Fusarium and allied fusarioid taxa (FUSA). 1.

Seven Fusarium species complexes are treated, namely F. aywerte species complex (FASC) (two species), F. buharicum species complex (FBSC) (five species), F. burgessii species complex (FBURSC) (three species), F. camptoceras species complex (FCAMSC) (three species), F. chlamydosporum species complex (FCSC) (eight species), F. citricola species complex (FCCSC) (five species) and the F. concolor species complex (FCOSC) (four species). New species include Fusicolla elongata from soil (Zimbabwe), and Neocosmospora geoasparagicola from soil associated with Asparagus officinalis (Netherlands). New combinations include Neocosmospora akasia, N. awan, N. drepaniformis, N. duplosperma, N. geoasparagicola, N. mekan, N. papillata, N. variasi and N. warna. Newly validated taxa include Longinectria gen. nov., L. lagenoides, L. verticilliforme, Fusicolla gigas and Fusicolla guangxiensis. Furthermore, Fusarium rosicola is reduced to synonymy under N. brevis. Finally, the genome assemblies of Fusarium secorum (CBS 175.32), Microcera coccophila (CBS 310.34), Rectifusarium robinianum (CBS 430.91), Rugonectria rugulosa (CBS 126565), and Thelonectria blattea (CBS 952.68) are also announced here. Citation: Crous PW, Sandoval-Denis M, Costa MM, Groenewald JZ, van Iperen AL, Starink-Willemse M, Hernández-Restrepo M, Kandemir H, Ulaszewski B, de Boer W, Abdel-Azeem AM, Abdollahzadeh J, Akulov A, Bakhshi M, Bezerra JDP, Bhunjun CS, Câmara MPS, Chaverri P, Vieira WAS, Decock CA, Gaya E, Gené J, Guarro J, Gramaje D, Grube M, Gupta VK, Guarnaccia V, Hill R, Hirooka Y, Hyde KD, Jayawardena RS, Jeewon R, Jurjevic Z, Korsten L, Lamprecht SC, Lombard L, Maharachchikumbura SSN, Polizzi G, Rajeshkumar KC, Salgado-Salazar C, Shang Q-J, Shivas RG, Summerbell RC, Sun GY, Swart WJ, Tan YP, Vizzini A, Xia JW, Zare R, González CD, Iturriaga T, Savary O, Coton M, Coton E, Jany J-L, Liu C, Zeng Z-Q, Zhuang W-Y, Yu Z-H, Thines M (2022). Fusarium and allied fusarioid taxa (FUSA). 1. Fungal Systematics and Evolution 9: 161-200. doi: 10.3114/fuse.2022.09.08.

Calculation of protein requirements; a comparison of calculations based on bodyweight and fat free mass.

BACKGROUND & AIMS: In dietary practice, it is common to estimate protein requirements on actual bodyweight, but corrected bodyweight (in cases with BMI <20 kg/m2 and BMI ≥30 kg/m2) and fat free mass (FFM) are also used. Large differences on individual level are noticed in protein requirements using these different approaches. To continue this discussion, the answer is sought in a large population to the following question: Will choosing actual bodyweight, corrected bodyweight or FFM to calculate protein requirements result in clinically relevant differences? METHODS: This retrospective database study, used data from healthy persons ≥55 years of age and in- and outpatients ≥18 years of age. FFM was measured by air displacement plethysmography technology or bioelectrical impedance analysis. Protein requirements were calculated as 1) 1.2 g (g) per kilogram (kg) actual bodyweight or 2) corrected bodyweight or 3) 1.5 g per kg FFM. To compare these three approaches, the approach in which protein requirement is based on FFM, was used as reference method. Bland-Altman plots with limits of agreement were used to determine differences, analyses were performed for both populations separately and stratified by BMI category and gender. RESULTS: In total 2291 subjects were included. In the population with relatively healthy persons (n = 506, ≥55 years of age) mean weight is 86.5 ± 18.2 kg, FFM is 51 ± 12 kg and in the population with adult in- and outpatients (n = 1785, ≥18 years of age) mean weight is 72.5 ± 18.4 kg, FFM is 51 ± 11 kg. Clinically relevant differences were found in protein requirement between actual bodyweight and FFM in most of the participants with overweight, obesity or severe obesity (78-100%). Using corrected bodyweight, an overestimation in 48-92% of the participants with underweight, healthy weight and overweight is found. Only in the Amsterdam UMC population, protein requirement is underestimated when using the approach of corrected bodyweight in participants with severe obesity. CONCLUSION: The three approaches in estimation of protein requirement show large differences. In the majority of the population protein requirement based on FFM is lower compared to actual or corrected bodyweight. Correction of bodyweight reduces the differences, but remain unacceptably large. It is yet unknown which method is the best for estimation of protein requirement. Since differences vary by gender due to differences in body composition, it seems more accurate to estimate protein requirement based on FFM. Therefore, we would like to advocate for more frequent measurement of FFM to determine protein requirements, especially when a deviating body composition is to be expected, for instance in elderly and persons with overweight, obesity or severe obesity.

