Effect of Regulatory Constraints on Fund Performance: New Evidence from UCITS Hedge Funds

We economically motivate and then test a range of hypotheses regarding performance and risk differences between UCITS-compliant and other hedge funds. The latter exhibit more suspicious return patterns than do absolute return UCITS (ARUs), but ARUs exhibit higher levels of operational risk. We find evidence of a strong liquidity premium: hedge funds offer investors less liquidity than do ARUs yet exhibit better risk-adjusted performance. Our findings are substantially unchanged under various robustness tests and adjustments for possible selection bias. The liquidity premium for ARUs and their lack of performance persistence have implications for both investors and policy makers

The effect of investment constraints on hedge fund investor returns

This paper examines the effect of investor-level real-world investment constraints, including several which had not been studied before, on hedge fund performance and its persistence. Using a large consolidated database, we demonstrate that hedge fund performance persistence is significantly reduced when rebalancing rules reflect fund size restrictions and liquidity constraints, but remains statistically significant at higher rebalancing frequencies. Hypothetical investor portfolios that incorporate additional minimum diversification constraints and minimum investment requirements suggest that the performance and its persistence documented in earlier studies of hedge funds is not easily exploitable, especially by large investors

Quantitative bile and serum proteomics for the screening and differential diagnosis of primary sclerosing cholangitis

BackgroundPrimary sclerosing cholangitis (PSC) is a chronic liver disease characterized by biliary strictures, cholestasis, and a markedly increased risk of cholangiocarcinoma. New markers for the screening and differential diagnosis of PSC are needed. In this pilot study, we have analyzed both the bile and serum proteomic profiles of 80 PSC patients and non-PSC controls (n = 6 for bile and n = 18 for serum).AimThe aim of this study was to discover candidates for new biomarkers for the differential diagnosis of PSC.MethodsBile and serum samples were processed and subsequently analyzed using ultra performance liquid chromatography-ultra definition mass spectrometry (UPLC-UDMSE). Further analysis included statistical analyses such as receiver operating characteristic curve analysis as well as pathway analysis using Ingenuity Pathway Analysis.Results and conclusionsIn bile, we discovered 64 proteins with significantly different levels between the groups, with fold changes of up to 129. In serum, we discovered 112 proteins with significantly different levels. Receiver operating characteristic curve analysis found multiple proteins with high area under the curve values, up to 0.942, indicating that these serum proteins are of value as new non-invasive classifiers of PSC. Pathway analysis revealed multiple canonical pathways that were enriched in the dataset, which have roles in bile homeostasis and metabolism. We present several serum proteins that could serve as new blood-based markers for the diagnosis of PSC after further validation. The measurement of serum levels of these proteins could be of use in the screening of patients with suspected PSC.Peer reviewe

Quantitative N-glycoproteomics reveals altered glycosylation levels of various plasma proteins in bloodstream infected patients

Bloodstream infections are associated with high morbidity and mortality with rates varying from 10–25% and higher. Appropriate and timely onset of antibiotic therapy influences the prognosis of these patients. It requires the diagnostic accuracy which is not afforded by current gold standards such as blood culture. Moreover, the time from blood sampling to blood culture results is a key determinant of reducing mortality. No established biomarkers exist which can differentiate bloodstream infections from other systemic inflammatory conditions. This calls for studies on biomarkers potential of molecular profiling of plasma as it is affected most by the molecular changes accompanying bloodstream infections. N-glycosylation is a post-translational modification which is very sensitive to changes in physiology. Here we have performed targeted quantitative N-glycoproteomics from plasma samples of patients with confirmed positive blood culture together with age and sex matched febrile controls with negative blood culture reports. Three hundred and sixty eight potential N-glycopeptides were quantified by mass spectrometry and 149 were further selected for identification. Twenty four N-glycopeptides were identified with high confidence together with elucidation of the peptide sequence, N-glycosylation site, glycan composition and proposed glycan structures. Principal component analysis, orthogonal projections to latent structures-discriminant analysis (S-Plot) and self-organizing maps clustering among other statistical methods were employed to analyze the data. These methods gave us clear separation of the two patient classes. We propose high-confidence N-glycopeptides which have the power to separate the bloodstream infections from blood culture negative febrile patients and shed light on host response during bacteremia. Data are available via ProteomeXchange with identifier PXD009048.Peer reviewe

