Why Humble Farmers May in Fact Grow Bigger Potatoes: A Call for Street-Smart Decision-Making in Sport.

BACKGROUND: The main task of applied sport science is to inform decision-making in sports practice, that is, enabling practitioners to compare the expectable outcomes of different options (e.g. training programs). MAIN BODY: The "evidence" provided may range from group averages to multivariable prediction models. By contrast, many decisions are still largely based on the subjective, experience-based judgement of athletes and coaches. While for the research scientist this may seem "unscientific" and even "irrational", it is important to realize the different perspectives: science values novelty, universal validity, methodological rigor, and contributions towards long-term advancement. Practitioners are judged by the performance outcomes of contemporary, specific athletes. This makes out-of-sample predictive accuracy and robustness decisive requirements for useful decision support. At this point, researchers must concede that under the framework conditions of sport (small samples, multifactorial outcomes etc.) near certainty is unattainable, even with cutting-edge methods that might theoretically enable near-perfect accuracy. Rather, the sport ecosystem favors simpler rules, learning by experience, human judgement, and integration across different sources of knowledge. In other words, the focus of practitioners on experience and human judgement, complemented-but not superseded-by scientific evidence is probably street-smart after all. A major downside of this human-driven approach is the lack of science-grade evaluation and transparency. However, methods are available to merge the assets of data- and human-driven strategies and mitigate biases. SHORT CONCLUSION: This work presents the challenges of learning, forecasting and decision-making in sport as well as specific opportunities for turning the prevailing "evidence vs. eminence" contrast into a synergy.

Value of Magnetic Resonance Imaging for Skeletal Bone Age Assessment in Healthy Male Children.

BACKGROUND: Skeletal bone age assessment for medical reasons is usually performed by conventional x-ray with use of ionizing radiation. Few pilot studies have shown the possible use of magnetic resonance imaging (MRI). PURPOSE: To comprehensively evaluate feasibility and value of MRI for skeletal bone age (SBA) assessment in healthy male children. MATERIALS AND METHODS: In this prospective cross-sectional study, 63 male soccer athletes with mean age of 12.35 ± 1.1 years were examined. All participants underwent 3.0 Tesla MRI with coronal T1-weighted turbo spin echo (TSE), coronal proton density (PD)-weighted turbo spin echo (TSE), and T1-weighted three-dimensional (3D) volume interpolated breath-hold examination (VIBE) sequence. Subsequently, SBA was assessed by 3 independent blinded radiologists with different levels of experience using the common Greulich-Pyle (GP) atlas and the Tanner-Whitehouse (TW2) method. RESULTS: In a mean total acquisition time of 5:04 ± 0:47 min, MR image quality was sufficient in all cases. MRI appraisal was significantly faster ( P < 0.0001) by GP with mean duration of 1:22 ± 0:08 min vs. 7:39 ± 0:28 min by TW. SBA assessment by GP resulted in mean age of 12.8 ± 1.2 years, by TW 13.0 ± 1.4 years. Interrater reliabilities were excellent for both GP (ICC = 0.912 (95% confidence interval [CI] = 0.868-0.944) and TW (ICC = 0.988 (95% CI = 0.980-0.992) and showed statistical significance ( P < 0.001). Subdivided, for GP, ICCs were 0.822 (95% CI = 0.680-0.907) and 0.843 (95% CI = 0.713-0.919) in Under 12 and Under 14 group. For TW, ICCs were 0.978 (95% CI = 0.958-0.989) in Under 12 and 0.979 (95% CI = 0.961-0.989) in Under 14 group. CONCLUSION: MRI is a clinically feasible, rapidly evaluable method to assess skeletal bone age of healthy male children. Using the Greulich-Pyle (GP) atlas or the Tanner-Whitehouse (TW2) method, reliable results are obtained independent of the radiologist's experience level.

Do you have a good all-around view? Evaluation of a decision-making skills diagnostic tool using 360° videos and head-mounted displays in elite youth soccer.

