Crinoids from Svalbard in the aftermath of the end-Permian mass extinction

The end−Permian mass extinction constituted a major event in the history of cri− noids. It led to the demise of the major Paleozoic crinoid groups including cladids, disparids, flexibles and camerates. It is widely accepted that a single lineage, derived from a late Paleo− zoic cladid ancestor (Ampelocrinidae), survived this mass extinction. Holocrinid crinoids (Holocrinus, Holocrinida) along with recently described genus Baudicrinus (Encrinida), the only crinoid groups known from the Early Triassic, are considered the stem groups for the post−Paleozoic monophyletic subclass Articulata. Here, we report preliminary data on unex− pectedly diverse crinoid faunas comprising at least four orders from the Lower Triassic (Induan and Olenekian) of Svalbard, extending their stratigraphic ranges deeper into the early Mesozoic. These findings strongly imply that the recovery of crinoids in the aftermath of the end−Permian extinction began much earlier at higher palaeolatitudes than in the central Tethys

Limited Benefit of Fish Consumption on Risk of Hip Fracture among Men in the Community-Based Hordaland Health Study

Hip fractures have a high prevalence worldwide. Few studies have investigated whether fish consumption is associated with risk of hip fractures. The objective of the present study was to investigate the effect of fish intake on the subsequent risk of a hip fracture because of the low number of studies on this topic. A community-based prospective cohort study of 2865 men and women from Hordaland county in Norway, born between 1925–1927 and enrolled in the study in 1997–1999. Information on hip fracture cases was extracted from hospital records until 31 December 2009. Baseline information on the intake of fish was obtained from a semi-quantitative food frequency questionnaire. Cox proportional hazard regression models with death as a competing risk were used to evaluate the association of fish intake with risk of hip fracture. During a mean (SD) follow-up time of 9.6 (2.7) years, 226 hip fractures (72 in men, 154 in women) were observed. The mean (SD) fish intake was 48 (25) g/1000 kcal. The association between fish intake and risk of hip fracture was not linear and displayed a threshold, with low intake of fish being associated with an increased risk of hip fracture in men (HR (Hazard Ratio) = 1.84, 95% CI 1.10, 3.08). In this community-based prospective study of men and women, a low intake of fish was associated with the risk of a hip fracture in men.publishedVersio

Measurement and calculation of levitation forces between magnets and granular superconductors

Recent developments indicate that exploitation of the phenomenon of magnetic levitation may become one of the most important near-term applications of high-T(sub c) superconductivity. Because of this, the interaction between a strong permanent magnet(PM) and bulk high-T(sub c) superconductor (HTSC) is currently a subject of much interest. We have studied central features of the mechanics of PM-HTSC systems of simple geometries. Here we report experimental results for the components of the levitation force, their associated stiffness and mechanical ac-loss. To analyze the observed behavior a theoretical framework based on critical-state considerations is developed. It will be shown that all the mechanical properties can be explained consistently at a quantitative level wing a minimum of model parameters

Most soil trophic guilds increase plant growth: a meta-analytical review

Trophic cascades are important drivers of plant and animal abundances in aquatic and aboveground systems, but in soils trophic cascades have been thought to be of limited importance due to omnivory and other factors. Here we use a meta-analysis of 215 studies with 1526 experiments that measured plant growth responses to additions or removals of soil organisms to test how different soil trophic levels affect plant growth. Consistent with the trophic cascade hypothesis, we found that herbivores and plant pathogens (henceforth pests) decreased plant growth and that predators of pests increased plant growth. The magnitude of this trophic cascade was similar to that reported for aboveground systems. In contrast, we did not find evidence for trophic cascades in decomposer- and symbiont-based (henceforth mutualist) food chains. In these food chains, mutualists increased plant growth and predators of mutualists also increased plant growth, presumably by increasing nutrient cycling rates. Therefore, mutualists, predators of mutualists and predators of pests all increased plant growth. Further, experiments that added multiple organisms from different trophic levels also increased plant growth. As a result, across the dataset, soil organisms increased plant growth 29% and non-pest soil organisms increased plant growth 46%. Omnivory has traditionally been thought to confound soil trophic dynamics, but here we suggest that omnivory allows for a simplified perspective of soil food webs – one in which most soil organisms increase plant growth by preying on pests or increasing nutrient cycling rates. An implication of this perspective is that processes that decrease soil organism abundance (e.g. soil tillage) are likely to decrease aboveground productivity. Synthesis Soil foodwebs have resisted generalizations due to their diversity and interconnectedness. Here we use results from a meta-analysis to inform a simplified perspective of soil foodwebs: one in which most soil trophic guilds increase plant growth. Our review also includes the first widespread support for the presence of trophic cascades in soils