Properties of Iron Primary Cosmic Rays: Results from the Alpha Magnetic Spectrometer.

We report the observation of new properties of primary iron (Fe) cosmic rays in the rigidity range 2.65 GV to 3.0 TV with 0.62×10^{6} iron nuclei collected by the Alpha Magnetic Spectrometer experiment on the International Space Station. Above 80.5 GV the rigidity dependence of the cosmic ray Fe flux is identical to the rigidity dependence of the primary cosmic ray He, C, and O fluxes, with the Fe/O flux ratio being constant at 0.155±0.006. This shows that unexpectedly Fe and He, C, and O belong to the same class of primary cosmic rays which is different from the primary cosmic rays Ne, Mg, and Si class.

Properties of Neon, Magnesium, and Silicon Primary Cosmic Rays Results from the Alpha Magnetic Spectrometer.

We report the observation of new properties of primary cosmic rays, neon (Ne), magnesium (Mg), and silicon (Si), measured in the rigidity range 2.15 GV to 3.0 TV with 1.8×10^{6} Ne, 2.2×10^{6} Mg, and 1.6×10^{6} Si nuclei collected by the Alpha Magnetic Spectrometer experiment on the International Space Station. The Ne and Mg spectra have identical rigidity dependence above 3.65 GV. The three spectra have identical rigidity dependence above 86.5 GV, deviate from a single power law above 200 GV, and harden in an identical way. Unexpectedly, above 86.5 GV the rigidity dependence of primary cosmic rays Ne, Mg, and Si spectra is different from the rigidity dependence of primary cosmic rays He, C, and O. This shows that the Ne, Mg, and Si and He, C, and O are two different classes of primary cosmic rays.

Long-term Liver-related Outcomes of Patients With Chronic Liver Diseases in Australia.

BACKGROUND & AIMS: Chronic liver disease is a major health burden that produces significant liver-related morbidity and mortality. We aimed to evaluate liver-related outcomes of patients with different causes of chronic liver disease in Australia. METHODS: We collected data from 10,933 patients with chronic liver disease assessed by Hepascore (a serum fibrosis model) in Western Australia from 2004 through 2015. We obtained records of liver-related death, transplantation, decompensation, and hepatocellular carcinoma from WA Data Linkage Unit databases. Competing risk analysis was used to calculate the cumulative risk of each clinical endpoint, and risks for clinical endpoints were compared among all causes of chronic liver disease. RESULTS: In our final cohort for analysis, 5566 patients had hepatitis C virus (HCV) infection, 1989 had HBV infection, 119 were infected with HBV and HCV, 955 had alcohol-associated liver disease, 1597 had non-alcoholic fatty liver disease (NAFLD), 123 had alcohol-associated liver disease and metabolic risk factors, 561 had autoimmune liver disease without overlap syndrome, and 23 autoimmune overlap syndrome. Significant differences among chronic liver diseases were observed in risk of all-cause death (P < .001), liver-related death (P < .001), liver transplantation (P < .001), and decompensation (P < .001) but not hepatocellular carcinoma (P=.095). Patients with alcohol-associated liver disease had the highest 5-year cumulative risk of liver-related death (17.1%) and the second-highest 5-year cumulative risk of decompensation (29.2%). Multivariate analysis found patients with alcohol-associated liver disease had significantly higher risks of liver-related death and decompensation than patients with HCV infection with hazard ratios (HRs) of 2.39 (95% CI, 1.88-3.03) and 3.42 (95% CI, 2.74-4.27), respectively. Patients with NAFLD had a significantly lower risk of liver related death and decompensation than patients with HCV infection, with HRs of 0.67 (95% CI, 0.48-0.95) and 0.70 (95% CI, 0.52-0.94) respectively. CONCLUSIONS: In an analysis of patients in Western Australia, we found patients with alcohol-associated liver disease to have significantly higher risk of decompensation and liver-related death than patients with HCV infection, whereas patients with NAFLD have significantly lower risks of either outcome.