Elite youth players' decision-making skills are considered important predictors of adult performance in soccer. The presentation of 360° videos in head-mounted displays offers new potential for the diagnostic of these skills in talent development programs. This study evaluated a new diagnostic tool using soccer-specific 360° videos for assessing decision-making skills in youth academy (YA) players. The evaluation consisted of players' subjective feedback as well as the analysis of diagnostic and prognostic validity. It was hypothesized that high-level YA players achieve better diagnostic results than regional-level players, and U19 outperform U17 players. Moreover, YA players' diagnostic results should be positively associated with future adult performance level. During the 2018/19 season, N = 48 youth players participated in the diagnostic procedures (split-half reliability r = .78). Participants were shown 54 videos which terminated when the central midfielder received a teammate's pass. Participants were then asked how to best continue playing. The subjective evaluation explored YA players' experiences with the diagnostic tool via quantitative ratings (e.g., "How exciting was the task?", "How involved did you feel in the game situation?") and additional interviews. Diagnostic validity was examined in a balanced cross-sectional 2 × 2-design (performance level x age group) and prognostic validity in a 3-year prospective design. Sensitivity and case-by-case analyses completed the evaluation. The YA players provided positive quantitative ratings regarding their experienced immersion into the environment. Players' qualitative feedback indicated general acceptance of the diagnostic tool as well as it offered recommendations for improvements. Confirming the diagnostic validity, ANOVA revealed significant main effects for performance level (p < .001, η2 = .29) and age group (p < .01, η2 = .14). Contributing to the prognostic validity, the diagnostic results discriminated between YA players achieving a higher and a lower adult performance level ("League 1-4" vs. "League 5 or below") in adulthood (p < .05; d = 0.80). A ROC curve and the AUC showed that the correct assignment to the adult performance levels is possible with a 71% probability. YA players with a high decision-making accuracy had a six times higher chance of playing in "League 1-4". The results demonstrated empirical evidence for the new diagnostic tool in terms of YA players' acceptance and validity coefficients exceeding effect sizes of former studies. The technology provides opportunities to test soccer-specific situations demanding an all-around view that were not testable in former experimental settings. Further technological advancements will enable the realization of improvements recommended by the players. Nonetheless, case-by-case analyses suggest caution in using such a diagnostic as a selection tool in talent development programs.

Emergence and antibody evasion of BQ, BA.2.75 and SARS-CoV-2 recombinant sub-lineages in the face of maturing antibody breadth at the population level.

BACKGROUND: The Omicron era of the COVID-19 pandemic commenced at the beginning of 2022 and whilst it started with primarily BA.1, it was latter dominated by BA.2 and the related sub-lineage BA.5. Following resolution of the global BA.5 wave, a diverse grouping of Omicron sub-lineages emerged derived from BA.2, BA.5 and recombinants thereof. Whilst emerging from distinct lineages, all shared similar changes in the Spike glycoprotein affording them an outgrowth advantage through evasion of neutralising antibodies. METHODS: Over the course of 2022, we monitored the potency and breadth of antibody neutralization responses to many emerging variants in the Australian community at three levels: (i) we tracked over 420,000 U.S. plasma donors over time through various vaccine booster roll outs and Omicron waves using sequentially collected IgG pools; (ii) we mapped the antibody response in individuals using blood from stringently curated vaccine and convalescent cohorts. (iii) finally we determine the in vitro efficacy of clinically approved therapies Evusheld and Sotrovimab. FINDINGS: In pooled IgG samples, we observed the maturation of neutralization breadth to Omicron variants over time through continuing vaccine and infection waves. Importantly, in many cases, we observed increased antibody breadth to variants that were yet to be in circulation. Determination of viral neutralization at the cohort level supported equivalent coverage across prior and emerging variants with isolates BQ.1.1, XBB.1, BR.2.1 and XBF the most evasive. Further, these emerging variants were resistant to Evusheld, whilst increasing neutralization resistance to Sotrovimab was restricted to BQ.1.1 and XBF. We conclude at this current point in time that dominant variants can evade antibodies at levels equivalent to their most evasive lineage counterparts but sustain an entry phenotype that continues to promote an additional outgrowth advantage. In Australia, BR.2.1 and XBF share this phenotype and, in contrast to global variants, are uniquely dominant in this region in the later months of 2022. INTERPRETATION: Whilst the appearance of a diverse range of omicron lineages has led to primary or partial resistance to clinically approved monoclonal antibodies, the maturation of the antibody response across both cohorts and a large donor pools importantly observes increasing breadth in the antibody neutralisation responses over time with a trajectory that covers both current and known emerging variants. FUNDING: This work was primarily supported by Australian Medical Foundation research grants MRF2005760 (SGT, GM & WDR), Medical Research Future Fund Antiviral Development Call grant (WDR), the New South Wales Health COVID-19 Research Grants Round 2 (SGT & FB) and the NSW Vaccine Infection and Immunology Collaborative (VIIM) (ALC). Variant modeling was supported by funding from SciLifeLab's Pandemic Laboratory Preparedness program to B.M. (VC-2022-0028) and by the European Union's Horizon 2020 research and innovation programme under grant agreement no. 101003653 (CoroNAb) to B.M.

