Likviditeetin hinnoittelu yrityslainoissa:ennustaako muutos arvopaperitason likviditeetissä yrityslainan tulevia tuottoja?

Tiivistelmä. Tutkielmassa selvitetään arvopaperitason likviditeetin muutosten vaikutusta yrityslainojen hintoihin ja tuotto-odotuksiin yhdysvaltalaisella joukkovelkakirjalaina-aineistolla vuosina 2007–2019. Tärkeimpänä tutkimuskysymyksenä on, ennustaako yksittäisen arvopaperin tasolla havaittu likviditeetin muutos yrityslainan tulevaa tuottoa. Toisena tutkimuskysymyksenä selvitetään, miten likviditeetin hinnoittelunopeus vaihtelee riippuen yrityslainan likviditeettitasosta ja luottoluokituksesta. Tutkielman keskeisinä tavoitteina on laajentaa ymmärrystä likviditeetin roolista arvopapereiden hinnoittelussa ja jatkaa arvopaperitason likviditeetin muutos -ilmiön tutkimusta osakemarkkinoiden ulkopuolelle. Samalla tämä on tiettävästi ensimmäinen tutkielma, joka käsittelee arvopaperitason likviditeetin muutoksen ja tuottojen välistä yhteyttä osakemarkkinoiden ulkopuolella. Suuri osa yrityslainamarkkinan kaupankäynnistä tapahtuu listattujen markkinoiden ulkopuolella niin sanotuilla OTC-markkinoilla. Yhdysvaltojen rahoitusalanviran viranomaiset keräävät ja raportoivat tiedot kaikista TRACE-ohjelmaan kuuluvien yritysten joukkovelkakirjalainoilla tehdyistä kaupoista. Likviditeetin määrittämiseen käytetään TRACE-ohjelmaan kuuluvien yrityslainojen toteutuneista kaupoista kerättyä päätöskurssiaineistoa, jonka perusteella muodostetaan kaupankäyntikustannuksia ja kaupankäynnin välittömyyttä estimoivat likviditeettimittarit. Kvantitatiivisesti toteutetun analyysin ensimmäisessä vaiheessa estimoidaan aikasarjakeskiarvot tutkielmassa käytettyjen muuttujien kuvaileville tunnusluvuille ja keskimääräiset aikasarjakorrelaatiot muuttujien välillä. Tarkemmassa analyysissä ja hypoteesien testauksessa hyödynnetään portfoliotason tarkastelua yhden ja kahden muuttujan lajittelulla. Portfoliotarkasteluissa verrataan portfolioiden tuottoja sekä luotto- ja korkoriskimuuttujilla laajennetun kolmen faktorin Fama-French-regressiomallin alfoja. Tuloksissa arvopaperitasolla havaittu likviditeetin muutos ei ennusta yrityslainan seuraavan kuukauden tuottoa tilastollisesti merkitsevällä tasolla. Likviditeetin muutoksen vaikutus yrityslainan hintaan on suurin yrityslainoilla, joilla on korkea likviditeettitaso ja matala tai keskitasoinen luottoluokitus. Tulokset vahvistavat käsitystä likviditeettitason vähäisestä merkityksestä yrityslainamarkkinoilla etenkin instituutiokoon toimeksiannoissa, joissa likviditeetin tarve on usein vähäinen muun muassa laajasti käytetyn osta ja pidä maturiteettiin -strategian vuoksi. Samalla selkeän näytön puuttuminen uudelle riskifaktorille tukee aiempia arvioita, joiden mukaan osakemarkkinoilla osaketason likviditeetin muutoksia seuraavat ylituotot ovat todennäköisesti seurausta lyhytaikaisesta hinnoitteluvirheestä

