Description of Naviculavanseea sp. nov. (Naviculales, Naviculaceae), a new species of diatom from the highly alkaline Lake Van (Republic of Türkiye) with complete characterisation of its organellar genomes and multigene phylogeny.

The current article describes Naviculavanseeasp. nov., a new species of diatom from Lake Van, a highly alkaline lake in Eastern Anatolia (Türkiye). The description is based on light and scanning electron microscopy performed on two monoclonal cultures. The complete nuclear rRNA clusters and plastid genomes have been sequenced for these two strains and the complete mitogenome for one of them. The plastome of both strains shows the probable loss of a functional ycf35 gene. They also exhibit two IB4 group I introns in their rrl, each encoding for a putative LAGLIDADG homing endonuclease, with the first L1917 IB4 intron reported amongst diatoms. The Maximum Likelihood phylogeny inferred from a concatenated alignment of 18S, rbcL and psbC distinguishes N.vanseea sp. nov. from the morphologically similar species Naviculacincta and Naviculamicrodigitoradiata.

That's out! How expert umpires make leg-before-wicket judgements in cricket.

Despite evidence that elite-level cricket umpires are highly accurate in making leg-before-wicket (LBW) judgements, there is limited understanding as to how they make these judgements. In this study, we explored the explicit LBW decision-making expertise of elite-level cricket umpires (N = 10) via 10 individual semi-structured interviews. Using thematic analysis, we aimed to identify the sources of information that umpires incorporate into their decision-making process. Results indicated that umpires engage in intentional pre-delivery information-gathering to guide their expectations, and to set context-specific parameters as to what would constitute an LBW dismissal. Not only do umpires use information about the ball trajectory, but they also use additional information about the condition of the pitch, the action-capabilities and susceptibilities of players, and the unique requirements of different match formats. Umpires reported employing a gaze-anchor strategy when gathering information for each delivery and described the process of this information as initially intuitive, before engaging in deeper post-hoc reasoning. Findings highlight the importance of including contextual information when exploring officials' decisions and may inform future training interventions for cricket umpires.

Self-Reported Late-Life Hypertension Is Associated with a Healthy Cognitive Status and Reduced Alzheimer's Disease Pathology Burden.

Background: While mid-life hypertension represents a risk factor for the development of Alzheimer's disease (AD), the risk after the age of 65 is less certain. Establishing relationships between late life hypertension and the pathological changes of AD could be crucial in understanding the relevance of blood pressure as a risk factor for this disorder. Objective: We investigated associations between self-reported late-life hypertension, cognitive status and AD pathology at death. The impact of antihypertensive medication was also examined. Methods: Using the Cornell Medical Index questionnaire, we ascertained whether participants had ever reported hypertension. We also noted use of antihypertensive medication. The donated brains of 108 individuals were assessed for AD pathology using consensus guidelines. Statistical analysis aimed to elucidate relationships between hypertension and AD pathology. Results: We found no associations between self-reported hypertension and cognitive impairment at death. However, those with hypertension were significantly more likely to exhibit lower levels of AD pathology as measured by Thal phase, Braak stage, CERAD score, and NIA-AA criteria-even after controlling for sex, level of education and presence of APOEɛ4 allele(s). No significant associations could be found when examining use of antihypertensive medications. Conclusions: Our findings suggest that late-life hypertension is associated with less severe AD pathology. We postulate that AD pathology may be promoted by reduced cerebral blood flow.

Methods matter: Exploring how expectations influence common actions.

Behavior in controlled laboratory studies is not always representative of what people do in daily life. This has prompted a recent shift toward conducting studies in natural settings. We wondered whether expectations raised by how the task is presented should also be considered. To find out, we studied gaze when walking down and up a staircase. Gaze was often directed at steps before stepping on them, but most participants did not look at every step. Importantly, participants fixated more steps and looked around less when asked to navigate the staircase than when navigating the same staircase but asked to walk outside. Presumably, expecting the staircase to be important made participants direct their gaze at more steps, despite the identical requirements when on the staircase. This illustrates that behavior can be influenced by expectations, such as expectations resulting from task instructions, even when studies are conducted in natural settings.

Difficult at dusk? Illuminating the debate on cricket ball visibility.

