Preterm labor: one syndrome, many causes.

PubMed

Romero, Roberto; Dey, Sudhansu K; Fisher, Susan J

2014-08-15

Preterm birth is associated with 5 to 18% of pregnancies and is a leading cause of infant morbidity and mortality. Spontaneous preterm labor, a syndrome caused by multiple pathologic processes, leads to 70% of preterm births. The prevention and the treatment of preterm labor have been long-standing challenges. We summarize the current understanding of the mechanisms of disease implicated in this condition and review advances relevant to intra-amniotic infection, decidual senescence, and breakdown of maternal-fetal tolerance. The success of progestogen treatment to prevent preterm birth in a subset of patients at risk is a cause for optimism. Solving the mystery of preterm labor, which compromises the health of future generations, is a formidable scientific challenge worthy of investment. Copyright © 2014, American Association for the Advancement of Science.

A five year review of the complications of progestogen only injectable contraceptive at the University of Port-Harcourt Teaching Hospital.

PubMed

Ojule, J D; Oriji, V K; Okongwu, C

2010-01-01

The injectable progestogen only contraceptive is a widely accepted method of contraception in our environment and very Iittle has been reported on its complications in our environment. The aim of the study was to highlight the complications associated with use of injectable Medroxyprogesterone Acetate and Norethisterone Enanthate in dients at the University of Part-Harcourt Teachng Hospital, Port-Harcou, south-south Nigeria. It was a 5 rear year retrospective study of the clients who accepted and used progestogen only injectable contraceptives (depot medroxyprogesterone acetate noerthistherone enantate) at the family planning units of the University of Port Horcowt Teaching Hospital between 1st January 2000 and 31st December 2004. The case flies of these clients were retrieved and their data extracted. The informolion included the dients sociodemographic characteristics, the types doses of of injectable contraceptives received and the side effects reported at the follow up visits. The data was coded and entered into a data bank and analysed using SPSS for windows 11.0 version. Seven hundred and seventy seven (777) injectable contraceptive acceptors out of the 1720 contraceptive acceptors during the study period. This accounted for 45.17% of the new acceptors over the 5 years period, making the injectable contraceptives the most commonly used method of birth control in UPTH. Five hundred and five (505) clients took depot medroxyprogesterone acetate (DMPA) while 272 used norethesterone enanthate (NE-ET). The mean age of the injectable contraceptive users was 31.31 +/- 5.5 years and the mean parity was 5.5 +/- 2.5 deliveries. The users reported multiple side effects with 579 episodes. Secondary amenorrhea was the commonest side effect occurring in 350 (45.34%) clients. Others were hypertension in 17 (2.94%) and metabolic disturbances in 14 (2.41%). Injectable progestogen only contraceptive is associated with multiple side effects, with secondary amenorrhoea being the most common. The contraceptive failure rate of this method in our women is low. Injectable progestogen only contraceptive is associated with multiple side effects, with secondary amenorrhoea being the most common. The contraceptive failure rate of this method women is low.

Analysis and occurrence of pharmaceuticals, estrogens, progestogens and polar pesticides in sewage treatment plant effluents, river water and drinking water in the Llobregat river basin (Barcelona, Spain)

NASA Astrophysics Data System (ADS)

Kuster, Marina; López de Alda, Maria José; Hernando, Maria Dolores; Petrovic, Mira; Martín-Alonso, Jordi; Barceló, Damià

2008-08-01

SummaryThis work investigated the presence of 21 emerging contaminants of various chemical groups (7 estrogens, 3 progestogens, 6 pharmaceuticals and personal care products (PPCPs), and 5 acidic pesticides) in the Llobregat river basin (NE Spain). Waters from the outlet of various sewage treatment plants (STP) and waterworks located along the river basin, as well as water samples from the river or its tributaries upstream and downstream of these plants were analysed in two pilot monitoring studies. Chemical analyses were performed by means of on-line or off-line solid-phase extraction followed by liquid chromatography-electrospray-tandem mass spectrometry. Methods detection limits (in ng/L) were ⩽0.85 for estrogens, ⩽3.94 for progestogens, ⩽30 for PPCPs, and ⩽0.99 for pesticides. Of the estrogens and progestogens analysed, only estrone-3-sulfate, estrone, estriol and progesterone were found to be present in the low nanogram per liter range in some of the samples investigated. Except for atenolol, all PPCPs studied (ibuprofen, diclofenac, clofibric acid, salicylic acid, and triclosan) could be identified at levels usually lower than 250 ng/L and up to 1200 ng/l (diclofenac). Of the various pesticides investigated (2,4-D, bentazone; MCPA, mecoprop and propanil) MCPA and 2,4-D were the most ubiquitous and abundant and bentazone the only one not detected. Individual concentrations were most often below 100 ng/L and never surpassed the EU limits.

Biological responses of progestogen metabolites in normal and cancerous human breast.

PubMed

Pasqualini, Jorge R; Chetrite, Gérard S

2010-12-01

At present, more than 200 progestogen molecules are available, but their biological response is a function of various factors: affinity to progesterone or other receptors, their structure, the target tissues considered, biological response, experimental conditions, dose, method of administration and metabolic transformations. Metabolic transformation is of huge importance because in various biological processes the metabolic product(s) not only control the activity of the maternal hormone but also have an important activity of its own. In this regard, it was observed that the 20-dihydro derivative of the progestogen dydrogesterone (Duphaston®) is significantly more active than the parent compound in inhibiting sulfatase and 17β-hydroxysteroid dehydrogenase in human breast cancer cells. Estrone sulfatase activity is also inhibited by norelgestromin, a norgestimate metabolite. Interesting information was obtained with a similar progestogen, tibolone, which is rapidly metabolized into the active 3α/3β-hydroxy and 4-ene metabolites. All these metabolites can inhibit sulfatase and 17β-hydroxysteroid dehydrogenase and stimulate sulfotransferase in human breast cancer cells. Another attractive aspect is the metabolic transformation of progesterone itself in human breast tissues. In the normal breast progesterone is mainly converted to 4-ene derivatives, whereas in the tumor tissue it is converted mostly to 5α-pregnane derivatives. 20α-Dihydroprogesterone is found mainly in normal breast tissue and possesses antiproliferative properties as well as the ability to act as an anti-aromatase agent. Consequently, this progesterone metabolite could be involved in the control of estradiol production in the normal breast and therefore implicated in one of the multifactorial mechanisms of the breast carcinogenesis process. In conclusion, a better understanding of both natural and synthetic hormone metabolic transformations and their control could potentially provide attractive new therapies for the treatment of hormone-dependent pathologies.

Progesterone and human cognition.

PubMed

Henderson, V W

2018-06-01

Progesterone is a neurosteroid and a neuroactive steroid, produced primarily by the corpus luteum and the placenta. In some animal models, progesterone affects cognitive performance, and its potential role in human cognition is especially germane to women. This role can be investigated through associations between peripheral concentrations of progesterone in blood or saliva and neuropsychological test results, through differences in cognitive profiles between women using menopausal hormone therapy with and without a progestogen, and through clinical trials. In naturally cycling reproductive-age women and pregnant women, there is no consistent relation between progesterone levels and cognition. In postmenopausal women within 6 years of menopause and not using hormone therapy, progesterone levels are positively associated with verbal memory and global cognition, but reported associations in older postmenopausal women are null. Some observational studies of postmenopausal women using hormone therapy raise concern of a small deleterious cognitive effect of progestogen (medroxyprogesterone acetate was most often reported in these studies), but this association may due to confounding factors. Small, short-term clinical trials of progesterone show no meaningful effect on cognition. The quality of evidence is low, but overall findings do not reveal consistent, clinically important effects of progesterone on cognitive function in women.

[Effects of progestogens on the metabolism of lipids and carbohydrates. Practical consequences (author's transl)].

PubMed

Ghéron, G

Estrogens which are one of the components of contraceptive less than pills greater than are incriminated in many cardiovascular accidents. These occur as a result of metabolic disorders (involving lipids and carbohydrates), of modifications in coagulation factors, etc. The possible influence of progestogens was ignored for a long time. The widespread use of these compounds, prescribed for contraception as well as during hormonal replacement therapy for absolute or relative luteinic insufficiency, makes careful monitoring of lipid and carbohydrate metabolism imperative. This position is strengthened by a preliminary review of the literature which leads to several conclusions concerning lipid and carbohydrate metabolism.

Benefits and risks of ovarian function and reproduction for cancer development and prevention.

PubMed

Schindler, Adolf E

2011-12-01

Ovarian function and menstrual cycle disturbances, pregnancy, and reproductive medicine procedures can either increase gynecological cancer risk or prevent cancer development. For ovarian cancer development, there are two hypotheses, which are connected with ovulation and gonadotropin secretion. Most of the ovarian cancers seem to be derived from displaced ovarian surfice epithelial cells. One year of ovulatory cycles increases the ovarian cancer risk by 6%. Ovulation between 22 and 29 years of age causes the highest risk increase per year. In contrast, progesterone or progestins appear to create protection. Lifestyle can affect or modify ovarian cancer risk. Breast cancer risk is very much related to age of menarche and menopause, pregnancy, and breast feeding. All of which are related to ovarian function and progestogenic impact that translates either into breast cancer risk increase or decrease. This is modified by body mass index, physical activity, and lifestyle in general. The risk of endometrial cancer is most closely related to endogenous progesterone during the menstrual cycle and pregnancy or by exogenous progestogens as in oral contraceptives. These effects are progestogen dose and time dependent. Endometrial cancer risk can also be increased by estrogen-producing tumors or long-term estrogen treatment.

A new progestogen-only medical therapy for outpatient management of acute, abnormal uterine bleeding: a pilot study.

PubMed

Ammerman, Stacy R; Nelson, Anita L

2013-06-01

The objective of this investigation was to study short-term efficacy and feasibility of a new progestogen-only treatment for outpatient management of acute abnormal uterine bleeding. This was a prospective, single-arm, pilot clinical trial of a progestogen-only bridging treatment for acute abnormal uterine bleeding in nonpregnant, premenopausal women in the Gynecologic Urgent Care Clinic at Harbor-UCLA Medical Center. Subjects were administered a depo-medroxyprogesterone acetate 150 mg intramuscular injection and given medroxyprogesterone acetate 20 mg to be taken orally every 8 hours for 3 days. The primary outcome measures included a percentage of women who stopped bleeding in 5 days, time to bleeding cessation, reduction in numbers of pads used, side effects, and patient satisfaction. All 48 women stopped bleeding within 5 days; 4 women had spotting only at the time of their last contact during the 5 day follow-up. Mean time to bleeding cessation was 2.6 days. Side effects were infrequent and patient satisfaction was high. Injection of depo-medroxyprogesterone acetate 150 mg intramuscularly combined with 3 days of oral medroxyprogesterone acetate 20 mg every 8 hours for 9 doses is an effective outpatient therapy for acute abnormal uterine bleeding. Copyright © 2013 Mosby, Inc. All rights reserved.

Fate of selected pesticides, estrogens, progestogens and volatile organic compounds during artificial aquifer recharge using surface waters.

PubMed

Kuster, Marina; Díaz-Cruz, Silvia; Rosell, Mònica; López de Alda, Miren; Barceló, Damià

2010-05-01

The artificial recharge of aquifers has become a valuable tool to increase water resources for drinking water production in many countries. In this work a total of 41 organic pollutants belonging to the classes of pesticides, estrogens, progestogens and volatile organic compounds (VOCs) have been monitored in the water from two artificial recharge plants located in Sweden and Denmark. The results from two sampling campaigns performed in each plant indicate good chemical status of the source water, as the contaminants detected were present at very low levels, far from those established in the legislation as maximum admissible concentrations (when existing) and far from those considered as a risk. Thus, of the 17 pesticides investigated, BAM (2,6-dichlorobenzamide), desethylatrazine, simazine, atrazine, terbuthylazine, diuron, metolachlor, and diazinon were the only compounds detected, and total pesticides levels were below 25ng L(-1), respectively. Estrone-3-sulfate was the only estrogen detected, at concentrations lower than 0.5ng L(-1). Progestogens were not found in any sample. Detected VOCs (benzene, toluene, ethylbenzene, and trichloroethylene) were below 0.04microg L(-1). The efficiency of elimination of these organic contaminants was poor as no significant decrease in their concentrations was observed through the recharge process.

Systematic review and meta-analysis of the association of combined oral contraceptives on the risk of venous thromboembolism: The role of the progestogen type and estrogen dose.

PubMed

Oedingen, Carina; Scholz, Stefan; Razum, Oliver

2018-05-01

Currently available combined oral contraceptives (COC) reportedly increase the risk of venous thromboembolism (VTE). We aimed to quantify this risk considering both progestogen type and estrogen dose. PubMed, Embase and LIVIVO were searched for relevant publications until April 2017. Case-control and cohort studies including healthy women taking COC and assessing incident VTE as outcome were selected. Adjusted relative risks (RR) with 95% confidence intervals (CI) derived from random effects model using a generic inverse-variance approach are reported. Overall, 1,359 references were identified and 17 studies were included in the meta-analysis. The pooled RR of VTE was associated with various COC, with the association depending on their respective estrogen dose and progestogen type. Compared to the reference, levonorgestrel with 30-40 μg ethinylestradiol, the overall risk of VTE was higher for all other COC. Preparations with desogestrel with 30-40 μg estrogen showed the highest relative risk (RR: 1.46; 95% CI: 1.33-1.59), while RRs for drospirenone (30-40 μg ethinylestradiol) and desogestrel (30-40/20 μg ethinylestradiol) were lower. COC containing gestodene and cyproterone with 30-40 μg estrogen showed the lowest risk (RR: 1.27; 95% CI: 1.15-1.41 and RR: 1.29; 95% CI: 1.12-1.49, respectively). Compared to levonorgestrel with 30-40 μg ethinylestradiol, all COC showed a significantly increased VTE risk. The association varied depending on the progestogen type and the dose of estrogen. Our results suggest that the prescription of COC with the lowest possible dose of ethinylestradiol may help to avoid VTE cases among young, healthy women. Copyright © 2018 Elsevier Ltd. All rights reserved.

