Search

Objective of this retrospective study was to determine if long-term continuous cardiac monitoring with Implantable loop recorder (ILR) in patients with Cryptogenic strokes or TIA is superior at detecting Atrial Fibrillation (AF) than 30-day Event Monitor (EM) and 48-hour Holter Monitor (HM). Furthermore, we aimed to deduce if uncovering AF leads to lower risk of future ischemic strokes, or reduction in mortality. In 20%-30% cases, the cause of stroke remained unexplained after diagnostic workup which has led to coining of the term, Cryptogenic Stroke (CS). Undiagnosed AF is a prime suspect in CS, but guidelines do not recommend initiation of anticoagulation unless AF has formally been detected. IRB approved retrospective study included patients with at least 1 episode of ischemic stroke or TIA without identifiable cause and was monitored with either HM, EM or ILR to diagnose any undiscovered AF. All patients (n = 531) had at least 1 year, and up to 3 years, of follow-up after device placement. Chi-Squared analysis and Multivariable logistic regression demonstrated no statistically significant difference among 3 devices for detection of AF within 1 month of index stroke but a significant difference in AF detection was observed at 6, 12 and 24 months. Cox proportional hazard model showed device type had no significant impact on secondary outcomes: Subsequent ischemic stroke or TIA, Initiation of anticoagulation, Mortality and Incidence of major bleeding. Despite the superiority of AF detection by ILR, it is not superior to HM or EM in lowering the risk of subsequent stroke or TIA, or in reducing mortality.

We have recently reported that hypobaric hypoxia (HH) reduces plasma volume (PV) in men by decreasing total circulating plasma protein (TCPP). Here, we investigated whether this applies to women and whether an inflammatory response and/or endothelial glycocalyx shedding could facilitate the TCCP reduction. We further investigated whether acute HH induces a short-lived diuretic response that was overlooked in our recent study, where only 24-h urine volumes were evaluated. In a strictly controlled crossover protocol, 12 women underwent two 4-day sojourns in a hypobaric chamber: one in normoxia (NX) and one in HH equivalent to 3,500-m altitude. PV, urine output, TCPP, and markers for inflammation and glycocalyx shedding were repeatedly measured. Total body water (TBW) was determined pre- and postsojourns by deuterium dilution. PV was reduced after 12 h of HH and thereafter remained 230-330 mL lower than in NX (P < 0.0001). Urine flow was 45% higher in HH than in NX throughout the first 6 h (P = 0.01) but lower during the second half of the first day (P < 0.001). Twenty-four-hour urine volumes (P ≥ 0.37) and TBW (P ≥ 0.14) were not different between the sojourns. TCPP was lower in HH than in NX at the same time points as PV (P < 0.001), but inflammatory or glycocalyx shedding markers were not consistently increased. As in men, and despite initially increased diuresis, HH-induced PV contraction in women is driven by a loss of TCPP and ensuing fluid redistribution, rather than by fluid loss. The mechanism underlying the TCPP reduction remains unclear but does not seem to involve inflammation or glycocalyx shedding.NEW & NOTEWORTHY This study is the first to investigate the mechanisms underlying plasma volume (PV) contraction in response to hypoxia in women while strictly controlling for confounders. PV contraction in women has a similar time course and magnitude as in men and is driven by the same mechanism, namely, oncotically driven redistribution rather than loss of fluid. We further report that hypoxia facilitates an increase in diuresis, that is, however, short-lived and of little relevance for PV regulation.

Mitral regurgitation is the most common valvular disease in the US and the second most common worldwide. Left untreated, it can lead to the development of heart failure, giving rise to increased mortality rates. Mitral valve intervention is usually indicated in severe mitral regurgitation at the onset of symptoms, even if the function of the left ventricle is preserved. A surgical approach is generally favored according to current guidelines, with excellent clinical outcomes. However, the emergence of novel data from contemporary trials indicates that percutaneous, catheter-based approach may have similar improvements in mortality outcomes while maintaining a superior safety profile when compared to the surgical approach. Here, we discuss transcatheter mitral valve repair as a treatment option for mitral regurgitation and summarize the major clinical trials which were recently conducted on transcatheter repair.

Cardiovascular disease remains the leading cause of death globally and here in the United States. Diet has a major impact on the pathogenesis of atherosclerosis and subsequent cardiovascular morbidity and mortality. An unhealthy diet is the most significant potential behavioral and modifiable risk factor for ischemic heart disease. Despite these established facts, dietary interventions are far less frequent than pharmaceutical and procedural interventions in the management of cardiovascular disease. The beneficial effects of a plant-based diet on cardiovascular morbidity and mortality have been demonstrated in a number of recent clinical studies. The significant findings of each study are discussed in this review article, highlighting the role of a healthy plant-based diet in improving cardiovascular outcomes. From a clinician’s standpoint, the knowledge and understanding of the facts and data points from these recent clinical studies would ensure more effective patient counseling on the substantial benefits of dietary interventions.