OBJECTIVES: Investigate the visibility of new and old red, white and pink cricket balls under lighting and background conditions experienced during a day-night cricket match. DESIGN: We modelled the luminance contrast signals available for a typical observer for a ball against backgrounds in a professional cricket ground, at different times of day. METHODS: Spectral reflectance (light reflected as a function of wavelength) was derived from laboratory measurements of new and old red, white and pink balls. We also gathered spectral measurements from backgrounds (pitch, grass, sightscreens, crowd, sky) and spectral illuminance during a day-night match (natural afternoon light, through dusk to night under floodlights) from Lord's Cricket Ground (London, UK). The luminance contrast of the ball relative to the background was calculated for each combination of ball, time of day, and background surface. RESULTS: Old red and old pink balls may offer little or no contrast against the grass, pitch and crowd. New pink balls can also be of low contrast against the crowd at dusk, as can pink and white balls (of any age) against the sky at dusk. CONCLUSIONS: Reports of difficulties with visibility of the pink ball are supported by our data. However, our modelling also shows that difficulties with visibility may also be expected under certain circumstances for red and white balls. The variable conditions in a cricket ground and the changing colour of an ageing ball make maintaining good visibility of the ball a challenge when playing day-night matches.

Future Surgical Leaders: Resident Perception Of Longitudinal Leadership And Non-Technical Skills Curriculum.

OBJECTIVE: A paucity of formal leadership training programs exists for residents, and outcomes of those are limited in reporting. Based on a robust needs assessment, our program created a longitudinal cohort curriculum, Future Surgical Leaders, for residents and fellows of all levels to provide training in nontechnical skills. Our objective was to evaluate surgical resident short-term outcomes and satisfaction with the Future Surgical Leaders (FSL) curriculum. DESIGN: Participants were sent a brief survey after each session of the curriculum from October 2020 to February 2022. The data was compiled after seventeen months of delivery. Likert Scale responses and text comments were analyzed with a 2-sample t-test and 2-way analysis of variance. SETTING: Academic tertiary institution. PARTICIPANTS: General surgery residents. RESULTS: Survey response rate from 54 sessions among all postgraduate year levels was 73%. Overall, 96% of residents/fellows either "agreed" or "strongly agreed" that the topics of the FSL curriculum were important to learn during surgical training. Only 24% of learners knew "a lot" or "a great deal" about the topics prior to the session which rose to 73% afterwards (p < 0.01). Each postgraduate year class showed statistically significant increase in knowledge. About 80% of learners wanted to investigate these topics further. Open comment questions identified themes requesting delivery of specific sessions earlier in residency training and positive overall attitudes toward the FSL curriculum. CONCLUSIONS: FSL is a satisfactory means of teaching leadership skills to surgical residents. Residents recognize the need to develop leadership skills prior to entering practice and want to learn more. The FSL curriculum may be considered for application at other surgical training programs.

Running together influences where you look.

To read this article, you have to constantly direct your gaze at the words on the page. If you go for a run instead, your gaze will be less constrained, so many factors could influence where you look. We show that you are likely to spend less time looking at the path just in front of you when running alone than when running with someone else, presumably because the presence of the other runner makes foot placement more critical.

Profile of Athletes With a Vision Impairment: Exploring Demographics and Ocular Pathologies of Athletes in Three Paralympic Sports.

OBJECTIVE: This study aimed to explore the profile of athletes with a vision impairment who compete in three Paralympic sports (goalball, vision impairment judo, and blind football). DESIGN: Descriptive and association analyses of the vision impairment athletes' profile were conducted. RESULTS: The typical athlete profile was a male (65.1%), aged 26-34 yrs (39.7%), from Europe (38.8%), representing a country with a high income (46.1%), and was diagnosed with a retinal-related ocular pathology (38.9%). In all three sports, the ages of the athletes were similar. In goalball, most athletes were from Europe, represented countries with a high income, and were diagnosed with retinal-, globe-, or neurological-related pathologies. In vision impairment judo, the majority of athletes were from Asia, represented countries with an upper middle income, and were diagnosed with retinal-, global-, or neurological-related pathologies. In blind football, most athletes were from Europe, represented countries with an upper middle income, and were diagnosed with retinal-, neurological-related ocular pathologies, or glaucoma. CONCLUSIONS: The homogeneity of the athletes' profile suggests that an effort is needed to target other parts of the vision impairment population to take part in vision impairment sports. Differences in the athletes' profiles across the sports provide information that may be useful for sport-specific talent identification.

Defining Pathologic Upstaging in cT1b Esophageal Cancer: Should We Consider Neoadjuvant Therapy?

