Optimal sample selection applied to information rich, dense data.

Dense data can be classified into superdense information-poor data (type 1 dense data) and dense information-rich data (type 2 dense data). Arbitrary, random, or optimal thinning may be applied to type 1 dense data to minimise computational burden and statistical issues (such as autocorrelation). In contrast, a prospective or retrospective optimal design can be applied to type 2 dense data to maximise information gain from limited resources (capital and/or time). Here we describe a retrospective optimal selection strategy for quantification of unbound drug concentration from a discrete set of plasma samples where the total drug concentration has been measured.

Oral docetaxel plus encequidar - A pharmacokinetic model and evaluation against IV docetaxel.

The development of optimized dosing regimens plays a crucial role in oncology drug development. This study focused on the population pharmacokinetic modelling and simulation of docetaxel, comparing the pharmacokinetic exposure of oral docetaxel plus encequidar (oDox + E) with the standard of care intravenous (IV) docetaxel regimen. The aim was to evaluate the feasibility of oDox + E as a potential alternative to IV docetaxel. The article demonstrates an approach which aligns with the FDA's Project Optimus which aims to improve oncology drug development through model informed drug development (MIDD). The key question answered by this study was whether a feasible regimen of oDox + E existed. The purpose of this question was to provide an early GO / NO-GO decision point to guide drug development and improve development efficiency. METHODS:  A stepwise approach was employed to develop a population pharmacokinetic model for total and unbound docetaxel plasma concentrations after IV docetaxel and oDox + E administration. Simulations were performed from the final model to assess the probability of target attainment (PTA) for different oDox + E dose regimens (including multiple dose regimens) in relation to IV docetaxel using AUC over effective concentration (AUCOEC) metric across a range of effective concentrations (EC). A Go / No-Go framework was defined-the first part of the framework assessed whether a feasible oDox + E regimen existed (i.e., a PTA ≥ 80%), and the second part defined the conditions to proceed with a Go decision. RESULTS:  The overall population pharmacokinetic model consisted of a 3-compartment model with linear elimination, constant bioavailability, constant binding mechanics, and a combined error model. Simulations revealed that single dose oDox + E regimens did not achieve a PTA greater than 80%. However, two- and three-dose regimens at 600 mg achieved PTAs exceeding 80% for certain EC levels. CONCLUSION:  The study demonstrates the benefits of MIDD using oDox + E as a motivating example. A population pharmacokinetic model was developed for the total and unbound concentration in plasma of docetaxel after administration of IV docetaxel and oDox + E. The model was used to simulate oDox + E dose regimens which were compared to the current standard of care IV docetaxel regimen. A GO / NO-GO framework was applied to determine whether oDox + E should progress to the next phase of drug development and whether any conditions should apply. A two or three-dose regimen of oDox + E at 600 mg was able to achieve non-inferior pharmacokinetic exposure to current standard of care IV docetaxel in simulations. A Conditional GO decision was made based on this result and further quantification of the "effective concentration" would improve the ability to optimise the dose regimen.

Personal Beliefs about Illness Questionnaire-Revised (PBIQ-R): Spanish adaptation in a clinical sample with psychotic disorders.

BACKGROUND: The way people with psychosis psychologically adapt and manage the diagnosis of such a mental disorder has been considered a key factor that contributes to the emergence and aggravation of emotional problems. These beliefs about illness can be very important due to their possible association with stigma and its implications in terms of loss of roles and social status. Given the importance of these personal beliefs about the specific diagnosis of psychosis, the Personal Beliefs about Illness Questionnaire (PBIQ) and PBIQ-R have been developed. AIMS: The present study aims to explore the psychometric characteristics of the Spanish version of the PBIQ-R in a sample of patients with a diagnosis of psychosis-related disorders. METHOD: Participants were 155 patients (54.8% male) of the Public Health Service in Andalusia (Spain). Those who consented to participate filled in the PBIQ-R, the Social Comparison Scale, and the PHQ-9 and GAD-7 to measure emotional symptoms. RESULTS: All dimensions showed adequate internal consistency values: Cronbach's alpha extends between .81 and .88; and McDonald's omega ranges between .87 and .92. The temporal reliability for an interval of 3-4 weeks was high. The correlations between the PBIQ-R dimensions and the other variables included in the study were significant and in the expected direction. The factor analysis of the principal components of the PBIQ-R dimensions revealed a single factor in each of the dimensions that explained 64-74%. CONCLUSIONS: The results support the reliability and validity of the Spanish version of the PBIQ-R.