Long-term outcomes and prognostic factors for survival of patients with ANCA-associated vasculitis.

BACKGROUND: Despite newer treatments with immunosuppressive agents, there still exists a considerable morbidity and mortality risk among patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Since 1994 the European Vasculitis Society (EUVAS) has aimed for an improved outcome for patients with AAV, conducting several prospective randomized controlled trials (RCTs). The aim for the present study was to further evaluate the long-term survival of patients with AAV included in seven RCTs conducted by the EUVAS as well as to identify potential prognostic factors. METHODS: Long-term follow-up data were collected from questionnaires sent to the principal investigators of the original RCTs (1995-2012): MEPEX, NORAM, CYCAZAREM, CYCLOPS, IMPROVE, RITUXVAS and MYCYC, comprising 848 patients, all newly diagnosed with AAV. Relative survival estimates are presented for the study cohorts. Demographic, clinical and laboratory characteristics at trial entry were studied as potential prognostic factors in multivariable models. RESULTS: A total of 478 (56%) patients had granulomatosis with polyangiitis (GPA) and 370 (44%) had microscopic polyangiitis (MPA) with a mean age at diagnosis of 58 ± 14 years. The median follow-up time was 8 years (interquartile range 2.9-13.6). During the observation period there were 305 deaths and the main causes were infections (26%), cardiovascular disease (14%) and malignancies (13%). When compared with a matched cohort (regarding country, age group and sex) from the background population there were 14.2% more deaths among our cohort of AAV patients at 5 years, 19.9% at 10 years, 28.8% at 15 years and 36.3% at 20 years. The excess mortality occurred in all age groups. The estimated median survival time (from diagnosis) was 17.8 years (95% confidence interval 15.7-20). Among variables measured at baseline, advanced age, male sex, low estimated glomerular filtration rate and low platelet count were identified as predictors of death in a multivariate Cox model. CONCLUSIONS: Patients with AAV still have an increased risk of mortality compared with the general population despite newer therapeutic regimens. Treatment complications and organ damage are the main causes of limited survival and infections remain the leading cause of mortality among patients with AAV.

SARS-CoV-2 Omicron BA.5: Evolving tropism and evasion of potent humoral responses and resistance to clinical immunotherapeutics relative to viral variants of concern.

BACKGROUND: Genetically distinct viral variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been recorded since January 2020. The introduction of global vaccine programs has contributed to lower COVID-19 hospitalisation and mortality rates, particularly in developed countries. In late 2021, Omicron BA.1 emerged, with substantially altered genetic differences and clinical effects from other variants of concern. Shortly after dominating global spread in early 2022, BA.1 was supplanted by the genetically distinct Omicron lineage BA.2. A sub-lineage of BA.2, designated BA.5, presently has an outgrowth advantage over BA.2 and other BA.2 sub-lineages. Here we study the neutralisation of Omicron BA.1, BA.2 and BA.5 and pre-Omicron variants using a range of vaccine and convalescent sera and therapeutic monoclonal antibodies using a live virus neutralisation assay. Using primary nasopharyngeal swabs, we also tested the relative fitness of BA.5 compared to pre-Omicron and Omicron viral lineages in their ability to use the ACE2-TMPRSS2 pathway. METHODS: Using low passage clinical isolates of Clade A.2.2, Beta, Delta, BA.1, BA.2 and BA.5, we determined humoral neutralisation in vitro in vaccinated and convalescent cohorts, using concentrated human IgG pooled from thousands of plasma donors, and licensed monoclonal antibody therapies. We then determined infectivity to particle ratios in primary nasopharyngeal samples and expanded low passage isolates in a genetically engineered ACE2/TMPRSS2 cell line in the presence and absence of the TMPRSS2 inhibitor Nafamostat. FINDINGS: Peak responses to 3 doses of BNT162b2 vaccine were associated with a 9-fold reduction in neutralisation for Omicron lineages BA.1, BA.2 and BA.5. Concentrated pooled human IgG from convalescent and vaccinated donors and BNT162b2 vaccination with BA.1 breakthrough infections were associated with greater breadth of neutralisation, although the potency was still reduced 7-fold across all Omicron lineages. Testing of clinical grade antibodies revealed a 14.3-fold reduction using Evusheld and 16.8-fold reduction using Sotrovimab for the BA.5. Whilst the infectivity of BA.1 and BA.2 was attenuated in ACE2/TMPRSS2 entry, BA.5 was observed to be equivalent to that of an early 2020 circulating clade and had greater sensitivity to the TMPRSS2 inhibitor Nafamostat. INTERPRETATION: Observations support all Omicron variants to significantly escape neutralising antibodies across a range of vaccination and/or convalescent responses. Potency of therapeutic monoclonal antibodies is also reduced and differs across Omicron lineages. The key difference of BA.5 from other Omicron sub-variants is the reversion in tropism back to using the well-known ACE2-TMPRSS2 pathway, utilised efficiently by pre-Omicron lineages. Monitoring if these changes influence transmission and/or disease severity will be key for ongoing tracking and management of Omicron waves globally. FUNDING: This work was primarily supported by Australian Medical Foundation research grants MRF2005760 (ST, GM & WDR), MRF2001684 (ADK and ST) and Medical Research Future Fund Antiviral Development Call grant (WDR), Medical Research Future Fund COVID-19 grant (MRFF2001684, ADK & SGT) and the New South Wales Health COVID-19 Research Grants Round 2 (SGT).