INTRODUCTION: Neoadjuvant chemoradiation therapy (NCRT) for cT1b esophageal cancer is not recommended despite the risk of pathologic upstaging with increased depth of penetration. We aimed to (1) define the rate of and factors associated with pathologic upstaging, (2) describe current trends in treatments, and (3) compare overall survival (OS) with and without NCRT for surgically resected cT1b lesions. METHODS: We used the 2020 National Cancer Database to identify patients with cT1b N0 esophageal cancer with or without pathologic upstaging who underwent removal of their tumor. We built multivariable logistic regression models to assess factors associated with pathologic upstaging. Survival was compared using log-rank analysis and modeled using multivariable Cox proportional hazards regressions. RESULTS: Out of 1106 patients with cT1b esophageal cancer, 17.3% (N = 191) had pathologic upstaging. A higher tumor grade (P = 0.002), greater tumor size (P < 0.001), and presence of lympho-vascular invasion (P < 0.001) were associated with pathologic upstaging. 8.0% (N = 114) of patients were treated with NCRT. Five-y OS was 49.4% for patients who received NCRT compared to 67.2% for upfront esophagectomy (P < 0.05). Pathologic upstaging was associated with decreased OS (pathologic upstaging 43.7% versus no pathologic upstaging 67.7%) (hazard ratio 2.12 [95% confidence interval, 1.70-2.65; P < 0.001]). Compared to esophagectomy, endoscopic local tumor excision was associated with a decreased OS (hazard ratio 1.50 [95% confidence interval, 1.19-1.89; P = 0.001]). CONCLUSIONS: Pathologic upstaging of cT1b lesions is associated with decreased OS. Esophagectomy is associated with a survival benefit over endoscopic local tumor excision for these lesions. NCRT is not associated with an increase in OS in cT1b lesions compared to upfront esophagectomy.

Maximising environmental pressure-response relationship signals from diatom-based metabarcoding in rivers.

DNA metabarcoding has been performed on a large number of river phytobenthos samples collected from the UK, using rbcL primers optimised for diatoms. Within this dataset the composition of non-diatom sequence reads was studied and the effect of including these in models for evaluating the nutrient gradient was assessed. Whilst many non-diatom taxonomic groups were detected, few contained the full diversity expected in riverine environments. This may be due to the performance of the current primers in characterising the wider phytobenthic community and influenced by the sampling method employed, as both were developed specifically for diatoms. Nevertheless, the study identified considerable diversity in some groups, e.g. Eustigmatophyceae and a wider distribution than previously thought for freshwater Phaeophyceae. These results offer a strong case for the benefits of metabarcoding for expanding knowledge of aquatic biodiversity in the UK and elsewhere. Many of the ASVs associated with non-diatoms showed significant pressure responses; however, models that included non-diatoms had similar predictive strength to those based on diatoms alone. Whilst limitations of the primers for assessing non-diatoms may play a role in explaining these results, the diatoms provide a strong signal along the nutrient gradient and other algae, therefore, add little unique information. We recommend that future developments should use ASVs to calculate metrics, with links to reference databases made as a final step to generate lists of taxa to support interpretation. Any further exploration of the potential of non-diatoms would benefit from access to a well-curated reference database, similar to diat.barcode. Such a database does not yet exist, and we caution against the indiscriminate use of NCBI GenBank as a taxonomic resource as many rbcL sequences deposited have not been curated.

Impact of Running With and Without a Guide on Short Distance Running Performance for Athletes With a Vision Impairment.

OBJECTIVE: This study aimed to investigate the difference of running with or without a guide on running performance (100, 200, and 400 m) for athletes with a vision impairment. DESIGN: Data including athletes' and guides' sex, age, and race times were extracted from 11 elite competitions. RESULTS: Male athletes predominantly ran without a guide (100 m = 91.4%, 200 m = 88.1%, 400 m = 84.8%), whereas female athletes mainly ran with a guide (100 m = 60.5%, 200 m = 80.0%, 400 m = 72.0%). No significant difference in 100-m race times was found between male athletes with or without a guide ( P = 0.647). For the 200 m ( P = 0.001) and 400 m ( P = 0.030), race times were significantly slower for male athletes running with a guide (mean rank 200 m = 36.80, 400 m = 33.57) compared to without a guide (mean rank 200 m = 19.43, 400 m = 21.69). Conversely, 100- ( P = 0.015), 200- ( P = 0.025), and 400-m ( P = 0.029) race times were significantly faster for female athletes with (mean rank 100 m = 18.25, 200 m = 13.71, 400 m = 11.00) compared with without a guide (mean rank 100 m = 27.74, 200 m = 22.67, 400 m = 21.69). CONCLUSIONS: Running with a guide affects vision impairment athletes' race times. The influence of running with a guide, and the gender mix of vision impairment athlete and guide, should be considered in any research with the aim of establishing a new classification system for vision impairment athletes.