Male contraceptive research steps back into spotlight.

PubMed

Bonn, D

1999-01-23

The goal of male hormonal contraception is to block spermatogenesis by suppressing the secretion of pituitary gonadotropins. Prospects are good for the development of such a male contraceptive, with at least one hormonal contraceptive for men potentially available within 5-7 years. Finding an acceptable, reversible, and preferably long-lasting hormonal contraceptive for men is a top priority of the World Health Organization (WHO). Considerable evidence suggests that an androgen, with or without a progestogen, can provide effective contraception and is well tolerated. Schering and Organon are planning to collaborate with WHO in developing hormonal contraception for men. Fred Wu of the University of Manchester, UK, will soon begin a trial comparing the effectiveness of new injectable testosterone undecanoate and testosterone buciclate formulations, with or without synthetic progestogens.

Serum androgen and gonadotropin levels decline after progestogen-induced withdrawal bleeding in oligomenorrheic women with or without polycystic ovaries.

PubMed

Anttila, L; Koskinen, P; Kaihola, H L; Erkkola, R; Irjala, K; Ruutiainen, K

1992-10-01

To examine the effect of short-term progestogen treatment on androgen, gonadotropin, and sex hormone-binding globulin (SHBG) levels in oligomenorrheic women. Comparative study of changes in hormonal parameters in patients with or without ultrasonographically diagnosed polycystic ovarian disease (PCOD). Open patient clinic of reproductive endocrinology at University Central Hospital of Turku, Finland. Seventy-five oligomenorrheic women with (n = 51) or without (n = 24) PCOD. Serum concentrations of testosterone (T), androstenedione (A), dehydroepiandrosterone sulfate, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and SHBG. The levels of T, A, LH, and the LH:FSH ratios decreased significantly after oral treatment with medroxyprogesterone acetate (10 mg/d for 10 days) in non-PCOD women and in women with PCOD decreasing the frequencies of pathological laboratory findings, in particular elevated levels of LH:FSH ratio and A in PCOD women and of LH:FSH ratio in non-PCOD women. The levels of T, A, and LH as well as the LH:FSH ratio were significantly higher in women with PCOD. Obesity was associated with high free androgen indices, low LH:FSH ratios, and low concentrations of LH, A, and SHBG. The serum samples for hormonal analyses used as an aid in diagnosing PCOD should be obtained without pretreatment with progestogen because it masks the biochemical findings of PCOD.

Clinical review: Breast development in trans women receiving cross-sex hormones.

PubMed

Wierckx, Katrien; Gooren, Louis; T'Sjoen, Guy

2014-05-01

In trans women (male-to-female transsexual persons), cross-sex hormone therapy is administered to induce feminization. Breast development is an important part of feminization for most trans women. The aim of this study is to assess the effect of cross-sex hormone therapy on breast development in adult trans women. Additionally, we aimed to investigate the benefit or harm of administration of progestogens on breast development. A review of the literature in Embase, Medline, The Cochrane Library, PsycINFO databases, PubMed, and Web of Knowledge until January 2014. Effects of cross-sex hormone therapy and progestogens on breast development in trans women. Only few studies with low quality of evidence addressed these topics. The available evidence suggests that breast development is insufficient for the majority of trans women and that type and dosage of hormonal therapy seem not to have an important role on final breast size. Our knowledge concerning the natural history and effects of different cross-sex hormone therapies on breast development in trans women is extremely sparse and based on low quality of evidence. Current evidence does not provide evidence that progestogens enhance breast development in trans women. Neither do they prove the absence of such an effect. This prevents us from drawing any firm conclusion at this moment and demonstrates the need for further research to clarify these important clinical questions. © 2014 International Society for Sexual Medicine.

Non-surgical interventions for the management of chronic pelvic pain.

PubMed

Cheong, Ying C; Smotra, Grisham; Williams, Amanda C de C

2014-03-05

Chronic pelvic pain is a common and debilitating condition; its aetiology is multifactorial, involving social, psychological and biological factors. The management of chronic pelvic pain is challenging, as despite interventions involving surgery, many women remain in pain without a firm gynaecological diagnosis. To assess the effectiveness and safety of non-surgical interventions for women with chronic pelvic pain. We searched the Menstrual Disorders and Subfertility Group Specialised Register. We also searched (from inception to 5 February 2014) AMED, CENTRAL, MEDLINE, EMBASE, PsycINFO, CINAHL and LILACS. We handsearched sources such as citation lists, trial registers and conference proceedings. Randomised controlled trials (RCTs) on non-surgical management of chronic pelvic pain were eligible for inclusion. We included studies of women with a diagnosis of pelvic congestion syndrome or adhesions but excluded those with pain known to be caused by endometriosis, primary dysmenorrhoea (period pain), active chronic pelvic inflammatory disease or irritable bowel syndrome. We considered studies of any non-surgical intervention, including lifestyle, physical, medical and psychological treatments. Study selection, quality assessment and data extraction were performed independently by two review authors. Meta-analysis was performed using the Peto odds ratio (Peto OR) for dichotomous outcomes and the mean difference (MD) for continuous outcomes, with 95% confidence intervals (CIs). The primary outcome measure was pain relief, and secondary outcome measures were psychological outcomes, quality of life, requirement for analgesia and adverse effects. The quality of the evidence was assessed by using GRADE methods. Twenty-one RCTs were identified that involved non-surgical management of chronic pelvic pain: 13 trials were included in the review, and eight were excluded. The studies included a total of 750 women-406 women in the intervention groups and 344 in the control groups. Included studies had high attrition rates, and investigators often did not blind adequately or did not clearly describe randomisation procedures. Medical treatment versus placebo Progestogen (medroxyprogesterone acetate (MPA)) was more effective than placebo at the end of treatment in terms of the number of women achieving a greater than 50% reduction in visual analogue scale (VAS) pain score immediately after treatment (Peto OR 3.00, 95% CI 1.70 to 5.31, two studies, n = 204, I(2) = 22%, moderate-quality evidence). Evidence of benefit was maintained up to nine months after treatment (Peto OR 2.09, 95% CI 1.18 to 3.71, two studies, n = 204, I(2) = 0%, moderate-quality evidence). Women treated with progestogen reported more adverse effects (e.g. weight gain, bloatedness) than those given placebo (high-quality evidence). The estimated effect of lofexidine on pain outcomes when compared with placebo was compatible with benefit and harm (Peto OR 0.42, 95% CI 0.11 to 1.61, one study, 39 women, low-quality evidence). Women in the lofexidine group reported more adverse effects (including drowsiness and dry mouth) than women given placebo (moderate-quality evidence). Head-to-head comparisons of medical treatments Head-to-head comparisons showed that women taking goserelin had greater improvement in pelvic pain score (MD 3, 95% CI 2.08 to 3.92, one study, n = 47, moderate-quality evidence) at one year than those taking progestogen. Women taking gabapentin had a lower VAS pain score than those taking amytriptyline (MD -1.50, 95% CI -2.06 to -0.94, n = 40, low-quality evidence). Study authors reported that no statistically significant difference was observed in the rate of adverse effects among women taking gabapentin compared with women given amytriptyline. The study comparing goserelin versus progestogen did not report on adverse effects. Psychological treatment Women who underwent reassurance ultrasound scans and received counselling were more likely to report improved pain than those treated with a standard 'wait and see' policy (Peto OR 6.77, 95% CI 2.83 to 16.19, n = 90, low-quality evidence). Significantly more women who had writing therapy as a disclosure reported improvement in pain than those in the non-disclosure group (Peto OR 4.47, 95% CI 1.41 to 14.13, n = 48, very low-quality evidence). No difference between groups in pain outcomes was noted when other psychological therapies were compared with standard care or placebo (quality of evidence ranged from very low to low). Studies did not report on adverse effects. Complementary therapy Distension of painful pelvic structures was more effective for pain when compared with counselling (MD 35.8, 95% CI 23.08 to 48.52 on a zero to 100 scale, one study, n = 48, moderate-quality evidence). No difference in pain levels was observed when magnetic therapy was compared with use of a control magnet (very low-quality evidence). Studies did not report on adverse effects.The results of studies examining psychological and complementary therapies could not be combined to yield meaningful results. Evidence of moderate quality supports progestogen as an option for chronic pelvic pain, with efficacy reported during treatment. In practice, this option may be most acceptable among women unconcerned about progestogenic adverse effects (e.g. weight gain, bloatedness-the most common adverse effects). Although some evidence suggests possible benefit of goserelin when compared with progestogen, gabapentin as compared with amytriptyline, ultrasound versus 'wait and see' and writing therapy versus non-disclosure, the quality of evidence is generally low, and evidence is drawn from single studies.Given the prevalence and healthcare costs associated with chronic pelvic pain in women, RCTs of other medical, lifestyle and psychological interventions are urgently required.

Progesterone receptor antagonism inhibits progestogen-related carcinogenesis and suppresses tumor cell proliferation.

PubMed

Lee, Oukseub; Choi, Mi-Ran; Christov, Konstantin; Ivancic, David; Khan, Seema A

2016-07-01

Blockade of the progestogen-progesterone receptor (PR) axis is a novel but untested strategy for breast cancer prevention. We report preclinical data evaluating telapristone acetate (TPA), ulipristal acetate (UPA), and mifepristone. Tumors were induced with medroxyprogesterone acetate (MPA) plus 7,12-dimethylbenz[a]anthracene (DMBA) in mice, and MPA or progesterone plus N-methyl-N-nitrosourea (MNU) in rats. Mammary gland histology, tumor incidence, latency, multiplicity, burden and histology were evaluated, along with immunohistochemical labeling of pHH3 (proliferation), CD34 (angiogenesis), and estrogen and progesterone receptors (ER and PR). A concentration gradient of TPA, UPA, and mifepristone was tested for growth inhibition of T47D spheroids. In mouse mammary glands, no tumors formed, but TPA opposed the pro-hyperplastic effects of MPA (p = 0.002). In rats, TPA decreased tumor incidence (p = 0.037 for MPA + TPA vs. MPA, and p = 0.032 for progesterone + TPA vs. progesterone) and tumor burden (p = 0.042 for progesterone + TPA vs. progesterone), with significant decreases in pHH3 and CD34 positive cells. TPA and UPA were superior to mifepristone in growth inhibition of T47D spheroids. TPA has consistent anti-tumorigenic effects in several models, which are accompanied by decreases in cell proliferation, angiogenesis, and hormone receptor expression. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

What Are the Common Treatments for Menstrual Irregularities?

MedlinePlus

... that is causing the menstrual problem, such as counseling and nutritional therapy for an eating disorder Treatment ... Rees, M. (2005). Progesterone/progestogen releasing intrauterine systems versus either placebo or any other medication for heavy ...

Drospirenone/ethinyl estradiol 3 mg/20 μg (24/4 day regimen): hormonal contraceptive choices – use of a fourth-generation progestin

PubMed Central

Bachmann, Gloria; Kopacz, Sharon

2009-01-01

The combined oral contraceptive pill (COC) consisting of drospirenone 3 mg/ethinyl estradiol 20 μg (3 mg DRSP/20 μg EE-24/4) supplies 24 days of pills with hormones followed by 4 days of hormone-free pills. This regimen is called the 24/4 regimen. The progesterone component of this oral contraceptive pill (OCP), drospirenone (DRSP), is a fourth-generation progestin that has potent progestogenic, antimineralocorticoid, and antiandrogenic activity, which are unique characteristics compared with the other progestogens contained in most of the other OCPs currently marketed. This formulation, in addition to being an effective long-term OCP, has the additional medical benefit of providing a good parallel treatment for premenstrual dysphoric disorder and moderate acne. The effectiveness of 3 mg DRSP/20 μg EE-24/4, its tolerability and safety, and its additional non-contraceptive benefits are discussed. PMID:19936169

Effects of a combined oral contraceptive containing 20 mcg of ethinylestradiol and 3 mg of drospirenone on the blood pressure, renin-angiotensin-aldosterone system, insulin resistance, and androgenic profile of healthy young women.

PubMed

Giribela, Cassiana Rosa Galvão; Consolim-Colombo, Fernanda Marciano; Nisenbaum, Marcelo Gil; Moraes, Tercio Lemos de; Giribela, Aricia Helena Galvão; Baracat, Edmund Chada; Melo, Nilson Roberto de

2015-01-01

Combined oral contraceptives (COCs) may increase the risk for cardiovascular disease depending on the ethynyl estradiol (EE) dose and the androgenicity of the progestogens. Our objective was to evaluate the impact of a COC containing 20 mcg EE + 3 mg drospirenone on blood pressure (BP), renin-angiotensin-aldosterone system, insulin resistance, and androgenic profile of healthy young women. Eighty-one healthy young women aged 30 ± 1 years (case group, n = 49, received COC; control group, n = 32, used no COC) were assessed twice, before and after the 6-month study. Statistical analysis employed the paired t-tests and expressed the data in mean and standard deviation. Results were as follows: no changes in BP or in BMI; a significant increase in aldosterone, plasma renin activity, triglycerides, and total cholesterol levels, but a non-significant increase in HDL and no significant changes in LDL levels (these parameters remained within normal ranges); a significant increase in the HOMA-IR index and a significant decrease in dehydroepiandrosterone sulfate (SDHEA), androstenedione, total testosterone, and free testosterone levels; no significant variations in the control group parameters. An oral contraceptive combination of a low EE dose and an anti-androgenic progestogen does not negatively influence the risk factors for a cardiovascular disease.

Steroids, reproductive endocrine function, and affect. A review.