The Sound of Interconnectivity; The European Vasculitis Society 2022 Report.

The first European Vasculitis Society (EUVAS) meeting report was published in 2017. Herein, we report on developments in the past 5 years which were greatly influenced by the pandemic. The adaptability to engage virtually, at this critical time in society, embodies the importance of networks and underscores the role of global collaborations. We outline state-of-the-art webinar topics, updates on developments in the last 5 years, and proposals for agendas going forward. A host of newly reported clinical trials is shaping practice on steroid minimization, maintenance strategies, and the role of newer therapies. To guide longer-term strategies, a longitudinal 10-year study investigating relapse, comorbidity, malignancy, and survival rates is at an advanced stage. Disease assessment studies are refining classification criteria to differentiate forms of vasculitis more fully. A large international validation study on the histologic classification of anti-neutrophil cytoplasmic antibody (ANCA) glomerulonephritis, recruiting new multicenter sites and comparing results with the Kidney Risk Score, has been conducted. Eosinophilic granulomatosis with polyangiitis (EGPA) genomics offers potential pathogenic subset and therapeutic insights. Among biomarkers, ANCA testing is favoring immunoassay as the preferred method for diagnostic evaluation. Consolidated development of European registries is progressing with an integrated framework to analyze large clinical data sets on an unprecedented scale.

Frequency and characteristics of bacterial and viral low-grade infections of the intervertebral discs: a prospective, observational study.

STUDY DESIGN: Monocentric, prospective, observational study. OBJECTIVE: The clinical relevance of bacterial colonization of intervertebral discs is controversial. This study aimed to determine a possible relationship between bacterial and viral colonization and low-grade infection of the discs. METHODS: We investigated 447 disc samples from 392 patients. Microbiological culture was used to examine the samples for bacterial growth, polymerase chain reaction (PCR) was used for detection of herpes simplex virus types 1 and 2 (HSV-1, HSV-2) and Cytomegalovirus (CMV), and histopathological analysis was used to detect signs of inflammation. The results were compared between subgroups organized according to gender, age, location of the samples, surgical approach, preoperative C-reactive protein (CRP), preoperative and 6 months postoperative Oswestry Disability Index (ODI) and Neck Disability Index (NDI), and Modic changes (MC) of the corresponding endplates. Also, we assessed the occurrence of postoperative infections within 6 months. RESULTS: Microbiological culture was positive in 38.78% of the analyzed intervertebral discs. Altogether, 180 bacteria were isolated. Coagulase-negative staphylococci (CONS) (23.41%) and Cutibacterium acnes (18.05%) were the most frequently detected microorganisms. None of HSV-1, HSV-2, or CMV were detected. Male patients (p = 0.00036) and cervical segments (p = 0.00001) showed higher rates of positive culture results. Ventral surgical approaches ( p < 0.001) and Type 2 MC (p = 0.0127) were significantly associated with a positive microbiological result ( p< 0.001). Neither pre- nor postoperative ODI and NDI are associated with positive culture results. In 4 (1.02%) patients, postoperative spondylodiscitis occurred. CONCLUSIONS: With 447 segments from 392 patients, we present one of the largest studies to date. While disc degeneration caused by HSV-1, HSV-2, and CMV seems unlikely, we found positive microbiological culture results in 38.78% of all discs. The role of local skin flora and sample contamination should be the focus of further investigations. LEVEL OF EVIDENCE: III. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (ID: NCT04712487, https://www. CLINICALTRIALS: gov/ct2/show/study/NCT04712487 ).

