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Background: Athletes commonly use creatine, caffeine, and sodium bicarbonate for performance enhancement. While their isolated effects are well-described, less is known about their potential additive effects., Methods: Following a baseline trial, we randomized 12 endurance-trained males (age: 25 ± 5 years, VO 2max : 56.7 ± 4.6 mL kg -1  min -1 ; mean ± SD) and 11 females (age: 25 ± 3 years, VO 2max : 50.2 ± 3.4 mL kg -1  min -1 ) to 5 days of creatine monohydrate (0.3 g kg -1  per day) or placebo loading, followed by a daily maintenance dose (0.04 g kg -1 ) throughout the study. After the loading period, subjects completed four trials in randomized order where they ingested caffeine (3 mg kg -1 ), sodium bicarbonate (0.3 g kg -1 ), placebo, or both caffeine and sodium bicarbonate before a maximal voluntary contraction (MVC), 15-s sprint, and 6-min time trial., Results: Compared to placebo, mean power output during 15-s sprint was higher following loading with creatine than placebo (+34 W, 95% CI: 10 to 58, p = 0.008), but with no additional effect of caffeine (+10 W, 95% CI: -7 to 24, p = 0.156) or sodium bicarbonate (+5 W, 95% CI: -4 to 13, p = 0.397). Mean power output during 6-min time trial was higher with caffeine (+12 W, 95% CI: 5 to 18, p = 0.001) and caffeine + sodium bicarbonate (+8 W, 95% CI: 0 to 15, p = 0.038), whereas sodium bicarbonate (-1 W, 95% CI: -7 to 6, p = 0.851) and creatine (-6 W, 95% CI: -15 to 4, p = 0.250) had no effects., Conclusion: While creatine and caffeine can enhance sprint- and time trial performance, respectively, these effects do not seem additive. Therefore, supplementing with either creatine or caffeine appears sufficient to enhance sprint or short intense exercise performance., (© 2024 The Authors. Scandinavian Journal of Medicine & Science In Sports published by John Wiley & Sons Ltd.)

Double-stranded RNA produced during viral replication and transcription activates both protein kinase R (PKR) and ribonuclease L (RNase L), which limits viral gene expression and replication through host shutoff of translation. In this study, we find that APOBEC3B forms a complex with PABPC1 to stimulate PKR and counterbalances the PKR-suppressing activity of ADAR1 in response to infection by many types of viruses. This leads to translational blockage and the formation of stress granules. Furthermore, we show that APOBEC3B localizes to stress granules through the interaction with PABPC1. APOBEC3B facilitates the formation of protein-RNA condensates with stress granule assembly factor (G3BP1) by protecting mRNA associated with stress granules from RNAse L-induced RNA cleavage during viral infection. These results not only reveal that APOBEC3B is a key regulator of different steps of the innate immune response throughout viral infection but also highlight an alternative mechanism by which APOBEC3B can impact virus replication without editing viral genomes., (© 2023. The Author(s).)

Background: Survival from colon cancer (CC) has improved considerably over the last decades, yet many survivors suffer from late sequelae from treatment. Typical symptoms of bowel dysfunction after treatment of CC are diarrhea, urge for defecation, fecal incontinence, bloating and constipation. Most CC survivors make dietary changes to alleviate bowel symptoms. We aimed to describe the self-perceived effects of diet on bowel function among CC survivors and the level of dietary information given., Materials and Methods: In this cross-sectional study, CC patients from four surgical departments in Denmark completed surveys regarding the effects of diet on their bowel function and whether they had previously received dietary advice. Data concerning sociodemographic characteristics and the surgical procedure (right-sided or left-sided hemicolectomy) were collected from the Danish Colorectal Cancer Group database. Forty-four healthcare professionals specialized in CC completed a questionnaire on how they advise CC. Descriptive statistics were applied., Results: Among 1544 patients invited, 1239 (80.4%) responded, and 844 met the inclusion criteria (53% males, median age 72.6 years, median time since surgery 742 days). Among these, 267 (32%) reported that food affected bowel function. Fat was perceived to have a negative effect in 193 (25%), spices in 149 (19%), sweets in 101 (13%) and meat in 99 (13%). There was no association between tumor site and food categories affecting bowel function ( p  = 0.078). Most healthcare professionals (93%) stated that their unit gave advice about diet, but only 24% of patients remembered such information., Conclusion: One-third of CC survivors perceive that food items, especially fat and spices have a negative impact on their bowel function. We found a major discrepancy between healthcare professionals reporting that they provide advice and the proportion of patients remembering this. There is an unmet need for further recognition of the role of diet in CC rehabilitation and for intervention studies of treatment principles.