Norsminde Fjord has received extensive geoarchaeological investigation, hosting one of the classic Stone Age shell midden sites in Denmark, and one of the best examples of the widespread oyster decline at the Mesolithic–Neolithic transition. Here, intra-shell δ18O (and δ13C) analyses from the common periwinkle Littorina littorea (L.) are used to infer inter-annual environmental changes at the Mesolithic–Neolithic transition (four from each period). This study utilises a modern δ18O L. littorea-salinity training set previously developed for the Limfjord, Denmark to quantify winter salinity. δ18O values range between +1.6% and +4.0% in the late Mesolithic and ‒6.3% to +2.0% in the early Neolithic. Using maximum δ18O values, winter salinity at the known temperature of growth cessation in L. littorea (i.e. +3.7 ± 1°C) for the first annual cycle of each shell ranges between 25.5 and 26.8 psu (standard deviation (SD): 0.56) for the late Mesolithic, with an average salinity of 26.1 psu. Early-Neolithic shells range between 19.4 and 28.2 psu (SD: 4.59) with an average salinity of 23.7 psu. No statistically significant change in salinity occurs between the late Mesolithic and early Neolithic. This result supports recent diatom/mollusc-based inferences that salinity was not the sole cause of the oyster decline, although some evidence is presented here for more variable seasonal salinity conditions in the early Neolithic, which (along sedimentary change and temperature deterioration) might have increased stress on oyster populations in some years. It is recommended here that for robust palaeoenvironmental inferences, where possible, multiple specimens should be used from the same time period in conjunction with multiproxy data.

Cardiovascular disease (CVD) is a major contributor to morbidity and mortality worldwide. An abundance of research demonstrated that low‑density lipoprotein cholesterol (LDL‑C) is an important risk factor for CVD that can be modified with the drug class hydroxymethylglutaryl‑CoA reductase inhibitors, or statins.Statins have an unequivocal benefit in reducing CVD risk across age groups for secondary prevention. However, the benefit of these drugs for primary prevention in adults older than 75 years of age remains equivocal and controversial. The global population is aging rapidly and primary CVD prevention recommendations to guide statin therapy above the age of 75 years are necessary. However, current trends in statin therapy illustrate that it is underutilized for primary prevention in that age group. Concerns exist regarding the higher incidence of common adverse events from statin use in the older population; however, there are no confirmatory data regarding these associations. In the light of available evidence, it is reasonable to offer statin therapy for primary prevention to all older individuals following a shared decision‑making process that takes life expectancy, polypharmacy, frailty, and potential adverse effects into consideration. Combination therapies with other agents for the management of dyslipidemia should be considered to facilitate the use of tolerable doses of statins. Future investigations of dyslipidemia therapies must appropriately include this at‑risk population to identify optimal drugs and drug combinations that have a high benefit‑to ‑risk ratio for the prevention of CVD in the very old.

Scope Within the last decade, quinoa seeds have gained much popularity as a new food and have recently been proposed as an appropriate food for early introduction in infants. Quinoa contains high levels of saponins, which are known for their adjuvant activity and effect on the intestinal barrier function. The aim of this study is to investigate the impact of quinoa on intestinal permeability and inflammation in comparison with the positive controls; cholera toxin (CT), and capsaicin. Methods and results The effect of quinoa on intestinal barrier function and inflammation is investigated in vitro using a Caco-2 cell line and in vivo using a Brown Norway rat model. Effects in vivo are analyzed by protein uptake, histology, gene expression, antibody levels, and flow cytometry. Quinoa and the positive controls all increased the intestinal permeability, but distinct patterns of absorbed protein are observed in the epithelium, Peyer's patches, lamina propria, and serum. The quinoa-mediated effect on intestinal barrier function is found to be distinct from the effect of the two positive controls. Conclusion The findings demonstrate the ability of quinoa to increase intestinal permeability and to promote compartment-specific protein uptake via mechanisms that may differ from CT and capsaicin.

