We consider prediction and uncertainty analysis for systems which are approximated using complex mathematical models. Such models, implemented as computer codes, are often generic in the sense that by a suitable choice of some of the model's input parameters the code can be used to predict the behaviour of the system in a variety of specific applications. However, in any specific application the values of necessary parameters may be unknown. In this case, physical observations of the system in the specific context are used to learn about the unknown parameters. The process of fitting the model to the observed data by adjusting the parameters is known as calibration. Calibration is typically effected by ad hoc fitting, and after calibration the model is used, with the fitted input values, to predict the future behaviour of the system. We present a Bayesian calibration technique which improves on this traditional approach in two respects. First, the predictions allow for all sources of uncertainty, including the remaining uncertainty over the fitted parameters. Second, they attempt to correct for any inadequacy of the model which is revealed by a discrepancy between the observed data and the model predictions from even the best-fitting parameter values. The method is illustrated by using data from a nuclear radiation release at Tomsk, and from a more complex simulated nuclear accident exercise.

https://www.jstor.org/stable/pdfplus/2680584.pdf

Bayesian Calibration of computer models

On robust estimation of the location parameter

These guidelines for the treatment of persons who have or are at risk for sexually transmitted diseases (STDs) were updated by CDC after consultation with a group of professionals knowledgeable in the field of STDs who met in Atlanta on April 18-30, 2009. The information in this report updates the 2006 Guidelines for Treatment of Sexually Transmitted Diseases (MMWR 2006;55[No. RR-11]). Included in these updated guidelines is new information regarding 1) the expanded diagnostic evaluation for cervicitis and trichomoniasis; 2) new treatment recommendations for bacterial vaginosis and genital warts; 3) the clinical efficacy of azithromycin for chlamydial infections in pregnancy; 4) the role of Mycoplasma genitalium and trichomoniasis in urethritis/cervicitis and treatment-related implications; 5) lymphogranuloma venereum proctocolitis among men who have sex with men; 6) the criteria for spinal fluid examination to evaluate for neurosyphilis; 7) the emergence of azithromycin-resistant Treponema pallidum; 8) the increasing prevalence of antimicrobial-resistant Neisseria gonorrhoeae; 9) the sexual transmission of hepatitis C; 10) diagnostic evaluation after sexual assault; and 11) STD prevention approaches.

Sexually transmitted diseases treatment guidelines, 2010.

These guidelines for the treatment of persons who have or are at risk for sexually transmitted diseases (STDs) were updated by CDC after consultation with a group of professionals knowledgeable in the field of STDs who met in Atlanta on April 30-May 2, 2013. The information in this report updates the Sexually Transmitted Diseases Treatment Guidelines, 2010 (MMWR Recomm Rep 2010;59 [No. RR-12]). These updated guidelines discuss 1) alternative treatment regimens for Neisseria gonorrhoeae; 2) the use of nucleic acid amplification tests for the diagnosis of trichomoniasis; 3) alternative treatment options for genital warts; 4) the role of Mycoplasma genitalium in urethritis/cervicitis and treatment-related implications; 5) updated HPV vaccine recommendations and counseling messages; 6) the management of persons who are transgender; 7) annual testing for hepatitis C in persons with HIV infection; 8) updated recommendations for diagnostic evaluation of urethritis; and 9) retesting to detect repeat infection. Physicians and other health-care providers can use these guidelines to assist in the prevention and treatment of STDs.

Sexually transmitted diseases treatment guidelines, 2015.

Herpes simplex virus (HSV) infections of humans have been documented since the advent of writing. The spectrum of disease was expanded to include primary and recurrent infections of mucous membranes (gingivostomatitis, herpes labialis, and genital HSV infections), keratoconjunctivitis, neonatal HSV infection, visceral HSV infections of the immunocompromised host, HSV encephalitis, Kaposi's varicella-like eruption, and an association with erythema multiforme. Cumulative experience suggests that factors associated with pregnancy may place both the mother and fetus at increased risk for severe infection, possibly because of altered cell-mediated immunity. The major risk to the fetus is with primary or initial genital HSV infection of the mother. PCR evaluation of cerebrospinal fluid can be utilized to monitor therapeutic outcome in patients with herpes simplex encephalitis. The use of HSV for gene therapy heralds a new era of herpes biology, the conversion of a hazardous foe into a user-friendly surgical tool. Asymptomatic shedding of virus can continue despite clinically effective suppression with acyclovir, so the possibility of person-to-person transmission persists. Newborns with HSV infections can be classified as having disease that is localized to the skin, eyes, and mouth; affects the central nervous system (CNS); or is disseminated. Drug resistance was considered rare and resistant isolates were thought to be less pathogenic until a series of acyclovir-resistant HSV isolates from patients with AIDS were characterized. The risk of nephrotoxicity can be minimized by administering acyclovir by slow infusion and ensuring adequate hydration.