Properties of Cosmic Helium Isotopes Measured by the Alpha Magnetic Spectrometer.

Precision measurements by the Alpha Magnetic Spectrometer (AMS) on the International Space Station of ^{3}He and ^{4}He fluxes are presented. The measurements are based on 100 million ^{4}He nuclei in the rigidity range from 2.1 to 21 GV and 18 million ^{3}He from 1.9 to 15 GV collected from May 2011 to November 2017. We observed that the ^{3}He and ^{4}He fluxes exhibit nearly identical variations with time. The relative magnitude of the variations decreases with increasing rigidity. The rigidity dependence of the ^{3}He/^{4}He flux ratio is measured for the first time. Below 4 GV, the ^{3}He/^{4}He flux ratio was found to have a significant long-term time dependence. Above 4 GV, the ^{3}He/^{4}He flux ratio was found to be time independent, and its rigidity dependence is well described by a single power law ∝R^{Δ} with Δ=-0.294±0.004. Unexpectedly, this value is in agreement with the B/O and B/C spectral indices at high energies.

Towards Understanding the Origin of Cosmic-Ray Electrons.

Precision results on cosmic-ray electrons are presented in the energy range from 0.5 GeV to 1.4 TeV based on 28.1×10^{6} electrons collected by the Alpha Magnetic Spectrometer on the International Space Station. In the entire energy range the electron and positron spectra have distinctly different magnitudes and energy dependences. The electron flux exhibits a significant excess starting from 42.1_{-5.2}^{+5.4} GeV compared to the lower energy trends, but the nature of this excess is different from the positron flux excess above 25.2±1.8 GeV. Contrary to the positron flux, which has an exponential energy cutoff of 810_{-180}^{+310} GeV, at the 5σ level the electron flux does not have an energy cutoff below 1.9 TeV. In the entire energy range the electron flux is well described by the sum of two power law components. The different behavior of the cosmic-ray electrons and positrons measured by the Alpha Magnetic Spectrometer is clear evidence that most high energy electrons originate from different sources than high energy positrons.

Towards Understanding the Origin of Cosmic-Ray Positrons.

Precision measurements of cosmic ray positrons are presented up to 1 TeV based on 1.9 million positrons collected by the Alpha Magnetic Spectrometer on the International Space Station. The positron flux exhibits complex energy dependence. Its distinctive properties are (a) a significant excess starting from 25.2±1.8 GeV compared to the lower-energy, power-law trend, (b) a sharp dropoff above 284_{-64}^{+91} GeV, (c) in the entire energy range the positron flux is well described by the sum of a term associated with the positrons produced in the collision of cosmic rays, which dominates at low energies, and a new source term of positrons, which dominates at high energies, and (d) a finite energy cutoff of the source term of E_{s}=810_{-180}^{+310} GeV is established with a significance of more than 4σ. These experimental data on cosmic ray positrons show that, at high energies, they predominantly originate either from dark matter annihilation or from other astrophysical sources.

Observation of Fine Time Structures in the Cosmic Proton and Helium Fluxes with the Alpha Magnetic Spectrometer on the International Space Station.

