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Background The 6-minute walk test is a widely used measure of physical function in healthy people and patients with chronic conditions. Few reports have compared 6-minute walk distance (6MWD) across different conditions, and limited knowledge is available about how common covariates [age, sex, body mass index (BMI)] differentially affect 6MWD. Our purposes were to examine the 6MWD in persons with chronic conditions, compare walk distances with healthy controls, and identify predictors of 6MWD. Methods Data were aggregated from previous studies. Participants with primary diagnoses of heart failure (HF), chronic obstructive pulmonary disease (COPD), type 2 diabetes, chronic kidney disease, and peripheral artery disease (PAD) were included. Univariate and multivariate general linear models were used to estimate the impact of each condition on the 6MWD. Results The sample included 429 adults (48% female) aged 63 ± 9 years. Participants with HF, COPD, and PAD walked shorter distances than healthy controls (all P < 0.01). Predictors differed by group. In the HF group, age, Black race, and male sex negatively affected 6MWD. In the type 2 diabetes group, older age and high BMI were associated with shorter distances walked. In the chronic kidney disease group, higher BMI, Black race, and male sex negatively impacted 6MWD. No covariates were associated with 6MWD in the PAD, COPD, or control groups. Conclusion We found wide variation in common, nondisease-specific predictors of the 6MWD and significantly lower 6MWDs compared with healthy controls. Our findings add to our knowledge of 6MWD among aging adults with common chronic diseases.

Higher scrutiny is befalling public payors regarding drug costs and patient access to medications. These issues exist in a complex contractual environment where minimal oversight of pharmacy claim adjudication and reimbursement practices can occur. The complexity of prescription benefits, and the lack of defined expectations or accountability in the system contribute to a sense of frustration by the public. Key areas of improvement for this sector of the health care industry include legislative and regulatory shifts requiring ongoing analyses, reporting, and accountability of pharmacy benefit managers (PBMs) in order to improve payment transparency. These improvements will enable plans to eliminate misaligned incentives in the industry and drive value. Changes in public sector programs should be comprehensive in their approach so that the policy will result in a reduction in costs, enhanced patient access, better patient safety, and improved health outcomes.

Although there has been a recent increase of research investment in Human Autonomy Teams (HATs), many significant technical challenges and research gaps persist. Specifically, recent reports indicate the need for shared situational awareness within HATs. Shared situational awareness is a necessary precursor for essential team mechanisms, such as communication, coordination, cooperation, cohesion, and trust. Various modeling techniques have approached agent situational/shared awareness; however, these approaches have been limited to simulation environments. In order to achieve HATs in real-world contexts, agents will need to leverage autonomous perception (e.g., vision, audition, and task knowledge) to gain situational awareness of their environment and teammates. In this paper, we discuss approaches toward agent shared situational awareness, challenges/limitations, and review our efforts toward developing shared situational awareness within our Vision Inference Action (VIA) model and ideas for future research.

Background Women veterans experience higher levels of stress-related symptoms than their civilian counterparts. Psychological stress is associated with greater inflammation and may increase risk for cardiovascular disease (CVD). Mindfulness-based stress reduction (MBSR) has been found to improve psychological well-being in other populations but no randomized controlled trials (RCT) have been conducted examining the impact of MBSR on well-being and inflammation in women veterans at risk for CVD. Objective Determine the effectiveness of MBSR in improving psychological well-being, cortisol, and inflammation associated with CVD in women veterans. Design The design is a RCT comparing MBSR to an active control condition (ACC) consisting of a health education program. Participants Women veterans (N=164) with risk factors for CVD from the Chicagoland area participated in the study. Intervention An 8-week MBSR program with weekly 2.5-h classes was compared to an ACC consisting of an 8-week health promotion education program with weekly 2.5-h classes. Main Measures The outcomes were psychological well-being [perceived stress, depressive symptoms, loneliness, and post-traumatic stress disorder (PTSD)] symptoms and stress-related markers, including diurnal salivary cortisol and cytokines interleukin-6 (IL-6) and interferon gamma (IFN-γ). Data were collected at baseline, 4 weeks (mid-point of intervention), 8 weeks (completion of intervention), and 6 months after completion of MBSR or ACC. Key Results Compared to the ACC, women who participated in MBSR reported less perceived stress, loneliness, and symptoms of PTSD. Although there were no significant differences between groups or changes over time in IL-6 or IFN-γ, participants in the MBSR program demonstrated a more rapid decline in diurnal salivary cortisol as compared to those in the ACC. Conclusions MBSR was found to improve psychological well-being and decrease diurnal salivary cortisol in women veterans at risk for CVD. Health care providers may consider MBSR for women veterans as a means by which to improve their psychological well-being.