/pdf/herpes-simplex-viruses-2ac5n3adkn.pdf

Herpes Simplex Viruses

Background Most persons who have serologic evidence of infection with herpes simplex virus (HSV) type 2 (HSV-2) are asymptomatic. Historically, it has been assumed that these persons have less frequent viral reactivation than those with symptomatic infection. Methods We conducted a prospective study to investigate genital shedding of HSV among 53 subjects who had antibodies to HSV-2 but who reported having no history of genital herpes, and we compared their patterns of viral shedding with those in a similar cohort of 90 subjects with symptomatic HSV-2 infection. Genital secretions of the subjects in both groups were sampled daily and cultured for HSV for a median of 94 days. Results HSV was isolated from the genital mucosa in 38 of the 53 HSV-2–seropositive subjects (72 percent) who reported no history of genital herpes, and HSV DNA was detected by the polymerase-chain-reaction assay in cultures prepared from genital mucosal swabs in 6 additional subjects. The rate of subclinical shedding of HSV in the su...

https://www.nejm.org/doi/pdf/10.1056/NEJM200003233421203

Reactivation of Genital Herpes Simplex Virus Type 2 Infection in Asymptomatic Seropositive Persons

Background The frequency, pattern, and anatomical sites of subclinical shedding of herpes simplex virus (HSV) in the genital tract, along with factors that predict such shedding, have not been well characterized. Methods We studied prospectively the clinical and virologic course of genital herpes in 110 women. The women kept symptom diaries and provided daily samples from the vulva, cervix, and rectum for viral culture. Results During a median follow-up of 105 days, subclinical shedding of virus was identified in 36 of 65 women (55 percent) with HSV type 2 (HSV-2), in 16 of 31 women (52 percent) with HSV type 1 (HSV-1) and HSV-2, and in 4 of 14 women (29 percent) with only HSV-1. Among women with genital HSV-2 infection, subclinical shedding occurred on a mean of 2 percent of the days. The mean duration of viral shedding during subclinical episodes was 1.5 days, as compared with 1.8 days during symptomatic episodes. HSV was isolated from several sites in the genital tract and rectum in 17 percent of subcl...

https://www.nejm.org/doi/pdf/10.1056/NEJM199509213331205

Virologic characteristics of subclinical and symptomatic genital herpes infections.

ContextNeonatal herpes most commonly results from fetal exposure to infected
maternal genital secretions at the time of delivery. The risk of transmission
from mother to infant as it relates to maternal herpes simplex virus (HSV)
serologic status and exposure to HSV in the maternal genital tract at the
time of labor has not been quantified. Furthermore, no data exist on whether
cesarean delivery, the standard of care for women with genital herpes lesions
at the time of delivery, reduces HSV transmission.ObjectiveTo determine the effects of viral shedding, maternal HSV serologic status,
and delivery route on the risk of transmission of HSV from mother to infant.DesignProspective cohort of pregnant women enrolled between January 1982 and
December 1999.SettingsA university medical center, a US Army medical center, and 5 community
hospitals in Washington State.PatientsA total of 58 362 pregnant women, of whom 40 023 had HSV cultures
obtained from the cervix and external genitalia and 31 663 had serum
samples tested for HSV.Main Outcome MeasureRates of neonatal HSV infection.ResultsAmong the 202 women from whom HSV was isolated at the time of labor,
10 (5%) had neonates with HSV infection (odds ratio [OR], 346; 95% confidence
interval [CI], 125-956 for neonatal herpes when HSV was isolated vs not isolated).
Cesarean delivery significantly reduced the HSV transmission rate among women
from whom HSV was isolated (1 [1.2%] of 85 cesarean vs 9 [7.7%] of 117 vaginal;
OR, 0.14; 95% CI, 0.02-1.08; P = .047). Other risk
factors for neonatal HSV included first-episode infection (OR, 33.1; 95% CI,
6.5-168), HSV isolation from the cervix (OR, 32.6; 95% CI, 4.1-260), HSV-1
vs HSV-2 isolation at the time of labor (OR, 16.5; 95% CI, 4.1-65), invasive
monitoring (OR, 6.8; 95% CI, 1.4-32), delivery before 38 weeks (OR, 4.4; 95%
CI, 1.2-16), and maternal age less than 21 years (OR, 4.1; 95% CI, 1.1-15).
Neonatal HSV infection rates per 100 000 live births were 54 (95% CI,
19.8-118) among HSV-seronegative women, 26 (95% CI, 9.3-56) among women who
were HSV-1–seropositive only, and 22 (95% CI, 4.4-64) among all HSV-2–seropositive
women.ConclusionNeonatal HSV infection rates can be reduced by preventing maternal acquisition
of genital HSV-1 and HSV-2 infection near term. It can also be reduced by
cesarean delivery and limiting the use of invasive monitors among women shedding
HSV at the time of labor.