Perspective on COVID-19 vaccination in patients with immune-mediated kidney diseases: consensus statements from the ERA-IWG and EUVAS.

Patients with immune-mediated kidney diseases are at increased risk of severe coronavirus disease 2019 (COVID-19). The international rollout of COVID-19 vaccines has provided varying degrees of protection and enabled the understanding of vaccine efficacy and safety. The immune response to COVID-19 vaccines is lower in most patients with immune-mediated kidney diseases; either related to immunosuppression or comorbidities and complications caused by the underlying disease. Humoral vaccine response, measured by the presence of antibodies, is impaired or absent in patients receiving rituximab, mycophenolate mofetil (MMF), higher doses of glucocorticoids and likely other immunosuppressants, such as cyclophosphamide. The timing between the use of these agents and administration of vaccines is associated with the level of immune response: with rituximab, vaccine response can only be expected once B cells start to recover and patients with transient discontinuation of MMF mount a humoral response more frequently. The emergence of new COVID-19 variants and waning of vaccine-induced immunity highlight the value of a booster dose and the need to develop mutant-proof vaccines. COVID-19 vaccines are safe, exhibiting a very low risk of de novo or relapsing immune-mediated kidney disease. Population-based studies will determine whether this is causal or coincidental. Such cases respond to standard management, including the use of immunosuppression. The Immunonephrology Working Group and European Vasculitis Society recommend that patients with immune-mediated kidney diseases follow national guidance on vaccination. Booster doses based on antibody measurements could be considered.

The role of HDL- and non-HDL-related parameters in cell-cholesterol efflux capacity.

BACKGROUND AND AIMS: The regulation of cell-cholesterol efflux is not completely understood. Our aim was to assess the role of HDL- and non-HDL-related parameters in ATP-binding cassette transporter-A1 (ABCA1) and scavenger receptor class B-type-I (SRBI) cell-cholesterol efflux capacity (CEC) in coronary heart disease (CHD) cases and controls. METHODS: Lipids and apoA-I-containing HDL particles (by 2D gel-electrophoresis and immunodetection) were measured in 534 statin-treated CHD patients and in 1076 age-, gender-, and BMI-matched controls. ABCA1-CEC and SRBI-CEC were measured in apoB-depleted serum of 100 cases and 100 controls. RESULTS: Cases had significantly higher concentrations of preß-1 particles (88%) and ABCA1-CEC (34%) compared to controls. ABCA1-CEC was positively correlated with the concentrations of preß-1 particles, triglycerides, small-dense (sd) LDL-C, and LDL-C in both cases and controls. Moreover, both the concentration and the functionality of preß-1 particles (ABCA1-CEC/mg preß-1) were positively associated with the concentrations of sdLDL-C and triglycerides. Cases had 27% lower levels of large HDL particles but similar SRBI-CEC compared to controls. SRBI-CEC was correlated positively with HDL-C, apoA-I, and large-HDL particle levels. However, the functionality of large-HDL particles (SRBI-CEC/mg large particles) was significantly and positively correlated with the preß-1/α-1 ratio, sdLDL-C, and triglycerides. CONCLUSIONS: CHD patients have significantly higher concentration, but less functional preß-1 particles in term of cholesterol efflux capacity compared to controls. Triglyceride-rich lipoproteins have significant influence on either the concentration or the functionality or both of HDL particles and consequently HDL-CEC.

Assessment of muscle volume using magnetic resonance imaging (MRI) in football players after hamstring injuries.