Unexplained chronic liver disease in Ethiopia: a cross-sectional study

BACKGROUND: Hepatitis B virus (HBV) infection is assumed to be the major cause of chronic liver disease (CLD) in sub-Saharan Africa. The contribution of other aetiological causes of CLD is less well documented and hence opportunities to modulate other potential risk factors are being lost. The aims of this study were to explore the aetiological spectrum of CLD in eastern Ethiopia and to identify plausible underlying risk factors for its development. METHODS: A cross-sectional study was undertaken between April 2015 and April 2016 in two public hospitals in Harar, eastern Ethiopia. The study population comprised of consenting adults with clinical and radiological evidence of chronic liver disease. The baseline evaluation included: (i) a semi-structured interview designed to obtain information about the ingestion of alcohol, herbal medicines and local recreational drugs such as khat (Catha edulis); (ii) clinical examination; (iii) extensive laboratory testing; and, (iv) abdominal ultrasonography. RESULTS: One-hundred-and-fifty patients with CLD (men 72.0%; median age 30 [interquartile range 25-40] years) were included. CLD was attributed to chronic HBV infection in 55 (36.7%) individuals; other aetiological agents were identified in a further 12 (8.0%). No aetiological factors were identified in the remaining 83 (55.3%) patients. The overall prevalence of daily khat use was 78.0%, while alcohol abuse, defined as > 20 g/day in women and > 30 g/day in men, was rare (2.0%). Histological features of toxic liver injury were observed in a subset of patients with unexplained liver injury who underwent liver biopsy. CONCLUSION: The aetiology of CLD in eastern Ethiopia is largely unexplained. The widespread use of khat in the region, together with histopathological findings indicating toxic liver injury, suggests an association which warrants further investigation

Thin superconducting disk with B-dependent Jc: Flux and current distributions

The critical state in a superconducting thin circular disk with an arbitrary magnetic field dependence of the critical sheet current, Jc(B), is analyzed. With an applied field Ba perpendicular to the disk, a set of coupled integral equations for the flux and current distributions is derived. The equations are solved numerically, and flux and current profiles are presented graphically for several commonly used Jc(B) dependences. It is shown that for small Ba the flux penetration depth can be described by an effective Bean model with a renormalized Jc entering the leading term. We argue that these results are qualitatively correct for thin superconductors of any shape. The results contrast the parallel geometry behavior, where at small Ba the B-dependence of the critical current can be ignored.Comment: RevTeX, 7 pages including 8 figure

Evaluation of immune responses in HIV infected patients with pleural tuberculosis by the QuantiFERON® TB-Gold interferon-gamma assay

<p>Abstract</p> <p>Background</p> <p>Diagnosis of tuberculous (TB) pleuritis is difficult and better diagnostic tools are needed. New blood based interferon-gamma (IFN-γ) tests are promising, but sensitivity could be low in HIV positive patients. The IFN-γ tests have not yet been validated for use in pleural fluid, a compartment with higher level of immune activation than in blood.</p> <p>Methods</p> <p>The QuantiFERON TB^®-Gold (QFT-TB) test was analysed in blood and pleural fluid from 34 patients presenting with clinically suspected pleural TB. Clinical data, HIV status and CD4 cell counts were recorded. Adenosine deaminase activity (ADA) analysis and TB culture were performed on pleural fluid.</p> <p>Results</p> <p>The patients were categorised as 'confirmed TB' (n = 12), 'probable TB' (n = 16) and 'non-TB' pleuritis (n = 6) based on TB culture results and clinical and biochemical criteria. The majority of the TB patients were HIV infected (82%). The QFT-TB in pleural fluid was positive in 27% and 56% of the 'confirmed TB' and 'probable TB' cases, respectively, whereas the corresponding sensitivities in blood were 58% and 83%. Indeterminate results in blood (25%) were caused by low phytohemagglutinin (PHA = positive control) IFN-γ responses, significantly lower in the TB patients as compared to the 'non-TB' cases (p = 0.02). Blood PHA responses correlated with CD4 cell count (r = 0.600, p = 0.028). In contrast, in pleural fluid indeterminate results (52%) were caused by high Nil (negative control) IFN-γ responses in both TB groups. Still, the Nil IFN-γ responses were lower than the TB antigen responses (p < 0.01), offering a conclusive test for half of the patients. We did not find any correlation between blood CD4 cell count and IFN-γ responses in pleural fluid.</p> <p>Conclusion</p> <p>The QFT-TB test in blood could contribute to the diagnosis of TB pleuritis in the HIV positive population. Still, the number of inconclusive results is too high to recommend the commercial QFT-TB test for routine use in pleural fluid in a TB/HIV endemic resource-limited setting.</p

Hyperpolarized [1,4-13C2]Fumarate Enables Magnetic Resonance-Based Imaging of Myocardial Necrosis.