The Mutational Profile of Unicystic Ameloblastoma

BRAF V600E is the most common mutation in conventional ameloblastoma (AM) of the mandible. In contrast, maxillary AMs appear to harbor more frequently RAS, FGFR2, or SMO mutations. Unicystic ameloblastoma (UAM) is considered a less aggressive variant of ameloblastoma, amenable to more conservative treatment, and classified as a distinct entity. The aim of this study was to characterize the mutation profile of UAM (n = 39) and to compare it to conventional AM (n = 39). The associations between mutation status and recurrence probability were also analyzed. In the mandible, 94% of UAMs (29/31, including 8/8 luminal, 6/8 intraluminal, and 15/15 mural subtypes) and 74% of AMs (28/38) revealed BRAF V600E mutations. Among the BRAF wild-type cases, 1 UAM showed a missense SMO mutation (p.L412F), whereas 2 NRAS (p.Q61R), 2 HRAS (p.Q61R), and 2 FGFR2 (p.C383R) activating mutations were identified in AM. Of the 3 maxillary UAMs, only 1 revealed a BRAF V600E mutation. Taken together, our findings demonstrate high frequency of activating BRAF V600E mutations in both UAM and AM of the mandible. In maxillary UAMs, the BRAF V600E mutation prevalence appears to be lower as was shown for AM previously. It could therefore be argued that UAM and AM are part of the spectrum of the same disease. AMs without BRAF V600E mutations were associated with an increased rate of local recurrence (P = 0.0003), which might indicate that routine mutation testing also has an impact on prognosis.Peer reviewe

Circulating pathogen-specific plasmablasts in female patients with upper genital tract infection

Mucosal antibodies constitute the first line of adaptive immune defence against invaders in the female genital tract (FGT), yet the sequence of events leading to their production is surprisingly poorly characterized. We explored the induction of pathogen-specific antibody-secreting cells (ASC) as a response to an acute infection in the upper FGT. We recruited 12 patients undergoing surgery due to an upper FGT infection (7/12 blood culture positive, 5/ 12 negative) and six healthy controls. Pathogens were sampled during surgery and PBMC collected in the acute phase of the disease (days 7-10). We searched by ELISPOT circulating pathogen-specific ASC and explored their frequency, immunoglobulin isotype distribution, and expressions of homing receptors (alpha(4)beta(7), L-selectin, and CLA). All patients had circulating ASC specific to the infective bacteria; the geometric mean was 434 (95%CI 155-1234) ASC (IgA + IgG + IgM)/10(6) PBMC. IgA ASC predominated in 7/12, IgG ASC in 3/12, and IgM ASC in 2/12 cases. Of all the pathogen-specific ASC, 60% expressed alpha(4)beta(7), 67% L-selectin, and 9% CLA. This study is the first to show induction of pathogen-specific ASC in the peripheral blood in bacterial infection in the human FGT. Our findings reveal that such FGT-originating pathogen-specific ASC are predominated by IgA ASC and exhibit a homing receptor profile resembling that of ASC in acute urinary tract infection. The data thus suggest a characteristic profile shared by the urogenital tract.Peer reviewe

Enumeration and isolation of cpe-positive Clostridium perfringens spores from feces.

A hydrophobic grid membrane filter-colony hybridization (HGMF-CH) method for the enumeration and isolation of cpe gene-carrying (cpe-positive) Clostridium perfringens spores from feces was developed. A 425-bp DNA probe specific for the cpe gene was sensitive and specific when tested with bacterial DNA and pure cultures. The enumeration of cpe-positive C. perfringens by the HGMF-CH method proved to be as sensitive as nested PCR combined with the most-probable number technique when tested with fecal samples from healthy individuals. With the aid of the HGMF-CH method, positive hybridization signals were detected from two out of seven fecal samples obtained from healthy individuals. Furthermore, cpe-positive C. perfringens was successfully isolated from both of these samples. The detection of cpe-positive C. perfringens by the HGMF-CH method is dependent on the ratio of cpe-positive C. perfringens colonies to total C. perfringens colonies growing on the HGMF-tryptose-sulfite-cycloserine plate. cpe-positive C. perfringens could be isolated if the ratio of cpe-positive C. perfringens spores to total C. perfringens spores was 6 x 10–5 or higher. The HGMF-CH method provides an aid in the investigation of fecal samples of patients suffering from food poisoning or other diseases caused by cpe-positive C. perfringens. The method also offers a new approach in the investigation of the epidemiology of cpe-positive C. perfringens strains

Free-of-charge long-acting reversible contraception : two-year discontinuation, its risk factors, and reasons