Aim: The aim was to study anorectal function in long-term survivors after combined, curatively intended, chemoradiotherapy and endorectal brachytherapy for low rectal cancer., Methods: This was a case-control design. We compared anorectal function by anal manometry, anal functional lumen imaging probe (EndoFLIP) and rectal bag distension in rectal cancer patients (RCPs) and healthy, normal subjects (NSs). Symptoms were assessed by the low anterior resection syndrome (LARS) and Wexner faecal incontinence scores., Results: Thirteen RCPs (12 men, median age 68 years, range 52-92) after 60 Gy radiotherapy, 5 Gy endorectal brachytherapy and oral tegafur-uracil with complete clinical response (median time since treatment 2.8 years, range 2.2-5.6) were compared to 15 NSs (14 men, median age 64 years, range 47-75). RCPs had lower than normal anal resting pressure, 38.6 mmHg (range 8.8-67.7) versus 58.8 mmHg (25.7-105.2) (P < 0.003), and squeeze pressure, 117 mmHg (55.2-203) versus 188 mmHg (103-248) (P < 0.01). Squeeze-induced pressure increase recorded by EndoFLIP was also lower in RCPs (q > 7.56, P < 0.001) as was the anal canal resistance to increasing distension (q = 3.13, P < 0.05). No differences in median rectal volume at first sensation (72 [22-158] vs. 82 [36-190] ml, P = 0.4) or at urge to defaecate (107 [42-227] vs. 132 [59-334] ml, P = 0.2) were found. However, maximum tolerable rectal volume was lower in RCPs (145 [59-319] vs. 222 [106-447] ml, P < 0.02). The median (range) low anterior resection syndrome score was 27 (0-39) for RCPs and 7 (0-23) for NSs (P < 0.001), while the Wexner score was 0 (0-5) versus 0 (0-4) (P = 0.56)., Conclusion: Radiotherapy combined with endorectal brachytherapy for rectal cancer causes long-term anorectal symptoms, impaired anal sphincter function and reduced rectal capacity., (© 2021 The Association of Coloproctology of Great Britain and Ireland.)

We investigated the effect of caffeine and acetaminophen on power output during a 6-min performance test, peripheral fatigue, and muscle protein kinase A (PKA) substrate phosphorylation. Fourteen men [age (means ± SD): 26 ± 6 yr; V̇o 2max : 63.9 ± 5.0 mL·min -1 ·kg -1 ] completed four randomized trials with acetaminophen (1,500 mg), caffeine (5 mg·kg body wt -1 ), combined caffeine and acetaminophen (caffeine + acetaminophen), or placebo. Mean power output during the 6-min performance test (placebo mean: 312 ± 41 W) was higher with caffeine (+5 W; 95% CI: 1 to 9; P = 0.017) and caffeine + acetaminophen (+6 W; 95% CI: 0 to 12; P = 0.049) than placebo, but not with acetaminophen (+1 W; 95% CI: -4 to 7; P = 0.529). Decline in quadriceps maximal isometric voluntary torque immediately after the performance test was lower (treatment × time; P = 0.035) with acetaminophen (-40 N·m; 95% CI: -53 to -30; P < 0.001) and caffeine + acetaminophen (-44 N·m; 95% CI: -58 to -30; P < 0.001) than placebo (-53 N·m; 95% CI: -71 to -39; P < 0.001) but was similar with caffeine (-54 N·m; 95% CI: -69 to -38; P < 0.001). Muscle phosphocreatine content decreased more during the performance test (treatment × time; P = 0.036) with caffeine + acetaminophen (-55 mmol·kg dry wt -1 ; 95% CI: -65 to -46; P < 0.001) than placebo (-40 mmol·kg dry wt -1 ; 95% CI: -52 to -24; P < 0.001). Muscle net lactate accumulation was not different from placebo (+85 mmol·kg dry wt -1 ; 95% CI: 60 to 110; P < 0.001) for any treatment (treatment × time; P = 0.066), being +75 mmol·kg dry wt -1 (95% CI: 51 to 99; P < 0.001) with caffeine, +76 mmol·kg dry wt -1 (95% CI: 58 to 96; P < 0.001) with acetaminophen, and +103 mmol·kg dry wt -1 (95% CI: 89 to 115; P < 0.001) with caffeine + acetaminophen. Decline in muscle ATP and glycogen content and increase in PKA substrate phosphorylation was not different between treatments (treatment × time; P > 0.1). Thus, acetaminophen provides no additive performance enhancing effect to caffeine during 6-min maximal cycling. In addition, change in PKA activity is likely not a major mechanism of performance improvement with caffeine. NEW & NOTEWORTHY Here, we show that acetaminophen does not provide additive performance improvement to caffeine during a 6-min cycling ergometer performance test, and that acetaminophen does not improve performance on its own. Neither substance affects peripheral fatigue, muscle glycolytic energy production, or phosphorylation of muscle proteins of importance for ion handling. In contrast to previous suggestions, increased epinephrine action on muscle cells does not appear to be a major contributor to the performance enhancement with caffeine.