Intratracheally Administered Peptide-Modified Lipid Admixture Containing Fasudil and/or DETA NONOate Ameliorates Various Pathologies of Pulmonary Arterial Hypertension.

This study examined the therapeutic potential of a combination therapy using fasudil, a Rho-kinase inhibitor, and DETA NONOate (DN), a nitric oxide donor, delivered as a lipid admixture modified with a cyclic homing peptide known as CAR (CAR-lipid mixture) for the treatment of pulmonary arterial hypertension (PAH). CAR-lipid mixtures were initially prepared via a thin-film hydration method and then combined with fasudil, DN, or a mixture of both. The therapeutic efficacy of this drug-laden lipid mixture was evaluated in a Sugen/Hypoxia (Su/Hx) rat model of PAH by measuring RV systolic pressure (RVSP), mean pulmonary arterial pressure (mPAP), Fulton indices, and assessing right ventricular (RV) functions, as well as evaluating pulmonary vascular morphology. Rats that received no treatment exhibited increases in RVSP, mPAP, Fulton indices, and changes in RV functional parameters. However, the treatment with the CAR-lipid mixture containing either fasudil or DN or a combination of both led to a decline in mPAP, RVSP, and Fulton indices compared to saline-treated rats. Similarly, rats that received these treatments showed concurrent improvement in various echocardiographic parameters such as pulmonary acceleration time (PAT), tricuspid annular plane systolic excursion (TAPSE), and ventricular free wall thickness (RVFWT). A significant decrease in the wall thickness of pulmonary arteries larger than 100 µm was observed with the combination therapy. The findings reveal that fasudil, DN, and their combination in a CAR-modified lipid mixture improved pulmonary hemodynamics, RV functions, and pathological alterations in the pulmonary vasculature. This study underscores the potential of combination therapy and targeted drug delivery in PAH treatment, laying the groundwork for future investigations into the optimization of these treatments, their long-term safety and efficacy, and the underlying mechanism of action of the proposed therapy.

Covalent fragment libraries in drug discovery-Design, synthesis, and screening methods.

As the development of drugs with a covalent mode of action is becoming increasingly popular, well-validated covalent fragment-based drug discovery (FBDD) methods have been comparatively slow to keep up with the demand. In this chapter the principles of covalent fragment reactivity, library design, synthesis, and screening methods are explored in depth, focussing on literature examples with direct applications to practical covalent fragment library design and screening. Further, questions about the future of the field are explored and potential useful advances are proposed.

The Missing Link: Lean Leadership.

People often equate "Lean" with the tools that are used to create efficiencies and standardize processes. However, implementing tools represents at most 20 percent of the effort in Lean transformations. The other 80 percent is expended on changing leaders' practices and behaviors, and ultimately their mindset. Senior management has an essential role in establishing conditions that enable 80 percent of the effort to succeed. Their involvement includes establishing governance arrangements that cross divisional boundaries, supporting a thorough, long-term vision of the organization's value-producing processes, and holding everyone accountable for meeting Lean commitments. This is accomplished through regular, direct involvement. When upper management sets the example, durable Lean success and an increasingly Lean leadership mindset follow.

CAR Selectively Enhances the Pulmonary Vasodilatory Effect of Fasudil in a Microsphere Model of Pulmonary Hypertension.

Background: Despite the approval of several medications for pulmonary hypertension, morbidity and mortality are unacceptably high. Systemic hypotension may limit the use of pulmonary hypertension medications. Objectives: This study aimed to assess whether the homing peptide CAR (CARSKNKDC) improves the vasodilatory selectivity of fasudil in the pulmonary circulation or systemic circulation in a porcine pulmonary hypertension model. Materials and Methods: Pulmonary hypertension (to approximately 2/3-3/4 systemic pressure levels) was induced by chronic and acute administration of microspheres in 3 micro Yucatan pigs (mean weight 19.9 kg, mean age 4.3 months). Fasudil (0.3 mg/kg) was administered without and with CAR (1.5 mg/kg), and the effect on aortic (Ao) and right ventricular (RV) pressure was recorded with indwelling catheters. Results: Immediately after fasudil administration, there was a decrease in Ao pressure followed by prompt recovery to baseline. The RV pressure decrease was progressive and sustained. Fasudil alone resulted in a 12% decrease in RV pressure, whereas co-administration of CAR with fasudil resulted in a 22% decrease in RV pressure (p < 0.0001). Fasudil alone caused an average decrease of 34% in the RV/Ao pressure ratio, and fasudil + CAR caused an average decrease of 40% in the RV/Ao pressure ratio (p < 0.0001). Conclusion: The homing peptide CAR selectively enhanced the acute vasodilatory effects of fasudil on the pulmonary vascular bed in a porcine experimental model of pulmonary hypertension.