Decreasing hospital burden of COVID-19 during the first wave in Regione Lombardia: an emergency measures context.

BACKGROUND: The aim of this study is to quantify the hospital burden of COVID-19 during the first wave and how it changed over calendar time; to interpret the results in light of the emergency measures introduced to manage the strain on secondary healthcare. METHODS: This is a cohort study of hospitalised confirmed cases of COVID-19 admitted from February-June 2020 and followed up till 17th July 2020, analysed using a mixture multi-state model. All hospital patients with confirmed COVID-19 disease in Regione Lombardia were involved, admitted from February-June 2020, with non-missing hospital of admission and non-missing admission date. RESULTS: The cohort consists of 40,550 patients hospitalised during the first wave. These patients had a median age of 69 (interquartile range 56-80) and were more likely to be men (60%) than women (40%). The hospital-fatality risk, averaged over all pathways through hospital, was 27.5% (95% CI 27.1-28.0%); and steadily decreased from 34.6% (32.5-36.6%) in February to 7.6% (6.3-10.6%) in June. Among surviving patients, median length of stay in hospital was 11.8 (11.6-12.3) days, compared to 8.1 (7.8-8.5) days in non-survivors. Averaged over final outcomes, median length of stay in hospital decreased from 21.4 (20.5-22.8) days in February to 5.2 (4.7-5.8) days in June. CONCLUSIONS: The hospital burden, in terms of both risks of poor outcomes and lengths of stay in hospital, has been demonstrated to have decreased over the months of the first wave, perhaps reflecting improved treatment and management of COVID-19 cases, as well as reduced burden as the first wave waned. The quantified burden allows for planning of hospital beds needed for current and future waves of SARS-CoV-2 i.

Computing the Expected Value of Sample Information Efficiently: Practical Guidance and Recommendations for Four Model-Based Methods.

Value of information (VOI) analyses can help policy makers make informed decisions about whether to conduct and how to design future studies. Historically a computationally expensive method to compute the expected value of sample information (EVSI) restricted the use of VOI to simple decision models and study designs. Recently, 4 EVSI approximation methods have made such analyses more feasible and accessible. Members of the Collaborative Network for Value of Information (ConVOI) compared the inputs, the analyst's expertise and skills, and the software required for the 4 recently developed EVSI approximation methods. Our report provides practical guidance and recommendations to help inform the choice between the 4 efficient EVSI estimation methods. More specifically, this report provides: (1) a step-by-step guide to the methods' use, (2) the expertise and skills required to implement the methods, and (3) method recommendations based on the features of decision-analytic problems.

Measuring adherence in social recovery therapy with people with first episode psychosis.

BACKGROUND: The SUPEREDEN3 study, a phase II randomized controlled trial, suggests that social recovery therapy (SRT) is useful in improving functional outcomes in people with first episode psychosis. SRT incorporates cognitive behavioural therapy (CBT) techniques with case management and employment support, and therefore has a different emphasis to traditional CBT for psychosis, requiring a new adherence tool. AIMS: This paper describes the SRT adherence checklist and content of the therapy delivered in the SUPEREDEN3 trial, outlining the frequency of SRT techniques and proportion of participants who received a full therapy dose. It was hypothesized that behavioural techniques would be used frequently, consistent with the behavioural emphasis of SRT. METHOD: Research therapists completed an adherence checklist after each therapy session, endorsing elements of SRT present. Data from 1236 therapy sessions were reviewed to determine whether participants received full, partial or no therapy dose. RESULTS: Of the 75 participants randomized to receive SRT, 57.3% received a full dose, 24% a partial dose, and 18.7% received no dose. Behavioural techniques were endorsed in 50.5% of sessions, with cognitive techniques endorsed in 34.9% of sessions. CONCLUSIONS: This report describes an adherence checklist which should be used when delivering SRT in both research and clinical practice. As hypothesized, behavioural techniques were a prominent feature of the SRT delivered in SUPEREDEN3, consistent with the behavioural emphasis of the approach. The use of this adherence tool would be considered essential for anyone delivering SRT looking to ensure adherence to the model.