Performance management systems often come with politically decided goals. Contemporary theory on political goal setting tells us that these goals may contain electoral benefits for politicians, but also that there may be drawbacks such as gaming by public employees. Despite a surge in the use of such goals and in the performance management literature in recent years, almost no research has been done on how citizens react to political goal setting. We introduce a theoretical model of goals that varies from the very quantitative and concrete targets to more broad and ambiguous visions. We test the model in a representative conjoint experiment in Denmark in which citizens are asked to evaluate and choose between daycare institutions. The conjoint is embedded within a survey experiment that assigns the respondents to information about either the political target for a given service area, the political vision for the same service area, or to the control group. We evaluate the target and vision treatments on whether citizens are more or less likely to choose a daycare institution, daycare performance, and how they attribute responsibility for government performance.

Various generic extraction methods have been used to determine pesticide residues, mycotoxins, and polycyclic aromatic hydrocarbons (PAHs) in food and animal feed to ensure consumer safety. However, these methods cannot extract all relevant compounds at an acceptable rate of recovery. This study presents a new extraction method. This new method facilitated the identification of 231 compounds, including 196 pesticides, 11 mycotoxins, and 24 PAHs over a broad range of polarities. These compounds were identified in various sample matrices, including those that are lipid-rich. The processed sample is first extracted with water, acetonitrile, formic acid, and heptane. The addition of ammonium formate results in separation into three phases and enables analysis of the aqueous phase. Solid-phase extraction clean-up procedures were performed as necessary followed by analysis by liquid or gas chromatography and mass spectrometry. Analyte recoveries were typically in the range of 70 - 120% with relative standard deviations below 20%.

An emerging literature in behavioral public administration shows that performance information affects the perceptions and choices of citizens vis-a-vis public services and programs. Methodologically, a significant share of these studies rely on hypothetical scenario experiments or they focus on citizen assessments of broader government entities that citizens have little or no direct interaction with or personal information about. Yet, among actual service users, performance data is only one among many sources of information, potentially limiting its influence. Service users might also engage in motivated reasoning, for instance, by questioning the validity and relevance of inconvenient information about service providers they are otherwise happy with, or whom they are responsible for choosing. In this study, we conducted a survey experiment in the field, offering true performance data to service users, namely parents with children in public schools. We consistently find little or no evidence that performance information affects user satisfaction, intended voice and exit behaviors, incumbency voting, or goal prioritization. These findings question the feasibility of using performance information disclosure to affect the judgments and choices of service users, with potentially important downstream effects on the incentives facing public service providers. An emerging literature in behavioral public administration shows that performance information affects the perceptions and choices of citizens vis-a-vis public services and programs. Methodologically, a significant share of these studies rely on hypothetical scenario experiments or they focus on citizen assessments of broader government entities that citizens have little or no direct interaction with or personal information about. Yet, among actual service users, performance data is only one among many sources of information, potentially limiting its influence. Service users might also engage in motivated reasoning, for instance, by questioning the validity and relevance of inconvenient information about service providers they are otherwise happy with, or whom they are responsible for choosing. In this study, we conducted a survey experiment in the field, offering true performance data to service users, namely parents with children in public schools. We consistently find little or no evidence that performance information affects user satisfaction, intended voice and exit behaviors, incumbency voting, or goal prioritization. These findings question the feasibility of using performance information disclosure to affect the judgments and choices of service users, with potentially important downstream effects on the incentives facing public service providers.

Supplemental Digital Content is available in the text., Background and Purpose: Stent-assisted coil embolization using the new generation Neuroform Atlas Stent System has shown promising safety and efficacy. The primary study results of the anterior circulation aneurysm cohort of the treatment of wide-neck, saccular, intracranial, aneurysms with the Neuroform Atlas Stent System (ATLAS trial [Safety and Effectiveness of the Treatment of Wide Neck, Saccular Intracranial Aneurysms With the Neuroform Atlas Stent System]) are presented. Methods: ATLAS IDE trial (Investigational Device Exemption) is a prospective, multicenter, single-arm, open-label study of wide-neck (neck ≥4 mm or dome-to-neck ratio 50%) at the target location. The primary safety end point was any major stroke or ipsilateral stroke or neurological death within 12 months. Adjudication of the primary end points was performed by an independent Imaging Core Laboratory and the Clinical Events Committee. Results: A total of 182 patients with wide-neck anterior circulation aneurysms at 25 US centers were enrolled. The mean age was 60.3±11.4 years, 73.1% (133/182) women, and 80.8% (147/182) white. Mean aneurysm size was 6.1±2.2 mm, mean neck width was 4.1±1.2 mm, and mean dome-to-neck ratio was 1.2±0.3. The most frequent aneurysm locations were the anterior communicating artery (64/182, 35.2%), internal carotid artery ophthalmic artery segment (29/182, 15.9%), and middle cerebral artery bifurcation (27/182, 14.8%). Stents were placed in the anticipated anatomic location in all patients. The study met both primary safety and efficacy end points. The composite primary efficacy end point of complete aneurysm occlusion (Raymond-Roy 1) without parent artery stenosis or aneurysm retreatment was achieved in 84.7% (95% CI, 78.6%–90.9%) of patients. Overall, 4.4% (8/182, 95% CI, 1.9%–8.5%) of patients experienced a primary safety end point of major ipsilateral stroke or neurological death. Conclusions: In the ATLAS IDE anterior circulation aneurysm cohort premarket approval study, the Neuroform Atlas stent with adjunctive coiling met the primary end points and demonstrated high rates of long-term complete aneurysm occlusion at 12 months, with 100% technical success and