This paper finds strong support for a Phillips curve that becomes nonlinear when inflation is “low”—which our baseline model defines as less than 3 percent. The nonlinear curve is steep when output is above potential (slack is negative) but flat when output is below potential (slack is positive) so that further increases in economic slack have little effect on inflation. This finding is consistent with evidence of downward nominal wage and price rigidity. When inflation is high, the Phillips curve is linear and relatively steep. These results are robust to placing the threshold between the high and low inflation regimes at 2, 3, or 4 percent inflation or for a threshold based on country-specific medians of inflation. In this nonlinear model, international factors play a large role in explaining headline inflation (albeit less so for core inflation), a role that has been increasing since the global financial crisis. These results provide evidence of channels which could boost inflation in the future, even if they were dormant before the Covid pandemic.

Easy read summary■The Power Threat Meaning Framework was written to help make sense of distress in terms of people’s experiences. It asks ‘what has happened to you?’, NOT ‘what is wrong with you?’■The Power Threat Meaning Framework could be useful for people working with people with learning disabilities and autism■We describe how we have adapted the Power Threat Meaning Framework for use in learning disability services.■More resources need to be developed with people who use these servicesThe Power Threat Meaning Framework (PTMF) was launched by the British Psychological Society in 2018 to offer an alternative classification system to pseudo-scientific practises of psychiatric diagnosis that regard certain ways of thinking, feeling and behaving as ‘symptoms’ of unevidenced ‘mental disorders’. In this article, we summarise what appealed to us about the PTMF and we describe some of the work we have undertaken to highlight how the Framework can be applied to support understanding of the experiences of people with diagnoses of intellectual disability in ways that centre attention to the negative operations of power on peoples’ lives.

Evidence-based management (EBM) is an increasingly advocated yet rarely adopted framework to assist in making organizational decisions. We investigate how cognitive reflection – the ability or disposition to question an intuitive response and rely instead on a more analytical process—influences decision-making accuracy in the context of EBM. Across three experimental studies (N = 332, 166 and 99), we determine the effects of using actively sought and passively sought evidence, in boundary conditions of cognitive and emotional load. Results of study 1 show that cognitive reflection is generally associated with higher decision-making accuracy, particularly in passive pathways to EBM, and when exposed to low cognitive load. Results of studies 2 and 3 support that passive pathways to EBM will result in higher accuracy, and that negative emotion inducing stimuli can strengthen the effect of cognitive reflection on evidence collection. The findings demonstrate that a contingency approach to EBM is critical, with the impact of cognitive reflection differing for situational constraints and for actively and passively sought evidence.

Platyhelminthes (flatworms) are a diverse invertebrate phylum useful for exploring life-history evolution. Within Platyhelminthes, only two clades develop through a larval stage: free-living polyclads and parasitic neodermatans. Neodermatan larvae are considered evolutionarily derived, whereas polyclad larvae are hypothesized to be ancestral due to ciliary band similarities among polyclad and other spiralian larvae. However, larval evolution has been challenging to investigate within polyclads due to low support for deeper phylogenetic relationships. To investigate polyclad life-history evolution, we generated transcriptomic data for 21 species of polyclads to build a well-supported phylogeny for the group. The resulting tree provides strong support for deeper nodes, and we recover a new monophyletic clade of early branching cotyleans. We then used ancestral state reconstructions to investigate ancestral modes of development within Polycladida and more broadly within flatworms. In polyclads, we were unable to reconstruct the ancestral state of deeper nodes with significant support because early branching clades show diverse modes of development. This suggests a complex history of larval evolution in polyclads that likely includes multiple losses and/or multiple gains. However, our ancestral state reconstruction across a previously published platyhelminth phylogeny supports a direct developing prorhynchid/polyclad ancestor, which suggests that a larval stage in the life cycle evolved along the polyclad stem lineage or within polyclads.

Uncertainty exogenous to organizations is pervasive, and yet espoused to have a negative impact on employee well-being. This chapter explores whether organizational ambidexterity might help mitigate the influence of exogenous uncertainty on employee well-being. Specifically, the job demands-resources theory is utilized to unpack how ambidexterity may be viewed as a “resource” to mitigate and/or potentially even a “demand” that exacerbates the negative impact of exogenous uncertainty on employee well-being. These rival hypotheses are explored in a field study (N = 540), and then an experiment (N = 160). The consistent finding was that exogenous uncertainty was experienced as a demand that exacerbates the negative effect of uncertainty on well-being. Thus it is revealed that organizational ambidexterity has the unanticipated consequence of amplifying a negative relationship between exogenous uncertainty and employee well-being, adding to the burden employees feel in coping with the unknown. Implications for managing exogenous uncertainty for employees’ well-being are unpacked, and future research is advocated. This ranges from organizational-level strategies with how organizational systems are embedded, at the individual level with employees’ taking agency, and taking into account the individual differences that predispose individuals to react differently.