Phylogenetic analyses of transcriptome data resolve familial assignments for genera of the red-algal Acrochaetiales-Palmariales Complex (Nemaliophycidae).

Phylogenetic analyses of transcriptome data for representatives of the red algal Acrochaetiales-Palmariales Complex provided robust support for the assignment of genera to the constituent families. In the Acrochaetiales, the genera Acrochaetium, Grania, and an unnamed genus-level lineage (Acrochaetiac sp._1Aus) were assigned to the Acrochaetiaceae, while Audouinella is placed in a resurrected Audouinellaceae and Rhodochorton and Rhododrewia constitute the resurrected Rhodochortonaceae. For the Palmariales, transcriptome data solidly support the inclusion of Camontagnea and Rhodothamniella in the Rhodothamniellaceae, Meiodiscus and Rubrointrusa in the Meiodiscaceae, Rhodonematella and Rhodophysema in the Rhodophysemataceae, while Devaleraea and Palmaria remained in the Palmariaceae. These analyses, however, questioned the monophyly of Palmaria, which prompted a second round of analyses using eight common red algal phylogenetic markers and including a broader sampling of red algal genera in our analyses. These results supported transfer of Palmaria callophylloides and P. mollis to the genus Devaleraea necessitating new combinations, and further added the genus Halosaccion to the Palmariaceae and the genera Kallymenicola and Rhodophysemopsis to the Meiodiscaceae. Finally, DNA barcode (mitochondrial COI-5P) and ITS data were explored and supported the continued recognition of Palmaria palmata as a single species in the North Atlantic.

Kelp transcriptomes provide robust support for interfamilial relationships and revision of the little known Arthrothamnaceae (Laminariales).

If ever there were "charismatic megaflora" of the sea, the Laminariales (kelp) would undoubtedly meet that designation. From the Northeast Pacific kelp forests to the less diverse, but nonetheless dense, kelp beds ranging from the Arctic to the cold temperate waters of the Southern Hemisphere, kelp provide habitat structure and food for a variety of productive marine systems. Consequently, kelp are well represented in the literature, however, understanding their evolution has proven challenging. We used a 152-gene phylogenomics approach to better resolve the phylogeny of the "derived" kelp families (viz., Agaraceae, Alariaceae, Laminariaceae, and Lessoniaceae). The formerly unresolved Egregia menziesii firmly joined a significantly expanded Arthrothamnaceae including Arthrothamnus, Cymathaere, Ecklonia, Macrocystis, Nereocystis, Pelagophycus, Postelsia, Pseudolessonia, Saccharina, and Streptophyllopsis, which rendered both the Laminariaceae and Lessoniaceae monogeneric. A published eight-gene alignment, the most marker-rich prior to this study, was expanded and analyzed to facilitate inclusion of Aureophycus. Although the topology was unchanged at the family level between the transcriptome data set relative to eight-gene analyses, the superior resolving power of the former was clearly established.

The Role of Th-17 Cells and γδ T-Cells in Modulating the Systemic Inflammatory Response to Severe Burn Injury.

Burns are a global public health problem, accounting for an estimated 265,000 deaths annually. Inflammation is essential in supplying the growth factors, cytokines and chemokines needed to recruit T-cells and myeloid cells to the site of a burn injury for wound healing. However, major burns generate a marked pathophysiological inflammatory response through a widespread release of abundant pro-inflammatory mediators that predispose patients to a systemic inflammatory response syndrome, sepsis and multi-organ failure. Recently, there has been promising investigation into the role of γδ T-cells and Th-17 cells in the regulation and propagation of this inflammatory response. This study reviews the current literature on the post-burn immune response.