PubMed

Frye, C A

2009-12-01

Although the effects of estrogen (E2) on mood have been studied for some time, there is controversy over the utility of hormone replacement therapy (HRT). Administration of E2 and/or other steroid hormones (e.g., progestogens, androgens, etc.) may be able to reduce increased anxiety and depression that is present with the onset of menopause. However, some studies indicate that E2 replacement does not significantly improve anxiety and/or depressive symptoms in all postmenopausal subjects. More recent data suggests that the efficacy of HRT could be based on a number of factors, including variety of E2-replacements available, the timing during or after menopause when HRT is initiated, and/or effects of other steroid hormones, such as progestogens and androgens. Notably, little attention has been paid to the possible synergistic effects of E2 that may require progestogens and/or androgens to produce positive outcomes in mood. Additionally, steroid hormones have a number of effects that influence anxiety and depression across the lifespan. As such, dose, timing, and combination of steroid replacement may explain these differences in behavioral outcome. With the increasing peri- to postmenopausal population, many women can expect to live nearly half their lifetime in a postmenopausal state. Therefore, examining these ambiguous findings is of critical importance. This review will focus on a synthesis of the available information regarding findings from animal and human studies in terms of effects of steroid hormones across the lifespan, different HRT options and their subsequent interactions in the brain and/or the hypothalamic-pituitary-adrenal axis, and effects on anxiety and depression.

Hormone replacement therapy is associated with gastro-oesophageal reflux disease: a retrospective cohort study.

PubMed

Close, Helen; Mason, James M; Wilson, Douglas; Hungin, A Pali S

2012-05-29

Oestrogen and progestogen have the potential to influence gastro-intestinal motility; both are key components of hormone replacement therapy (HRT). Results of observational studies in women taking HRT rely on self-reporting of gastro-oesophageal symptoms and the aetiology of gastro-oesophageal reflux disease (GORD) remains unclear. This study investigated the association between HRT and GORD in menopausal women using validated general practice records. 51,182 menopausal women were identified using the UK General Practice Research Database between 1995-2004. Of these, 8,831 were matched with and without hormone use. Odds ratios (ORs) were calculated for GORD and proton-pump inhibitor (PPI) use in hormone and non-hormone users, adjusting for age, co-morbidities, and co-pharmacy. In unadjusted analysis, all forms of hormone use (oestrogen-only, tibolone, combined HRT and progestogen) were statistically significantly associated with GORD. In adjusted models, this association remained statistically significant for oestrogen-only treatment (OR 1.49; 1.18-1.89). Unadjusted analysis showed a statistically significant association between PPI use and oestrogen-only and combined HRT treatment. When adjusted for covariates, oestrogen-only treatment was significant (OR 1.34; 95% CI 1.03-1.74). Findings from the adjusted model demonstrated the greater use of PPI by progestogen users (OR 1.50; 1.01-2.22). This first large cohort study of the association between GORD and HRT found a statistically significant association between oestrogen-only hormone and GORD and PPI use. This should be further investigated using prospective follow-up to validate the strength of association and describe its clinical significance.

The treatment of severe premenstrual syndrome with goserelin with and without 'add-back' estrogen therapy: a placebo-controlled study.

PubMed

Leather, A T; Studd, J W; Watson, N R; Holland, E F

1999-02-01

The study aimed to determine if the addition of daily low-dose oral estrogen with a cyclical progestogen given to young women using a depot gonadotropin-releasing hormone (GnRH) analog implant for the treatment of their premenstrual syndrome (PMS) would affect the clinical outcome. In a double-blind placebo-controlled study in a specialist premenstrual syndrome clinic setting, 60 women aged between 20 and 45 years were randomized to one of three treatment groups: Group A (placebo implant four weekly + placebo tablets daily), Group B (goserelin 3.6 mg implant four weekly + estradiol valerate 2 mg daily with norethisterone 5 mg from days 21-28 of a 28-day cycle) or Group C (goserelin 3.6 mg implant four weekly + placebo tablets daily). Differences between PMS scores at 2, 4 and 6 months were compared with pretreatment values. There was a significant improvement in PMS scores in Group C (Zoladex + placebo) after 2, 4 and 6 months of treatment when compared to pretreatment values and Group A (placebo + placebo). The addition of a low-dose oral estrogen with a cyclical progestogen to GnRH analog treatment (Group B) resulted in a less dramatic response when compared to pretreatment values and no significant improvement when compared to Group A (placebo + placebo) at 2, 4 and 6 months of treatment. The addition of a low-dose oral estrogen with a cyclical progestogen to depot GnRH analog therapy in the treatment of PMS reduces the clinical response.

Transcriptome response to hormonal manipulation of follicle-enclosed oocytes in rainbow trout

USDA-ARS?s Scientific Manuscript database

Captive fish often display reproductive dysfunction associated with follicle maturation. Gonadotropins and the progestogen maturation-inducing hormones (MIH) are important regulators of follicle maturation; however, their actions including regulating follicle maturation are not fully understood. The...

Integration of inorganic and isotopic geochemistry with endocrine disruption activity assays to assess risks to water resources near unconventional oil and gas development in Garfield County, CO.

NASA Astrophysics Data System (ADS)

Harkness, J.; Kassotis, C.; Cornelius, J.; Nagel, S.; Vengosh, A.

2016-12-01

The rise of hydraulic fracturing in the United States has sparked a debate about the impact of oil and gas development on the quality of water resources. Wastewater associated with hydraulic fracturing includes injection fluid that is a mixture of sand, freshwater and synthetic organic chemicals, flowback water that is a mixture of injection fluid and formation brine, and produced water that is primarily brine. The fluids range in salinity and chemical composition that can have different environmental impacts. We analyzed the inorganic and isotope geochemistry of 58 surface and groundwater samples near and away from unconventional oil and gas operations (UOG), along with hormonal profiles via bioassays. Cl (0.12 to 198 mg/L), Na (1.2 to 518 mg/L) and Sr (1.4 to 2410 ug/L) were higher in both groundwater and surface water near UOG wells. Four surface waters and one groundwater had Br/Cl indicative of brine contamination (>1.5x10-3). Three of the SW samples also had 87Sr/86Sr ratios similar to values found in produced or flowback water (0.7118 and 0.7158, respectively) from the Williams-Fork formation and elevated compared to background ratios (0.71062 to 0.7115). Increased progestogenic activity was observed in groundwater near UOG operations and inncreased estrogenic, androgenic, progestogenic, anti-androgenic, anti-progestogenic, and anti-glucocorticoid activities in surface water near UOG operations. The association of increased EDCs with inorganic and isotopic indicators of UOG wastewater provides evidence for possible environmental and health impacts from drilling activity.

Hormone replacement therapy is associated with gastro-oesophageal reflux disease: a retrospective cohort study

PubMed Central

2012-01-01

Background Oestrogen and progestogen have the potential to influence gastro-intestinal motility; both are key components of hormone replacement therapy (HRT). Results of observational studies in women taking HRT rely on self-reporting of gastro-oesophageal symptoms and the aetiology of gastro-oesophageal reflux disease (GORD) remains unclear. This study investigated the association between HRT and GORD in menopausal women using validated general practice records. Methods 51,182 menopausal women were identified using the UK General Practice Research Database between 1995–2004. Of these, 8,831 were matched with and without hormone use. Odds ratios (ORs) were calculated for GORD and proton-pump inhibitor (PPI) use in hormone and non-hormone users, adjusting for age, co-morbidities, and co-pharmacy. Results In unadjusted analysis, all forms of hormone use (oestrogen-only, tibolone, combined HRT and progestogen) were statistically significantly associated with GORD. In adjusted models, this association remained statistically significant for oestrogen-only treatment (OR 1.49; 1.18–1.89). Unadjusted analysis showed a statistically significant association between PPI use and oestrogen-only and combined HRT treatment. When adjusted for covariates, oestrogen-only treatment was significant (OR 1.34; 95% CI 1.03–1.74). Findings from the adjusted model demonstrated the greater use of PPI by progestogen users (OR 1.50; 1.01–2.22). Conclusions This first large cohort study of the association between GORD and HRT found a statistically significant association between oestrogen-only hormone and GORD and PPI use. This should be further investigated using prospective follow-up to validate the strength of association and describe its clinical significance. PMID:22642788

Effects and Mechanisms of 3α,5α,-THP on Emotion, Motivation, and Reward Functions Involving Pregnane Xenobiotic Receptor

PubMed Central

Frye, Cheryl A.; Paris, J. J.; Walf, A. A.; Rusconi, J. C.

2011-01-01

Progestogens [progesterone (P4) and its products] play fundamental roles in the development and/or function of the central nervous system during pregnancy. We, and others, have investigated the role of pregnane neurosteroids for a plethora of functional effects beyond their pro-gestational processes. Emerging findings regarding the effects, mechanisms, and sources of neurosteroids have challenged traditional dogma about steroid action. How the P4 metabolite and neurosteroid, 3α-hydroxy-5α-pregnan-20-one (3α,5α-THP), influences cellular functions and behavioral processes involved in emotion/affect, motivation, and reward, is the focus of the present review. To further understand these processes, we have utilized an animal model assessing the effects, mechanisms, and sources of 3α,5α-THP. In the ventral tegmental area (VTA), 3α,5α-THP has actions to facilitate affective, and motivated, social behaviors through non-traditional targets, such as GABA, glutamate, and dopamine receptors. 3α,5α-THP levels in the midbrain VTA both facilitate, and/or are enhanced by, affective and social behavior. The pregnane xenobiotic receptor (PXR) mediates the production of, and/or metabolism to, various neurobiological factors. PXR is localized to the midbrain VTA of rats. The role of PXR to influence 3α,5α-THP production from central biosynthesis, and/or metabolism of peripheral P4, in the VTA, as well as its role to facilitate, or be increased by, affective/social behaviors is under investigation. Investigating novel behavioral functions of 3α,5α-THP extends our knowledge of the neurobiology of progestogens, relevant for affective/social behaviors, and their connections to systems that regulate affect and motivated processes, such as those important for stress regulation and neuropsychiatric disorders (anxiety, depression, schizophrenia, drug dependence). Thus, further understanding of 3α,5α-THP’s role and mechanisms to enhance affective and motivated processes is essential. PMID:22294977

Resumption of ovarian function, the metabolic profile and body condition in Brahman cows (Bos indicus) is not affected by the combination of calf separation and progestogen treatment.

PubMed

Díaz, Ramiro; Galina, Carlos S; Rubio, Ivette; Corro, Manuel; Pablos, José Luis; Rodríguez, Ana; Orihuela, Agustín

2017-10-01

To evaluate the effect of different calf separation procedures after a progestogen treatment on the resumption of ovarian function, body condition and metabolic profile, 59 multiparous Brahman cows grazing on a mixed grass pasture were studied. No supplementation was given at any time. Body condition score (BCS), fat thickness (FAT) and blood metabolites were measured fortnightly from the beginning of the last trimester of gestation until 96days postpartum. At 30days postpartum all animals received a progesterone (P4)-releasing device (CIDR) which was withdrawn 9days later when prostaglandin F2α was applied. At this time, treatments TW (n=28), where calves were separated from their dams for 48h; RS (n=21), calves were allowed to suckle once a day for 1h; and continuous suckling (CS; n=10). Ovarian function was assessed by blood concentrations of progesterone on days -14, -9, 10, 13, 30 and 33 after CIDR removal. At the end of the experimental period, an average of 20% of the cows had not initiated estrous cycles. There were no changes of FAT or BCS during the last trimester of pregnancy in all cows (P>0.05). During the postpartum period cows of all groups lost (P<0.05) BCS and FAT with a nadir at 60-80days postpartum, regardless of treatment. At 10days after CIDR withdrawal the percentage of cows having ovulations was 75, 61 and 80 (P>0.05) for TW, RS and CS groups. Blood metabolites follow a similar pattern in the three groups. With the conditions of the present study, the method of calf separation after a progestogen treatment, does not affect the resumption of ovarian function or metabolic profile. Copyright © 2017 Elsevier B.V. All rights reserved.

Progestin withdrawal at parturition in the mare.

PubMed

Legacki, Erin L; Corbin, C J; Ball, B A; Wynn, M; Loux, S; Stanley, S D; Conley, A J

2016-10-01

Mammalian pregnancies need progestogenic support and birth requires progestin withdrawal. The absence of progesterone in pregnant mares, and the progestogenic bioactivity of 5α-dihydroprogesterone (DHP), led us to reexamine progestin withdrawal at foaling. Systemic pregnane concentrations (DHP, allopregnanolone, pregnenolone, 5α-pregnane-3β, 20α-diol (3β,20αDHP), 20α-hydroxy-5α-dihydroprogesterone (20αDHP)) and progesterone) were monitored in mares for 10days before foaling (n=7) by liquid chromatography-mass spectrometry. The biopotency of dominant metabolites was assessed using luciferase reporter assays. Stable transfected Chinese hamster ovarian cells expressing the equine progesterone receptor (ePGR) were transfected with an MMTV-luciferase expression plasmid responsive to steroid agonists. Cells were incubated with increasing concentrations (0-100nM) of progesterone, 20αDHP and 3α,20βDHP. The concentrations of circulating pregnanes in periparturient mares were (highest to lowest) 3α,20βDHP and 20αDHP (800-400ng/mL respectively), DHP and allopregnanolone (90 and 30ng/mL respectively), and pregnenolone and progesterone (4-2ng/mL). Concentrations of all measured pregnanes declined on average by 50% from prepartum peaks to the day before foaling. Maximum activation of the ePGR by progesterone occurred at 30nM; 20αDHP and 3α,20βDHP were significantly less biopotent. At prepartum concentrations, both 20αDHP and 3α,20βDHP exhibited significant ePGR activation. Progestogenic support of pregnancy declines from 3 to 5days before foaling. Prepartum peak concentrations indicate that DHP is the major progestin, but other pregnanes like 20αDHP are present in sufficient concentrations to play a physiological role in the absence of DHP. The authors conclude that progestin withdrawal associated with parturition in mares involves cessation of pregnane synthesis by the placenta. © 2016 Society for Reproduction and Fertility.

