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The classical treatment of multivariate extreme values is through componentwise ordering, though in practice most interest is in actual extreme events. Here the point process of observations which are extreme in at least one component is considered. Parametric models for the dependence between components must satisfy certain constraints. Two new techniques for generating such models are presented. Aspects of the statistical estimation of the resulting models are discussed and are illustrated with an application to oceanographic data.

The paper describes how the Voronoi-Delaunay approach can be used for investigation of the structural heterogeneity during the process of liquid crystallization. The basic geometric structure for the analysis is the Voronoi network (the Voronoi diagram in a 3-dimensional space). Every site of the Voronoi network is associated with a Delaunay simplex: four neighboring atoms representing the simplest element of the liquid structure. Having a quantitative measure for the shape of Simplexes, we suggest to mark (color) Voronoi sites according to a given physical criterion. As a result, the structural investigation is reduced to a task of cluster analysis on a network. Evolution of aggregates of atoms comprised of tetrahedral configurations is studies on an example of Lennard-Jones liquid crystallization. The experiments show that pseudocrystalline aggregates of pentagonal bipyramids spring up along with the genuine crystalline nuclei. The pseudonuclei can stimulate crystallization at the first stage of the process, but slows it down in the final stage of fusion of crystal regions. The results obtained are important for in-depth understanding of the process of the homogeneous crystallization of simple liquids.

We study the limiting behavior of uniform measures on finite-dimensional simplices as the dimension tends to infinity and a discrete analog of this problem, the limiting behavior of uniform measures on compositions. It is shown that the coordinate distribution of a typical point in a simplex, as well as the distribution of summands in a typical composition with given number of summands, is exponential. We apply these assertions to obtain a more transparent proof of our result on the limit shape of partitions with given number of summands, refine the estimate on the number of summands in partitions related to a theorem by Erdős and Lehner about the asymptotic absence of repeated summands, and outline the proof of the sharpness of this estimate.

In the late 1940s, A. N. Kolmogorov suggested a remarkably simple example of a transitive, but not ergodic, action of the group of all permutations of positive integers. It turned out that such examples arise, as a rule, in the theory of actions of non--locally compact groups, and for locally compact groups this phenomenon cannot happen. Kolmogorov's example also helps to give a correct definition of the decomposition into ergodic components and orbit partition for actions of general groups.

Background Herpes simplex virus type 2 (HSV-2) is a common sexually transmitted infection (STI) primarily acquired through sexual contact. In 2000, the World Health Organization (WHO) for the first time reported the association of STIs with male infertility. Infertility is described as the inability to achieve a clinical pregnancy after engaging in regular, unprotected sexual intercourse for a year or more. HSV-2 infection is a significant concern for infertility, with evidence suggesting it can contribute to a range of reproductive complications. The seroprevalence of HSV-2 among infertile men in Iran has not yet been determined. Therefore, we conducted a case-control study to examine the seroprevalence of HSV-2 in multiple subgroups of infertile men with abnormal sperm parameters (Case) and individuals seeking sex selection services and those with normal sperm parameters (Control). Method Blood samples were collected from infertile males seeking fertility treatment, and those seeking sex selection at the Avicenna Infertility Clinic in Tehran, Iran between July 2023 and February 2024. Demographic and clinical data were collected through a questionnaire. Anti-HSV-2 IgG antibodies (Abs) were detected using a commercially available ELISA kit [Herpes simplex 2 (gG2 purified), Vircell, Spain]. Results Of the 486 samples that met the eligibility criteria, 420 were tested. The ELISA testing was performed on 98 control, 32 Teratozoospermia (T), 45 Asthenozoospermia (A), 48 Oligoteratozoospermia (OTA), 50 Azoospermia (Azo), and 147 Teratozooasthenospermia (TA) samples. Thirteen samples came out positive for HSV-2 IgG Abs (3.41% case and 2.04% control group). Of these 13 positive samples, 7 were from the TA group, 2 from the T group, 2 from the Azo group, and 2 control. The age (43.15 ± 5.10 vs. 37.74 ± 6.20, p  = 0·0020) and marriage duration (12.54 ± 6.88 vs. 8.12 ± 4.95, p  = 0·0019) were significantly higher in the HSV-2 IgG Ab positive group. Conclusion The results of this study enhance our understanding of the epidemiology of HSV-2 in individuals seeking infertility treatment. It can be inferred that the seroprevalence of HSV-2 IgG among patients referring to an infertility treatment clinic in Tehran is relatively low. The study also indicates that the chance of HSV-2 infection increases with age. The highest number of positive cases in the TA suggests that HSV-2 may adversely affect sperm motility and morphology.