IntroductionBotrynema, a genus of medusozoans in the trachyline family Halicreatidae, currently contains two species: B. brucei and B. ellinorae, distinguished by the presence or absence, respectively, of an apical knob as a diagnostic character. However, no study has corroborated if these taxonomic diagnoses have a biological and evolutionary basis. Therefore, in this study we attempted to address the question “do the two nominal species in the genus Botrynema represent independent phylogenetic lineages, or two phenotypic variants of a single species?MethodsIn this study we took advantage of legacy collections from different research expeditions across the globe from 2000 to 2021 to study the phylogenetics and taxonomy of the genus Botrynema.ResultsB. brucei and B. ellinorae present partially overlapping vertical distributions in the Arctic and as a whole in the Arctic the genus seems to be limited to the Atlantic water masses. The phylogenetic reconstruction based on the concatenated alignment corroborates the validity of the family Halicreatidae and of genus Botrynema as monophyletic groups. However no clear differentiation was found between the two presently accepted species, B. ellinorae and B. brucei.DiscussionBased on the evidence we gathered, we conclude that while the genus Botrynema does contain at least two species lineages, these lineages are not concordant with current species definitions. The species B. ellinorae is reassigned as a subspecies of B. brucei and diagnostic characters are provided.

Metal-free C–H insertion via flow photolysis of aryldiazoacetates 3–5 with increased reaction efficiency in the presence of 4,4′-dimethoxybenzophenone.

Hydrological impacts of climate change are prompting water resource and flood hazard management to adapt to non-stationary conditions. Among the factors influencing these policy decisions is the qu...

Purpose To assess the effect of a 12 week resistance or aerobic training intervention on markers of cardio-metabolic function and sleep among male rotational shift workers. Method Thirty-eight sedentary, apparently healthy, male rotational shift workers were recruited and randomly allocated to a non-exercise control (CON) group, 3 sessions/week of moderate intensity continuous (MICT), or resistance training (RT) for 12 weeks in a semi-supervised setting. Pre- and post-testing assessed markers of cardio-metabolic function including peak oxygen uptake (VO2peak), glucose metabolism, insulin sensitivity, body composition, inflammatory markers, and 14 day actigraphy sleep assessment. Results Mean session attendance across the intervention was 25 (± 7) of a possible 36 sessions. A significant group by time interaction was observed for MICT, with lower c-reactive protein (CRP) values observed post-training (P = 0.049). A significant effect for time was observed for both MICT (n = 9; P = 0.04) and RT (n = 10; P = 0.021), increasing total sleep time (TST) following a night shift post-intervention. Data redistribution regarding exercise adherence: < 24 (N-ADHERE) or ≥ 24 (ADHERE) resulted in significant pre-to-post reduction in body fat (P = 0.024) and fat mass percentage (P = 0.014) among ADHERE. No differences were observed for any intervention group on insulin sensitivity, glucose metabolism or oxygen uptake. Conclusion The results of the current study support exercise as a valid intervention to improve the cardio-metabolic health of rotational shift workers. Average sessional attendance suggests shift workers face barriers to exercise that may need to be addressed to improve health outcomes.

Biological applications of phosphorescent probes for sensing molecular oxygen (O

The aim of this study was to develop and externally validate a score for use in dental settings to identify those at risk of undiagnosed nondiabetic hyperglycemia (NDH) or type 2 diabetes (T2D). The Studies of Health in Pomerania (SHIP) project comprises 2 representative population-based cohort studies conducted in northeast Germany. SHIP-TREND-0, 2008 to 2012 (the development data set) had 3,339 eligible participants, with 329 having undiagnosed NDH or T2D. Missing data were replaced using multiple imputation. Potential covariates were selected for inclusion in the model using backward elimination. Heuristic shrinkage was used to reduce overfitting, and the final model was adjusted for optimism. We report the full model and a simplified paper-based point-score system. External validation of the model and score employed an independent data set comprising 2,359 participants with 357 events. Predictive performance, discrimination, calibration, and clinical utility were assessed. The final model included age, sex, body mass index, smoking status, first-degree relative with diabetes, presence of a dental prosthesis, presence of mobile teeth, history of periodontal treatment, and probing pocket depths ≥5 mm as well as prespecified interaction terms. In SHIP-TREND-0, the model area under the curve (AUC) was 0.72 (95% confidence interval [CI] 0.69, 0.75), calibration in the large was −0.025. The point score AUC was 0.69 (95% CI 0.65, 0.72), with sensitivity of 77.0 (95% CI 76.8, 77.2), specificity of 51.5 (95% CI 51.4, 51.7), negative predictive value of 94.5 (95% CI 94.5, 94.6), and positive predictive value of 17.0 (95% CI 17.0, 17.1). External validation of the point score gave an AUC of 0.69 (95% CI 0.66, 0.71), sensitivity of 79.2 (95% CI 79.0, 79.4), specificity of 49.9 (95% CI 49.8, 50.00), negative predictive value 91.5 (95% CI 91.5, 91.6), and positive predictive value of 25.9 (95% CI 25.8, 26.0). A validated prediction model involving dental variables can identify NDH or undiagnosed T2DM. Further studies are required to validate the model for different European populations.