Effect of contraceptive steroids on monoamine oxidase activity

PubMed Central

Southgate, Jennifer; Collins, G. G. S.; Pryse-Davies, J.; Sandler, M.

1969-01-01

Cyclical variations in monoamine oxidase activity during the human menstrual cycle, specific to the endometrium and modified in women undergoing contraceptive steroid treatment, may reflect changes in hormonal environment. Treatment of rats with individual constituents of the contraceptive pill causes analogous changes: oestrogens inhibit and progestogens potentiate uterine monoamine oxidase activity. ImagesFig. 2Fig. 3

Environmental gestagens activate fathead minnow (Pimephales promelas) nuclear progesterone and androgen receptors in vitro

EPA Science Inventory

Gestagen is a collective term for endogenous and synthetic progesterone receptor (PR) ligands. In teleost fishes, 17á,20â-dihydroxy-4-pregnen-3-one (DHP) and17á,20â,21- trihydroxy-4-pregnen-3-one (20â-S) are the predominant progestogens, whereas in other vertebrates the major pro...

Antiandrogenic and antimineralocorticoid health benefits of COC containing newer progestogens: dienogest and drospirenone.

PubMed

Regidor, Pedro-Antonio; Schindler, Adolf E

2017-10-10

Data have demonstrated that COCs, besides offering a satisfactory and safe contraception, offer a variety of non-contraceptive health benefits and therapeutic positive aspects. Many prescribes and users, however, do not realize these positive aspects especially the non-contraceptive health benefits. While the contraceptive use is the primary indication for COC use for most women, these users should be advised in regard of the non-contraceptive benefits when contraception is discussed and prescribed. Using COCs specifically for non-contraceptive indications is an off-label use in many clinical situations (only some exceptions as e.g. acne vulgaris in some countries are allowed clinical entities for the use of these drugs). Therefore, appropriate discussions with the patient regarding this fact should performed and documented by the prescribing physicians. Independent of the off-label situation, COCs containing the newer progestogens dienogest and drospirenone with their antiandrogenic and antimineralocorticoid health benefits play an important role in the management of many diseases and their use should therefore be considered by clinician's. This review will focus on the effects of these COCs on the endometrium, the skin, the fat tissue and the premenstrual syndrome.

Risk Factors for Breast Cancer, Including Occupational Exposures

PubMed Central

Meo, Margrethe; Vainio, Harri

2011-01-01

The knowledge on the etiology of breast cancer has advanced substantially in recent years, and several etiological factors are now firmly established. However, very few new discoveries have been made in relation to occupational risk factors. The International Agency for Research on Cancer has evaluated over 900 different exposures or agents to-date to determine whether they are carcinogenic to humans. These evaluations are published as a series of Monographs (www.iarc.fr). For breast cancer the following substances have been classified as "carcinogenic to humans" (Group 1): alcoholic beverages, exposure to diethylstilbestrol, estrogen-progestogen contraceptives, estrogen-progestogen hormone replacement therapy and exposure to X-radiation and gamma-radiation (in special populations such as atomic bomb survivors, medical patients, and in-utero exposure). Ethylene oxide is also classified as a Group 1 carcinogen, although the evidence for carcinogenicity in epidemiologic studies, and specifically for the human breast, is limited. The classification "probably carcinogenic to humans" (Group 2A) includes estrogen hormone replacement therapy, tobacco smoking, and shift work involving circadian disruption, including work as a flight attendant. If the association between shift work and breast cancer, the most common female cancer, is confirmed, shift work could become the leading cause of occupational cancer in women. PMID:22953181

Botanical modulation of menopausal symptoms: Mechanisms of action?

PubMed Central

Hajirahimkhan, Atieh; Dietz, Birgit M.; Bolton, Judy L.

2013-01-01

Menopausal women suffer from a variety of symptoms, including hot flashes and night sweats which can affect quality of life. Although hormone therapy (HT) has been the treatment of choice for relieving these symptoms, HT has been associated with increased breast cancer risk leading many women to search for natural, efficacious, and safe alternatives such as botanical supplements. Data from clinical trials suggesting that botanicals have efficacy for menopausal symptom relief, have been controversial and several mechanisms of action have been proposed including estrogenic, progestogenic, and serotonergic pathways. Plant extracts with potential estrogenic activities include soy, red clover, kudzu, hops, licorice, rhubarb, yam, and chasteberry. Botanicals with reported progestogenic activities are red clover, hops, yam, and chasteberry. Serotonergic mechanisms have also been proposed since women taking antidepressants often report reduction in hot flashes and night sweats. Black cohosh, kudzu, kava, licorice, and dong quai all either have reported 5-HT7 ligands or inhibit serotonin re-uptake, therefore have potential serotonergic activities. Understanding the mechanisms of action of these natural remedies used for women’s health, could lead to more efficacious formulations and to the isolation of active components which have the potential of becoming effective medications in the future. PMID:23408273

Breast cancer and steroid metabolizing enzymes: the role of progestogens.

PubMed

Pasqualini, Jorge R

2009-12-01

It is well documented that breast tissue, both normal and cancerous, contains all the enzymatic systems necessary for the bioformation and metabolic transformation of estrogens, androgens and progesterone. These include sulfatases, aromatase, hydroxysteroid-dehydrogenases, sulfotransferases, hydroxylases and glucuronidases. The control of these enzymes plays an important role in the development and pathogenesis of hormone-dependent breast cancer. As discussed in this review, various progestogens including dydrogesterone and its 20alpha-dihydro-derivative, medrogestone, promegestone, nomegestrol acetate and norelgestromin can reduce intratissular levels of estradiol in breast cancer by blocking sulfatase and 17beta-hydroxysteroid-dehydrogenase type 1 activities. A possible correlation has been postulated between breast cell proliferation and estrogen sulfotransferase activity. Progesterone is largely transformed in the breast; normal breast produces mainly 4-ene derivatives, whereas 5alpha-derivatives are most common in breast cancer tissue. It has been suggested that this specific conversion of progesterone may be involved in breast carcinogenesis. In conclusion, treatment with anti-aromatases combined with anti-sulfatase or 17beta-hydroxysteroid-dehydrogenase type 1 could provide new therapeutic possibilities in the treatment of patients with hormone-dependent breast cancer. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Sex steroids and neurogenesis.

PubMed

Heberden, Christine

2017-10-01

The brain has long been known as a dimorphic organ and as a target of sex steroids. It is also a site for their synthesis. Sex steroids in numerous ways can modify cerebral physiology, and along with many processes adult neurogenesis is also modulated by sex steroids. This review will focus on the effects of the main steroids, estrogens, androgens and progestogens, and unveil some aspects of their partly disclosed mechanisms of actions. Gonadal steroids act on different steps of neurogenesis: cell proliferation seems to be increased by estrogens only, while androgens and progestogens favor neuronal renewal by increasing cell survival; differentiation is a common target. Aging is characterized by a cognitive deficiency, paralleled by a decrease in the rate of neuronal renewal and in the levels of circulating gonadal hormones. Therefore, the effects of gonadal hormones on the aging brain are important to consider. The review will also be expanded to related molecules which are agonists to the nuclear receptors. Sex steroids can modify adult neuronal renewal and the extensive knowledge of their actions on neurogenesis is essential, as it can be a leading pathway to therapeutic perspectives. Copyright © 2017 Elsevier Inc. All rights reserved.

Antiandrogenic and antimineralocorticoid health benefits of COC containing newer progestogens: dienogest and drospirenone

PubMed Central

Regidor, Pedro-Antonio; Schindler, Adolf E.

2017-01-01

Data have demonstrated that COCs, besides offering a satisfactory and safe contraception, offer a variety of non-contraceptive health benefits and therapeutic positive aspects. Many prescribes and users, however, do not realize these positive aspects especially the non-contraceptive health benefits. While the contraceptive use is the primary indication for COC use for most women, these users should be advised in regard of the non-contraceptive benefits when contraception is discussed and prescribed. Using COCs specifically for non-contraceptive indications is an off-label use in many clinical situations (only some exceptions as e.g. acne vulgaris in some countries are allowed clinical entities for the use of these drugs). Therefore, appropriate discussions with the patient regarding this fact should performed and documented by the prescribing physicians. Independent of the off-label situation, COCs containing the newer progestogens dienogest and drospirenone with their antiandrogenic and antimineralocorticoid health benefits play an important role in the management of many diseases and their use should therefore be considered by clinician’s. This review will focus on the effects of these COCs on the endometrium, the skin, the fat tissue and the premenstrual syndrome. PMID:29137347

Combined administration of levonorgestrel and testosterone induces more rapid and effective suppression of spermatogenesis than testosterone alone: a promising male contraceptive approach.

PubMed

Bebb, R A; Anawalt, B D; Christensen, R B; Paulsen, C A; Bremner, W J; Matsumoto, A M

1996-02-01

Studies using high dose testosterone (T) administration in normal men as a male contraceptive have resulted in azoospermia rates of only 50-70%. Previous studies of T and progestogen combinations have shown comparable rates of azoospermia, but have been uncontrolled or used T in doses less than that associated with maximal suppression of sperm production. We conducted a randomized, placebo-controlled, single blind trial comparing 6 months of T enanthate administration (100 mg, im, weekly) with the same dose of T enanthate in conjunction with the progestogen levonorgestrel (LNG; 500 micrograms, orally, daily) in 36 normal men, aged 20-42 yr (n = 18 in each group). The primary end points were induction of azoospermia or severe oligospermia (< 3 million sperm/mL). The combination of T plus LNG was much more effective in suppressing sperm production than T alone. Sixty-seven percent of the T plus LNG group (12 of 18) and 33% of the T alone group (6 of 18) achieved azoospermia by 6 months (P = 0.06). Severe oligospermia or azoospermia developed in 94% of the T plus LNG (17 of 18) group compared to 61% of the T alone group (11 of 18; P < 0.05). T plus LNG also suppressed sperm production more rapidly than T alone. Time to azoospermia was 9.9 +/- 1.0 vs. 15.3 +/- 1.9 weeks in the T plus LNG and T alone groups, respectively (mean +/- SEM; P < 0.05). Serum high density lipoprotein cholesterol decreased 21.7 +/- 3.6% in men given T plus LNG (P < 0.05), compared to only a 1.8 +/- 3.8% decrease in men in the T alone group. Average weight gain was 5.3 +/- 0.8 kg in the T plus LNG group and 2.3 +/- 0.9 kg in the T alone group (P < 0.05). Acne and increase in hemoglobin were similar in the two groups. We conclude that combination hormonal therapy with T plus a progestogen might offer a reversible male contraceptive approach with a more rapid onset of action and more reliable induction of both azoospermia and severe oligospermia than T alone.

A prospective study on the effects on hemostasis of two oral contraceptives containing drospirenone in combination with either 30 or 20 microg ethinyl estradiol and a reference containing desogestrel and 30 microg ethinyl estradiol.

PubMed

Kluft, Cornelis; Endrikat, Jan; Mulder, Simone M; Gerlinger, Christoph; Heithecker, Renate

2006-04-01

In this open-label, randomized study, we assessed the effects on hemostasis of two combined oral contraceptives containing drospirenone (DRSP) as progestogen component. Three milligrams of DRSP, a progestogen with antimineralocorticoid activity, was combined with either 30 or 20 microg ethinyl estradiol (EE) (DRSP/30EE; DRSP/20EE) and compared with a preparation containing 150 microg desogestrel (DSG) and 30 microg ethinyl estradiol (DSG/30EE). A total of 75 healthy female volunteers aged 18-35 years were enrolled. The hemostasis variables were measured in the medication-free precycle (baseline); in the first, third and sixth treatment cycle; and in the follow-up phase. The target variables for comparison were the relative changes from baseline to Cycle 6. Data of 25 volunteers in each group were valid for the per-protocol evaluation. Most changes in hemostasis variables were similar in the three treatment groups. All procoagulatory variables and the anticoagulatory variable protein C antigen increased slightly, while protein S antigen and activity decreased. For fibrinogen and protein S activity, the changes were statistically significant: less pronounced with DRSP/20EE compared to DSG/30EE at Cycle 6. There were no statistically significant differences in the changes of antifibrinolytic variables, the global clotting tests and D-dimer. All pairwise comparisons of DRSP/30EE vs. DSG/30EE yielded nonsignificant results; however, there was a trend of a lower impact of DRSP/20EE on nearly all hemostatic parameters compared to the 30EE products. All three study treatments were safe and well tolerated by the volunteers and provided adequate contraceptive reliability. The changes in the hemostatic variables for DRSP/20EE were less pronounced compared to DSG/30EE and DRSP/30EE. The results were in accordance with previous reports on effects of similar OCs.

Missed pills: frequency, reasons, consequences and solutions.

PubMed

Chabbert-Buffet, Nathalie; Jamin, Christian; Lete, Iñaki; Lobo, Paloma; Nappi, Rossella E; Pintiaux, Axelle; Häusler, Günther; Fiala, Christian

2017-06-01

Oral hormonal contraception is an effective contraceptive method as long as regular daily intake is maintained. However, a daily routine is a constraint for many women and can lead to missed pills, pill discontinuation and/or unintended pregnancy. This article describes the frequency of inconsistent use, the consequences, the risk factors and the possible solutions. The article comprises a narrative review of the literature. Forgetting one to three pills per cycle is a frequent problem among 15-51% of users, generally adolescents. The reasons for this are age, inability to establish a routine, pill unavailability, side effects, loss of motivation and lack of involvement in the initial decision to use oral contraceptives. The consequences are 'escape ovulations' and, possibly, unintended pregnancy. Solutions are either to use a long-acting method or, for women who prefer to take oral contraceptives, use a continuous or long-cycle regimen to reduce the risks of follicular development and thus the likelihood of ovulation and unintended pregnancy. A progestogen with a long half-life can increase ovarian suppression. For women deciding to use oral contraceptives, a shortened or eliminated hormone-free interval and a progestogen with a long half-life may be an option to reduce the negative consequences of missed oral contraceptive pills.