Objectives: The skin is the largest sensory organ of the human body and plays a fundamental role in regulating body temperature. However, adaptive alterations in skin functions and morphology have only vaguely been associated with physiological responses to cold stress or sensation of ambient temperatures. We previously found that loss of acyl-CoA-binding protein (ACBP) in keratinocytes upregulates lipolysis in white adipose tissue and alters hepatic lipid metabolism, suggesting a link between epidermal barrier functions and systemic energy metabolism., Methods: To assess the physiological responses to loss of ACBP in keratinocytes in detail, we used full-body ACBP -/- and skin-specific ACBP -/- knockout mice to clarify how loss of ACBP affects 1) energy expenditure by indirect calorimetry, 2) response to high-fat feeding and a high oral glucose load, and 3) expression of brown-selective gene programs by quantitative PCR in inguinal WAT (iWAT). To further elucidate the role of the epidermal barrier in systemic energy metabolism, we included mice with defects in skin structural proteins (ma/ma Flg ft/ft ) in these studies., Results: We show that the ACBP -/- mice and skin-specific ACBP -/- knockout mice exhibited increased energy expenditure, increased food intake, browning of the iWAT, and resistance to diet-induced obesity. The metabolic phenotype, including browning of the iWAT, was reversed by housing the mice at thermoneutrality (30 °C) or pharmacological β-adrenergic blocking. Interestingly, these findings were phenocopied in flaky tail mice (ma/ma Flg ft/ft ). Taken together, we demonstrate that a compromised epidermal barrier induces a β-adrenergic response that increases energy expenditure and browning of the white adipose tissue to maintain a normal body temperature., Conclusions: Our findings show that the epidermal barrier plays a key role in maintaining systemic metabolic homeostasis. Thus, regulation of epidermal barrier functions warrants further attention to understand the regulation of systemic metabolism in further detail., (Copyright © 2020 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Background: Circulating follistatin (Fst) binds activin A and thereby regulates biological functions such as muscle growth and β-cell survival. However, Fst and activin A's implication in metabolic regulation is unclear., Objective: To investigate circulating Fst and activin A in obesity and type 2 diabetes (T2D) and determine their association with metabolic parameters. Further, to examine regulation of Fst and activin A by insulin and the influence of obesity and T2D hereon., Methods: Plasma Fst and activin A levels were analyzed in obese T2D patients (N = 10) closely matched to glucose-tolerant lean (N = 12) and obese (N = 10) individuals in the fasted state and following a 4-h hyperinsulinemic-euglycemic clamp (40 mU·m-2·min-1) combined with indirect calorimetry., Results: Circulating Fst was ~30% higher in patients with T2D compared with both lean and obese nondiabetic individuals (P < .001), while plasma activin A was unaltered. In the total cohort, fasting plasma Fst correlated positively with fasting plasma glucose, serum insulin and C-peptide levels, homeostasis model assessment of insulin resistance, and hepatic and adipose tissue insulin resistance after adjusting for age, gender and group (all r > 0.47; P < .05). However, in the individual groups these correlations only achieved significance in patients with T2D (not plasma glucose). Acute hyperinsulinemia at euglycemia reduced circulating Fst by ~30% (P < .001) and this response was intact in patients with T2D. Insulin inhibited FST expression in human hepatocytes after 2 h and even further after 48 h., Conclusions: Elevated circulating Fst, but not activin A, is strongly associated with measures of insulin resistance in patients with T2D. However, the ability of insulin to suppress circulating Fst is preserved in T2D., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

A key feature of life's diversity is that some species are common but many more are rare. Nonetheless, at global scales, we do not know what fraction of biodiversity consists of rare species. Here, we present the largest compilation of global plant diversity to quantify the fraction of Earth's plant biodiversity that are rare. A large fraction, ~36.5% of Earth's ~435,000 plant species, are exceedingly rare. Sampling biases and prominent models, such as neutral theory and the k-niche model, cannot account for the observed prevalence of rarity. Our results indicate that (i) climatically more stable regions have harbored rare species and hence a large fraction of Earth's plant species via reduced extinction risk but that (ii) climate change and human land use are now disproportionately impacting rare species. Estimates of global species abundance distributions have important implications for risk assessments and conservation planning in this era of rapid global change., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Purpose: Stenosis of the superficial femoral artery (SFA) induces complex blood flow with increased velocities. Disease assessment is performed with Doppler ultrasound and digital subtraction angiography (DSA), but Doppler ultrasound is limited by angle dependency and DSA by ionizing radiation. An alternative is the vector flow imaging method based on transverse oscillation (TO), an angle-independent vector velocity technique using ultrasound. In this study, flow complexity and velocity measured with TO were compared with DSA for the assessment of stenosis in the SFA., Materials and Methods: The vector concentration, a measure of flow complexity, and the velocity ratio obtained from the stenosis and a disease-free adjacent vessel segment, were estimated with TO in 11 patients with a total of 16 stenoses of the SFA. TO data were compared with the corresponding stenosis degree percentage obtained with DSA., Results: The correlation between the vector concentration and DSA was very strong (R=0.93; p<0.001; 95% confidence interval (CI): 0.81-0.98), while only moderate for velocity ratio and DSA (R=0.50; p<0.07; 95% CI: 0.00-0.80). The correlation coefficients that were found were significantly different (p<0.005) without overlapping CI., Conclusion: The study indicated that flow changes in the SFA induced by stenosis can be quantified with TO, and that stenosis grading may be improved by estimation of flow complexity instead of velocity ratio. TO is a potential diagnostic tool for the assessment of atherosclerosis and peripheral arterial disease.