An injection and mixing element for delivery and monitoring of inhaled nitric oxide.

BACKGROUND: Inhaled nitric oxide (NO) is a selective pulmonary vasodilator used primarily in the critical care setting for patients concurrently supported by invasive or noninvasive positive pressure ventilation. NO delivery devices interface with ventilator breathing circuits to inject NO in proportion with the flow of air/oxygen through the circuit, in order to maintain a constant, target concentration of inhaled NO. METHODS: In the present article, a NO injection and mixing element is presented. The device borrows from the design of static elements to promote rapid mixing of injected NO-containing gas with breathing circuit gases. Bench experiments are reported to demonstrate the improved mixing afforded by the injection and mixing element, as compared with conventional breathing circuit adapters, for NO injection into breathing circuits. Computational fluid dynamics simulations are also presented to illustrate mixing patterns and nitrogen dioxide production within the element. RESULTS: Over the range of air flow rates and target NO concentrations investigated, mixing length, defined as the downstream distance required for NO concentration to reach within ±5 % of the target concentration, was as high as 47 cm for the conventional breathing circuit adapters, but did not exceed 7.8 cm for the injection and mixing element. CONCLUSION: The injection and mixing element has potential to improve ease of use, compatibility and safety of inhaled NO administration with mechanical ventilators and gas delivery devices.

A Preliminary Test of the Interpersonal Psychological Theory of Suicidal Behavior in Young People With a First Episode of Psychosis.

OBJECTIVES: The interpersonal-psychological theory (IPT) of suicidal behavior suggests that an individual who does not feel they belong and believes they are a burden combined with the capability to attempt suicide is more likely to attempt suicide. The study aimed to investigate this hypothesis in the context of psychosis. METHOD: Young people with a first episode of psychosis (N = 45) who considered suicide, attempted suicide, and had no history of suicide or attempt were compared on self-report measures of suicidal desire, capability for suicide, and substance use. RESULTS: No significant differences were found between groups in terms of suicidal desire or capability. All participants perceived they were a burden, did not feel they belonged, and had the capability for suicide. Poisoning (n = 22) was the most frequently reported method of a suicide attempt. Of those who had attempted suicide, 50% (n = 7) reported that it had been related to a psychotic episode. Of the participants, 30 reported previous suicidal ideation mainly to completely end or stop the distress they were experiencing. Levels of depression were significantly different between groups; moderate levels of depression were reported in the suicidal ideation and attempt groups. CONCLUSION: The concepts of IPT appear to resonate with the experience of psychosis, regardless of suicidality. Specific features of psychosis and their influence on suicidality are worth further exploration.

The Effects of Diesel Exhaust Pollution on Floral Volatiles and the Consequences for Honey Bee Olfaction.

There is growing evidence of a substantial decline in pollinators within Europe and North America, most likely caused by multiple factors such as diseases, poor nutrition, habitat loss, insecticides, and environmental pollution. Diesel exhaust could be a contributing factor to this decline, since we found that diesel exhaust rapidly degrades floral volatiles, which honey bees require for flower recognition. In this study, we exposed eight of the most common floral volatiles to diesel exhaust in order to investigate whether it can affect volatile mediated plant-pollinator interaction. Exposure to diesel exhaust altered the blend of common flower volatiles significantly: myrcene was considerably reduced, ß-ocimene became undetectable, and ß-caryophyllene was transformed into its cis-isomer isocaryophyllene. Proboscis extension response (PER) assays showed that the alterations of the blend reduced the ability of honey bees to recognize it. The chemically reactive nitrogen oxides fraction of diesel exhaust gas was identified as capable of causing degradation of floral volatiles.

Left hemispheric lateral preference and high neuroticism predict disinhibition in two go/no-go experiments.