Concomitant progressive supranuclear palsy and Lewy body pathology presenting with circumscribed visual memory loss: A clinicopathological case.

A 70-year-old man presented to the clinic with impairment of visual memory and marked predominantly right sided mesial temporal lobe atrophy on imaging. He died 6 years following symptom onset and neuropathological examination showed concomitant progressive supranuclear palsy and Lewy body pathology. Although he did not fulfil clinical criteria for either condition at presentation, we propose that interactions between the two pathologies in mesial temporal regions could result in this atypical clinical phenotype.

Distinct tau folds initiate templated seeding and alter the post-translational modification profile.

Pathological tau accumulates in the brain in tauopathies such as Alzheimer's disease, Pick's disease, progressive supranuclear palsy and corticobasal degeneration, and forms amyloid-like filaments incorporating various post-translational modifications (PTMs). Cryo-electron microscopic (cryo-EM) studies have demonstrated that tau filaments extracted from tauopathy brains are characteristic of the disease and share a common fold(s) in the same disease group. Furthermore, the tau PTM profile changes during tau pathology formation and disease progression, and disease-specific PTMs are detected in and around the filament core. In addition, templated seeding has been suggested to trigger pathological tau amplification and spreading in vitro and in vivo, although the molecular mechanisms are not fully understood. Recently, we reported that the cryo-EM structures of tau protofilaments in SH-SY5Y cells seeded with patient-derived tau filaments show a core structure(s) resembling that of the original seeds. Here, we investigated PTMs of tau filaments accumulated in the seeded cells by liquid chromatography/tandem mass spectrometry and compared them with the PTMs of patient-derived tau filaments. Examination of insoluble tau extracted from SH-SY5Y cells showed that numerous phosphorylation, deamidation and oxidation sites detected in the fuzzy coat in the original seeds were well reproduced in SH-SY5Y cells. Moreover, templated tau filament formation preceded both truncation of the N-/C-terminals of tau and PTMs in and around the filament core, indicating these PTMs may predominantly be introduced after the degradation of the fuzzy coat.

The effects of simulated vision impairment on performance in football.

Footballers with vision impairment (VI) are eligible to compete in the Para sport if they meet a minimum impairment criteria (MIC) based on measures of their visual acuity (VA) and/or visual field. Despite the requirements of the International Paralympic Committee Athlete Classification Code that each sport uses an evidence-based classification system, VI football continues to use a medical-based system that lacks evidence to demonstrate the relationship between impairment and performance in the sport. The aim of this study was to systematically simulate vision loss to establish the minimum level of impairment that would affect performance in futsal. Nineteen skilled sighted players completed tests of individual technical skill and anticipation performance under six levels of simulated blur that decreased both VA and contrast sensitivity (CS). VA needed to be reduced to a level of acuity that represents worse vision than that currently used for inclusion in VI football before meaningful decreases in performance were observed. CS did not have a clear effect on football performance. These findings produce the first evidence for the minimum impairment criteria in VI football and suggest a more severe degree of impairment may be required for the MIC.

Integrative Analysis Unveils the Correlation of Aminoacyl-tRNA Biosynthesis Metabolites with the Methylation of the SEPSECS Gene in Huntington's Disease Brain Tissue.

The impact of environmental factors on epigenetic changes is well established, and cellular function is determined not only by the genome but also by interacting partners such as metabolites. Given the significant impact of metabolism on disease progression, exploring the interaction between the metabolome and epigenome may offer new insights into Huntington's disease (HD) diagnosis and treatment. Using fourteen post-mortem HD cases and fourteen control subjects, we performed metabolomic profiling of human postmortem brain tissue (striatum and frontal lobe), and we performed DNA methylome profiling using the same frontal lobe tissue. Along with finding several perturbed metabolites and differentially methylated loci, Aminoacyl-tRNA biosynthesis (adj p-value = 0.0098) was the most significantly perturbed metabolic pathway with which two CpGs of the SEPSECS gene were correlated. This study improves our understanding of molecular biomarker connections and, importantly, increases our knowledge of metabolic alterations driving HD progression.