We present the precision measurement from May 2011 to May 2017 (79 Bartels rotations) of the proton fluxes at rigidities from 1 to 60 GV and the helium fluxes from 1.9 to 60 GV based on a total of 1×10^{9} events collected with the Alpha Magnetic Spectrometer aboard the International Space Station. This measurement is in solar cycle 24, which has the solar maximum in April 2014. We observed that, below 40 GV, the proton flux and the helium flux show nearly identical fine structures in both time and relative amplitude. The amplitudes of the flux structures decrease with increasing rigidity and vanish above 40 GV. The amplitudes of the structures are reduced during the time period, which started one year after solar maximum, when the proton and helium fluxes steadily increase. Above ∼3 GV the p/He flux ratio is time independent. We observed that below ∼3 GV the ratio has a long-term decrease coinciding with the period during which the fluxes start to rise.

Precision Measurement of Cosmic-Ray Nitrogen and its Primary and Secondary Components with the Alpha Magnetic Spectrometer on the International Space Station.

A precision measurement of the nitrogen flux with rigidity (momentum per unit charge) from 2.2 GV to 3.3 TV based on 2.2×10^{6} events is presented. The detailed rigidity dependence of the nitrogen flux spectral index is presented for the first time. The spectral index rapidly hardens at high rigidities and becomes identical to the spectral indices of primary He, C, and O cosmic rays above ∼700 GV. We observed that the nitrogen flux Φ_{N} can be presented as the sum of its primary component Φ_{N}^{P} and secondary component Φ_{N}^{S}, Φ_{N}=Φ_{N}^{P}+Φ_{N}^{S}, and we found Φ_{N} is well described by the weighted sum of the oxygen flux Φ_{O} (primary cosmic rays) and the boron flux Φ_{B} (secondary cosmic rays), with Φ_{N}^{P}=(0.090±0.002)×Φ_{O} and Φ_{N}^{S}=(0.62±0.02)×Φ_{B} over the entire rigidity range. This corresponds to a change of the contribution of the secondary cosmic ray component in the nitrogen flux from 70% at a few GV to <30% above 1 TV.

Observation of Complex Time Structures in the Cosmic-Ray Electron and Positron Fluxes with the Alpha Magnetic Spectrometer on the International Space Station.

We present high-statistics, precision measurements of the detailed time and energy dependence of the primary cosmic-ray electron flux and positron flux over 79 Bartels rotations from May 2011 to May 2017 in the energy range from 1 to 50 GeV. For the first time, the charge-sign dependent modulation during solar maximum has been investigated in detail by leptons alone. Based on 23.5×10^{6} events, we report the observation of short-term structures on the timescale of months coincident in both the electron flux and the positron flux. These structures are not visible in the e^{+}/e^{-} flux ratio. The precision measurements across the solar polarity reversal show that the ratio exhibits a smooth transition over 830±30 days from one value to another. The midpoint of the transition shows an energy dependent delay relative to the reversal and changes by 260±30 days from 1 to 6 GeV.

Topically used corticosteroids: What is the big picture of drug product degradation?

Corticosteroids are widely used in topical formulations such as creams (aqueous) and ointments (non-aqueous). The generally used corticosteroids show large molecular resemblance, where especially the 20-keto-21-hydroxyl group bound to the 17 carbon is important for their chemical stability. Oxidation in both aqueous and non-aqueous environment occurs for triamcinolone acetonide (TCA), hydrocortisone (HC) and desoximethasone (DS). Besides the 20-keto-21-hydroxyl group, TCA, HC and DS have different other moieties attached to the same C17. These moieties are shown to influence not only the type of degradation product formed but also the degradation kinetics. Seven degradation products are found in total and a degradation mechanism is proposed. Furthermore the transesterfication of betamethasone-17-valerate to betamethasone-21-valerate is shown to occur both in aqueous and non-aqueous environment. Finally, a comprehensive scheme of degradation pathways is presented that is applicable for both aqueous and non-aqueous formulations.

Observation of New Properties of Secondary Cosmic Rays Lithium, Beryllium, and Boron by the Alpha Magnetic Spectrometer on the International Space Station.