Urinary extracellular vesicles carry multiple activators and regulators of coagulation

Cells shape their extracellular milieu by secreting intracellular products into the environment including extracellular vesicles which are lipid-bilayer limited membrane particles. These vesicles carry out a range of functions, including regulation of coagulation, via multiple contributor mechanisms. Urinary extracellular vesicles are secreted by various cells, lining the urinary space, including the nephron and bladder. They are known to have procoagulant properties, however, the details of this function, beyond tissue factor are not well known. The aim of the study was to access the role of urinary extracellular vesicles in impacting coagulation upon supplementation to plasma. This could indicate their physiological function upon kidney injury or pathology. Supplementation to standard human plasma and plasmas deficient in various coagulation factors was used for this purpose, and calibrated automated thrombogram (CAT (R)) was the major technique applied. We found that these vesicles contain multiple coagulation-related factors, and their lipid composition affects coagulation activities of plasma upon supplementation. Remarkably, these vesicles can restore thrombin generation in FVII, FVIII, FIX and FXI -deficient plasmas. This study explores the multiple roles of urinary extracellular vesicles in coagulation in in vitro blood coagulation and implies their importance in its regulation by several mechanisms.Peer reviewe

Expression of Toll-like receptors in nasal epithelium in allergic rhinitis

Toll-like receptors (TLRs) are important in barrier homeostasis, but their role in airborne allergies is not fully understood. The aim was to evaluate baseline and allergen-induced expression of TLR proteins in nasal epithelium during allergic rhinitis. Nineteen otherwise healthy non-smoking volunteers both allergic to birch pollen and non-allergic controls were enrolled. We took nasal biopsies before and after off-seasonal intranasal birch pollen or diluent challenge. The expression of epithelial TLR1-7, TLR9-10, and MyD88 proteins was immunohistochemically evaluated from the nasal biopsies. The TLR1-3 and TLR5-10 mRNAs were observed by RNA-microarray. Baseline epithelial expression of TLR proteins was wide and identical in controls and atopics. After off-seasonal intranasal birch pollen challenge, a negative change in the expression score of TLR1 and TLR6 proteins was detected in the atopic group. TLR mRNA expression was not affected by birch pollen challenge. Nasal epithelium seems to express all known TLRs. The mechanisms by which TLR1, and TLR6 proteins could affect pollen allergen transport need further studies.Peer reviewe

Molecular Mechanisms of Nasal Epithelium in Rhinitis and Rhinosinusitis

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Application of the UHPLC-DIA-HRMS Method for Determination of Cheese Peptides

Until now, cheese peptidomics approaches have been criticised for their lower throughput. Namely, analytical gradients that are most commonly used for mass spectrometric detection are usually over 60 or even 120 min. We developed a cheese peptide mapping method using nano ultra-high-performance chromatography data-independent acquisition high-resolution mass spectrometry (nanoUHPLC-DIA-HRMS) with a chromatographic gradient of 40 min. The 40 min gradient did not show any sign of compromise in milk protein coverage compared to 60 and 120 min methods, providing the next step towards achieving higher-throughput analysis. Top 150 most abundant peptides passing selection criteria across all samples were cross-referenced with work from other publications and a good correlation between the results was found. To achieve even faster sample turnaround enhanced DIA methods should be considered for future peptidomics applications.Peer reviewe

Birch pollen allergen immunotherapy reprograms nasal epithelial transcriptome and recovers microbial diversity

Peer reviewe