Although disinhibition is widely implicated in impulse-control-related psychopathologies, debate remains regarding the underlying approach and avoidance processes of this construct. In two studies, we simultaneously tested three competing models in which varying levels of extraversion, neuroticism, and hemispheric lateral preference are associated with disinhibition. In both studies (Study 1, N = 92; Study 2, N = 124), undergraduate students were randomly allocated to one of two versions of the go/no-go task: one where participants were primed through reward to make more "go" responses and another where no such priming occurred. Neuroticism, extraversion, and hemispheric lateral preference measures were also collected. Across both studies, disinhibition was greatest in individuals who reported both a left hemispheric lateral preference and high neuroticism. This pattern was only found for those who were primed through reward to make more "go" responses. There was no association with extraversion. Contrary to previous research, our results suggest that left hemispheric asymmetry and neuroticism and not extraversion drive disinhibited approach, following the establishment of a prepotent approach response set. This has salient implications for the theoretical understanding of disinhibited behavior, as well as for the study of continued maladaptive approach behavior.

Examining the influence of community leaders and other community actors on immunisation practices in Australia: A national cross-sectional study.

BACKGROUND: Variation in COVID-19 vaccination coverage and increasing vaccine hesitancy are well documented, especially amongst ethnic minority populations and current channels of vaccine and communication have been found to be inadequate. It has been suggested that more be done to utilise community-led pathways to improve vaccine readiness in ethnic minority communities in Australia. The study aimed to explore receptiveness towards the role of different actors and methods of communication about immunisation. METHODS: A cross-sectional survey of 1,227 adults in Australia was conducted to examine the roles of various actors in promoting vaccine uptake. Chi-square analyses and independent samples t-tests were used to identify significant associations between sociodemographic characteristics, vaccine practices, and vaccine information-seeking behaviours and (1) COVID-19 vaccine uptake (at least one dose) and (2) speaking a language other than English. RESULTS: At the time of the survey, 93% of respondents had received at least one dose of the COVID-19 vaccine. There were significant associations between COVID-19 vaccine uptake and: perceived capacity to locate accurate and timely vaccine information; receiving the COVID-19 vaccination information from a Nurse or Pharmacist; and receiving a vaccine recommendation by a GP. Additionally, respondents who spoke a language other than English reported were significantly more likely to have received information from family, friends, workplaces, local councils, religious centres, community leaders, and religious leaders than those who only spoke English. CONCLUSION: Significant variations in vaccine practices and vaccine information-seeking behaviours were found, especially in those who speak a language other than English. To enhance vaccine uptake and to address vaccine hesitancy in Australia, vaccine promotion strategies and health communication efforts require significant consideration of information accessibility and communication source preferences.

Use of Novel National Data Sets to Monitor Chemotherapy Use and Outcomes: A Retrospective Cohort Study of Non-Small-Cell Lung Cancer in Aotearoa New Zealand.

PURPOSE: Te Aho o Te Kahu, the New Zealand Cancer Control Agency, is establishing a systemic anticancer therapy (SACT) database (Anti-Cancer Therapy-Nationally Organized Workstream [ACT-NOW]) which can be linked to other national health data collections. In this article, we explore the application of ACT-NOW data in the monitoring of uptake and outcomes after the public funding of pemetrexed in Aotearoa New Zealand. METHODS: We used the ACT-NOW collection to identify patients with advanced nonsquamous non-small-cell lung cancer, who were treated with first-line platinum-based doublet chemotherapy over an 8-year period. Data were extracted for a period of 4 years before and 4 years after the national funding of pemetrexed (November 1, 2017). Treatments were classified as historical platinum doublet (cisplatin or carboplatin with gemcitabine, vinorelbine, paclitaxel, or docetaxel) or platinum pemetrexed doublet (cisplatin or carboplatin with pemetrexed). The primary outcome was the proportion of patients receiving each treatment type, before and after November 1, 2017. To prototype linkage to outcomes data, we evaluated hospitalization and 1-year overall survival (OS) rates by treatment. RESULTS: A total of 331 patients were included from four cancer centers. All patients (116 of 116) who were treated with first-line platinum-based doublet chemotherapy between November 2013 and November 2017 received historical platinum doublet chemotherapy. After the introduction of pemetrexed, between November 2017 and November 2021, 94% (203 of 215) were treated with platinum pemetrexed doublet chemotherapy and 6% (12 of 215) with historical platinum doublet chemotherapy. Linkage to outcomes data for 1-year OS, hospitalization rates, and lengths of stay outcome data were achievable. CONCLUSION: The ACT-NOW data set has the potential to facilitate evaluation of the impact of national-level SACT funding decisions on prescribing practice and specific patient outcomes. Our results support the use of these data to inform resource planning and quality improvement.