We report on the observation of new properties of secondary cosmic rays Li, Be, and B measured in the rigidity (momentum per unit charge) range 1.9 GV to 3.3 TV with a total of 5.4×10^{6} nuclei collected by AMS during the first five years of operation aboard the International Space Station. The Li and B fluxes have an identical rigidity dependence above 7 GV and all three fluxes have an identical rigidity dependence above 30 GV with the Li/Be flux ratio of 2.0±0.1. The three fluxes deviate from a single power law above 200 GV in an identical way. This behavior of secondary cosmic rays has also been observed in the AMS measurement of primary cosmic rays He, C, and O but the rigidity dependences of primary cosmic rays and of secondary cosmic rays are distinctly different. In particular, above 200 GV, the secondary cosmic rays harden more than the primary cosmic rays.

Development and validation of a stability-indicating HPLC-UV method for the determination of triamcinolone acetonide and its degradation products in an ointment formulation.

A stability indicating high performance liquid chromatography method has been developed for the determination of triamcinolone acetonide (TCA) and its main degradation products in ointment formulations. The method, based on extensive stress testing using metal salts, azobisisobutyronitrile, acid, base and peroxide, showed that TCA undergoes oxidative degradation. All degradation products were identified using HPLC mass spectrometry. Separation and quantification was achieved using an Altima C18 RP18 HP column (250×4.6mm2, with 5µm particles) using a mobile phase consisting of acetonitrile and water buffered at pH 7 using 10mM phosphate buffer. A gradient mode was operated at a flow rate of 1.5ml/min and detection was at 241nm. The method showed linearity for TCA and Impurity C in 0.02-125% of the workload, both square roots of the correlation coefficients were larger than 0.9999. Repeatability and intermediate precision were performed by six consecutive injections of both 1.25% and 125% of the work load for both TCA and Impurity C divided equally over two days. RSD were 0.6% and 0.7% for TCA and 0.5% and 0.1% for Impurity C respectively. Accuracy was determined as well, the average recoveries were 99.5% (±0.1%, n=3) for TCA and 96.9% (±1.3%, n=3) for impurity C respectively from spiked ointment samples. The robustness was also evaluated by variations of column (old vs new), mobile phase pH and filter retention. The applicability of the method was evaluated by analysis of a commercial ointment formulation. Interestingly, the extensive stress tests were able to predict all degradation products of TCA in a long term stability ointment sample.

Improved Hepascore in hepatitis C predicts reversal in risk of adverse outcome.

AIM: To establish if serial Hepascore tests (referred to as delta Hepascore) in those with chronic hepatitis C (CHC) correlate with the increase and/or decrease in risk of liver related complications. METHODS: Three hundred and forty-six CHC patients who had two Hepascore tests performed were studied. During 1944 patient years follow-up 28 (8.1%) reached an endpoint. The Hepascore is a serum test that provides clinically useful data regarding the stage of liver fibrosis and subsequent clinical outcomes in chronic liver disease. RESULTS: Patients with a baseline Hepascore > 0.75 had a significantly increased rate of reaching a composite endpoint consisting of hepatocellular carcinoma, liver death, and/or decompensation (P < 0.001). In those with an initial Hepascore > 0.75, a subsequent improved Hepascore showed a significantly decreased risk for the composite endpoint (P = 0.004). There were no negative outcomes in those with a stable or improved delta Hepascore. The minimum time between tests that was found to give a statically significant result was in those greater than one year (P = 0.03). CONCLUSION: In conclusion, Hepascore is an accurate predictor of liver related mortality and liver related morbidity in CHC patients. Of note, we have found that there is a decreased risk of mortality and morbidity in CHC patients when the patient has an improving delta Hepascore. Repeat Hepascore tests, when performed at a minimum one-year interval, may be of value in routine clinical practice to predict liver related clinical outcomes and to guide patient management.

Psychosocial care for children with haemophilia and their parents in the Netherlands.