BACKGROUND Patient satisfaction with in-person medical visits includes patient-clinician engagement. However, communication, empathy, and other relationship-centered care measures in virtual visits have not been adequately investigated. OBJECTIVE This study aims to comprehensively consider patient experience, including relationship-centered care measures, to assess patient satisfaction during virtual visits. METHODS We conducted a large survey study with open-ended questions to comprehensively assess patients’ experiences with virtual visits in a diverse patient population. Adults with a virtual visit between June 21, 2017, and July 12, 2017, were invited to complete a survey of 21 Likert-scale items and textboxes for comments following their visit. Factor analysis of the survey items revealed three factors: experience with technology, patient-clinician engagement, and overall satisfaction. Multivariable logistic regression was used to test the associations among the three factors and patient demographics, clinician type, and prior relationship with the clinician. Using qualitative framework analysis, we identified recurrent themes in survey comments, quantitatively coded comments, and computed descriptive statistics of the coded comments. RESULTS A total of 65.7% (426/648) of the patients completed the survey; 64.1% (273/426) of the respondents were women, and the average age was 46 (range 18-86) years. The sample was geographically diverse: 70.2% (299/426) from Ohio, 6.8% (29/426) from Florida, 4.2% (18/426) from Pennsylvania, and 18.7% (80/426) from other states. With regard to insurance coverage, 57.5% (245/426) were undetermined, 23.7% (101/426) had the hospital’s employee health insurance, and 18.7% (80/426) had other private insurance. Types of virtual visits and clinicians varied. Overall, 58.4% (249/426) of patients had an on-demand visit, whereas 41.5% (177/426) had a scheduled visit. A total of 41.8% (178/426) of patients had a virtual visit with a family physician, 20.9% (89/426) with an advanced practice provider, and the rest had a visit with a specialist. Most patients (393/423, 92.9%) agreed that their virtual visit clinician was interested in them as a person, and their virtual visit made it easy to get the care they needed (383/421, 90.9%). A total of 81.9% (344/420) of respondents agreed or strongly agreed that their virtual visit was as good as an in-person visit by a clinician. Having a prior relationship with their virtual visit clinician was associated with less comfort and ease with virtual technology among patients (odds ratio 0.58, 95% CI 0.35-0.98). In terms of technology, patients found the interface easy to use (392/423, 92.7%) and felt comfortable using it (401/423, 94.8%). Technical difficulties were associated with lower odds of overall satisfaction (odds ratio 0.46, 95% CI 0.28-0.76). CONCLUSIONS Patient-clinician engagement in virtual visits was comparable with in-person visits. This study supports the value and acceptance of virtual visits. Evaluations of virtual visits should include assessments of technology and patient-clinician engagement, as both are likely to influence patient satisfaction.

How climate and ecology affect key cultural transformations remains debated in the context of long-term socio-cultural development because of spatially and temporally disjunct climate and archaeological records. The introduction of agriculture triggered a major population increase across Europe. However, in Southern Scandinavia it was preceded by ~500 years of sustained population growth. Here we show that this growth was driven by long-term enhanced marine production conditioned by the Holocene Thermal Maximum, a time of elevated temperature, sea level and salinity across coastal waters. We identify two periods of increased marine production across trophic levels (P1 7600–7100 and P2 6400–5900 cal. yr BP) that coincide with markedly increased mollusc collection and accumulation of shell middens, indicating greater marine resource availability. Between ~7600–5900 BP, intense exploitation of a warmer, more productive marine environment by Mesolithic hunter-gatherers drove cultural development, including maritime technological innovation, and from ca. 6400–5900 BP, underpinned a ~four-fold human population growth., How the development of human societies is influenced through their ecological environment and climatic conditions has been the subject of intensive debate. Here, the authors present multi-proxy data from southern Scandinavia which suggests that pre-agricultural population growth there was likely influenced by enhanced marine production.