The contribution of shame to post-psychotic trauma.

OBJECTIVES: The current study examined shame in a clinical sample recovering from a first episode of psychosis by focusing on the contribution of different types of shame to post-psychotic trauma while controlling for current affective symptoms. DESIGN: The study used a cross-sectional correlational design. METHOD: Fifty individuals who met the criteria for a psychotic disorder whose acute psychotic symptoms were in remission completed measures of internal and external shame associated with psychosis, general shame, post-psychotic trauma, and depression. RESULTS: Post-psychotic trauma symptoms were correlated with internal and external shame associated with psychosis and general shame. However, the relation between post-psychotic trauma and external shame associated with psychosis remained after controlling for general shame and current affective symptoms. In addition, internal shame had a stronger association with depression. Thus, internal and external shame due to psychosis had different associations with different types of post-psychotic emotional dysfunction. CONCLUSIONS: The results support the importance of assessing shame as a multi-faceted construct and suggest that assessing shame directly associated with mental illness is a worthwhile endeavour.

hybpiper-nf and paragone-nf: Containerization and additional options for target capture assembly and paralog resolution.

Premise: The HybPiper pipeline has become one of the most widely used tools for the assembly of target capture data for phylogenomic analysis. After the production of locus sequences and before phylogenetic analysis, the identification of paralogs is a critical step for ensuring the accurate inference of evolutionary relationships. Algorithmic approaches using gene tree topologies for the inference of ortholog groups are computationally efficient and broadly applicable to non-model organisms, especially in the absence of a known species tree. Methods and Results: We containerized and expanded the functionality of both HybPiper and a pipeline for the inference of ortholog groups, providing novel options for the treatment of target capture sequence data, and allowing seamless use of the outputs of the former as inputs for the latter. The Singularity container presented here includes all dependencies, and the corresponding pipelines (hybpiper-nf and paragone-nf, respectively) are implemented via two Nextflow scripts for easier deployment and to vastly reduce the number of commands required for their use. Conclusions: The hybpiper-nf and paragone-nf pipelines are easily installed and provide a user-friendly experience and robust results to the phylogenetic community. They are used by the Australian Angiosperm Tree of Life project. The pipelines are available at https://github.com/chrisjackson-pellicle/hybpiper-nf and https://github.com/chrisjackson-pellicle/paragone-nf.

The effects of leadership levels and gender on leader well-being.

Previous research examining differences in levels of well-being between leaders and nonleaders has yielded mixed results. To explain the inconsistencies, we compare levels of well-being among nonleaders, mid-level leaders, and high-level leaders. Drawing from the job demands-resources model (Bakker & Demerouti, 2007, 2017) and the expanded version proposed by Crawford et al. (2010), we anticipate mid-level leaders will have lower levels of well-being compared to senior leaders and nonleaders, and females will be more vulnerable than males in mid-level leadership. In Study 1, we use multilevel models and propensity score matching (N = 24,067) and find mid-level leaders have worse general health conditions compared to nonleaders and high-level leaders, and that this effect is more pronounced among females. In Study 2, we collect experience sampling data from workers (N = 86; 1,634 observations) who completed a short survey four times daily for five consecutive working days. Mid-level leaders report more end-of-day negative emotions than high-level leaders and nonleaders, mediated by higher job demands and lower levels of job control to combat the negative effects of job demands; an effect that is particularly pronounced among female respondents. In Study 3, we use a two-wave time-lagged survey study (N = 330) and find middle managers have more challenge and hindrance job demands than nonleaders, and insufficient job control to offset the negative effects of job demands. Female middle managers report the most physical health symptoms and enjoy less eudaemonic well-being than their male counterparts. We conclude that leadership levels and gender have important and overlooked impacts on well-being. (PsycInfo Database Record (c) 2023 APA, all rights reserved).