INTRODUCTION: Children growing up with haemophilia are at greater risk for psychosocial problems than their healthy peers. Providing psychosocial care to children with haemophilia and their families is indispensable, since psychosocial factors can have a significant impact on health and health-related quality of life (HRQOL). AIMS: Our aim was to give a description of psychosocial care provided by the multidisciplinary team of the Hemophilia Comprehensive Care Centre (HCCC) at the Emma Children's Hospital in Amsterdam, the Netherlands. With this overview, other caregivers and hospitals can benefit in organizing their psychosocial care for children with haemophilia. METHODS: The focus of the psychosocial care provided by the multidisciplinary team is on preventing psychosocial problems and medical-related stress, and supporting and equipping the child with haemophilia and its parents with as many skills as possible to lead an independent life with a high HRQOL. RESULTS: Core elements of the psychosocial care are therefore monitoring and screening of HRQOL (e.g. in daily clinical practice via www.hetklikt.nu), psychoeducation (haemophilia camp, haemophilia school, disease-specific activities, meetings for girls, parent meetings), practical help (Emma at Work, an employment agency for adolescents and young adults; Educational Facility and school visits), psychosocial interventions (the On Track group intervention and the Haemophilia Coping and Perception Test) and individual care (psychological counselling and referrals). CONCLUSION: By providing this overview of psychosocial support offered and by sharing this knowledge, psychosocial care can become more structured and consistent between HCCCs around the world. Potentially, processes and outcomes of care can be improved.

Disease transmission in animal transfer networks.

Infectious diseases transmission is strongly determined by who contacts whom. Bovine tuberculosis (bTB) caused by Mycobacterium bovis is a worldwide burden for animal populations. One of the major transmission mechanism between herd is the transfer of infectious animal. In East Africa, pastoralists may receive or bestow livestock to create and strengthen social relationships. Here, we used a network approach to examine the relative importance of such cattle transfer in the transmission of bTB. First, a total of 2550 cattle from 102 herds were tested using the comparative intradermal tuberculin test to assess the presence of bTB infected cattle in the herd. A herd was considered bTB positive if it had at least one tuberculin reactor animal. Next, we calculated the centrality of each herd in the cattle transfer network using four established measures of social network centralization: degree, betweenness, closeness and fragmentation. The relationships between the network centrality measures and bTB infection were examined using generalized linear mixed models (GLMM). We found that a herd's in-degree in the social network was positively correlated with the risk of being infected with bTB (b=4.2, 95%CI=2.1-5.7; p<0.001). A herd that was close to many others (i.e., had a higher closeness index) had a larger chance of acquiring bTB infection (b=2.1, 95%CI=1.4-2.8; p<0.001). Betweenness centrality was also positively associated with the presence of bTB infection. There was a negative relationship between the fragmentation index and bTB infection (b=-2.7, 95%CI=-4.9-1.3; p<0.001). The study clearly demonstrated that the extent to which a herd is connected within a network has significant implications for its probability of being infected. Further, the results are in accordance with our expectation that connectivity and the probability that a herd will transmit the disease to other herds in the network are related.

Observation of the Identical Rigidity Dependence of He, C, and O Cosmic Rays at High Rigidities by the Alpha Magnetic Spectrometer on the International Space Station.

We report the observation of new properties of primary cosmic rays He, C, and O measured in the rigidity (momentum/charge) range 2 GV to 3 TV with 90×10^{6} helium, 8.4×10^{6} carbon, and 7.0×10^{6} oxygen nuclei collected by the Alpha Magnetic Spectrometer (AMS) during the first five years of operation. Above 60 GV, these three spectra have identical rigidity dependence. They all deviate from a single power law above 200 GV and harden in an identical way.

Precision Measurement of the Boron to Carbon Flux Ratio in Cosmic Rays from 1.9 GV to 2.6 TV with the Alpha Magnetic Spectrometer on the International Space Station.

Knowledge of the rigidity dependence of the boron to carbon flux ratio (B/C) is important in understanding the propagation of cosmic rays. The precise measurement of the B/C ratio from 1.9 GV to 2.6 TV, based on 2.3 million boron and 8.3 million carbon nuclei collected by AMS during the first 5 years of operation, is presented. The detailed variation with rigidity of the B/C spectral index is reported for the first time. The B/C ratio does not show any significant structures in contrast to many cosmic ray models that require such structures at high rigidities. Remarkably, above 65 GV, the B/C ratio is well described by a single power law R^{Δ} with index Δ=-0.333±0.014(fit)±0.005(syst), in good agreement with the Kolmogorov theory of turbulence which predicts Δ=-1/3 asymptotically.