Muscle injuries of the hamstrings are among the most frequent in football and a main cause for significant time away from training and competition. The purpose of this study was to prospectively evaluate the loss of muscle volume in recreational football players three and six weeks after initial trauma. We hypothesized that significant muscle volume loss occurs within 6 weeks after the initial injury event. Twenty recreational football players (mean-age=25 ± 4years; mean-height=181 ± 8cm; mean-weight=81 ± 10kg) with type3a (minor partial muscle tear) and type3b (moderate partial muscle tear) injuries were included. Muscle volume was determined using established methods for the hamstrings and the quadriceps femoris muscle within 3 days and after 3 and 6 weeks following the initial injury. The injured hamstrings lost 6.5% (mean=64 cm3(95%CI=31-98 cm3), p<0.001), the healthy hamstrings lost 2.1% (mean=21 cm3(3-44 cm3),p=0.096) of muscle volume after six weeks. The quadriceps in the injured leg lost 3.8% (mean=78 cm3(51-104 cm3), p<0.001) and 4.5% (83 cm3 (45-121 cm3), p<0.001) in the healthy leg. Muscle volume loss inversely correlated with activity levels in the healthy leg for the quadriceps (r=0.96 (0.90-0.98); R2=0.92; p<0.001) and the hamstrings (r=0.72 (0.40-0.88); R2=0.51; p<0.001), as well as the quadriceps in the injured leg (r=0.70 (0.37-0.87); R2=0.49; p<0.001), but not the injured hamstrings. Muscle volume ratio of hamstrings to quadriceps in the control limb was 0.52 ± 0.06 and 0.53 ± 0.06 in the injured leg. The rehabilitation period of six weeks did not have a relevant negative or a positive effect on ratios. Significant muscle volume loss in the upper thigh occurs in recreational soccer players within three, and within six weeks after a hamstring injury and lies between 2% and 7%.

Modelling the concentration of anti-SARS-CoV-2 immunoglobulin G in intravenous immunoglobulin product batches.

BACKGROUND: Plasma-derived intravenous immunoglobulin (IVIg) products contain a dynamic spectrum of immunoglobulin (Ig) G reactivities reflective of the donor population from which they are derived. We sought to model the concentration of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG which could be expected in future plasma pool and final-product batches of CSL Behring's immunoglobulin product Privigen. STUDY DESIGN AND METHODS: Data was extracted from accessible databases, including the incidence of coronavirus disease 2019 and SARS-CoV-2 vaccination status, antibody titre in convalescent and vaccinated groups and antibody half-life. Together, these parameters were used to create an integrated mathematical model that could be used to predict anti-SARS-CoV-2 antibody levels in future IVIg preparations. RESULTS: We predict that anti-SARS-CoV-2 IgG concentration will peak in batches produced in mid-October 2021, containing levels in the vicinity of 190-fold that of the mean convalescent (unvaccinated) plasma concentration. An elevated concentration (approximately 35-fold convalescent plasma) is anticipated to be retained in batches produced well into 2022. Measurement of several Privigen batches using the Phadia™ EliA™ SARS-CoV-2-Sp1 IgG binding assay confirmed the early phase of this model. CONCLUSION: The work presented in this paper may have important implications for physicians and patients who use Privigen for indicated diseases.

Determination of neutralising anti-SARS-CoV-2 antibody half-life in COVID-19 convalescent donors.

Despite the burgeoning field of coronavirus disease-19 (COVID-19) research, the persistence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralising antibodies remains unclear. This study validated two high-throughput immunological methods for use as surrogate live virus neutralisation assays and employed them to examine the half-life of SARS-CoV-2 neutralising antibodies in convalescent plasma donations made by 42 repeat donors between April and September 2020. SARS-CoV-2 neutralising antibody titres decreased over time but typically remained above the methods' diagnostic cut-offs. Using this longitudinal data, the average half-life of SARS-CoV-2 neutralising antibodies was determined to be 20.4 days. SARS-CoV-2 neutralising antibody titres appear to persist in the majority of donors for several months. Whether these titres confer protection against re-infection requires further study and is of particular relevance as COVID-19 vaccines become widely available.

Interaction of Soybean Varieties and Heat Treatments and Its Effect on Growth Performance and Nutrient Digestibility in Broiler Chickens.

As production of European soybeans is expected to grow, optimal processing conditions need to be ensured for small and heterogeneous batches of soybeans. The effect of different soybean varieties, as well as heat treatments, on the growth performance and nutrient digestibility in broiler chickens was investigated. Two varieties, regarded as heat stable and heat labile after preliminary experiments, were partially de-oiled and thermally processed at 110 °C for 20 min and 120 °C for 20 min. The resulting soybean cakes were integrated into a mash diet and subjected to a 36-day long feeding experiment. A total of 336 one-day-old broiler chickens were divided into 24 pens, resulting in 6 replicates per treatment. With application of the 110 °C treatment, analysis of soybean cakes showed that the commonly required reduction in trypsin inhibitor activity (TIA) was only reached with one soybean variety. The higher processing temperature of 120 °C ensured sufficient TIA reductions in both soybean varieties. Elevated TIA concentrations resulted in decreased growth performances (p < 0.05) of the chickens, whereas no negative effect from overheating on growth performance appeared. Total-tract nitrogen retention (p < 0.05) and pre-caecal digestibility of several amino acids (p < 0.10) decreased with higher processing temperatures but had no negative effects on growth performance. In conclusion, the results indicate that processing conditions adjusted to the different varieties are essential to ensure optimal product quality.