Holocene sedimentation patterns and environmental development in Aarhus Bay, Denmark, were reconstructed based on proxy analyses of two sediment cores (M1 and M5). Together, the two cores offer an opportunity to examine the history of the area during the past c. 10 000 years. The investigation consisted of acoustic mapping and multi-proxy analyses of the sediment cores including macrofossils, sediment physical properties, sediment accumulation rates, grain size, and X-ray fluorescence elemental counts. Radiocarbon dating of the two sediment successions revealed that they cover the periods c. 10 000–3700 cal. a BP (M1) and c. 4400 cal. a BP to the present (M5). The data from the M1 site indicate the presence of a near-shore lake environment between c. 10 000 and 9000 cal. a BP. The first intrusion of marine water into the area is dated to c. 9000 cal. a BP. In the following c. 1300 years, brackish-water conditions prevailed in the area characterized by a mixture of taxa from marine, limnic and terrestrial habitats, reflecting a shallow estuarine environment. Around 7700 cal. a BP full marine conditions were established, accompanied by a marked increase in sedimentation rates. The changes to full marine conditions and higher sedimentation rates are probably due to a significant sea-level rise leading to flooding of former land areas and intensified erosion. A subsequent distinct decrease in sedimentation rates around 6350 cal. a BP is presumably linked to a previously documented sea-level drop about this time. Continuous sedimentation ceased around 3700 cal. a BP in the central part of the bay, most probably due to a major sea-level lowering involving widespread erosion. In the eastern and deeper part of the bay, sedimentation continued until today. Fully marine conditions prevailed there for at least the last 4400 years.

Studies of the resting brain measurements of cerebral blood flow (CBF) show large interindividual and regional variability, but the metabolic basis of this variability is not fully established. The aim of the present study was to reassess regional and interindividual relationships between cerebral perfusion and glucose metabolism in the resting brain. Regional quantitative measurements of CBF and cerebral metabolic rate of glucose (CMRglc) were obtained in 24 healthy young men using dynamic [15O]H2O and [18F]fluorodeoxyglucose positron emission tomography (PET). Magnetic resonance imaging measurements of global oxygen extraction fraction (gOEF) and metabolic rate of oxygen ([Formula: see text]) were obtained by combined susceptometry-based sagittal sinus oximetry and phase contrast mapping. No significant interindividual associations between global CBF, global CMRglc, and [Formula: see text] were observed. Linear mixed-model analysis showed a highly significant association of CBF with CMRglc regionally. Compared with neocortex significantly higher CBF values than explained by CMRglc were demonstrated in infratentorial structures, thalami, and mesial temporal cortex, and lower values were found in the striatum and cerebral white matter. The present study shows that absolute quantitative global CBF measurements appear not to be a valid surrogate measure of global cerebral glucose or oxygen consumption, and further demonstrates regionally variable relationship between perfusion and glucose metabolism in the resting brain that could suggest regional differences in energy substrate metabolism. NEW & NOTEWORTHY Using method-independent techniques the study cannot confirm direct interindividual correlations of absolute global values of perfusion with oxygen or glucose metabolism in the resting brain, and absolute global perfusion measurements appear not to be valid surrogate measures of cerebral metabolism. The ratio of both perfusion and oxygen delivery to glucose metabolism varies regionally, also when accounting for known methodological regional bias in quantification of glucose metabolism.

This study examined to what extent the human cerebral and femoral circulation contribute to free radical formation during basal and exercise-induced responses to hypoxia. Healthy participants (5♂, 5♀) were randomly assigned single-blinded to normoxic (21% O2) and hypoxic (10% O2) trials with measurements taken at rest and 30 min after cycling at 70% of maximal power output in hypoxia and equivalent relative and absolute intensities in normoxia. Blood was sampled from the brachial artery (a), internal jugular and femoral veins (v) for non-enzymatic antioxidants (HPLC), ascorbate radical (A•-, electron paramagnetic resonance spectroscopy), lipid hydroperoxides (LOOH) and low density lipoprotein (LDL) oxidation (spectrophotometry). Cerebral and femoral venous blood flow was evaluated by transcranial Doppler ultrasound (CBF) and constant infusion thermodilution (FBF). With 3 participants lost to follow up (final n = 4♂, 3♀), hypoxia increased CBF and FBF (P = 0.041 vs. normoxia) with further elevations in FBF during exercise (P = 0.002 vs. rest). Cerebral and femoral ascorbate and α-tocopherol consumption (v a) and increased LDL oxidation during hypoxia (P < 0.043-0.049 vs. normoxia) implying free radical-mediated lipid peroxidation subsequent to inadequate antioxidant defense. This was pronounced during exercise across the femoral circulation in proportion to the increase in local O2 uptake (r = -0.397 to -0.459, P = 0.037-0.045) but unrelated to any reduction in PO2. These findings highlight considerable regional heterogeneity in the oxidative stress response to hypoxia that may be more attributable to local differences in O2 flux than to O2 tension.