Cnidarians are critical members of aquatic communities and have been an experimental system for a diversity of research areas ranging from development to biomechanics to global change biology. Yet we still lack a well-resolved, taxonomically balanced, cnidarian tree of life to place this research in appropriate phylogenetic context. To move towards this goal, we combined data from 26 new anthozoan transcriptomes with 86 previously published cnidarian and outgroup datasets to generate two 748-locus alignments containing 123,051 (trimmed) and 449,935 (untrimmed) amino acids. We estimated maximum likelihood phylogenies for both matrices under partitioned and unpartitioned site-homogeneous and site-heterogenous models of substitution. We used the resulting topology to constrain a phylogenetic analysis of 1,814 small subunit ribosomal (18S) gene sequences from GenBank. Our results confirm the position of Ceriantharia (tube-dwelling anemones), a historically recalcitrant group, as sister to the rest of Hexacorallia across all phylogenies regardless of data matrix or model choice. We also find unanimous support for the sister relationship of Endocnidozoa and Medusozoa and propose the name Operculozoa for the clade uniting these taxa. Our 18S hybrid phylogeny provides insight into relationships of 15% of extant taxa. Together these data are an invaluable resource for comparative cnidarian research and provide perspective to guide future refinement of cnidarian systematics.

SIGNIFICANCE: This paper serves as a reply to the Commentary by Brown and Gibbons (S Afr J Sci. 2022;118(9/10), Art. #12590) on our recently published paper on systematics of the moon jellyfish genus Aurelia (Lawley et al. PeerJ 2021;9, e11954)). We emphasise that we are not advocating for the routine use of molecular data alone in taxonomic diagnoses, rather that it is a valid approach in cases where, after detailed analyses, morphological features are shown to be unreliable

Observations of changes in phenology have provided some of the strongest signals of the effects of climate change on terrestrial ecosystems. The International Tundra Experiment (ITEX), initiated in the early 1990s, established a common protocol to measure plant phenology in tundra study areas across the globe. Today, this valuable collection of phenology measurements depicts the responses of plants at the colder extremes of our planet to experimental and ambient changes in temperature over the past decades. The database contains 150,434 phenology observations of 278 plant species taken at 28 study areas for periods of 1 to 26 years. Here we describe the full dataset to increase the visibility and use of these data in global analyses, and to invite phenology data contributions from underrepresented tundra locations. Portions of this tundra phenology database have been used in three recent syntheses, some datasets are expanded, others are from entirely new study areas, and the entirety of these data are now available at the Polar Data Catalogue., Arctic Science, 8 (3), ISSN:2368-7460

Background Fatigability has recently emerged in oncology as a concept that anchors patients’ perceptions of fatigue to defined activities of specified duration and intensity. This study aimed to examine the psychometric properties of the Korean version of the Pittsburgh Fatigability Scale (K-PFS) for women with breast cancer. Methods This cross-sectional study involved 196 women with breast cancer recruited from a tertiary hospital in Seoul, Korea. Reliability was evaluated using Cronbach’s alpha, and confirmatory factor analysis was conducted to examine the factor structure of the K-PFS. Four goodness-of-fit values were evaluated: (1) the comparative fit index (CFI), (2) the Tucker–Lewis index (TLI), (3) the root mean square error of approximation (RMSEA), and (4) the standardized root mean square residual (SRMR). Results Of the 196 survivors, 71.1% had greater physical fatigability (K-PFS Physical score ≥ 15) and 52.6% had greater mental fatigability (K-PFS Mental score ≥ 13). The Cronbach’s alpha coefficient for the total K-PFS scale was 0.926, and the coefficients for the physical and mental fatigability domains were 0.870 and 0.864, respectively. In the confirmatory factor analysis for physical fatigability, the SRMR value (0.076) supported goodness of fit, but other model fit statistics did not (CFI = 0.888, TLI = 0.826, and RMSEA = 0.224). For mental fatigability, although three goodness-of-fit values were acceptable (CFI = 0.948, TLI = 0.919, and SRMR = 0.057), the RMSEA value (0.149) did not indicate good model fit. However, each item coefficient was statistically significant (> 0.5), and the K-PFS was therefore found to be valid from a theoretical perspective. Conclusion This study provides meaningful information on the reliability and validity of the K-PFS instrument, which was developed to meet an important need in the context of breast cancer survivors. Additional research should examine its test–retest reliability and construct validity with performance measures.