BACKGROUND: Since 2013, the residents of the city of Vantaa, Finland, have been offered their first long-acting reversible contraceptive method (levonorgestrel-releasing intrauterine system, implant, and copper intrauterine device) free of charge. OBJECTIVE: The primary aim of this study was to assess the 2-year cumulative discontinuation rates of long-acting reversible contraceptive methods when provided free of charge for first-time users in a real-world setting. Additional aims were to describe factors associated with discontinuation and to evaluate the reasons for discontinuation. STUDY DESIGN: This is a retrospective register-based cohort study of 2026 nonsterilized women aged 15 to 44 years, who initiated a free-of-charge long-acting contraceptive method in 2013-2014 in the city of Vantaa. Removals within 2 years after method initiation and reasons for discontinuation were obtained from electronic health records and from national registers. We calculated the 2-year cumulative incidence rates of discontinuation with 95% confidence intervals for each method. Furthermore, we assessed crude and adjusted incidence rate ratios of discontinuation with 95% confidence interval by Poisson regression models comparing implants and copper intrauterine device with levonorgestrel-releasing intrauterine systems. RESULTS: During the 2 -year follow-up, 514 women discontinued, yielding a cumulative discontinuation rate of 28.3 per 100 women-years (95% confidence interval, 26.2-30.4). Among the 1199 women who initiated the levonorgestrel-releasing intrauterine system, the cumulative discontinuation rate was 24.2 per 100 women-years (95% confidence interval, 21.7-26.9); among the 642 implant users, 33.3 per 100 women-years (95% confidence interval, 29.5-37.4); and among the 185 copper intrauterine device users, 37.8 per 100 women-years (95% confidence interval, 31.0-45.7). Compared with women aged 30 to 44 years, women aged 15 to 19 years (adjusted incidence rate ratio, 1.58; 95% confidence interval, 1.17-2.14) and 20 to 29 years (adjusted incidence rate ratio, 1.35; 95% confidence interval, 1.11-1.63) were more likely to discontinue. We observed a higher discontinuation rate in women who had given birth within the previous year (adjusted incidence rate ratio, 1.36; 95% confidence interval, 1.13-1.65), spoke a native language other than Finnish or Swedish (adjusted incidence rate ratio, 1.31; 95% confidence interval, 1.06-1.63), and had a history of a sexually transmitted infection (adjusted incidence rate ratio, 1.62; 95% confidence interval, 1.07-2.46). No association was found in marital status, overall parity, history of induced abortion, socioeconomic status, education level, or smoking status. The most common reason for discontinuation was bleeding disturbances, reported by 21% of women who discontinued the levonorgestrel-releasing intrauterine system, by 71% who discontinued the implant, and by 41% who discontinued the copper intrauterine device. One in 4 women who discontinued the copper intrauterine device reported heavy menstrual bleeding, whereas only 1% who discontinued the levonorgestrel-releasing intrauterine system and none who discontinued implants reported this reason. Abdominal pain was the reported reason for discontinuation in 20% of both intrauterine device users and in only 2% who discontinued implants. CONCLUSION: At 2 years, the use of implants and copper intrauterine devices was more likely to be discontinued than that of the levonorgestrelreleasing intrauterine system. Women younger than 30 years and those who gave birth in the preceding year, spoke a native language other than Finnish or Swedish, or had a history of sexually transmitted infections were more likely to discontinue. The levonorgestrel-releasing intrauterine system was least likely to be removed owing to bleeding disturbances.YPeer reviewe

Estradiol Valerate Vs. Ethinylestradiol In Combined Oral Contraceptives : Effects On The Pituitary-Ovarian Axis

Context There are limited studies comparing the effects of combined oral contraceptives (COCs) containing natural estrogens and synthetic ethinylestradiol (EE) on reproductive hormones. Objective To compare estradiol valerate (EV)+dienogest (DNG), EE+DNG, and DNG alone (an active control) on levels of follicle stimulating hormone (FSH), luteinizing hormone, Anti-Mullerian hormone (AMH), ovarian steroids, sex hormone binding globulin (SHBG), and the Free Androgen Index (FAI). Design Spin-off study from a randomized trial. Setting Outpatient setting at Helsinki and Oulu University Hospitals, Finland. Participants 59 healthy, 18-35-year-old ovulatory women were enrolled. Three women discontinued. The groups were comparable as regards age and body mass index. Interventions EV 2mg+DNG 2-3mg (n=20), EE 0.03mg+DNG 2mg (n=20) and DNG 2mg (n=19) were used continuously for nine weeks. Blood samples were drawn at baseline, and at 5 and 9 weeks. Main Outcome Measures EV+DNG suppressed FSH by -27% (-51:-3) (median [95%CI]) vs. EE+DNG, -64% (-78: -51), P=0.04, but AMH levels decreased similarly by -9% (-18: -0.1) vs. -13% (-28:0.2), P=0.38, respectively. EV+DNG increased SHBG levels by 56% (30:82) and EE+DNG by 385% (313:423), PPeer reviewe