Treatment of fibroadenomatous hyperplasia in cats with aglépristone.

PubMed

Görlinger, S; Kooistra, H S; van den Broek, A; Okkens, A C

2002-01-01

Fibroadenomatous hyperplasia (FAH) is characterized by a rapid proliferation of mammary stroma and duct epithelium of 1 or more glands and predominantly affects younger female cats. Endogenous progesterone and exogenous progestogens play an important role in the genesis of FAH. The presence of progesterone receptors in fibroadenomatous tissue allows for targeted endocrine therapy with progesterone receptor blockers. We report on 22 young cats with FAH, none of which had responded to the withdrawal of progestogens or ovariectomy. The common signs were tachycardia (11 cats); skin ulceration, painful mammary glands, or both (16 cats); lethargy (8 cats); and anorexia (4 cats). The cats were treated with subcutaneous injections of the progesterone receptor blocker aglépristone on 1 (7 cats, 20 mg/kg) or 2 consecutive days (15 cats, 10 mg/kg/d) once weekly. All but 1 cat responded with a complete and lasting remission of signs after 1-4 weeks of treatment. Two cats had a short-term skin irritation at the site of the aglépristone injection. Two pregnant cats with FAH aborted after treatment with aglépristone and subsequently developed endometritis. In conclusion, the results of this study demonstrate that FAH in cats can be treated successfully with the progesterone receptor blocker aglépristone.

Risk of venous thromboembolism from use of oral contraceptives containing different progestogens and oestrogen doses: Danish cohort study, 2001-9

PubMed Central

Nielsen, Lars Hougaard; Skovlund, Charlotte Wessel; Skjeldestad, Finn Egil; Løkkegaard, Ellen

2011-01-01

Objective To assess the risk of venous thromboembolism from use of combined oral contraceptives according to progestogen type and oestrogen dose. Design National historical registry based cohort study. Setting Four registries in Denmark. Participants Non-pregnant Danish women aged 15-49 with no history of thrombotic disease and followed from January 2001 to December 2009. Main outcome measures Relative and absolute risks of first time venous thromboembolism. Results Within 8 010 290 women years of observation, 4307 first ever venous thromboembolic events were recorded and 4246 included, among which 2847 (67%) events were confirmed as certain. Compared with non-users of hormonal contraception, the relative risk of confirmed venous thromboembolism in users of oral contraceptives containing 30-40 µg ethinylestradiol with levonorgestrel was 2.9 (95% confidence interval 2.2 to 3.8), with desogestrel was 6.6 (5.6 to 7.8), with gestodene was 6.2 (5.6 to 7.0), and with drospirenone was 6.4 (5.4 to 7.5). With users of oral contraceptives with levonorgestrel as reference and after adjusting for length of use, the rate ratio of confirmed venous thromboembolism for users of oral contraceptives with desogestrel was 2.2 (1.7 to 3.0), with gestodene was 2.1 (1.6 to 2.8), and with drospirenone was 2.1 (1.6 to 2.8). The risk of confirmed venous thromboembolism was not increased with use of progestogen only pills or hormone releasing intrauterine devices. If oral contraceptives with desogestrel, gestodene, or drospirenone are anticipated to increase the risk of venous thromboembolism sixfold and those with levonorgestrel threefold, and the absolute risk of venous thromboembolism in current users of the former group is on average 10 per 10 000 women years, then 2000 women would need to shift from using oral contraceptives with desogestrel, gestodene, or drospirenone to those with levonorgestrel to prevent one event of venous thromboembolism in one year. Conclusion After adjustment for length of use, users of oral contraceptives with desogestrel, gestodene, or drospirenone were at least at twice the risk of venous thromboembolism compared with users of oral contraceptives with levonorgestrel. PMID:22027398

Overview of the response of anoestrous ewes to the ram effect.

PubMed

Ungerfeld, R; Forsberg, M; Rubianes, E

2004-01-01

The present review summarises knowledge of the reproductive response of anoestrous ewes to the introduction of rams - in other words, the ram effect. The ovarian and endocrine response, the factors that determine whether ewes will respond or not (associated with both the stimulus and the receptivity of the ewes) and some aspects of practical management are discussed. Information on the use of the ram effect to stimulate post-partum, prepubertal and cyclic ewes is also given. New insights are provided on ovarian response patterns, including recently collected information on luteal responses. The existence of delayed ovulation (5-7 days after the introduction of the rams) followed by luteal phases of normal or short length, luteal cysts and luteinised follicles is reported after scanning the ovaries with ultrasound. Endocrine parameters for depth of anoestrus, such as LH pulsatility and FSH concentrations, and how the concentrations of these hormones should be considered are discussed. Particular attention is paid to the observation of spontaneous, higher LH pulsatility and higher FSH concentrations in anoestrous ewes that respond to rams with luteal phases than in those that fail to respond. The use of progestogen priming and single progestogen administration and the possible advantages for synchronisation of oestrus are also discussed. Other factors that should be considered before the ram effect is applied, such as the strength of the stimulus and some practical considerations, are also included.

A three-year comparative study of continuation rates, bleeding patterns and satisfaction in Australian women using a subdermal contraceptive implant or progestogen releasing-intrauterine system.

PubMed

Weisberg, Edith; Bateson, Deborah; McGeechan, Kevin; Mohapatra, Lita

2014-02-01

BACKGROUND Long-acting reversible contraceptive methods (LARCs) are safe, highly effective, readily reversible, and require no action on the part of the user following insertion. Early discontinuation may put women at increased risk of unintended pregnancy. METHODS Following insertion of a progestogen-only subdermal implant or intrauterine system (IUS) at Family Planning NSW, women 18 years and older completed a questionnaire about their choice. At 6 weeks, 6, 12, 24 and 36 months by telephone or online they completed a questionnaire about bleeding patterns, side effects, satisfaction, and reasons for discontinuation. RESULTS Two hundred IUS users and 149 implant users were enrolled. The former were generally older, married or in a de-facto relationship, and had children. Forty-seven percent of implant users discontinued within three years compared to 27% of IUS users (p = 0.002). In the first two years amenorrhoea was more frequent in implant users. Frequent bleeding/spotting was more prevalent in the first year of IUS use but over time was twice as prevalent in implant users. Infrequent bleeding/spotting was more common in IUS users. CONCLUSION Both devices are highly effective and acceptable cost-effective methods. While LARCs should be promoted to women of all ages seeking contraception, early discontinuation due to unacceptable bleeding highlights the need for pre-insertion counselling.

Added health benefits of the levonorgestrel contraceptive intrauterine system and other hormonal contraceptive delivery systems.

PubMed

Fraser, Ian S

2013-03-01

It has been recognized for well over half a century that hormonal preparations designed as contraceptives are also capable of offering health benefits through the treatment and prevention of benign gynecological disease and even some systemic conditions. Increasing attention is now being paid to the extent and detail of such added health benefits, and it is becoming clear that the long-acting, low-dose, hormonal contraceptive delivery systems may offer particular advantages in this regard. Conventional databases were thoroughly searched, especially for publications from 2006 to 2012, which addressed non-contraceptive-related indications for therapy and prevention. A considerable literature now exists to demonstrate the multiple and substantial noncontraceptive health benefits of long-acting progestogen-releasing systems, especially the levonorgestrel-releasing intrauterine system. These benefits mainly relate to disturbances of menstruation and related symptoms, such as heavy menstrual bleeding (due to many causes); iron deficiency; pelvic pain, especially around endometriosis; and endometrial hyperplasia. The long-acting estrogen-progestogen systems may carry similar added health benefits to those of the combined oral contraceptives, but data are still lacking. Added health benefits are now becoming an important part of the contraceptive choice equation, and the long-acting delivery systems are recognized as suitable primary therapies for a range of gynecological disorders. Copyright © 2013 Elsevier Inc. All rights reserved.

Effects of the addition of methyltestosterone to combined hormone therapy with estrogens and progestogens on sexual energy and on orgasm in postmenopausal women.

PubMed

Penteado, S R Lenharo; Fonseca, A M; Bagnoli, V R; Abdo, C H Najar; Júnior, J M Soares; Baracat, E Chada

2008-02-01

To evaluate the effect of the addition of methyltestosterone to estrogen and progestogen therapy on postmenopausal sexual energy and orgasm. Sixty postmenopausal women in a stable relationship with a partner capable of intercourse, and presenting sexual complaints that appeared after menopause, were randomly divided into two groups: EP (n = 29) received one tablet of equine estrogens (CEE) 0.625 mg plus medroxyprogesterone acetate (MPA) 2.5 mg and one capsule of placebo; EP + A (n = 31) received one tablet of CEE 0.625 mg plus MPA 2.5 mg and one capsule of methyltestosterone 2.0 mg; The treatment period was 12 months. The effects of treatment on sexual energy were assessed using the Sexual Energy Change Scale. The ability to reach orgasm in sexual relations with the partner was verified through monthly calendars and by calculating the ratio between monthly frequency of orgasms in sexual relations and monthly sexual frequency. There was a significant relationship between improvement in level of sexual energy and the addition of methyltestosterone to CEE/MPA treatment (p = 0.021). No significant effect on orgasmic capacity was noted after the treatment period. Addition of methyltestosterone to CEE/MPA therapy may increase sexual energy, but might not affect the ability to obtain orgasm in sexual relations.

Management of menopause-associated vasomotor symptoms: Current treatment options, challenges and future directions

PubMed Central

Pachman, Deirdre R; Jones, Jason M; Loprinzi, Charles L

2010-01-01

Hot flashes are one of the most common and distressing symptoms associated with menopause, occurring in more than 75% of postmenopausal women. They are especially problematic in breast cancer patients since some breast cancer therapies can induce hot flashes. For mild hot flashes, it is proposed that behavioral modifications are the first step in management. Hormonal therapies, including estrogens and progestogens, are the most well known effective agents in relieving hot flashes; however, the safety of these agents is controversial. There is an increasing amount of literature on nonhormonal agents for the treatment of hot flashes. The most promising data regard newer antidepressant agents such as venlafaxine, which reduces hot flashes by about 60%. Gabapentin is another nonhormonal agent that is effective in reducing hot flashes. While many complimentary therapies, including phytoestrogens, black cohosh, and dehydroepiandrosterone, have been explored for the treatment of hot flashes; none can be recommended at this time. Furthermore, there is a lack of strong evidence to support exercise, yoga, or relaxation for the treatment of hot flashes. Paced respirations and hypnosis appear to be promising enough to warrant further investigation. Another promising nonpharmacological therapy, currently under investigation, involves a stellate ganglion block. PMID:21072305

Emergency contraceptive pills as a backup for lactational amenorrhea method (LAM) of contraception: a randomized controlled trial.

PubMed

Shaaban, Omar M; Hassen, Shaimaa G; Nour, Sanna A; Kames, Mervat A; Yones, Entsar M

2013-03-01

The use of breastfeeding as a method of birth spacing occasionally ends in "unplanned pregnancy." This is due to unexpected expiration of one or more of the lactation amenorrhea method (LAM) prerequisites. The current study tests a new concept that the in-advance provision of single packet of progestogen emergency contraception (EC) pills during the postpartum LAM counseling may decrease the incidence of unplanned pregnancy during breastfeeding. This was a registered two-armed randomized controlled trial (NCT 01111929). Women intending to breastfeed and to postpone pregnancy for 1 year or more were approached. They received adequate postpartum contraceptive counseling. Women intending to use LAM were randomly assigned to one of two groups. The LAM-only group received the proper LAM counseling and did not receive counseling about EC. The LAM-EC group received counseling for both LAM and EC with in-advance provision of one packet of EC pills. They were advised to use these pills if one of the prerequisites of LAM expires and sexual relation has occurred before the initiation of another regular contraceptive protection. All the participants were advised that they need to use another regular method upon expiration of any of the LAM prerequisites. Eligible women were 1158 parturients randomized into two equal groups. Forty-four percent of the women provided with EC used them. Significantly more women in the LAM-EC group initiated regular contraception within or shortly after the first 6 months postpartum when compared with those in the LAM-only group (30.5% vs. 7.3%, respectively; p=.0004). Pregnancy occurred in 5% of the LAM-only group as compared with 0.8% in the LAM-EC group (p=.005). Minimal side effects were reported after EC use. In-advance provision of EC pills can increase the rate of initiation of regular contraception once one or more of the prerequisites of LAM expire. Consequently, the use of EC pills as a temporary backup of LAM can decrease the incidence of unplanned pregnancy during breastfeeding. The use of progestogen EC pill during lactation is safe and tolerable. Copyright © 2013 Elsevier Inc. All rights reserved.

Effect of hormone therapy on lean body mass, falls, and fractures: 6-year results from the Women's Health Initiative hormone trials.

PubMed

Bea, Jennifer W; Zhao, Qiuhong; Cauley, Jane A; LaCroix, Andrea Z; Bassford, Tamsen; Lewis, Cora E; Jackson, Rebecca D; Tylavsky, Frances A; Chen, Zhao

2011-01-01

Loss of lean body mass with aging may contribute to falls and fractures. The objective of this analysis was to determine if taking postmenopausal hormone therapy (or HT: estrogen plus progestogen therapy or estrogen therapy alone) favorably affects age-related changes in lean body mass and if these changes partially account for decreased falls or fractures with HT. Participants randomly assigned to either estrogen plus progestogen therapy (n = 543) or control (n = 471) and estrogen therapy alone (n = 453) or control (n = 474) and receiving dual-energy x-ray absorptiometry scans to estimate body composition during the Women's Health Initiative were evaluated. Falls and fracture occurrence were obtained by annual self-report. Fractures were confirmed by a clinical chart review. At 6 years postrandomization, lean body mass was not different between HT and control groups. Although lean body mass positively influenced bone mineral density, independent of HT status, the preserved lean body mass observed in the HT arms in the first 3 years did not significantly contribute to models evaluating HT influence on falls and fractures between years 3 and 6. Women taking at least 80% of their medication in the HT arms demonstrated fewer falls compared with placebo; this difference was not attributable to change in lean body mass. Despite early preservation of lean body mass with HT (3 y), HT did not ameliorate long-term (6 y) loss in lean body mass with aging.

