Local semicircle law with imprimitive variance matrix

We extend the proof of the local semicircle law for generalized Wigner matrices given in MR3068390 to the case when the matrix of variances has an eigenvalue -1. In particular, this result provides a short proof of the optimal local Marchenko-Pastur law at the hard edge (i.e. around zero) for sample covariance matrices X*X, where the variances of the entries of X may vary

Local spectral statistics of Gaussian matrices with correlated entries

We prove optimal local law, bulk universality and non-trivial decay for the off-diagonal elements of the resolvent for a class of translation invariant Gaussian random matrix ensembles with correlated entries

Stability of the matrix Dyson equation and random matrices with correlations

We consider real symmetric or complex hermitian random matrices with correlated entries. We prove local laws for the resolvent and universality of the local eigenvalue statistics in the bulk of the spectrum. The correlations have fast decay but are otherwise of general form. The key novelty is the detailed stability analysis of the corresponding matrix valued Dyson equation whose solution is the deterministic limit of the resolvent

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

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

Middle Ear Barotraumas in Commercial Aircrew

BACKGROUND: Middle ear (ME) barotraumas are the most common condition in aviation medicine, sometimes seriously compromising flight safety. Considering this and the ever-increasing amount of commercial aviation, a detailed overview is warranted. METHODS: In this survey study, an anonymous, electronic questionnaire was distributed to commercial aircrew of the three major commercial airlines operating in Finland (N = 3799), covering 93% of the target population (i.e., all commercial aircrew operating in Finland, N = 4083). Primary outcomes were self-reported prevalence, clinical characteristics, and health and occupational effects of ME barotraumas in flight. Secondary outcomes were adjusted odds ratios (OR) for frequency of ME barotraumas with respect to possible risk factors. RESULTS: Response rate was 47% (N = 1789/3799), with 85% (N 1516) having experienced ME barotraumas in flight. Of those affected, 60% had used medications, 5% had undergone surgical procedures, and 48% had been on sick leave due to ME barotraumas (40% during the last year). Factors associated with ME barotraumas included a high number of upper respiratory tract infections [>= 3 URTIs/yr vs. 0 LIRTIs/yr: OR, 9.02; 95% confidence interval (CI) 3.99-20.39] and poor subjective performance in Valsalva ("occasionally" vs."a lways" successful: OR, 7.84; 95% CI 3.97-15.51) and Toynbee ("occasionally" vs."always" successful: OR, 9.06; 95% CI 2.67-30.78) maneuvers. CONCLUSION: ME barotraumas were reported by 85% of commercial aircrew.They lead to an increased need for medications, otorhinolaryngology-related surgical procedures, and sickness absence from flight duty. Possible risk factors include a high number of URTIs and poor performance in pressure equalization maneuvers.Peer reviewe

Sinus Barotraumas in Commercial Aircrew

BACKGROUND: Sinus barotraumas are a common condition in aviation medicine, sometimes compromising flight safety and even permanently grounding aircrew. Considering this and the ever-increasing amount of commercial aviation, a thorough examination is required. METHODS: In this survey study, an anonymous, electronic questionnaire was distributed to commercial aircrew of the three major commercial airlines operating in Finland (N = 3799), covering 93% of the target population (i.e., all commercial aircrew operating in Finland, N = 4083). Primary outcomes were self-reported prevalence, clinical characteristics, and health and occupational effects of sinus barotraumas in flight. Secondary outcomes were adjusted odds ratios (OR) for frequency of sinus barotraumas with respect to possible risk factors. RESULTS: Response rate was 47% (N = 1789/3799), with 61% (N = 1088) of the respondents having experienced sinus barotraumas in flight. Of those affected, 59% had used medications, 18% had undergone surgical procedures, and 53% had been on sick leave due to sinus barotraumas (38% during the last year) in flight. Factors associated with sinus barotraumas were female sex [OR, 2.47; 95% confidence interval (CI) 1.35-4.50] and a high number of upper respiratory tract infections (>= 3 vs.Peer reviewe

Wittgenstein's Thought Experiments and Relativity Theory

In this paper, I discuss the similarity between Wittgenstein’s use of thought experiments and Relativity Theory. I begin with introducing Wittgenstein’s idea of “thought experiments” and a tentative classification of different kinds of thought experiments in Wittgenstein’s work. Then, after presenting a short recap of some remarks on the analogy between Wittgenstein’s point of view and Einstein’s, I suggest three analogies between the status of Wittgenstein’s mental experiments and Relativity theory: the topics of time dilation, the search for invariants, and the role of measuring tools in Special Relativity. This last point will help to better define Wittgenstein’s idea of description as the core of his philosophical enterprise

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

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