Background: Psychiatric patients with colorectal cancer may have delayed diagnosis and be oncologically undertreated., Methods: The Danish Colorectal Cancer Group database comprised 25,194 colorectal cancer patients (CRC), (colon cancer (CC, n = 16,641), rectal cancer (RC, n = 8553)), having an operation in 2007-2013, were alive at least 30 days after operation, of which 422 have had at least one hospital contact for a serious psychiatric disorder; ICD-10: DF20-29: primary psychotic disorders, or DF30-39: affective disorders (exposed) in a period of 3650-120 days before the operation date. Pearson chi-squared test for cancer stage was calculated. Odds Ratio (OR) with 95% confidence interval (CI) for having had a palliative vs an intended curative aim of the operative treatment for CRC patients (cohort 1), and for having an oncological treatment for each cancer site CC or RC (cohort 2 and 3) in patients with and without a psychiatric history was estimated. We adjusted the OR for: age, gender, comorbidity index, cancer stage, socio-economic position group, and educational level., Results: A higher cancer stage at the time of operation in patients with psychiatric disorders compared with patients without such a history was seen and may possibly point towards a delay in the diagnosis or in the treatment of CC in patients with psychiatric disorders. They also had decreased adjusted OR for having an oncological treatment, OR 0.55, 95% CI (0.40-0.76)), which was not explained by cancer stage. For patients with RC no difference was seen., Conclusions: Attention for CC patients with pre-existing serious psychiatric disorders is recommended.

Purpose: Atherosclerotic arteries are challenging to evaluate quantitatively using spectral Doppler ultrasound because of the turbulent flow conditions that occur in relation to the atherosclerotic stenoses. Vector velocity ultrasound is angle independent and provides flow information, which could potentially improve the diagnosis of arterial stenoses. The purpose of the study is to distinguish significant stenoses in the superficial femoral artery (> 50% diameter reduction) from non-significant stenoses based on velocity ratios derived from the commercially available vector velocity ultrasound technique Vector Flow Imaging (VFI)., Materials and Methods: Velocity ratios (intrastenotic blood flow velocity divided by pre- or poststenotic velocity) from a total of 16 atherosclerotic stenoses and plaques in the superficial femoral artery of 11 patients were obtained using VFI. The stenosis degree, expressed as percentage diameter reduction of the artery, was determined from digital subtraction angiography and compared to the velocity ratios., Results: A velocity ratio of 2.5 was found to distinguish clinically relevant stenoses with>50% diameter reduction from clinically non-relevant stenoses with<50% diameter reduction and the difference was statistically significant., Conclusion: The study indicates that VFI is a potential future tool for the evaluation of arterial stenoses.

The effect of tapering following a period of high-volume sprint interval training (SIT) and a basic volume of aerobic training on performance and muscle adaptations in moderately trained runners was examined. Eleven (8 men, 3 women) runners [maximum oxygen uptake (V̇o 2max ): 56.8 ± 2.9 ml·min -1 ·kg -1 ; mean ± SD] conducted high-volume SIT (HV; 20 SIT sessions; 8-12 × 30 s all-out) for 40 days followed by 18 days of tapering (TAP; 4 SIT sessions; 4 × 30 s all-out). Before and after HV as well as midway through and at the end of TAP, the subjects completed a 10-km running test and a repeated running test at 90% of vV̇o 2max to exhaustion (RRT). In addition, a biopsy from the vastus lateralis muscle was obtained at rest. Performance during RRT was better ( P < 0.01) at the end of TAP than before HV (6.8 ± 0.5 vs. 5.6 ± 0.5 min; means ± SE), and 10-km performance was 2.7% better ( P < 0.05) midway through (40.7 ± 0.7 min) and at the end of (40.7 ± 0.6 min) TAP than after HV (41.8 ± 0.9 min). The expression of muscle Na + -K + -ATPase (NKA)α 1 , NKAβ 1 , phospholemman (FXYD1), and sarcoplasmic reticulum calcium transport ATPase (SERCA1) increased ( P < 0.05) during HV and remained higher during TAP. In addition, oxygen uptake at 60% of vV̇o 2max was lower ( P < 0.05) at the end of TAP than before and after HV. Thus short-duration exercise capacity and running economy were better than before the HV period together with higher expression of muscle proteins related to Na + /K + transport and Ca 2+ reuptake, while 10-km performance was not significantly improved by the combination of HV and tapering. NEW & NOTEWORTHY Short-duration performance became better after 18 days of tapering from ~6 wk of high-volume sprint interval training (SIT), whereas 10-km performance was not significantly affected by the combination of high-volume SIT and tapering. Higher expression of muscle NKAα 1 , NKAβ 1 , FXYD1, and SERCA1 may reflect faster Na + /K + transport and Ca 2+ reuptake that could explain the better short-duration performance. These results suggest that the type of competition should determine the duration of tapering to optimize performance.