Oral Progestogens Versus Levonorgestrel-Releasing Intrauterine System for Treatment of Endometrial Intraepithelial Neoplasia.

PubMed

Marnach, Mary L; Butler, Kristina A; Henry, Michael R; Hutz, Catherine E; Langstraat, Carrie L; Lohse, Christine M; Casey, Petra M

2017-04-01

Limited therapeutic guidelines exist regarding medical therapy, ideal dosing, duration of therapy, or recommendations for timing of endometrial reassessment for women with endometrial intraepithelial neoplasia (EIN) who desire fertility preservation or who are not optimal surgical candidates. We aimed to determine the effectiveness of oral progestogens (OP) versus the levonorgestrel-releasing intrauterine system (LNG IUS) in the medical treatment of EIN. We retrospectively identified women with EIN at our institution from 2007 through 2014 and compared the outcomes of those treated with OP versus LNG IUS. Among 390 women, 296 were initially treated with OP and 94 with LNG IUS. Baseline characteristics of the patient groups were comparable, except for higher median body mass index in the LNG IUS group versus the OP group (37 kg/m 2 vs. 31 kg/m 2 ; p < 0.001). Among 332 women with follow-up endometrial biopsies (263 OP and 69 LNG IUS), EIN subcategory 1 (benign endometrial hyperplasia) resolved in 83% and 87% of patients, respectively (p = 0.31). Rates of resolution of EIN subcategory 2 (endometrial intraepithelial neoplasia) were also similar between groups (68% vs. 62%; p = 0.82). In women with EIN subcategory 3 (endometrial adenocarcinoma), 22% of those using LNG IUS and one of two women treated with OP had resolution of disease as of last follow-up. OP and LNG IUS offer similar endometrial protection for women with EIN. LNG IUS offers convenience, minimal adverse effects, reversibility, and long-term endometrial protection.

[Action of hormones at the molecular level].

PubMed

Korolkovas, A

1973-03-01

A review of the literature (the list of citations is available from the author on request) is given on the molecular pharmacology of steroid hormones and on efforts to isolate androgen, estrogen, and progestogen receptors with the object of understanding the mechanism of action at the cellular and molecular levels. Complementarity is the necessary factor for interaction between drug and chemoreceptor or the tension induced by proximity, as in the case of enzyme-substrate interaction. In reacting with a receptor, the drug molecule is seen as being, in general, in a state of least energy. Binding forces are the same as those operating in the interior of simple molecules. 2 factors are of special importance to the complex action of drug-receptor: the distribution of the electron charge in each and the molecular conformation of each. A number of examples illustrates this structure-activity relationship. For steroid hormones, 3 stereochemical aspects are significant for their molecular action: 1) binding sites (equatorial or axial), 2) the position of substituents, and 3) the form of cyclohexane (bound and most stable or free and thermodynamically less stable). The mode of action of steroid hormones is outlined, including a diagram of gene regulation and the function of operons and messenger RNA. Androgens, estrogens, and progestogens each owe their specific biological activity to interaction with a macromolecular receptor, such interaction presumably being due to complementarity between receptor and hormone surfaces. Several theories to account for this interaction are discussed and diagrammed.

One year daily changes in fecal sexual steroids of two captive female cheetahs (Acinonyx jubatus) in Italy.

PubMed

Vernocchi, Valentina; Morselli, Maria Giorgia; Faustini, Massimo; Gabai, Gianfranco; Da Dalt, Laura; Luvoni, Gaia Cecilia

2018-04-01

The present study evaluated changes of fecal sexual steroids in two female cheetahs (Geijsha and Duchessa) in Northern Italy throughout one year. Wet feces were collected daily from two sibling animals of the same age, housed with conspecific males and managed in the same conditions, and estrogens and progestogens concentrations were analyzed by radioimmunoassay (RIA). Evidence of ovarian activity based on regular fluctuation in estrogen excretion was demonstrated in both females. None of the animals was continuously cycling, as follicular activity was interrupted by anestrous periods, during the spring and early winter. No significant increases of progestogens were recorded after the estrogen peaks, indicating that induced or spontaneous ovulations did not occur during the observation period. The wavelet decomposition evidenced the temporal pattern of ovarian activity in the two females, underlying throughout the year a more pronounced rhythmical ovarian estrogenic activity in Geijsha than in Duchessa. However, this statistical approach had a smoothing effect in depicting the hormonal patterns and the number of follicular phases might be lower than that revealed by the iterative method. In this study, RIA on wet feces performed very well to determine sexual steroid concentrations, and an ovarian activity interrupted by anestrous periods along the year in captive cheetahs co-housed in a small group was demonstrated. More information on estrous behavior of captive cheetahs were obtained in this study, but the effects of husbandry and management conditions on natural reproductive physiology of this species remain to elucidate. Copyright © 2018 Elsevier B.V. All rights reserved.

Adolescent females and hormonal contraception: a retrospective study in primary care.

PubMed

Krishnamoorthy, Narayanan; Simpson, Colin D; Townend, John; Helms, Peter J; McLay, James S

2008-01-01

The aim of this study was to assess change in the number of adolescent females prescribed hormonal contraception in primary care following the publication in the United Kingdom of the Social Exclusion Unit report on Teenage Pregnancy. We conducted a retrospective observational study of 320 primary care practices in Scotland. Hormonal contraceptive prescribing to girls aged <16 years and those aged 16-19 years was assessed for April 1 to March 31 for the study years 2000-2001 to 2005-2006 from Scottish primary care practice data. Between 2000-2001 and 2005-2006, the proportion of girls aged <16 years and those 16-19 years who were prescribed hormonal contraception by their primary care physicians increased by 82% (p < .001) and 53% (p < .001) respectively. The increase became significant from age 12 years for the combined oral contraceptive, 14 years for the progestogen-only pill, and 15 years for depot progestogens. By 2005-2006, 2.9% of girls aged <16 years and 40.5% of those aged 16-19 years were prescribed some form of hormonal contraception by their primary care physicians. The small number of girls aged <12 years who were prescribed hormonal contraception remained constant over the study period. Since the publication in the United Kingdom of the Social Exclusion Unit Report on Teenage Pregnancy, there has been a significant increase in the number of female adolescents aged > or =12 years prescribed hormonal contraception by their primary care physicians. However the number of individuals prescribed hormonal contraception still remains relatively low in comparison to the reported levels of sexual activity among adolescents in the United Kingdom.

Drug use before and during pregnancy in Serbia.

PubMed

Odalovic, Marina; Vezmar Kovacevic, Sandra; Ilic, Katarina; Sabo, Ana; Tasic, Ljiljana

2012-10-01

Observation of drug use patterns during pregnancy is necessary for the recognition of potential bad practices and improvement of safe drug use in pregnancy. To investigate prescription and over the counter drug use among Serbian women in the 6 months before pregnancy and in the first 6 months of pregnancy, and to evaluate the drugs used according to the risk to a fetus. Setting Six maternity care units and five community pharmacies. A multi-center study was performed in Serbia during the period from March 2009-March 2010. A self-reporting questionnaire was used as a data source. Food and Drug Administration (FDA) risk classification system was used to determine the risk of used drugs for the fetus. Differences between subgroups were assessed using McNemar's test on paired proportions. Main outcome measure Proportion of women exposed to drugs or class of drugs. The overall drug exposure was higher in pregnancy (34.7 %) than before pregnancy (29.9 %), p > 0.05, in the cohort of 311 pregnant women. A significantly greater prescription drug use, 19.0 versus 27.3 % of women, p < 0.05, and less selfmedication with over the counter drugs in pregnancy, 15.1 versus 8.7 %, p < 0.05, were observed. Commonly used drugs were musculoskeletal drugs, analgesics/antipyretics and respiratory system drugs before pregnancy (13.8, 12.5, and 6.4 % of women, respectively), and progestogens, analgesics/antipyretics, and antibiotics for the systemic use in pregnancy (9.0, 7.7, and 7.4 %, respectively). A greater exposure to drugs belonging to the FDA risk category A (3.9 vs. 60.8 %, p < 0.05), B (18.0 vs. 19.6 %, p > 0.05), C (10.0 vs. 10.3 %, p > 0.05) and D (2.9 vs. 10.9 %, p < 0.05), as well as less exposure to drugs belonging to category X (0.3 vs. 0 %, p > 0.05) were observed in pregnancy. Folic acid was used by 60.8 % of women in pregnancy, and by only 3.9 % before pregnancy. Besides higher overall drug use in pregnancy than before pregnancy, particularly the use of progestogens, and, subsequently, D category drugs, less selfmedication with over the counter drugs was observed in pregnancy. Insufficient use of folic acid before pregnancy requires public health service activities.

Endocrine basis for recurrent pregnancy loss.

PubMed

Ke, Raymond W

2014-03-01

Common endocrinopathies are a frequent contributor to spontaneous and recurrent miscarriage. Although the diagnostic criteria for luteal phase defect (LPD) is still controversial, treatment of patients with both recurrent pregnancy loss and LPD using progestogen in early pregnancy seems beneficial. For patients who are hypothyroid, thyroid hormone replacement therapy along with careful monitoring in the preconceptual and early pregnancy period is associated with improved outcome. Women with polycystic ovary syndrome (PCOS) have an increased risk of pregnancy loss. Management of PCOS with normalization of weight or metformin seems to reduce the risk of pregnancy loss. Copyright © 2014 Elsevier Inc. All rights reserved.

Reproductive analysis of male and female captive jaguars (Panthera onca) in a Colombian zoological park.

PubMed

Jimenez Gonzalez, Santiago; Howard, Jo Gayle; Brown, Janine; Grajales, Henry; Pinzón, Jorge; Monsalve, Haydy; Moreno, María Angélica; Jimenez Escobar, Claudia

2017-02-01

A reproductive analysis of a captive group of jaguars (Panthera onca; n = 6) at the Santacruz Zoological Foundation in Cundinamarca, Colombia, was conducted by performing a longitudinal, noninvasive, hormonal analysis of estradiol and progestogens in females and of androgens in males. During four seasons, female jaguars confined in solitary were evaluated for ovarian activity and spontaneous ovulation, male jaguars for testicular activity. A second hormonal follow-up was conducted in the females after administration of gonadotropins. Hormones were extracted from fecal samples of three females (n = 3) and two males (n = 2). Estradiol measurements were obtained by RIA and progestogens by enzyme immunoassay. The linear mixed-effect regression showed that there was a significant effect of seasons in the concentrations of estradiol (chi square = 15.97, degrees of freedom = 3, P < 0.01). Posthoc comparisons of all pairs of seasonal means were conducted according to Tukey's honest significant difference, revealing significant differences between seasons: Dry 1 versus Rains 2 (P < 0.01), Rains 1 versus Rains 2 (P < 0.05), and Dry 2 versus Rains 2 (P < 0.05). Elevations of progestogens compatible with spontaneous ovulation occurred in three jaguars, and the linear mixed-effect regression showed that there was also a significant effect of seasons (chi square = 28.56, degrees of freedom = 3, P < 0.01). Posthoc comparisons showed significant differences only between seasons: Dry 2 versus Rains 2 (P < 0.01). The season with the lowest average concentration was Rains 2 (October, November, and December). During this season, periods of anestrous were registered that lasted between 31 and 83 days. The three females presented estradiol peaks after the administration of eCG. A noninvasive longitudinal analysis for androgens was also made (males 1 and 2) over the course of 1 year, and no significant differences were found between the different seasons. A seminal analysis of three adult male jaguars (Panthera onca; n = 3) was also performed after electroejaculation under general anesthesia (male 1 and 2) and by a postmortem epididymal wash (male 3). The mean concentration of spermatozoids was 5.7 × 10 6 ± 1.1 × 10 6 spermatozoa/mL. The progressive motility + standard deviation averaged 80%. The percentage of normal spermatozoids obtained by electroejaculation was 80 ± 2.8%, and the abnormalities found more frequently were head defects (7 ± 1.4%). The seminal fluid obtained by epididymal flush contained 35 ± 1.4% normal spermatozoids, and the most frequent abnormalities found corresponded to distal cytoplasmic droplets (39 ± 11.3%). Copyright © 2016 Elsevier Inc. All rights reserved.

Efficiency of different hormonal treatments for estrus synchronization in tropical Santa Inês sheep.

PubMed

Texeira, Tarcísio Alves; da Fonseca, Jeferson Ferreira; de Souza-Fabjan, Joanna Maria Gonçalves; de Rezende Carvalheira, Luciano; de Moura Fernandes, Daniel Andrews; Brandão, Felipe Zandonadi

2016-03-01

The aim of this study was to evaluate the effect of (i) the duration of hormone treatment with progestogen sponges during the seasonal anestrus and (ii) the administration of two doses of prostaglandin at 7 days apart during the breeding season on reproductive parameters of Santa Inês ewes. In experiment 1, 32 ewes received intravaginal MAP sponges for 6 (G6 days), 9 (G9 days), or 12 (G12days) days and 75 μg D-cloprostenol i.m. and 300 IU eCG i.m. 1 day before sponge removal. In experiment 2, 23 ewes received two doses of 0.48-mg sodium cloprostenol i.m. 7 days apart. Ovarian follicular dynamic was assessed through transrectal ultrasonography. Blood samples were collected daily to determine progesterone concentrations. In experiment 1, estrus and ovulation rates did not differ (P > 0.05) among protocols and between cyclic and acyclic ewes at the beginning of the experiment. The G9 days treatment showed a lower dispersion of ovulations in relation to onset of estrus when compared to G6 days and G12 days. In experiment 2, all ewes exhibit estrus and ovulated after the second dose of prostaglandin, although ewes that were in diestrus at D0 showed subluteal concentrations of progesterone during the follicle development stage of the treatment. In conclusion, the use of progestogen device during 9 days promotes lower dispersion of ovulation when compared to its use for 6 or 12 days, and the protocol of two doses of prostaglandin 7 days apart synchronizes estrus efficiently but results in follicular development under low progesterone concentrations.