Identification of Clostridium species and DNA fingerprinting of Clostridium perfringens by amplified fragment length polymorphism analysis

An amplified fragment length polymorphism (AFLP) method was applied to 129 strains representing 24 different Clostridium species, with special emphasis on pathogenic clostridia of medical or veterinary interest, to assess the potential of AFLP for identification of clostridia. In addition, the ability of the same AFLP protocol to type clostridia at the strain level was assessed by focusing on Clostridium perfringens strains. All strains were typeable by AFLP, so the method seemed to overcome the problem of extracellular DNase production. AFLP differentiated all Clostridium species tested, except for Clostridium ramosum and Clostridium limosum, which clustered together with a 45% similarity level. Other Clostridium species were divided into species-specific clusters or occupied separate positions. Wide genetic diversity was observed among Clostridium botulinum strains, which were divided into seven species-specific clusters. The same AFLP protocol was also suitable for typing C. perfringens at the strain level. A total of 29 different AFLP types were identified for 37 strains of C. perfringens; strains initially originating from the same isolate showed identical fingerprinting patterns and were distinguished from unrelated strains. AFLP proved to be a highly reproducible, easy-to-perform, and relatively fast method which enables high throughput of samples and can serve in the generation of identification libraries. These results indicate that the AFLP method provides a promising tool for the identification and characterization of Clostridium species

Segregation of Ni at early stages of radiation damage in NiCoFeCr solid solution alloys

Defect evolution under irradiation is investigated in a set of single-phase concentrated solid solution alloys (SP-CSAs) containing Ni with Co, Fe and/or Cr. We show that atomic segregation of Ni takes place already at very early stages of radiation damage in the 2-4 element SP-CSAs containing Fe or Cr, well below 1 dpa. We arrive at this conclusion by following the evolution of positron annihilation signals as a function of irradiation dose in single crystal samples, complemented by molecular dynamics simulations in the same model systems for high entropy alloys (HEAs). This manifestation of short-range order calls attention to composition fluctuations at the atomic level in irradiated HEAs. Ion irradiation may induce short-range order in certain alloys due to chemically biased elemental diffusion. The work highlights the necessity of updating the assumption of a totally random arrangement in the irradiated alloys, even though the alloys before irradiation have random arrangements of different chemical elements. (C) 2020 Acta Materialia Inc. Published by Elsevier Ltd.Peer reviewe

Combined oral contraceptives containing estradiol valerate vs ethinylestradiol on coagulation : A randomized clinical trial