Older adults with preclinical cognitive impairment can have chronic conditions and lifestyle factors that influence health. Sedentary behavior is common in older adults with and without chronic kidney disease (CKD). The objective of the current study was to determine the differences in sedentary behavior for older adults with preclinical cognitive impairment with and without CKD. Our study evaluated 48 older adults with preclinical cognitive impairment with and without CKD who underwent assessment of sedentary behavior via accelerometry. We found that older adults with preclinical cognitive impairment with and without CKD were sedentary, but there were no significant differences between groups. Fragmentation index was different ( p < 0.05), with a lower fragmentation index found in those with CKD. Sedentary behavior should be assessed and evaluated as a potential target for interventions to improve health in these at-risk older adults; however, further investigation is needed. [ Journal of Gerontological Nursing, 47 (6), 35–42.]

Single-molecule measurements of protein dynamics help unveil the complex conformational changes and transitions that occur during ligand binding and catalytic processes. Using high-resolution single-molecule nanocircuit techniques, we have investigated differences in the conformational dynamics and transitions of lysozyme interacting with three ligands: peptidoglycan substrate, substrate-based chitin analogue, and indole derivative inhibitors. While processing peptidoglycan, lysozyme followed one of the two mechanistic pathways for the hydrolysis of the glycosidic bonds: a concerted mechanism inducing direct conformational changes from open to fully closed conformations or a nonconcerted mechanism involving transient pauses in intermediate conformations between the open and closed conformations. In the presence of either chitin or an indole inhibitor, lysozyme was unable to access the fully closed conformation where catalysis occurs. Instead, lysozymes' conformational closures terminated at slightly closed, "excited" conformations that were approximately one-quarter of the full hinge-bending range. With the indole inhibitor, lysozyme reached this excited conformation in a single step without any evidence of rate-liming intermediates, but the same conformational motions with chitin involved three hidden, intermediate processes and features similar to the nonconcerted peptidoglycan mechanism. The similarities suggest that these hidden processes involve attempts to accommodate imperfectly aligned polysaccharides in the active site. The results provide a detailed glimpse of the enzyme-ligand interplay at the crux of molecular recognition, enzyme specificity, and catalysis.

Simple and fast methods for the detection of target genes with single-nucleotide specificity could open up genetic research and diagnostics beyond laboratory settings. We recently reported a biosensor for the electronic detection of unamplified target genes using liquid-gated graphene field-effect transistors employing an RNA-guided catalytically deactivated CRISPR-associated protein 9 (Cas9) anchored to a graphene monolayer. Here, using unamplified genomic samples from patients and by measuring multiple types of electrical response, we show that the biosensors can discriminate within one hour between wild-type and homozygous mutant alleles differing by a single nucleotide. We also show that biosensors using a guide RNA-Cas9 orthologue complex targeting genes within the protospacer-adjacent motif discriminated between homozygous and heterozygous DNA samples from patients with sickle cell disease, and that the biosensors can also be used to rapidly screen for guide RNA-Cas9 complexes that maximize gene-targeting efficiency.

Introduction The emergence of the novel coronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and the coronavirus disease COVID-19 has impacted enormously on non-COVID-19-related hospital care. Curtailment of intensive care unit (ICU) access threatens complex surgery, particularly impacting on outcomes for time-sensitive cancer surgery. Oesophageal cancer surgery is a good example. This study explored the impact of the pandemic on process and short-term surgical outcomes, comparing the first wave of the pandemic from April to June in 2020 with the same period in 2019. Methods Data from all four Irish oesophageal cancer centres were reviewed. All patients undergoing resection for oesophageal malignancy from 1 April to 30 June inclusive in 2020 and 2019 were included. Patient, disease, and peri-operative outcomes (including COVID-19 infection) were compared. Results In 2020, 45 patients underwent oesophagectomy, and 53 in the equivalent period in 2019. There were no differences in patient demographics, co-morbidities, or use of neoadjuvant therapy. The median time to surgery from neoadjuvant therapy was 8 weeks in both 2020 and 2019. There were no significant differences in operative interventions between the two time periods. There was no difference in operative morbidity in 2020 and 2019 (28% vs 40%, p = 0.28). There was no in-hospital mortality in either period. No patient contracted COVID-19 in the perioperative period. Conclusions Continuing surgical resection for oesophageal cancer was feasible and safe during the COVID-19 pandemic in Ireland. The national response to this threat was therefore successful by these criteria in the curative management of oesophageal cancer.