Potential of the Red Alga Dixoniella grisea for the Production of Additives for Lubricants.

There is an increasing interest in algae-based raw materials for medical, cosmetic or nutraceutical applications. Additionally, the high diversity of physicochemical properties of the different algal metabolites proposes these substances from microalgae as possible additives in the chemical industry. Among the wide range of natural products from red microalgae, research has mainly focused on extracellular polymers for additive use, while this study also considers the cellular components. The aim of the present study is to analytically characterize the extra- and intracellular molecular composition from the red microalga Dixoniella grisea and to evaluate its potential for being used in the tribological industry. D. grisea samples, fractionated into extracellular polymers (EPS), cells and medium, were examined for their molecular composition. This alga produces a highly viscous polymer, mainly composed of polysaccharides and proteins, being secreted into the culture medium. The EPS and biomass significantly differed in their molecular composition, indicating that they might be used for different bio-additive products. We also show that polysaccharides and proteins were the major chemical compounds in EPS, whereas the content of lipids depended on the separation protocol and the resulting product. Still, they did not represent a major group and were thus classified as a potential valuable side-product. Lyophilized algal fractions obtained from D. grisea were found to be not toxic when EPS were not included. Upon implementation of EPS as a commercial product, further assessment on the environmental toxicity to enchytraeids and other soil organisms is required. Our results provide a possible direction for developing a process to gain an environmentally friendly bio-additive for application in the tribological industry based on a biorefinery approach.

Treatment Options for Scrotal Migration of Ventriculoperitoneal Shunts: Case Illustration and Systematic Review of 48 Cases.

BACKGROUND: Scrotal migration of intact or disconnected tubing is a rare complication of ventriculoperitoneal shunts. While some illustrative case reports can be found in the literature, a systematic review on treatment options is lacking. OBJECTIVE: To propose the first literature-based treatment algorithm on scrotal shunt migration. METHODS: We conducted a literature search using the keywords: "VP," "ventriculoperitoneal," "shunt," and "scrotum." We identified 36 publications with 48 cases reported including our index case. RESULTS: Median age at presentation was 13.5 mo (3 d to 65 yr) which was 4 mo (3 d to 72 mo) after last shunt-related surgery. All patients had scrotal swelling, 39 (81%) patients presented without other symptoms, 4 (8%) had additionally local pain, and 4 (8%) patients presented with symptoms of shunt dysfunction. Treatment was surgically in all but one case where spontaneous resolution without repeat migration occurred. In 3 of 4 patients who had either subcutaneous shortening or abdominal repositioning of the shunt without hernia repair, scrotal shunt migration recurred within the following month. Whereas the surgical treatment with reposition of the migrated catheter back into the peritoneal cavity via a groin incision plus hernia repair yielded a definite treatment in all 26 performed cases, the revision rate was significantly higher in the shunt revision without hernia repair cohort (P = .0009). CONCLUSION: Scrotal shunt migration is a rare shunt complication with good recovery when treated surgically. We recommend hernia repair in addition to either manual or surgical repositioning of migrated tubing.

[18F]fluorodeoxyglucose-positron emission tomography and glucose-transporter type 1 expression in untreated primary small bowel adenocarcinoma.

BACKGROUND: Literature reporting [18F]fluorodexoyglucose positron emission tomography (FDG-PET) of small bowel adenocarcinoma, a rare tumor, is sparse. To assess FDG uptake in small bowel adenocarcinoma, we retrospectively analyzed a large, single-center database and determined the expression of glucose-transporter type 1 (GLUT-1). METHODS: Screening of PET datasets in the database (N.=28,961 scans) for untreated histologically-confirmed primary small bowel adenocarcinoma revealed evaluable PET datasets for eight patients. Maximum and peak standardized uptake values (SUVmax and SUVpeak, respectively) were calculated via volume-of-interest (VOI) analysis. Additionally, GLUT-1 expression on tumor specimens was prospectively immunohistochemically assessed. RESULTS: All primary tumors showed high FDG uptake: mean SUVmax was 9.5±2.6 (range: 5.0-13.0) and SUVpeak, 8.1±2.3 (range: 3.9-10.7). Corresponding biopsy specimens (N.=7) demonstrated high GLUT-1 expression. CONCLUSIONS: Primary small bowel adenocarcinomas have a high GLUT-1 expression. Tumor lesions consistently demonstrated high FDG uptake pre-treatment, suggesting FDG-PET utility in staging and follow-up of these tumors.