Species distribution models (SDMs) are widely used in ecology and conservation. Presence-only SDMs such as MaxEnt frequently use natural history collections (NHCs) as occurrence data, given their huge numbers and accessibility. NHCs are often spatially biased which may generate inaccuracies in SDMs. Here, we test how the distribution of NHCs and MaxEnt predictions relates to a spatial abundance model, based on a large plot dataset for Amazonian tree species, using inverse distance weighting (IDW). We also propose a new pipeline to deal with inconsistencies in NHCs and to limit the area of occupancy of the species. We found a significant but weak positive relationship between the distribution of NHCs and IDW for 66% of the species. The relationship between SDMs and IDW was also significant but weakly positive for 95% of the species, and sensitivity for both analyses was high. Furthermore, the pipeline removed half of the NHCs records. Presence-only SDM applications should consider this limitation, especially for large biodiversity assessments projects, when they are automatically generated without subsequent checking. Our pipeline provides a conservative estimate of a species' area of occupancy, within an area slightly larger than its extent of occurrence, compatible to e.g. IUCN red list assessments.

Background: Hirschsprung's disease is a rare condition caused by congenital malformation of the gastrointestinal tract affecting 1:5000 children. Not much is known about risk factors for development of Hirschsprung's disease. Two clinical cases of hirschsprung's disease led to an investigation of the association between maternal use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy and development of Hirschsprung's Disease in the newborn child. The study examined a nationwide, unselected cohort of children born in Denmark from 1 January 1996 until 12 March 2016 (n = 1,256,317). We applied multivariate models to register-based data to estimate the odds ratio of Hirschsprung's disease, adjusting for possible confounders. The studied exposure period for SSRIs were 30 days prior to conception to the end of the first trimester., Results: In the main exposed cohort the prevalence of Hirschsprung's disease was 16/19.807 (0.08%) compared to 584/1.236.510 (0.05%) in the unexposed cohort. In women who redeemed a minimum of one prescription of selective serotonin reuptake inhibitors, the adjusted odds ratio for development of Hirschsprung's disease was 1.76 (95%CI: 1.07-2.92). In women who redeemed a minimum of two prescriptions, the adjusted odds ratio for Hirschsprung's disease was 2.34 (95% CI: 1.21-4.55)., Conclusions: Our data suggest that early maternal use of selective serotonin reuptake inhibitors is significantly associated with the development of Hirschsprung's disease in the newborn child. Treatment of depression during pregnancy always has to be weighed against the risks posed by untreated maternal depression. Our results have to be confirmed in other studies.

Species within the marine toxic dinoflagellate genus Dinophysis are phagotrophic organisms that exploit chloroplasts (kleptochloroplasts) from other protists to perform photosynthesis. Dinophysis spp. acquire the kleptochloroplasts from the ciliate Mesodinium rubrum, which in turn acquires the chloroplasts from a unique clade of cryptophytes. Dinophysis spp. digest the prey nuclei and all other cell organelles upon ingestion (except the kleptochloroplasts) and they are therefore believed to constantly acquire new chloroplasts as the populations grow. Previous studies have, however, indicated that Dinophysis can keep the kleptochloroplasts active during long term starvation and are able to produce photosynthetic pigments when exposed to prey starvation. This indicates a considerable control over the kleptochloroplasts and the ability of Dinophysis to replicate its kleptochloroplasts was therefore re-investigated in detail in this study. The kleptochloroplasts of Dinophysis acuta and Dinophysis acuminata were analyzed using confocal microscopy and 3D bioimaging software during long term starvation experiments. The cell concentrations were monitored to confirm cell divisions and samples were withdrawn each time a doubling had occurred. The results show direct evidence of kleptochloroplastidic division and that the decreases in total kleptochloroplast volume, number of kleptochloroplasts and number of kleptochloroplast centers were not caused by dilution due to cell divisions. This is the first report of division of kleptochloroplasts in any protist without the associated prey nuclei. This indicates that Dinophysis spp. may be in a transitional phase towards possessing permanent chloroplasts, which thereby potentially makes it a key organism to understand the evolution of phototrophic protists.

The extent to which pre-Columbian societies altered Amazonian landscapes is hotly debated. We performed a basin-wide analysis of pre-Columbian impacts on Amazonian forests by overlaying known archaeological sites in Amazonia with the distributions and abundances of 85 woody species domesticated by pre-Columbian peoples. Domesticated species are five times more likely than nondomesticated species to be hyperdominant. Across the basin, the relative abundance and richness of domesticated species increase in forests on and around archaeological sites. In southwestern and eastern Amazonia, distance to archaeological sites strongly influences the relative abundance and richness of domesticated species. Our analyses indicate that modern tree communities in Amazonia are structured to an important extent by a long history of plant domestication by Amazonian peoples., (Copyright © 2017, American Association for the Advancement of Science.)