Although humans have impacted their environment over millennia, details of these impacts, especially on aquatic systems, is still surprisingly scarce despite potential disturbance by early land use. This study examined a high-resolution radiocarbon-dated Holocene record from the Danish Lake Vaeng, using geochemical and biological proxies, and related the observed impacts to other lake records with catchment disturbance. The results indicate a lengthy and varying history of aquatic eutrophication linked to human activity. Modest impacts on the lake coincided with the first signs of landscape disturbance during the Neolithic (c. 4500 cal. yrs BP). Observed impacts intensified in the Late Bronze and Pre-Roman Iron Age. Viking Age/Medieval deforestation and erosional inputs to the lake associated with new ploughing technology (1200 cal. yrs BP), however, led to a major reorganisation of the aquatic ecosystem. Filamentous bloom-forming cyanobacteria, common today in heavily culturally impacted lakes, reached a historical maxima. The lake ecosystem subsequently recovered somewhat but remains eutrophic to date. The erosion record from Lake Vaeng shows a striking similarity with other Danish lake records, especially the notable increase in Medieval Period catchment inputs, which are observed in other European lacustrine records. Numerous European lowland lakes may have shifted into a degraded ecological state millennia ago, but degradation intensified during the onset of the Medieval Period. Hence, assuming pre-industrial conditions as relatively pristine reference baselines for more recent cultural eutrophication could be flawed in landscapes intensively used by humans for millennia.

Background: The mechanisms underlying red blood cell (RBC)–mediated hypoxic vasodilation remain controversial, with separate roles for nitrite ( ) and S -nitrosohemoglobin (SNO-Hb) widely contested given their ability to transduce nitric oxide bioactivity within the microcirculation. To establish their relative contribution in vivo, we quantified arterial-venous concentration gradients across the human cerebral and femoral circulation at rest and during exercise, an ideal model system characterized by physiological extremes of O 2 tension and blood flow. Methods: Ten healthy participants (5 men, 5 women) aged 24±4 (mean±SD) years old were randomly assigned to a normoxic (21% O 2 ) and hypoxic (10% O 2 ) trial with measurements performed at rest and after 30 minutes of cycling at 70% of maximal power output in hypoxia and equivalent relative and absolute intensities in normoxia. Blood was sampled simultaneously from the brachial artery and internal jugular and femoral veins with plasma and RBC nitric oxide metabolites measured by tri-iodide reductive chemiluminescence. Blood flow was determined by transcranial Doppler ultrasound (cerebral blood flow) and constant infusion thermodilution (femoral blood flow) with net exchange calculated via the Fick principle. Results: Hypoxia was associated with a mild increase in both cerebral blood flow and femoral blood flow ( P P r =0.680–0.769, P gradients reflecting consumption (arterial>venous; P arterial; P P P P S -nitrosothiols ( P >0.05). Conclusions: These findings suggest that hypoxia and, to a far greater extent, exercise independently promote arterial-venous delivery gradients of intravascular nitric oxide, with deoxyhemoglobin-mediated reduction identified as the dominant mechanism underlying hypoxic vasodilation.

The well-known and widespread replacement of oysters (abundant during the Mesolithic period) by cockles and mussels in many Danish Stone Age shell middens ca. 5900 cal yrs BP coincides with the transition to agriculture in southern Scandinavia. This human resource shift is commonly believed to reflect changing resource availability, driven by environmental and/or climatic change at the Mesolithic-Neolithic transition rather than cultural choice. While several hypotheses have been proposed to explain the “Mesolithic-Neolithic oyster decline”, an explanation based on a sudden freshening of the inner Danish waters has received most attention. Here, for the first time, we test and refute this long-standing hypothesis that declining salinity explains the marked reduction in oysters identified within numerous shell middens across coastal Denmark at the Mesolithic-Neolithic transition using quantitative and qualitative salinity inference from several, independent proxies (diatoms, molluscs and foraminifera) from multiple Danish fjord sites. Alternatively, we attribute the oyster decline to other environmental causes (particularly changing sedimentation), ultimately driven by external climatic forcing. Critical application of such high-quality environmental archives can reinvigorate archaeological debates and can aid in understanding and managing environmental change in increasingly impacted coastal regions.