GnRH and prostaglandin-based synchronization protocols as alternatives to progestogen-based treatments in sheep.

PubMed

Rekik, M; Haile, A; Abebe, A; Muluneh, D; Goshme, S; Ben Salem, I; Hilali, M El-Dine; Lassoued, N; Chanyalew, Y; Rischkowsky, B

2016-12-01

The study investigated, for cycling sheep, synchronizing protocols simultaneously to the standard "P" protocol using progestogens priming with intravaginal devices and gonadotropin. In November 2014, 90 adult Menz ewes were assigned to either the "P" protocol, "PGF" treatment where oestrus and ovulation were synchronized using two injections of prostaglandin 11 days apart or a "GnRH" treatment where the ewes had their oestrus and ovulation synchronized with GnRH (day 0)-prostaglandin (day 6)-GnRH (day 9) sequence. The ewes were naturally mated at the induced oestrus and the following 36 days. Plasma progesterone revealed that 92% of the ewes were ovulating before synchronization and all, except one, ovulated in response to the applied treatments. All "P" ewes exhibited oestrus during the 96-hr period after the end of the treatments in comparison with only 79.3% and 73.3% for "PGF" and "GnRH" ewes, respectively (p < .05). Onset and duration of oestrus were affected by the hormonal treatment (p < .05); "GnRH" ewes showed oestrus earliest and had the shortest oestrous duration. Lambing rate from mating at the induced oestrus was lower for "P" than for "PGF" ewes (55.6% and 79.3%, respectively; p < .05). The same trait was also lower for "P" than for "PGF" and "GnRH" ewes (70.4%, 89.7% and 86.7%, respectively; p < .05) following the 36-day mating period. Prostaglandin and GnRH analogue-based protocols are promising alternatives for both controlled natural mating and fixed insemination of Menz sheep after the rainy season when most animals are spontaneously cycling. © 2016 Blackwell Verlag GmbH.

Fetal programming: prenatal testosterone treatment leads to follicular persistence/luteal defects; partial restoration of ovarian function by cyclic progesterone treatment.

PubMed

Manikkam, Mohan; Steckler, Teresa L; Welch, Kathleen B; Inskeep, E Keith; Padmanabhan, Vasantha

2006-04-01

Prenatal testosterone (T) excess during midgestation leads to estrous cycle defects and polycystic ovaries in sheep. We hypothesized that follicular persistence causes polycystic ovaries and that cyclic progesterone (P) treatment would overcome follicular persistence and restore cyclicity. Twice-weekly blood samples for P measurements were taken from control (C; n = 16) and prenatally T-treated (T60; n = 14; 100 mg T, im, twice weekly from d 30-90 of gestation) Suffolk sheep starting before the onset of puberty and continuing through the second breeding season. A subset of C and T60 sheep were treated cyclically with a modified controlled internal drug-releasing device for 13-14 d every 17 d during the first anestrus (CP, 7; TP, 6). Transrectal ovarian ultrasonography was performed for 8 d in the first and 21 d in the second breeding season. Prenatal T excess reduced the number, but increased the duration of progestogenic cycles, reduced the proportion of ewes with normal cycles, increased the proportion of ewes with subluteal cycles, decreased the proportion of ewes with ovulatory cycles, induced the occurrence of persistent follicles, and reduced the number of corpora lutea in those that cycled. Cyclic P treatment in anestrus, which produced one third the P concentration seen during luteal phase of cycle, did not reduce the number of persistent follicles, but increased the number of progestogenic cycles while reducing their duration. These findings suggested that follicular persistence might contribute to the polycystic ovarian morphology. Cyclic P treatment was able to only partially restore follicular dynamics, but this may be related to the low replacement concentrations of P achieved.

A cost-effectiveness analysis of hormone replacement therapy in the menopause.

PubMed

Cheung, A P; Wren, B G

1992-03-02

To evaluate the cost-effectiveness of hormone replacement therapy in the menopause with particular reference to osteoporotic fracture and myocardial infarction. The multiple-decrement form of the life table was the mathematical model used to follow women of age 50 through their lifetime under the "no hormone replacement" and "hormone replacement" assumptions. Standard demographic and health economic techniques were used to calculate the corresponding lifetime differences in direct health care costs (net costs in dollars) and health effects ("net effectiveness" in terms of life expectancy and quality, in "quality-adjusted life-years"). This was then expressed as a cost-effectiveness ratio or the cost ($) per quality-adjusted life-year (QALY) for each of the chosen hormone replacement regimens. All women of age 50 in New South Wales, Australia (n = 27,021). The analysis showed that the lifetime net increments in direct medical care costs were largely contributed by hormone drug and consultation costs. Hormone replacement was associated with increased quality-adjusted life expectancy, a large percentage of which was attributed to a relief of menopausal symptoms. Cost-effectiveness ratios ranged from under 10,000 to over a million dollars per QALY. Factors associated with improved cost-effectiveness were prolonged treatment duration, the presence of menopausal symptoms, minimum progestogen side effects (in the case of oestrogen with progestogen regimens), oestrogen use after hysterectomy and the inclusion of cardiac benefits in addition to fracture prevention. Hormone replacement therapy for symptomatic women is cost-effective when factors that enhance its efficiency are considered. Short-term treatment of asymptomatic women for prevention of osteoporotic fractures and myocardial infarction is an inefficient use of health resources. Cost-effectiveness of hormone replacement in asymptomatic women is dependent on the magnitude of cardiac benefits associated with hormone use and the treatment duration.

Effect of tibolone and its principal metabolites (3α- and 3β-hydroxy, 3α-sulfate, and 4-ene derivatives) on estrone sulfatase activity in normal and cancerous human breast tissue.

PubMed

Chetrite, Gérard S; Cortes-Prieto, Joaquin; Pasqualini, Jorge R

2011-12-01

Tibolone (Org-OD14) is the active substance of Livial®, a synthetic steroid with the structure 7α,17α-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn-3-one, possessing weak tissue-specific estrogenic, progestogenic, and androgenic properties, used to treat menopausal complaints. After oral administration, tibolone is extensively metabolized into the 3α-(Org-4904) and 3β-(Org-30126) hydroxy derivatives with estrogenic properties, its 4-ene (Org-OM38) isomer with progestogenic/androgenic activities, and the 3α-sulfate (Org-34322) derivative, a major biologically inactive circulating form. We compared the dose response of tibolone and its metabolites on estrone sulfatase activity [conversion of estrone sulfate (E1S) to estrone (E1)] in normal and cancerous human breast tissues. Tissue minces were incubated with physiological concentrations of [3H]-E1S (5×10-9M) alone or in the presence of tibolone and its metabolites (concentration range: 5×10-7to 5×10-5M) for 4 h. Tritiated E1, estradiol (E2), and E1S were separated and evaluated quantitatively by thin-layer chromatography. The sulfatase activity was significantly higher in cancerous breast but strongly inhibited by tibolone and the different metabolites, whereas 3α- and 3β-hydroxy derivatives were the most potent inhibitors. This very significant inhibitory effect of tibolone and its principal metabolites on the enzyme involved in E2biosynthesis in the human breast provides interesting perspectives to study the biological responses of these compounds in trials with breast cancer patients.

Pharmacokinetics of two low-dose levonorgestrel-releasing intrauterine systems and effects on ovulation rate and cervical function: pooled analyses of phase II and III studies.

PubMed

Apter, Dan; Gemzell-Danielsson, Kristina; Hauck, Brian; Rosen, Kimberly; Zurth, Christian

2014-06-01

To assess the pharmacokinetics and pharmacodynamics of levonorgestrel intrauterine system (LNG-IUS) 13.5 mg and LNG-IUS 19.5 mg (total content). Pooled pharmacokinetic and pharmacodynamic analyses of phase II and III studies. Randomized, open-label, multicenter studies. Nulliparous and parous women. Levonorgestrel intrauterine system 13.5 mg, LNG-IUS 19.5 mg, or LNG-IUS 20 μg/24 h (total content 52 mg). Pharmacokinetics of LNG, ovulation rate, cervical function, and endometrium effects. The in vivo LNG release rate of LNG-IUS 13.5 mg was approximately 14 μg/24 h after 24 days, declining progressively to 5 μg/24 h after 3 years. The average LNG serum concentration over 3 years of use was 74.3 ng/L, 114 ng/L, and 218 ng/L for LNG-IUS 13.5 mg, LNG-IUS 19.5 mg, and LNG-IUS 20 μg/24 h, respectively. All treatments showed very similar progestogenic effects on cervical mucus, with low and similar cervical scores throughout treatment. Ovulation was observed in the majority of women in all groups where assessment was possible, although there was a lower incidence of anovulation with LNG-IUS 13.5 mg and LNG-IUS 19.5 mg compared with LNG-IUS 20 μg/24 h. The progestogenic effect on the endometrium was marked in all three LNG-IUS groups. Levonorgestrel intrauterine system 13.5 mg and LNG-IUS 19.5 mg result in alower systemic exposure to LNG, lower incidence of anovulation, and similar progestin impact on the endometrium and cervical function compared with LNG-IUS 20 μg/24 h. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Use of the World Health Organization's Medical Eligibility Criteria for Contraceptive Use Guidance in sub-Saharan African Countries: A Cross-Sectional Study.

PubMed

Chen, Melissa J; Gaffield, Mary E; Kiarie, James

2016-09-28

Given recent updates to the postpartum contraception recommendations in the fifth edition of the Medical Eligibility Criteria for Contraceptive Use (MEC), published by the World Health Organization (WHO), the purpose of this qualitative study was to assess the extent to which national family planning policies in sub-Saharan African countries are in agreement with the WHO MEC, particularly with regard to postpartum contraceptive use. WHO headquarters sent questionnaires to country-level focal points to complete with their Ministry of Health counterparts. Between February and May 2016, 23 of 32 (72%) surveys were completed. All respondents reported that their countries had used the MEC document in the past, with most reporting that they had used the guidance as a reference (n = 20, 87%), for training purposes (n = 19, 83%), to change clinical practices (n = 17, 74%), and to develop national policies (n = 16, 70%). While many respondents (16, 70%) indicated their countries already include immediate postpartum intrauterine device insertion among breastfeeding women in their family planning policies, few reported currently allowing use of progestogen-only pills (n = 8, 35%) or implants (n = 8, 35%) during the immediate postpartum period (i.e., less than 48 hours after delivery) for breastfeeding women. A higher percentage of respondents indicated their countries allowed breastfeeding women the option of progestogen-only pills (n = 16, 70%) and implants (n = 13, 57%) between 48 hours and 6 weeks postpartum. Findings from this baseline assessment suggest that many countries may benefit from training and policy formulation support to adapt both new WHO MEC updates as well as existing recommendations from previous MEC revisions into national family planning guidelines. © Chen et al.

A randomised study comparing the effect on ovarian activity of a progestogen-only pill (POP) containing desogestrel and a new POP containing drospirenone in a 24/4 regimen.

PubMed

Duijkers, Ingrid J M; Heger-Mahn, Doris; Drouin, Dominique; Skouby, Sven

2015-01-01

Progestogen-only pills (POPs) are safer with respect to cardiovascular risks than contraceptives containing estrogens. Despite the increased contraceptive efficacy of a desogestrel-only pill compared with a traditional POP, POPs are still not widely used due to an unpredictable bleeding pattern. A new POP containing 4 mg drospirenone has been developed with a 24/4 intake regimen which may improve the bleeding pattern. The objectives of this study were to investigate ovulation inhibition with the new drospirenone-only pill in comparison with the desogestrel-only pill and, in addition, to assess the effects on cervical mucus permeability and bleeding. Sixty-four healthy volunteers with proven ovulatory cycles were randomised and treated with either the drospirenone-only or the desogestrel-only pill during two 28-day cycles. Follicular diameter, endometrial thickness, and serum estradiol (E2) and progesterone concentrations were measured and Hoogland scores were determined. Additionally, cervical mucus scores, bleeding and return of ovulation were assessed. Both treatments effectively inhibited ovulation. Follicular diameter, E2 levels and Hoogland scores were equal, demonstrating efficient ovarian suppression. One subject in each group had a Hoogland score of 6, but the criteria for normal luteal activity were not fulfilled. In both groups, ovulation did not occur before day 9 of the post-treatment cycle. Cervical mucus permeability was suppressed in both groups. The median number of bleeding and spotting days was lower in the drospirenone group. The new drospirenone-only pill inhibited ovulation as effectively as the desogestrel-only pill despite the 4-day hormone-free interval.

European Code against Cancer 4th Edition: Medical exposures, including hormone therapy, and cancer.