OBJECTIVES: The aim of this study was to determine if hyperpolarized [1,4-13C2]malate imaging could measure cardiomyocyte necrosis after myocardial infarction (MI). BACKGROUND: MI is defined by an acute burst of cellular necrosis and the subsequent cascade of structural and functional adaptations. Quantifying necrosis in the clinic after MI remains challenging. Magnetic resonance-based detection of the conversion of hyperpolarized [1,4-13C2]fumarate to [1,4-13C2]malate, enabled by disrupted cell membrane integrity, has measured cellular necrosis in vivo in other tissue types. Our aim was to determine whether hyperpolarized [1,4-13C2]malate imaging could measure necrosis after MI. METHODS: Isolated perfused hearts were given hyperpolarized [1,4-13C2]fumarate at baseline, immediately after 20 min of ischemia, and after 45 min of reperfusion. Magnetic resonance spectroscopy measured conversion into [1,4-13C2]malate. Left ventricular function and energetics were monitored throughout the protocol, buffer samples were collected and hearts were preserved for further analyses. For in vivo studies, magnetic resonance spectroscopy and a novel spatial-spectral magnetic resonance imaging sequence were implemented to assess cardiomyocyte necrosis in rats, 1 day and 1 week after cryo-induced MI. RESULTS: In isolated hearts, [1,4-13C2]malate production became apparent after 45 min of reperfusion, and increased 2.7-fold compared with baseline. Expression of dicarboxylic acid transporter genes were negligible in healthy and reperfused hearts, and lactate dehydrogenase release and infarct size were significantly increased in reperfused hearts. Nonlinear regression revealed that [1,4-13C2]malate production was induced when adenosine triphosphate was depleted by >50%, below 5.3 mmol/l (R2 = 0.904). In vivo, the quantity of [1,4-13C2]malate visible increased 82-fold over controls 1 day after infarction, maintaining a 31-fold increase 7 days post-infarct. [1,4-13C2]Malate could be resolved using hyperpolarized magnetic resonance imaging in the infarct region one day after MI; [1,4-13C2]malate was not visible in control hearts. CONCLUSIONS: Malate production in the infarcted heart appears to provide a specific probe of necrosis acutely after MI, and for at least 1 week afterward. This technique could offer an alternative noninvasive method to measure cellular necrosis in heart disease, and warrants further investigation in patients

Treatment with Anti-HER2 Chimeric Antigen Receptor Tumor-Infiltrating Lymphocytes (CAR-TILs) Is Safe and Associated with Antitumor Efficacy in Mice and Companion Dogs

Patients with metastatic melanoma have a historically poor prognosis, but recent advances in treatment options, including targeted therapy and immunotherapy, have drastically improved the outcomes for some of these patients. However, not all patients respond to available treatments, and around 50% of patients with metastatic cutaneous melanoma and almost all patients with metastases of uveal melanoma die of their disease. Thus, there is a need for novel treatment strategies for patients with melanoma that do not benefit from the available therapies. Chimeric antigen receptor-expressing T (CAR-T) cells are largely unexplored in melanoma. Traditionally, CAR-T cells have been produced by transducing blood-derived T cells with a virus expressing CAR. However, tumor-infiltrating lymphocytes (TILs) can also be engineered to express CAR, and such CAR-TILs could be dual-targeting. To this end, tumor samples and autologous TILs from metastasized human uveal and cutaneous melanoma were expanded in vitro and transduced with a lentiviral vector encoding an anti-HER2 CAR construct. When infused into patient-derived xenograft (PDX) mouse models carrying autologous tumors, CAR-TILs were able to eradicate melanoma, even in the absence of antigen presentation by HLA. To advance this concept to the clinic and assess its safety in an immune-competent and human-patient-like setting, we treated four companion dogs with autologous anti-HER2 CAR-TILs. We found that these cells were tolerable and showed signs of anti-tumor activity. Taken together, CAR-TIL therapy is a promising avenue for broadening the tumor-targeting capacity of TILs in patients with checkpoint immunotherapy-resistant melanoma