The addition of non-pollen palynomorphs (NPPs) to pollen analytical studies has improved the interpretational frame, especially concerning the local regime in anthropogenically disturbed environments. Using advanced ordination techniques this paper explores the variation of NPP-assemblages and the indicative value of individual NPP-types by comparison to independent classical proxies. Sediment samples from a forest hollow at Tårup Lund, Denmark, covering the last 5,500 years, were prepared for NPP-analysis using a non-aggressive procedure. Correlations between non-pollen palynomorphs and sediment, pollen and macrofossil inferred environmental explanatory variables were studied based on a constant counting sum of NPPs. This approach identified main drivers influencing NPP assemblage composition and indicated that a change in these drivers occurred at the onset of the Pre-Roman Iron Age. Twelve known and 12 specific, but so far unknown, NPPs correlating with the environmental variables were identified and their possible indicator value presented. The mild preparation procedure resulted in a very large dataset allowing for sub-assemblages to be explored separately. This approach indicated the potential for identifying further environmental indicators among these groups.

Mycotoxins are fungi-born metabolites that can contaminate foods through mould-infected crops. They are a significant food/feed-safety issue across the globe and represent a substantial financial burden for the world economy. Moreover, with a changing climate and fungal biota, there is now much discussion about emerging mycotoxins that are measurable at significant levels in crops world-wide. Unfortunately, we still know very little about the bioavailability and toxic potentials of many of these less characterized mycotoxins, including the large family of enniatins. In this study, we present new occurrence data for enniatin A, A1, B, B1 and beauvericin in four Danish crops: oat, wheat, and barley from the 2010 harvest, and rye from 2011 harvest. The occurrence of the four enniatins were B > B1 > A1 > A. Enniatin B was detected in 100% of tested samples regardless of crop type. In addition to occurrence data, we report a proof-of-concept study using a human-relevant high-content hepatotoxicity, or "quadroprobe," assay to screen mycotoxins for their cytotoxic potential. The assay was sensitive for most cytotoxic compounds in the 0.009-100 µM range. Among eight tested mycotoxins (enniatin B, beauvericin, altenariol, deoxynivalenol, aflatoxin B1, andrastin A, citrinin, and penicillic acid), enniatin B and beauvericin showed significant cytotoxicity at a concentration lower than that for aflatoxin B1, which is the archetypal acute hepatotoxic and liver-carcinogenic mycotoxin. Hence, the quadroprobe hepatotoxicity assay may become a valuable assessment tool for toxicity assessment of mycotoxins in the future. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1658-1664, 2017.

Purpose To compare mean global cerebral blood flow (CBF) measured by phase-contrast mapping magnetic resonance imaging (PCM MRI) and by 15O-H2O positron emission tomography (PET) in healthy subjects. PCM MRI is increasingly being used to measure mean global CBF, but has not been validated in vivo against an accepted reference technique. Materials and Methods Same-day measurements of CBF by 15O-H2O PET and subsequently by PCM MRI were performed on 22 healthy young male volunteers. Global CBF by PET was determined by applying a one-tissue compartment model with measurement of the arterial input function. Flow was measured in the internal carotid and vertebral arteries by a noncardiac triggered PCM MRI sequence at 3T. The measured flow was normalized to total brain weight determined from a volume-segmented 3D T1-weighted anatomical MR-scan. Results Mean CBF was 34.9 ± 3.4 mL/100 g/min measured by 15O-H2O PET and 57.0 ± 6.8 mL/100 g/min measured by PCM MRI. The measurements were highly correlated (P = 0.0008, R2 = 0.44), although values obtained by PCM MRI were higher compared to 15O-H2O PET (absolute and relative differences were 22.0 ± 5.2 mL/100 g/min and 63.4 ± 14.8%, respectively). Conclusion This study confirms the use of PCM MRI for quantification of global CBF, but also that PCM MRI systematically yields higher values relative to 15O-H2O PET, probably related to methodological bias. Level of Evidence: 3 J. Magn. Reson. Imaging 2017;45:692–699.

