal of bringing this theme back into the scientific consciousness and extending and deepening our understanding of such systems, we develop a taxonomy that emphasizes the fundamental characteristics of continuous flow dynamics. Subsequently, we complexify the treated systems in such a way as to illustrate the popular cascade model (Ashby, Psychological Review, 89, 599-607, 1982; McClelland, Psychological Review, 86, 287-330, 1979) and use it to simulate the classic findings of Eriksen and colleagues (Eriksen & Hoffman, Perception & Psychophysics, 12(2), 201-204, 1972).