Effect of serologic status and cesarean delivery on transmission rates of herpes simplex virus from mother to infant.

Neonatal herpes infection most often is a result of fetal exposure to infected maternal genital secretions at delivery. Cesarean section long has been the standard of care for women bearing lesions of genital herpes at the time of delivery, but it is not clear that this lowers the risk of transmitting herpes simplex virus (HSV). A prospective group of 40,023 women, seen in 1982-1999, had HSV cultures from the cervix and external genitalia, and 31,663 submitted serum samples to determine the HSV-1 and HSV-2 serologic status. HSV was isolated from 202 women at the time of labor, 10 of whom (5%) had an infected infant. Isolating HSV at the time of delivery was a major risk factor for neonatal herpes. All 3 women who had primary HSV-1 infection and shed virus infected their infants, as did one of 6 women with primary HSV-2 infection. Viral transmission also was noted in 4 of 16 women with nonprimary first-episode of HSV-2 infection and 2 of 11 with reactivated HSV-1 infection. None of 140 women who shed virus from reactivated HSV-2 infected their infants. Only 1 of 85 cesarean deliveries in women with herpetic lesions resulted in an infected infant, compared to 7.7% of 117 vaginal deliveries; the odds ratio was 0.14. Among women from whom HSV was isolated, genital lesions present at the time of delivery correlated with a reduced risk of neonatal herpes. Risk factors for neonatal HSV infection included isolating HSV from the cervix, invasive monitoring, delivery before 38 weeks gestation, and a maternal age less than 21 years. A lack of maternal antibodies to the type of virus shed was associated with a much increased risk of transmission. Rates of neonatal HSV infection per 100,000 live births were 54 in HSV-seronegative women. 26 in women who were seropositive only for HSV-1, and 22 for all HSV-2-seropositive women. It is clear that preventing maternal acquisition of genital herpes near term may reduce the risk of transmitting HSV infection to the newborn infant. Other effective strategies are to limit invasive monitoring in women who shed HSV when in labor and to perform cesarean delivery when the mother has genital herpes.

Effect of serologic status and cesarean delivery on transmission rates of herpes simplex virus from mother to infant

A total of 48 eye globes were collected and analyzed to estimate ages of bowhead whales using the aspartic acid racemization technique. In this technique, age is estimated based on intrinsic changes in the D and L enantiomeric isomeric forms of aspartic acid in the eye lens nucleus. Age estimates were successful for 42 animals. Racemization rate (kAsp) for aspartic acid was based on data from earlier studies of humans and fin whales; the estimate used was 1.18 10-3/year. The D/L ratio at birth ((D/L)0) was estimated using animals less than or equal to 2 years of age (n = 8), since variability in the D/L measurements is large enough that differences among ages in this range are unmeasurable. The (D/L)0 estimate was 0.0285. Variance of the age estimates was obtained using the delta method. Based on these data, growth appears faster for females than males, and age at sexual maturity (age at length 12-13 m for males and 13-13.5 m for females) occurs at around 25 years of age. Growth slows markedly for both se...

Judith Zeh

Papers

Reactivation of Genital Herpes Simplex Virus Type 2 Infection in Asymptomatic Seropositive Persons

Virologic characteristics of subclinical and symptomatic genital herpes infections.

Effect of serologic status and cesarean delivery on transmission rates of herpes simplex virus from mother to infant.

Effect of serologic status and cesarean delivery on transmission rates of herpes simplex virus from mother to infant

Age and growth estimates of bowhead whales (Balaena mysticetus) via aspartic acid racemization