Purpose: Critical differences state by how much 2 test results have to differ in order to be significantly different. Critical differences for discrimination scores have been available for several decades, but they do not exist for speech reception thresholds (SRTs). This study presents and discusses how critical differences for SRTs can be estimated by Monte Carlo simulations. As an application of this method, critical differences are proposed for a 5-word sentences test (a matrix test) using 2 widely implemented adaptive test procedures., Method: For each procedure, simulations were performed for different parameters: the number of test sentences, the j factor, the distribution of the subjects' true SRTs, and the slope of the discrimination function. For 1 procedure and 1 parameter setting, simulation data are compared with results found by listening tests (experimental data)., Results: The critical differences were found to depend on the parameters tested, including interactive effects. The critical differences found by simulation agree with data found experimentally., Conclusions: As the critical differences for SRTs rely on multiple parameters, they must be determined for each parameter setting individually. However, with knowledge of the test setup, rules of thumb can be derived.

Introduction: Walking is endorsed as health enhancing and is the most common type of physical activity among older adults. Accelerometers are superior to self-reports when measuring steps, however, if they are to be used by clinicians the validity is of great importance. The aim of this study was to investigate the criterion validity of Mother and ActiGraph wGT3X-BT in measuring steps by comparing the devices to a hand tally under controlled conditions in healthy participants., Methods: Thirty healthy participants were fitted with a belt containing the sensor of Mother (Motion Cookie) and ActiGraph. Participants walked on a treadmill for two minutes at each of the following speeds; 3.2, 4.8, and 6.4 km/h. The treadmill walking was video recorded and actual steps were subsequently determined by using a hand tally. Wilcoxon's signed ranks test was used to determine whether Mother and ActiGraph measured an identical number of steps compared to the hand tally. Intraclass correlation coefficients were calculated to determine the relationship and Root Mean Square error was calculated to investigate the average error between the devices and the hand tally. Percent differences (PD) were calculated for between-instrument agreement (Mother vs. the hand tally and ActiGraph vs. the hand tally) and PDs below 3% were interpreted as acceptable and clinically irrelevant., Results: Mother and ActiGraph under-counted steps significantly compared to the hand tally at all walking speeds ( p  < 0.001). Mother had a median of total differences of 9.5 steps (IQR = 10) and ActiGraph 59 steps (IQR = 77). Mother had smaller PDs at all speeds especially at 3.2 km/h (2.5% compared to 26.7%). Mother showed excellent ICC values ≥0.88 (0.51-0.96) at all speeds whilst ActiGraph had poor and fair to good ICC values ranging from 0.03 (-0.09-0.21) at a speed of 3.2 km/h to 0.64 (0.16-0.84) at a speed of 6.4 km/h., Conclusion: Mother provides valid measures of steps at walking speeds of 3.2, 4.8, and 6.4 km/h with clinically irrelevant deviations compared to a hand tally while ActiGraph only provides valid measurements at 6.4 km/h based on the 3% criterion. These results have significant potential for valid objective measurements of low walking speeds. However, further research should investigate the validity of Mother in patients at even slower walking speeds and in free-living conditions., Competing Interests: The authors declare there are no competing interests.

Introduction: Cognitive impairments are frequent in stroke. Cognitive testing is important for research, prognostication and planning in sub-acute stroke, but poses difficulties due to aphasia, hemineglect, hemiplegia and fatigue. We present the first steps towards a validation of a novel iPad-based test battery: Cognitive Assessment at Bedside for iPad (CABPad)., Patients and Methods: Stroke patients and age matched healthy controls were tested with CABPad including tests for aphasia, neglect, episodic memory, attention span, executive function, working memory, mental speed, anosognosia, motor speed and depression. A re-test was performed after 1 month. Furthermore, a group of stroke patients was tested with CABPad and traditional neuropsychological tests., Results: Fifty-four patients and 48 healthy controls were included in the first phase. Fifty-three patients (98%) were able to complete at least one test and 50 (92%) all tests at the first test point. Mean test duration in patients was 39 min (range 30-60). We found significant differences in test results at baseline between the two groups. Episodic memory mean difference: 8.5 (95% confidence interval: 4.3, 12.7). Symbol Digit Coding mean difference: 16.3 (95% confidence interval: 10.8, 21.7). The second phase included 16 patients. We found adequate to excellent correlation in the majority of the tests. The CABPad Speech Comprehension test and the Auditory Word Recognition subtest of the Western Aphasia Battery correlated with r = 0.82, p  < 0.001., Conclusion: CABPad is useful for cognitive testing in stroke patients. It is easy to use for the examiner and patients alike. Immobile patients can be tested at bedside, irrespectively of upper extremity paresis, and the assessment can be performed in a relatively short timespan., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: CABPad was developed and is sold by neuropsychologist Palle Møller Pedersen, Cognisoft Aps.

Objective: Examination of Danish data for medico-legal compensations regarding hearing disabilities. The study purposes are: (1) to investigate whether discrimination scores (DSs) relate to patients' subjective experience of their hearing and communication ability (the latter referring to audio-visual perception), (2) to compare DSs from different discrimination tests (auditory/audio-visual perception and without/with noise), and (3) to relate different handicap measures in the scaling used for compensation purposes in Denmark., Design: Data from a 15 year period (1999-2014) were collected and analysed., Study Sample: The data set includes 466 patients, from which 50 were omitted due to suspicion of having exaggerated their hearing disabilities., Results: The DSs relate well to the patients' subjective experience of their speech perception ability. By comparing DSs for different test setups it was found that adding noise entails a relatively more difficult listening condition than removing visual cues. The hearing and communication handicap degrees were found to agree, whereas the measured handicap degrees tended to be higher than the self-assessed handicap degrees., Conclusions: The DSs can be used to assess patients' hearing and communication abilities. The difference in the obtained handicap degrees emphasizes the importance of collecting self-assessed as well as measured handicap degrees.