Background Infections may be etiologic or contribute to Alzheimer’s disease (AD) pathology. Evidence from neuroscience, epidemiology, and electronic health records data implicates herpes simplex viruses in AD, but controlled clinical trials of anti‐herpetic drugs have not been conducted. Method In 120 participants at 3 U.S. sites with mild AD, or mild cognitive impairment (MCI) with positive AD biomarkers, the anti‐herpetic oral drug valacyclovir at 4 g/day, repurposed as an anti‐AD drug, was compared to placebo (60 valacyclovir, 60 placebo) in a Phase 2 randomized, double‐blind, parallel group trial. Seropositivity to herpes simplex virus (HSV) 1 or 2 was required. Acyclovir, the main metabolite of valacyclovir, was measured in plasma and in CSF in a subsample. The primary outcome was change in the 11‐item Alzheimer’s Disease Assessment Scale‐Cognitive Subscale (ADAS‐Cog11); secondary outcomes included the Alzheimer’s Disease Cooperative Study‐Activities of Daily Living (ADCS‐ADL) scale, Montreal Cognitive Assessment (MoCA), and neuroimaging conducted at baseline and 78 weeks utilizing 18FFlorbetapir PET (mean of six brain regions), structural MRI indices, and 18FMK‐6240 PET tau imaging in a subsample. Result Mixed model analyses adjusted for baseline score of the variable. The primary outcome, ADAS‐Cog11 score, showed greater worsening on valacyclovir than placebo at 78 weeks (LS Means difference 3.91, 95% CI 1.03 to 6.8, p =.01) with non‐significant differences at 12, 26 and 52 weeks in the same direction. ADCS‐ADL, the main functional measure, and other secondary clinical outcomes did not differ significantly between the treatment groups. Change in amyloid burden for 18FFlorbetapir PET and tau for 18FMK‐6240 PET, and MRI cortical thickness and hippocampal volume, showed no treatment group differences. Mean plasma acyclovir concentration following oral doses of 4 g/day was 7140±5780 ng/ml (66 samples) and CSF acyclovir concentrations were 1260±460 ng/ml at week 12 (n =6) and 1270±1100 ng/ml at week 78 (n =3), which confirmed CNS penetration for valacyclovir. Adverse events did not differ significantly between valacyclovir and placebo. Conclusion Valacyclovir was not efficacious as an antiviral treatment for participants with AD and herpes simplex virus seropositivity. The potential etiological role of herpes simplex viruses in AD needs re‐consideration.

Non-human primates (NHP) share a close relationship with humans due to a genetic homology of 75–98.5%. NHP and humans have highly similar tissue structures, immunity, physiology, and metabolism and thus often can act as hosts to the same pathogens. Agriculture, meat consumption habits, tourism development, religious beliefs, and biological research have led to more extensive and frequent contact between NHPs and humans. Deadly viruses, such as rabies virus, herpes B virus, Marburg virus, Ebola virus, human immunodeficiency virus, and monkeypox virus can be transferred from NHP to humans. Similarly, herpes simplex virus, influenza virus, and yellow fever virus can be transmitted to NHP from humans. Infectious pathogens, including viruses, bacteria, and parasites, can affect the health of both primates and humans. A vast number of NHP-carrying pathogens exhibit a risk of transmission to humans. Therefore, zoonotic infectious diseases should be evaluated in future research. This article reviews the research evidence, diagnostic methods, prevention, and treatment measures that may be useful in limiting the spread of several common viral pathogens via NHP and providing ideas for preventing zoonotic diseases with epidemic potential.