Ultrasonographic intestinal muscularis thickening has not been described as an imaging feature of canine inflammatory bowel disease. In this retrospective case series, patients were identified by searching sonographic reports for "muscularis" and/or "muscular layer." Patients were included if small intestinal muscularis thickening was reported, and sonographic images and histopathological samples of the small intestine were available for review. Cases with small intestines nodules, masses, or complete loss of wall layering were excluded. Sonographic images were retrospectively evaluated for jejunal muscularis layer thickness, and ratios of intestinal layer measurements were performed. Histological samples were retrospectively reviewed. Thirteen dogs met inclusion criteria: all dogs had sonographic intestinal muscularis thickening relative to the submucosa (1.0, range of 1.3-2.5), and most dogs had muscular layer thickness above normal published ranges (11/13; all 13/13 above the weight-specific mean). More than half of the patients had overall normal wall thickness (11/13) and several had normal mucosal echogenicity (6/13). Therefore, in some dogs, the only sonographic abnormality in the small intestine was muscularis thickening. No dogs had lymphadenomegaly. Endoscopic partial-thickness (n = 11, duodenum and/or ileum) or surgical full-thickness (n = 2) samples confirmed inflammatory bowel disease. Direct comparison between jejunum sonographic characteristics and histology features was limited due to both partial thickness biopsies and lack of direct comparison between anatomical locations of ultrasonographic assessment and biopsy site. However, no cases that met the inclusion criteria had normal small intestinal histology. Comparable to cats, dogs with ultrasonographic intestinal muscularis thickening may have inflammatory bowel disease, and further workup for enteropathy is indicated.

Platyhelminthes (flatworms) are a diverse invertebrate phylum that are useful for exploring life history evolution. Within Platyhelminthes, only two clades develop through a larval stage: free-living polyclads and parasitic neodermatans. Neodermatan larvae are considered evolutionarily derived, whereas polyclad larvae are hypothesized to be retained from the last common ancestor of Platyhelminthes – and Spiralia – due to ciliary band similarities among polyclad and other spiralian larvae. However, larval evolution has been challenging to investigate within polyclads due to low support for deeper phylogenetic relationships. To investigate polyclad life history evolution, we generated transcriptomic data for 21 species of polyclads to build a well-supported phylogeny for the group. We then used ancestral state reconstruction to investigate ancestral modes of development (direct vs indirect) within Polycladida, and flatworms in general. The resulting tree provides strong support for deeper nodes and we recover a new monophyletic clade of early branching cotyleans. Early branching clades of acotyleans and cotyleans possess diverse modes of development, suggesting a complex history of larval evolution in polyclads that likely includes multiple losses and/or multiple gains. Our ancestral state reconstructions in a previous platyhelminth phylogeny also suggests that similarities in larval morphology between flatworms and other phyla may have re-emerged secondarily or are convergently evolved.

Novel ring-disubstituted tert-butyl phenylcyanoacrylates, RPhCH=C(CN)CO2C(CH3)3, where R is 3-bromo-4-methoxy, 5-bromo-2-methoxy, 2-chloro-3-methoxy, 2-fluoro-4-methoxy, 2-fluoro-6-methoxy, 3-fluoro-4-methoxy, 5-fluoro-2-methoxy, 3-iodo-4-methoxy, 5-iodo-2-methoxy were prepared and copolymerized with styrene. The acrylates were synthesized by the piperidine catalyzed Knoevenagel condensation of ring-substituted benzaldehydes and tret-butyl cyanoacetate, and characterized by CHN analysis, IR, 1H and 13C NMR. All the acrylates were copolymerized with styrene in solution with radical initiation at 70C. The compositions of the copolymers were calculated from nitrogen analysis.

Neurological conditions like neurodevelopmental disorders and neurodegenerative diseases are quite complex and often exceedingly difficult for patients. Most of these conditions are due to a mutation in a critical gene. There is no cure for the majority of these neurological conditions and the availability of disease-modifying therapeutics is quite rare. The lion’s share of the treatments that are available only provide symptomatic relief, as such, we are in desperate need of an effective therapeutic strategy for these conditions. Considering the current drug development landscape, gene therapy is giving us hope as one such effective therapeutic strategy. Consistent efforts have been made to develop gene therapy strategies using viral and non-viral vectors of gene delivery. Here, we have discussed both of these delivery methods and their properties. We have summarized the relative advantages and drawbacks of viral and non-viral vectors from the perspectives of safety, efficiency, and productivity. Recent developments such as clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-mediated gene editing and its use in vivo have been described here as well. Given recent advancements, gene therapy shows great promise to emerge as a next-generation therapeutic for many of the neurodevelopmental and neurodegenerative conditions.