A method for vector velocity volume flow estimation is presented, along with an investigation of its sources of error and correction of actual volume flow measurements. Volume flow errors are quantified theoretically by numerical modeling, through flow phantom measurements, and studied in vivo. This paper investigates errors from estimating volumetric flow using a commercial ultrasound scanner and the common assumptions made in the literature. The theoretical model shows, e.g. that volume flow is underestimated by 15%, when the scan plane is off-axis with the vessel center by 28% of the vessel radius. The error sources were also studied in vivo under realistic clinical conditions, and the theoretical results were applied for correcting the volume flow errors. Twenty dialysis patients with arteriovenous fistulas were scanned to obtain vector flow maps of fistulas. When fitting an ellipsis to cross-sectional scans of the fistulas, the major axis was on average 10.2mm, which is 8.6% larger than the minor axis. The ultrasound beam was on average 1.5mm from the vessel center, corresponding to 28% of the semi-major axis in an average fistula. Estimating volume flow with an elliptical, rather than circular, vessel area and correcting the ultrasound beam for being off-axis, gave a significant (p=0.008) reduction in error from 31.2% to 24.3%. The error is relative to the Ultrasound Dilution Technique, which is considered the gold standard for volume flow estimation for dialysis patients. The study shows the importance of correcting for volume flow errors, which are often made in clinical practice., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Amazonia is the most biodiverse rainforest on Earth, and the debate over how many tree species grow there remains contentious. Here we provide a checklist of all tree species collected to date, and describe spatial and temporal trends in data accumulation. We report 530,025 unique collections of trees in Amazonia, dating between 1707 and 2015, for a total of 11,676 species in 1225 genera and 140 families. These figures support recent estimates of 16,000 total Amazonian tree species based on ecological plot data from the Amazonian Tree Diversity Network. Botanical collection in Amazonia is characterized by three major peaks, centred around 1840, 1920, and 1980, which are associated with flora projects and the establishment of inventory plots. Most collections were made in the 20th century. The number of collections has increased exponentially, but shows a slowdown in the last two decades. We find that a species' range size is a better predictor of the number of times it has been collected than the species' estimated basin-wide population size. Finding, describing, and documenting the distribution of the remaining species will require coordinated efforts at under-collected sites.

Estimates of extinction risk for Amazonian plant and animal species are rare and not often incorporated into land-use policy and conservation planning. We overlay spatial distribution models with historical and projected deforestation to show that at least 36% and up to 57% of all Amazonian tree species are likely to qualify as globally threatened under International Union for Conservation of Nature (IUCN) Red List criteria. If confirmed, these results would increase the number of threatened plant species on Earth by 22%. We show that the trends observed in Amazonia apply to trees throughout the tropics, and we predict that most of the world's >40,000 tropical tree species now qualify as globally threatened. A gap analysis suggests that existing Amazonian protected areas and indigenous territories will protect viable populations of most threatened species if these areas suffer no further degradation, highlighting the key roles that protected areas, indigenous peoples, and improved governance can play in preventing large-scale extinctions in the tropics in this century.

The purpose of the study was to perform a clinical comparison of synthetic aperture sequential beamforming tissue harmonic imaging (SASB-THI) sequences with a conventional imaging technique, dynamic receive focusing with THI (DRF-THI). Both techniques used pulse inversion and were recorded interleaved using a commercial ultrasound system (UltraView 800, BK Medical, Herlev, Denmark). Thirty-one patients with malignant focal liver lesions (confirmed by biopsy or computed tomography/magnetic resonance) were scanned. Detection of malignant focal liver lesions and preference of image quality were evaluated blinded off-line by eight radiologists. In total, 2,032 evaluations of 127 image sequences were completed. The sensitivity (77% SASB-THI, 76% DRF-THI, p = 0.54) and specificity (71% SASB-THI, 72% DRF-THI, p = 0.67) of detection of liver lesions and the evaluation of image quality (p = 0.63) did not differ between SASB-THI and DRF-THI. This study indicates the ability of SASB-THI in a true clinical setting., (Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Background: The 5'-triphosphorylated, 2'-5'-linked oligoadenylate polyribonucleotides (2-5As) are central to the interferon-induced antiviral 2-5A system. The 2-5As bind and activate the RNase L, an endoRNase degrading viral and cellular RNA leading to inhibition of viral replication. The 2-5A system is tightly controlled by synthesis and degradation of 2-5As. Whereas synthesis is mediated by the 2'-5' oligoadenylate synthetase family of enzymes, degradation seems to be orchestrated by multiple enzyme nucleases including phosphodiesterase 12, the ectonucleotide pyrophosphatase/phosphodiesterase 1 and the A-kinase anchoring protein 7., Results: Here we present assay tools for identification and characterization of the enzymes regulating cellular 2-5A levels. A procedure is described for the production of 2'-5' oligoadenylates, which are then used as substrates for development and demonstration of enzyme assays measuring synthetase and nuclease activities, respectively. The synthetase assays produce only a single reaction product allowing for very precise kinetic assessment of the enzymes. We present an assay using dATP and the A(pA)3 tetramer core as substrates, which requires prior isolation of A(pA)3. A synthetase assay using either of the dNTPs individually together with NAD(+) as substrates is also presented. The nuclease reactions make use of the isolated 2'-5' oligoadenylates in producing a mixture of shorter reaction products, which are resolved by ion-exchange chromatography to determine the enzyme activities. A purified human 2'-5' oligoadenylate synthetase and a purified human phosphodiesterase 12 along with crude extracts expressing those proteins, are used to demonstrate the assays., Conclusions: This paper comprises an assay toolbox for identification and characterization of the synthetases and nucleases regulating cellular 2-5A levels. Assays are presented for both enzyme families. The assays can also be used to address a broader cellular role of the OAS enzymes, based on the multiple substrate specificity intrinsic to these proteins.