Introduction Contraceptives containing ethinylestradiol (EE) induce changes in the coagulation system and are associated with a risk of venous thromboembolism. However, studies comparing the effects of combined oral contraceptives containing EE and low-potency estrogens (ie, estradiol [E-2] and estradiol valerate [EV]) on coagulation biomarkers are limited. This study represents secondary outcomes of a randomized trial comparing combined oral contraceptives containing EV + dienogest (DNG), EE + DNG, and DNG alone on selected coagulation biomarkers. We could compare the specific effects of the different estrogen components owing to the inclusion of preparations containing the same progestin. Material and methods We enrolled 59 healthy, 18- to 35-year-old, non-smoking women, of whom three discontinued. The participants were randomly allocated to 9 weeks of continuous treatment with EV 2 mg + DNG 2-3 mg (n = 20), EE 0.03 mg + DNG 2 mg (n = 20), or DNG 2 mg (n = 19). Blood samples were collected at baseline and after 9 weeks. We assessed coagulation in vitro by thrombin generation using the Calibrated Automated Thrombogram. Thrombin generation was evaluated by lag time, time to thrombin peak, thrombin peak, and endogenous thrombin potential in response to tissue factor (1 pm). In vivo coagulation assessment was based on levels of prothrombin fragment 1 + 2 (F1 + 2) (thrombin generation) and D-dimer (fibrin turnover). Clinical trial registration: NCT02352090. Results Lag time and time to thrombin peak remained unaltered after exposure to EV + DNG, whereas EE + DNG shortened both lag time (mean percentage change -24%, 95% confidence interval [CI] -32% to -15%; p < 0.01) and time to thrombin peak (-26%, 95% CI -37% to -16%; p < 0.01). EV + DNG induced lower thrombin peak and endogenous thrombin potential than EE + DNG (peak; +45%, 95% CI 22%-67% vs +147%,95% CI 96%-198%; p < 0.01, and endogenous thrombin potential; +26%, 95% CI 15%-38% vs +64%, 95% CI 51%-76%; p < 0.01). Median F1 + 2 levels remained unchanged with EV + DNG (p = 0.22) but increased within normal ranges with EE + DNG (from 152 pmol/L, 95% CI 127-206] pmol/L to 194 pmol/L, 95% CI 149-250 pmol/L, p = 0.04). The within-group change in D-dimer levels was not significant in any of the groups. DNG alone did not affect these biomarkers. Conclusions Both in vitro and in vivo thrombin generation was lower after exposure to EV + DNG compared with EE + DNG. The lower thrombin generation measures after treatment with EV + DNG indicate less enhancement of coagulation potential and suggest that EV may be favorable to EE as a component of combined oral contraceptives.Peer reviewe

Combined oral contraceptives containing estradiol valerate vs ethinylestradiol on coagulation : A randomized clinical trial

Introduction Contraceptives containing ethinylestradiol (EE) induce changes in the coagulation system and are associated with a risk of venous thromboembolism. However, studies comparing the effects of combined oral contraceptives containing EE and low-potency estrogens (ie, estradiol [E-2] and estradiol valerate [EV]) on coagulation biomarkers are limited. This study represents secondary outcomes of a randomized trial comparing combined oral contraceptives containing EV + dienogest (DNG), EE + DNG, and DNG alone on selected coagulation biomarkers. We could compare the specific effects of the different estrogen components owing to the inclusion of preparations containing the same progestin. Material and methods We enrolled 59 healthy, 18- to 35-year-old, non-smoking women, of whom three discontinued. The participants were randomly allocated to 9 weeks of continuous treatment with EV 2 mg + DNG 2-3 mg (n = 20), EE 0.03 mg + DNG 2 mg (n = 20), or DNG 2 mg (n = 19). Blood samples were collected at baseline and after 9 weeks. We assessed coagulation in vitro by thrombin generation using the Calibrated Automated Thrombogram. Thrombin generation was evaluated by lag time, time to thrombin peak, thrombin peak, and endogenous thrombin potential in response to tissue factor (1 pm). In vivo coagulation assessment was based on levels of prothrombin fragment 1 + 2 (F1 + 2) (thrombin generation) and D-dimer (fibrin turnover). Clinical trial registration: NCT02352090. Results Lag time and time to thrombin peak remained unaltered after exposure to EV + DNG, whereas EE + DNG shortened both lag time (mean percentage change -24%, 95% confidence interval [CI] -32% to -15%; p < 0.01) and time to thrombin peak (-26%, 95% CI -37% to -16%; p < 0.01). EV + DNG induced lower thrombin peak and endogenous thrombin potential than EE + DNG (peak; +45%, 95% CI 22%-67% vs +147%,95% CI 96%-198%; p < 0.01, and endogenous thrombin potential; +26%, 95% CI 15%-38% vs +64%, 95% CI 51%-76%; p < 0.01). Median F1 + 2 levels remained unchanged with EV + DNG (p = 0.22) but increased within normal ranges with EE + DNG (from 152 pmol/L, 95% CI 127-206] pmol/L to 194 pmol/L, 95% CI 149-250 pmol/L, p = 0.04). The within-group change in D-dimer levels was not significant in any of the groups. DNG alone did not affect these biomarkers. Conclusions Both in vitro and in vivo thrombin generation was lower after exposure to EV + DNG compared with EE + DNG. The lower thrombin generation measures after treatment with EV + DNG indicate less enhancement of coagulation potential and suggest that EV may be favorable to EE as a component of combined oral contraceptives.Peer reviewe