In this work, staurozoans of two distinct morphotypes are reported in Kitsunezaki (Ishinomaki City, Miyagi, Japan) in the years following the Great East Japan Earthquake and Tsunami. Staurozoa specimens were collected from Eisenia and Gelidium macroalgal beds at the Kitsunezaki survey site (October 2019–July 2021). Morphological observations indicated that the Kitsunezaki staurozoans represented two species, Haliclystus inabai and Calvadosia nagatensis, but molecular analyses of the genetic markers 16S rRNA and COI suggested that the former actually encompasses two distinct lineages, H. inabai and a cryptic as yet unnamed species. Phylogenetic analysis reveals the two H. inabai lineages are separated by significant divergences for both gene markers. H. inabai lineage 1 includes specimens sampled with molecular sequences from Hokkaido (Japan) and Kitsunezaki (Japan), whereas H. inabai lineage 2 includes sequences from Victoria (Australia), Kitsunezaki, as well as populations that appeared in a lab in Germany and aquariums in Tsuruoka and Kagoshima (Japan) and Québec (Canada). Conversely, C. nagatensis from Kitsunezaki appears to be a species distributed only in the temperate NW Pacific. Observations on early life stages of H. inabai lineage 2 within aquarium tanks permitted confirmation of the presence of “microhydrula” settled larva, frustules, and elongated settled larvae. C. nagatensis was collected from the Kitsunezaki survey site in warm months only, and always exhibited gonads, while H. inabai stauromedusae were collected in most months throughout the year, with gonads usually present irrespective of season. An extensive literature review covering more than 100 years and observations in this study revealed seaweed and seagrass as the primary substrates for these two Staurozoa species. Our findings show C. nagatensis is associated with just two types of algal substrates and seagrass, while H. inabai has a much broader substrate preference, consistent with its wider geographic distribution. These findings have contributed to our understanding of Staurozoa epibiotic associations in exposed bays during the recovery period following a major natural disaster.

Hopelessness is associated with decreased physical activity (PA) and increased adverse events and death in patients with ischemic heart disease (IHD). Rates of PA in patients with IHD continue to be low in both hospital‐based cardiac rehabilitation and home settings. While researchers have investigated strategies to increase PA among patients with IHD, interventions to promote PA specifically in IHD patients who report hopelessness are lacking. We describe the protocol for a NIH‐funded randomized controlled trial designed to establish the effectiveness of a 6‐week intervention (Heart Up!) to promote increased PA in IHD patients who report hopelessness. Participants (n = 225) are randomized to one of three groups: (1) motivational social support (MSS) from a nurse, (2) MSS from a nurse plus significant other support (SOS), or (3) attention control. Aims are to: (1) test the effectiveness of 6 weeks of MSS and MSS with SOS on increasing mean minutes per day of moderate to vigorous PA; (2) determine the effects of change in moderate to vigorous PA on hopelessness; and (3) determine if perceived social support and motivation (exercise self‐regulation) mediate the effects of the intervention on PA. A total of 69 participants have been enrolled to date. The protocol has been consistently and accurately used by research personnel. We address the protocol challenges presented by the COVID‐19 pandemic and steps taken to maintain fidelity to the intervention. Findings from this study could transform care for IHD patients who report hopelessness by promoting self‐management of important PA goals that can contribute to better health outcomes.

Canine cutaneous mast cell tumors (ccMCTs) have a highly variable biological behavior and accurate prognostication is essential for therapeutic intervention. Internal tandem duplications (ITD) of exon 11 are the most commonly detected c-kit mutation in ccMCTs and are associated with poor prognosis and increased cellular proliferation. The prognostic value of detecting mutations in other exons of c-kit has not been systematically examined. In this study, we analyzed the prognostic value of ITD mutations of exon 8 in c-kit of ccMCTs in comparison to ccMCTs with ITD mutations of exon 11 and ccMCTs without mutations of exon 8 or 11. The mutational status, histological grade, KIT expression pattern, Ki67 index, AgNOR (argyrophilic nucleolar organizing region) score, and Ag67 score were determined in 221 ccMCTs, and outcome was available for 101 dogs. ITD mutations of exon 8 were found in 73/221 (33%), of exon 11 in 100/221 (45%), and none of these mutations in 50/221 (22%) of ccMCTs. None of the dogs with mutations of exon 8 died due to suspected ccMCT-related cause, but 23% dogs with ccMCTs with mutations of exon 11 died due to suspected ccMCT-related cause. Prognostic parameters in ccMCTs with exon 11 mutations were commonly associated with a high proliferative activity and poor prognosis, while prognostic markers in ccMCTs with mutations of exon 8 had lower values similar to those observed in ccMCTs without mutations in exons 8 or 11 of c-kit. This study indicates that screening for ITD mutations in exon 8 in ccMCTs may be helpful to identify less aggressive ccMCTs and may be recommended as a supplementary prognostic test.