Background and Purpose: It is unclear whether mobile-bearing (MB) total knee arthroplasties reduce the risk of tibial component loosening compared to fixed-bearing (FB) designs. This randomized study investigated implant migration, periprosthetic bone mineral density (BMD), and patient-reported outcomes (Oxford knee score)-all at 2 years-for the P.F.C. Sigma Cruciate Retaining total knee arthroplasty., Patients and Methods: 50 osteoarthritis patients were allocated to either FB or MB tibial articulation., Results and Interpretation: At 2 years, the mean total translation (implant migration) was higher for the FB implant (0.30 mm, SD 0.22) than for the MB implant (0.17 mm, SD 0.09) (p = 0.04). BMD decreased between baseline and 1-year follow-up. At 2-year follow-up, BMD was close to the baseline level. The knee scores of both groups improved equally well. The FB tibial implant migrated more than the MB, but this was not clinically significant. The mobile polyethylene presumably partly absorbs the force transmitted to the metal tibial tray, thereby reducing micromotion.

The vector velocity method Transverse Oscillation (TO) implemented on a conventional ultrasound (US) scanner (ProFocus, BK Medical, Herlev, Denmark) can provide real-time, angle-independent estimates of the cardiac blood flow. During cardiac surgery, epicardial US examination using TO was performed on (A) 3 patients with healthy aortic valve and (B) 3 patients with aortic valve stenosis. In group B, the systolic flow of the ascending aorta had higher velocities, was more aliased and chaotic. The jet narrowed to 44% of the lumen compared to 75% in group A and with a vector concentration, a measure of flow complexity, of 0.41 compared to 0.87 in group A. The two groups had similar secondary flow of the ascending aorta with an average rotation frequency of 4.8 Hz. Simultaneous measurements were obtained with spectral Doppler (SD) and a thermodilution technique (TD). The mean difference in peak systolic velocity compared to SD in group A was 22% and 45% in B, while the mean difference in volume flow compared to TD in group A was 30% and 32% in B. TO can potentially reveal new information of cardiac blood flow, and may become a valuable diagnostic tool in the evaluation of patients with cardiovascular diseases., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Medical ultrasound imaging using synthetic aperture sequential beamforming (SASB) has for the first time been used for clinical patient scanning. Nineteen patients with cancer of the liver (hepatocellular carcinoma or colorectal liver metastases) were scanned simultaneously with conventional ultrasound and SASB using a commercial ultrasound scanner and abdominal transducer. SASB allows implementation of the synthetic aperture technique on systems with restricted data handling capabilities due to a reduction in the data rate in the scanner by a factor of 64. The image quality is potentially maintained despite the data reduction. A total of 117 sequences were recorded and evaluated blinded by five radiologists from a clinical perspective. Forty-eight percent of the evaluations were in favor of SASB, 33% in favor of conventional ultrasound and 19 % were equal, that is, a clear, but non-significant trend favoring SASB over conventional ultrasound (p = 0.18), despite the substantial data reduction., (Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Volume flow in arteriovenous fistulas for hemodialysis was measured using the angle-independent ultrasound technique Vector Flow Imaging and compared with flow measurements using the ultrasound dilution technique during dialysis. Using an UltraView 800 ultrasound scanner (BK Medical, Herlev, Denmark) with a linear transducer, 20 arteriovenous fistulas were scanned directly on the most superficial part of the fistula just before dialysis. Vector Flow Imaging volume flow was estimated with two different approaches, using the maximum and the average flow velocities detected in the fistula. Flow was estimated to be 242 mL/min and 404 mL/min lower than the ultrasound dilution technique estimate, depending on the approach. The standard deviations of the two Vector Flow Imaging approaches were 175.9 mL/min and 164.8 mL/min compared with a standard deviation of 136.9 mL/min using the ultrasound dilution technique. The study supports that Vector Flow Imaging is applicable for volume flow measurements., (Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)