Helheim Glacier ranks among the fastest flowing and most ice discharging outlets of the Greenland Ice Sheet (GrIS). After undergoing rapid speed-up in the early 2000s, understanding its long-term mass balance and dynamic has become increasingly important. Here, we present the first record of direct Holocene ice-marginal changes of the Helheim Glacier following the initial deglaciation. By analysing cores from lakes adjacent to the present ice margin, we pinpoint periods of advance and retreat. We target threshold lakes, which receive glacial meltwater only when the margin is at an advanced position, similar to the present. We show that, during the period from 10.5 to 9.6 cal ka BP, the extent of Helheim Glacier was similar to that of todays, after which it remained retracted for most of the Holocene until a re-advance caused it to reach its present extent at c. 0.3 cal ka BP, during the Little Ice Age (LIA). Thus, Helheim Glacier's present extent is the largest since the last deglaciation, and its Holocene history shows that it is capable of recovering after several millennia of warming and retreat. Furthermore, the absence of advances beyond the present-day position during for example the 9.3 and 8.2 ka cold events as well as the early-Neoglacial suggest a substantial retreat during most of the Holocene.

Erythropoietin (EPO) is expressed in human brain tissue, but its exact role is unknown. EPO may improve the efficiency of oxidative metabolism and has neuroprotective properties against hypoxic injuries in animal models. We aimed to investigate the effect of recombinant human EPO (rHuEPO) administration on healthy cerebral metabolism in humans during normoxia and during metabolic stress by inhalation of 10% O2hypoxic air. Twenty-four healthy men participated in a two-arm double-blind placebo-controlled trial. rHuEPO was administered as a low dose (5,000 IU) over 4 wk ( n = 12) or as a high dose (500 IU·kg body wt−1·day−1) for three consecutive days ( n = 12). Global cerebral blood flow (CBF) and metabolic rate of glucose (CMRglc) were measured with positron emission tomography. CBF, metabolic rate of oxygen ([Formula: see text]), and cerebral lactate concentration were measured by magnetic resonance imaging and spectroscopy. Low-dose treatment increased hemoglobin and was associated with a near-significant decrease in CBF during baseline normoxia. High-dose treatment caused no change in CBF. Neither treatment had an effect on normoxia CMRglc, [Formula: see text], or lactate concentration or an effect on the cerebral metabolic response to inhalation of hypoxic air. In conclusion, the study found no evidence for a direct effect of rHuEPO on cerebral metabolism.NEW & NOTEWORTHY We demonstrate with magnetic resonance imaging and positron emission tomography that administration of erythropoietin does not have a substantial direct effect on healthy human resting cerebral blood flow or effect on cerebral glucose and oxygen metabolism. Also, administration of erythropoietin did not have a direct effect on the metabolic response to acute hypoxic stress in healthy humans, and a suggested neuroprotective effect from erythropoietin is therefore likely not a direct effect of erythropoietin on cerebral metabolism.

This study was initiated to evaluate the impact of intracranial radiosurgery for non-malignant indications on a patient’s quality of life (QOL).The study sample includes a total of 31 patients treated with single-fraction Gamma Knife radiosurgery (GKRS) for a non-malignant indication. Patients were treated at the Cleveland Clinic from 2005 through 2007 and all underwent pretreatment evaluation including screening for depression and anxiety, serum hemoglobin, hematocrit, calcium, albumin and thyroid stimulating hormone. Each patient was followed prospectively for eight weeks after treatment using a validated tool to assess fatigue and a separate questionnaire assessing quality of life. Dose and volume of GKRS were based on institutional practice and indication. The 13 question Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-F) was used to assess fatigue. Six additional questions assessing QOL outcomes not measured by the FACIT-F were added. Patients completed the questionnaire prior to GKRS and weekly for eight weeks. Questionnaires were scored using the FACIT scoring guidelines with a maximum score of 52. The additional questions were scored similarly with higher scores correlating with better QOL. The indications for treatment were arteriovenous malformation (5), schwannoma (12), trigeminal neuralgia (7), meningioma (4), pituitary adenoma (2), and glomus tumor (1). Median radiosurgery dose was 15 Gy (range 12-82 Gy). Doses for trigeminal neuralgia were prescribed to the 100% isodose line (IDL) while other lesions were treated to approximately the 50% IDL. Median volume of tissue treated was 2.5 cc (range 0.132-15.4 cc). Analysis of the 31 patients and 227 person-weeks of follow-up shows that GKRS does not adversely impact fatigue and QOL during the first 8 weeks after treatment. Mean FACIT-F score was 43 at baseline and 41, 43, 45, 43, 46, 44, 45, 47 at weeks 1-8 respectively after GKRS. In addition, questions assessing patients’ quality of life, and ability to work and exercise showed no decline after GKRS. Mean baseline score for these questions was 13 and 18, 19, 19, 19, 20, 19, 19 and 21 at weeks 1-8 after GK. This analysis of a prospective data set indicates that Gamma Knife radiosurgery does not adversely impact levels of fatigue or quality of life during the first 8 weeks after treatment for benign indications.