Arrhythmia in Cardiac Sarcoidosis.

Cardiac sarcoidosis (CS) is a complex disease that can manifest as a diverse array of arrhythmias. CS patients may be at higher risk for sudden cardiac death (SCD), and, in some cases, SCD may be the first presenting symptom of the underlying disease. As such, identification, risk stratification, and management of CS-related arrhythmia are crucial in the care of these patients. Left untreated, CS carries significant arrhythmogenic morbidity and mortality. Cardiac manifestations of CS are a consequence of an inflammatory process resulting in the myocardial deposition of noncaseating granulomas. Endomyocardial biopsy remains the gold standard for diagnosis; however, biopsy yield is limited by the patchy distribution of the granulomas. As such, recent guidelines have improved clinical diagnostic pathways relying on advanced cardiac imaging to help in the diagnosis of CS. To date, corticosteroids are the best studied agent to treat CS but are associated with significant risks and limited benefits. Implantable cardioverter-defibrillators have an important role in SCD risk reduction. Catheter ablation in conjunction with antiarrhythmics seems to reduce ventricular arrhythmia burden. However, the appropriate selection of these patients is crucial as ablation is likely more helpful in the setting of a myocardial scar substrate versus arrhythmia driven by active inflammation. Further studies investigating CS pathophysiology, the pathway to diagnosis, arrhythmogenic manifestations, and SCD risk stratification will be crucial to reduce the high morbidity and mortality of this disease.

Regadenoson-induced T-wave heterogeneity complements coronary stenosis detection by myocardial perfusion imaging in men and women.

AIMS: We analysed whether incorporating electrocardiographic interlead T-wave heterogeneity (TWH) with myocardial perfusion imaging (MPI) during pharmacologic stress improves detection of flow-limiting lesions (FLL). METHODS AND RESULTS: Medical records of all 103 patients at our institution who underwent stress testing with regadenoson (0.4 mg IV bolus) within 3 months of coronary angiography from September 2017 to March 2019 were studied. Cases (N = 59) had angiographically significant FLL (≥50% of left main or ≥70% of other epicardial coronary arteries ≥2 mm in diameter); controls (N = 44) were normal or had non-FLL. TWH, i.e., interlead splay of T waves, was assessed from precordial leads V4-6 by second central moment analysis. Maximum TWHV4-6 levels during regadenoson stress were 68% higher in cases than in controls (P < 0.0001). TWHV4-6 generated areas under the receiver-operating characteristic (ROC) curve of 0.79 in men (P < 0.0001) and 0.71 in women (P = 0.007). In men, the ROC-guided 54-µV TWHV4-6 cut-point for FLL produced adjusted odds of 7.3 [95% confidence interval (CI): 1.3-41.5, P = 0.03], 79% sensitivity, and 78% specificity. In women, the ROC-guided 35-µV TWHV4-6 cut-point produced adjusted odds of 4.5 (95% CI: 1.1-18.9, P = 0.04), 84% sensitivity, and 52% specificity. Adding TWHV4-6 to MPI determinations reduced false-positive results by 70%, more than doubled true-negative results, and improved adjusted odds ratio to 6.8 (95% CI: 2.2-21.4, P = 0.001) with specificity of 78% in men and 86% in women. CONCLUSION: This observational study is the first to demonstrate the benefit of combining TWHV4-6 with MPI to enhance FLL detection during MPI with regadenoson in both men and women.

Dynamic 3D proteomes reveal protein functional alterations at high resolution in situ.

Biological processes are regulated by intermolecular interactions and chemical modifications that do not affect protein levels, thus escaping detection in classical proteomic screens. We demonstrate here that a global protein structural readout based on limited proteolysis-mass spectrometry (LiP-MS) detects many such functional alterations, simultaneously and in situ, in bacteria undergoing nutrient adaptation and in yeast responding to acute stress. The structural readout, visualized as structural barcodes, captured enzyme activity changes, phosphorylation, protein aggregation, and complex formation, with the resolution of individual regulated functional sites such as binding and active sites. Comparison with prior knowledge, including other 'omics data, showed that LiP-MS detects many known functional alterations within well-studied pathways. It suggested distinct metabolite-protein interactions and enabled identification of a fructose-1,6-bisphosphate-based regulatory mechanism of glucose uptake in E. coli. The structural readout dramatically increases classical proteomics coverage, generates mechanistic hypotheses, and paves the way for in situ structural systems biology.