Background Glioblastoma multiforme (GBM) is associated with remarkably poor prognosis, and its treatment is challenging. This investigation aimed to evaluate the safety of suicide gene therapy using allogeneic adipose tissue-derived mesenchymal stem cells (ADSCs) carrying herpes simplex virus-thymidine kinase (HSV-TK) gene for the first time in patients with recurrent GBM. Methods This study was a first-in-human, open-label, single-arm, phase I clinical trial with a classic 3 + 3 dose escalation design. Patients who did not undergo surgery for their recurrence were included and received this gene therapy protocol. Patients received the intratumoral stereotactic injection of ADSCs according to the assigned dose followed by prodrug administration for 14 days. The first dosing cohort (n = 3) received 2.5 × 10 5 ADSCs; the second dosing cohort (n = 3) received 5 × 10 5 ADSCs; the third dosing cohort (n = 6) received 10 × 10 5 ADSCs. The primary outcome measure was the safety profile of the intervention. Results A total of 12 patients with recurrent GBM were recruited. The median follow-up was 16 (IQR, 14-18.5) months. This gene therapy protocol was safe and well tolerated. During the study period, eleven (91.7%) patients showed tumor progression, and nine (75.0%) died. The median overall survival (OS) was 16.0 months (95% CI 14.3–17.7) and the median progression-free survival (PFS) was 11.0 months (95% CI 8.3–13.7). A total of 8 and 4 patients showed partial response and stable disease, respectively. Moreover, significant changes were observed in volumetric analysis, peripheral blood cell counts, and cytokine profile. Conclusions The present clinical trial, for the first time, showed that suicide gene therapy using allogeneic ADSCs carrying the HSV-TK gene is safe in patients with recurrent GBM. Future phase II/III clinical trials with multiple arms are warranted to validate our findings and further investigate the efficacy of this protocol compared with standard therapy alone. Trial registration : Iranian Registry of Clinical Trials (IRCT), IRCT20200502047277N2. Registered 8 October 2020, https://www.irct.ir/ .

Coal is an important resource that is closely related to people’s lives and plays an irreplaceable role. However, coal mine safety accidents occur from time to time in the process of working underground. Therefore, this paper proposes a coal mine environmental safety early warning model to detect abnormalities and ensure worker safety in a timely manner by assessing the underground climate environment. In this paper, support vector machine (SVM) parameters are optimized using an improved artificial hummingbird algorithm (IAHA), and its safety level is classified by combining various environmental parameters. To address the problems of insufficient global exploration capability and slow convergence of the artificial hummingbird algorithm during iterations, a strategy incorporating Tent chaos mapping and backward learning is used to initialize the population, a Levy flight strategy is introduced to improve the search capability during the guided foraging phase, and a simplex method is introduced to replace the worst value before the end of each iteration of the algorithm. The IAHA-SVM safety warning model is established using the improved algorithm to classify and predict the safety of the coal mine environment as one of four classes. Finally, the performance of the IAHA algorithm and the IAHA-SVM model are simulated separately. The simulation results show that the convergence speed and the search accuracy of the IAHA algorithm are improved and that the performance of the IAHA-SVM model is significantly improved.

Few comparative data are available internationally to examine health differences by transgender identity. A barrier to monitoring the health and well-being of transgender people is the lack of inclusion of measures to assess natal sex/gender identity status in surveys. Data were from a cross-sectional anonymous online survey of members (n > 36,000) of a sexual networking website targeting men who have sex with men in Spanish- and Portuguese-speaking countries/territories in Latin America/the Caribbean, Portugal, and Spain. Natal sex/gender identity status was assessed using a two-step method (Step 1: assigned birth sex, Step 2: current gender identity). Male-to-female (MTF) and female-to-male (FTM) participants were compared to non-transgender males in age-adjusted regression models on socioeconomic status (SES) (education, income, sex work), masculine gender conformity, psychological health and well-being (lifetime suicidality, past-week depressive distress, positive self-worth, general self-rated health, gender related stressors), and sexual health (HIV-infection, past-year STIs, past-3 month unprotected anal or vaginal sex). The two-step method identified 190 transgender participants (0.54 %; 158 MTF, 32 FTM). Of the 12 health-related variables, six showed significant differences between the three groups: SES, masculine gender conformity, lifetime suicidality, depressive distress, positive self-worth, and past-year genital herpes. A two-step approach is recommended for health surveillance efforts to assess natal sex/gender identity status. Cognitive testing to formally validate assigned birth sex and current gender identity survey items in Spanish and Portuguese is encouraged.