Physical inactivity and sleep disturbance are more problematic in patients with chronic obstructive pulmonary disease (COPD) than in healthy individuals. The purpose of the study was to identify impacts of nighttime sleep on next-day physical activity in COPD patients. The study included 52 COPD patients reporting disturbed sleep. Sleep and physical activity were measured using an accelerometer for 5 days. Increased sleep latency was associated with less next-day physical activity during the afternoon (4-6 p.m.). Greater waking duration/times were associated with less next-morning (6-8 a.m.) physical activity. Greater total sleep time was associated with less next-morning (12-9 a.m.) physical activity, and greater sleep efficiency was associated with less next-morning (1-3 a.m.) and more next-evening (6-7 p.m.) physical activity. Results suggest that sleep disturbance had varying influences on next-day hourly physical activity. These results support the potential value of sleep management in promoting physical activity in COPD patients.

Coaching is increasingly being used in the health sector, with staff and patients. Despite this increase there is only a small body of empirical evidence that demonstrates the effectiveness of coaching in health care settings.Objectives:This study evaluated the effectiveness of a workplace coaching programme (WCP) aimed at enhancing the work behaviours and well-being of 17 managers in a large Australian teaching hospital.Design:A within-group, pre-post test study design was used.Methods:The WCP consisted of needs-based workshops and group and individual coaching over a six-month period. Positive social science provided the theoretical underpinning for the WCP, and this was applied through an integrated solution-focused, cognitive-behavioural methodology. A questionnaire was used to collect data at two time points. Data was analysed using the Wilcoxon Sign Rank Test.Results:Participation in coaching was associated with significantly enhanced proactivity, core performance, goal-attainment, self-insight, motivation, positive affect, and autonomy. Significant effects on self-reflection, negative affect and psychological well-being were not found.Conclusion:The study provides preliminary evidence in favour of workplace coaching as an effective approach for facilitating work effectiveness. Further research utilising larger sample sizes and controlled study designs is warranted.

BACKGROUND: Cognitive impairment is a common complication of aging that is also associated with chronic kidney disease (CKD). Vascular dysfunction has been implicated as a potential cause of cognitive impairment in older adults, with particular deficits noted in those with CKD. AIMS: To determine the differences in cognitive function and vascular compliance in older adults with and without CKD with preclinical cognitive impairment and the relationship between these factors. METHODS: Utilizing a cross-sectional approach, 48 older adults with preclinical cognitive impairment (24 with and 24 without CKD) were evaluated for performance on a test of global cognition and executive function, and vascular compliance via tonometry and ultrasound. RESULTS: Cognitive function and some indicators of vascular function were significantly different in older adults with and without CKD. Global cognition was correlated with carotid-femoral pulse wave velocity (r= −0.36, p =0.02) in the entire sample. Vascular function was not correlated with executive function. DISCUSSION: Older adults with preclinical cognitive impairment and CKD had different cognitive and vascular function than those without CKD, and certain indicators of vascular function may have a relationship with cognitive function in older adults. CONCLUSIONS: The findings of this study support the assessment of cognitive and vascular function in older adults with and without CKD with preclinical cognitive impairment.

This registry-based study evaluated the contribution of center characteristics to kidney transplant outcomes in adult first kidney transplant recipients in Australia and New Zealand between 2004 and 2014. Primary outcomes were mortality and graft failure, and secondary outcomes were transplant complications. Overall, 6970 transplants from 17 centers were included. For deceased donor transplants, 5-year patient and graft survival rates varied considerably (81.0-93.9% and 72.2-88.3%, respectively). Variations in mortality and graft failure were partially reduced after adjustment for patient characteristics (1% and 20% reductions) and more markedly reduced after adjustment for center characteristics (41% and 55% reductions). For living donor transplants, 5-year patient and graft survival rates varied (89.7-100% and 79.2-96.9%, respectively). Centers with high average total ischemic times (>14 h) were associated with higher mortality for both deceased (adjusted hazard ratio [(AHR] 2.24, 95% CI 1.21-4.13) and living donor transplants (AHR 1.76, 95% CI 1.02-3.04). Small center size (