PubMed

Friis, Søren; Kesminiene, Ausrele; Espina, Carolina; Auvinen, Anssi; Straif, Kurt; Schüz, Joachim

2015-12-01

The 4th edition of the European Code against Cancer recommends limiting - or avoiding when possible - the use of hormone replacement therapy (HRT) because of the increased risk of cancer, nevertheless acknowledging that prescription of HRT may be indicated under certain medical conditions. Current evidence shows that HRT, generally prescribed as menopausal hormone therapy, is associated with an increased risk of cancers of the breast, endometrium, and ovary, with the risk pattern depending on factors such as the type of therapy (oestrogen-only or combined oestrogen-progestogen), duration of treatment, and initiation according to the time of menopause. Carcinogenicity has also been established for anti-neoplastic agents used in cancer therapy, immunosuppressants, oestrogen-progestogen contraceptives, and tamoxifen. Medical use of ionising radiation, an established carcinogen, can provide major health benefits; however, prudent practices need to be in place, with procedures and techniques providing the needed diagnostic information or therapeutic gain with the lowest possible radiation exposure. For pharmaceutical drugs and medical radiation exposure with convincing evidence on their carcinogenicity, health benefits have to be balanced against the risks; potential increases in long-term cancer risk should be considered in the context of the often substantial and immediate health benefits from diagnosis and/or treatment. Thus, apart from HRT, no general recommendations on reducing cancer risk were given for carcinogenic drugs and medical radiation in the 4th edition of European Code against Cancer. It is crucial that the application of these measures relies on medical expertise and thorough benefit-risk evaluation. This also pertains to cancer-preventive drugs, and self-medication with aspirin or other potential chemopreventive drugs is strongly discouraged because of the possibility of serious, potentially lethal, adverse events. Copyright © 2015 International Agency for Research on Cancer. Published by Elsevier Ltd. All rights reserved.

Effects of synthetic gestagens on fish reproduction.

PubMed

Zeilinger, Jana; Steger-Hartmann, Thomas; Maser, Edmund; Goller, Stephan; Vonk, Richardus; Länge, Reinhard

2009-12-01

Although it is well known that estrogenic steroidal hormones are able to affect the sexual development and reproduction of fish at low concentrations, no data on environmental effects of the class of progestogenic hormones are available yet. Synthetic gestagens (progestins) are a component in oral contraceptives. Upon their use, a fraction of the progestins will be excreted via urine into the aquatic environment. On the basis of their pharmacological action in mammals, it is supposed that fish reproduction is the most sensitive endpoint for the progestin treatment. In order to test this assumption, the effects of two progestins currently marketed in contraceptive formulations, levonorgestrel (LNG) and drospirenone (DRSP), were investigated in adult fathead minnows (Pimephales promelas) following an Organization for Economic Cooperation and Development 21-d fish reproduction screening assay draft protocol with additional end points. Levonorgestrel was tested at measured concentrations of 0.8, 3.3, and 29.6 ng/L, and DRSP at concentrations of 0.66, 6.5, and 70 microg/L. Both tested progestins caused an inhibition of reproduction. For LNG, this occurred at concentrations of >or=0.8 ng/L, no no-observed-effect concentration (NOEC) could be defined. Higher concentrations resulted in masculinization of females with de novo synthesis of nuptial tubercles. Drospirenone treatment, however, affected the reproductive success of fathead minnow at concentrations of 6.5 microg/L and higher with a clear dose-response relationship and a NOEC of 0.66 microg/L, which is above environmentally relevant concentrations.

Steroid hormone runoff from agricultural test plots applied with municipal biosolids

USGS Publications Warehouse

Yang, Yun-Ya; Gray, James L.; Furlong, Edward T.; Davis, Jessica G.; ReVollo, Rhiannon C.; Borch, Thomas

2012-01-01

The potential presence of steroid hormones in runoff from sites where biosolids have been used as agricultural fertilizers is an environmental concern. A study was conducted to assess the potential for runoff of seventeen different hormones and two sterols, including androgens, estrogens, and progestogens from agricultural test plots. The field containing the test plots had been applied with biosolids for the first time immediately prior to this study. Target compounds were isolated by solid-phase extraction (water samples) and pressurized solvent extraction (solid samples), derivatized, and analyzed by gas chromatography–tandem mass spectrometry. Runoff samples collected prior to biosolids application had low concentrations of two hormones (estrone -1 and androstenedione -1) and cholesterol (22.5 ± 3.8 μg L-1). In contrast, significantly higher concentrations of multiple estrogens (-1), androgens (-1), and progesterone (-1) were observed in runoff samples taken 1, 8, and 35 days after biosolids application. A significant positive correlation was observed between antecedent rainfall amount and hormone mass loads (runoff). Hormones in runoff were primarily present in the dissolved phase (<0.7-μm GF filter), and, to a lesser extent bound to the suspended-particle phase. Overall, these results indicate that rainfall can mobilize hormones from biosolids-amended agricultural fields, directly to surface waters or redistributed to terrestrial sites away from the point of application via runoff. Although concentrations decrease over time, 35 days is insufficient for complete degradation of hormones in soil at this site.

Oral progestogen combined with testosterone as a potential male contraceptive: additive effects between desogestrel and testosterone enanthate in suppression of spermatogenesis, pituitary-testicular axis, and lipid metabolism.

PubMed

Wu, F C; Balasubramanian, R; Mulders, T M; Coelingh-Bennink, H J

1999-01-01

The effects of a synthetic oral progestogen, desogestrel (DSG), administered with low dose testosterone (T) were investigated to determine the optimal combination for suppression of gonadotropins and spermatogenesis to targets compatible with effective male contraception. Twenty-four healthy male volunteers (33.2 +/- 0.9 yr) were randomly assigned to 3 groups (n = 8) to receive: 1) 300 microg DSG orally daily and 100 mg T enanthate, i.m., weekly; 2) 300 microg DSG and 50 mg T enanthate; or 3) 150 microg DSG and 100 mg T enanthate for 24 weeks. To investigate the individual contribution to the combined action, DSG was administered alone for the first 3 weeks, and T enanthate was added on day 22. After 24-week treatment, sperm density in 78% (18 of 23) of the subjects became azoospermic, whereas 91.7% (22 of 24) and 95.8% (23 of 24) suppressed to less than 1 million/mL and less than 3 million/mL, respectively. The 300 microg DSG with 50 mg T enanthate combination induced azoospermia in 8 of 8 subjects, and the suppression of sperm density was significantly greater than that in the 300 microg DSG/100 mg T enanthate group, but was not different from that in the 150 microg DSG/100 mg T enanthate group. DSG (300 or 150 microg daily) alone in the first 3 weeks suppressed LH, FSH, and T to 60.6%, 48.0%, and 35.4%, respectively, of the baseline. Addition of T enanthate (50 and 100 mg weekly) raised plasma T to the physiological range and induced a further fall in LH and FSH to the limits of assay detection. There was no consistent difference in mean LH and FSH levels among the three groups during treatment or recovery, except that FSH remained detectable in a higher proportion of samples from the group receiving 300 microg DSG with 50 mg T enanthate. Total cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol decreased by 9.3 +/- 1.7%, 10.3 +/- 2.6%, and 7.7 +/- 2.8%, respectively, during treatment with DSG alone with no difference between 300 and 150 microg. Addition of T enanthate (both 50 and 100 mg weekly) induced a further fall only in high density lipoprotein cholesterol to 22.6 +/- 3.7% from the baseline. In summary, the combined actions of oral DSG with low doses of T enanthate were highly effective in suppressing pituitary-testicular functions in adult men. The optimal regimen for inducing azoospermia was 300 microg DSG daily with 50 mg T enanthate weekly. Oral DSG exerted discernible effects on lipid metabolism. We conclude that the combination of oral progestogens with low dose T is a promising approach to achieve effective reversible male contraception.

Estrogen increases latencies to seizures and levels of 5α-pregnan-3α-ol-20-one in hippocampus of wild-type, but not 5α-reductase knockout, mice

PubMed Central

Osborne, Danielle M.; Frye, Cheryl A.

2013-01-01

Sex steroids can influence seizures. Estrogen (E2), progesterone (P4), and its metabolite, 5α-pregnan-3α-ol-20-one (3α,5α-THP), in particular, have received much attention for exerting these effects. Typically, it is thought that E2 precipitates seizures, and progestogens, such as P4 and 3α,5α-THP, attenuate seizures. However, E2 may also have antiseizure effects, perhaps in part through its enhancement of the formation of 3α,5α-THP, which has GABAA/benzodiazepine receptor agonist-like actions. To test this hypothesis, male and female, castrated or ovariectomized, wild-type and 5α-reductase knockout mice were implanted with Silastic capsules of E2 or vehicle and then administered pentylenetetrazol (85 mg/kg, ip). Wild-type, but not 5α-reductase knockout, mice administered E2 had significantly longer latencies to myoclonus and increased levels of 3α,5α-THP in the hippocampus. Thus, some of the anticonvulsive effects of E2 may involve formation of 3α,5α-THP in the hippocampus. PMID:19782646

Fertility after contraception or abortion.

PubMed

Huggins, G R; Cullins, V E

1990-10-01

There is a very small correlation, if any, between the prior use of OCs and congenital malformations, including Down's syndrome. There are few, if any, recent reports on masculinization of a female fetus born to a mother who took an OC containing 1 mg of a progestogen during early pregnancy. However, patients suspected of being pregnant and who are desirous of continuing that pregnancy should not continue to take OCs, nor should progestogen withdrawal pregnancy tests be used. Concern still exists regarding the occurrence of congenital abnormalities in babies born to such women. The incidence of postoperative infection after first trimester therapeutic abortion in this country is low. However, increasing numbers of women are undergoing repeated pregnancy terminations, and their risk for subsequent pelvic infections may be multiplied with each succeeding abortion. The incidence of prematurity due to cervical incompetence or surgical infertility after first trimester pregnancy terminations is not increased significantly. Asherman's syndrome may occur after septic therapeutic abortion. The pregnancy rate after treatment of this syndrome is low. The return of menses and the achievement of a pregnancy may be slightly delayed after OCs are discontinued, but the fertility rate is within the normal range by 1 year. The incidence of postpill amenorrhea of greater than 6 months' duration is probably less than 1%. The occurrence of the syndrome does not seem to be related to length of use or type of pill. Patients with prior normal menses as well as those with menstrual abnormalities before use of OCs may develop this syndrome. Patients with normal estrogen and gonadotropin levels usually respond with return of menses and ovulation when treated with clomiphene. The rate for achievement of pregnancy is much lower than that for patients with spontaneous return of menses. The criteria for defining PID or for categorizing its severity are diverse. The incidence of PID is higher among IUD users than among patients taking OCs or using a barrier method. The excess risk of PID among IUD users, with the exception of the first few months after insertion, is related to sexually transmitted diseases and not the IUD. Women with no risk factors for sexually transmitted diseases have little increased risk of PID or infertility associated with IUD use. There appears to be no increased risk of congenital anomalies, altered sex ratio, or early pregnancy loss among spermicide users. All present methods of contraception entail some risk to the patient. The risk of imparied future fertility with the use of any method appears to be low.(ABSTRACT TRUNCATED AT 400 WORDS)

Medical management of heavy menstrual bleeding

PubMed Central

Maybin, Jacqueline A; Critchley, Hilary OD

2016-01-01

Women with benign heavy menstrual bleeding have the choice of a number of medical treatment options to reduce their blood loss and improve quality of life. The role of the clinician is to provide information to facilitate women in making an appropriate choice. Unfortunately, many options can be associated with hormonal side effects, prevention of fertility and lack of efficacy, leading to discontinuation and progression to surgical interventions. Herein, we discuss the various options currently available to women, including antifibrinolytics, nonsteroidal anti-inflammatory preparations, oral contraceptive pills and oral, injectable and intrauterine progestogens. In addition, we describe the more novel option of selective progesterone receptor modulators and their current benefits and limitations. PMID:26695687

Metabolic and cardiovascular impact of oral contraceptives in polycystic ovary syndrome.

PubMed

Soares, G M; Vieira, C S; de Paula Martins, W; Dos Reis, R M; de Sá, M F S; Ferriani, R A

2009-01-01

Chronic anovulation, polycystic ovarian morphology and hyperandrogenism are the diagnostic criteria for polycystic ovary syndrome (PCOS). Metabolic disturbances are more common in PCOS women who are prone to develop metabolic syndrome and to present higher levels of some cardiovascular disease risk marker. Oral contraceptives are widely used in PCOS, but conflicting data have been reported regarding their impact on carbohydrate and lipid metabolism on PCOS women. This paper presents a critical evaluation of combined oral contraceptives (COCs) metabolic effect - carbohydrate metabolism and insulin sensitivity, lipid metabolism, haemostasis, body weight, arterial pressure and cardiovascular impact - on PCOS women. Because of the paucity of data on the impact of COCs on cardiovascular and metabolic parameters in PCOS patients, most of there commendations are based on studies involving ovulatory women. The use of low-dose COCs is preferable in PCOS, especially among patients with glucose intolerance, insulin resistance and uncomplicated diabetes mellitus. Although reported as a side effect of COCs, marked weight gain has not been confirmed among users. However, when arterial hypertension or elevated risk for thromboembolism is present, progestogen-only hormonal contraceptives should be used instead of COCs. Regarding dyslipidaemia, COCs reduce low-density lipoprotein and total cholesterol and elevate high-density lipoprotein and triglycerides, and therefore are not recommended for women with high triglycerides levels. The choice of a COC, which alleviates the PCOS-induced hyperandrogenism without significant negative impact on cardiovascular risk, is one of the greatest challenges faced by gynaecologists nowadays.

Reproductive Health Assessment of Female Elephants in North American Zoos and Association of Husbandry Practices with Reproductive Dysfunction in African Elephants (Loxodonta africana)

PubMed Central

Meehan, Cheryl L.; Hogan, Jennifer N.; Morfeld, Kari A.; Carlstead, Kathy

2016-01-01

As part of a multi-institutional study of zoo elephant welfare, we evaluated female elephants managed by zoos accredited by the Association of Zoos and Aquariums and applied epidemiological methods to determine what factors in the zoo environment are associated with reproductive problems, including ovarian acyclicity and hyperprolactinemia. Bi-weekly blood samples were collected from 95 African (Loxodonta africana) and 75 Asian (Elephas maximus) (8–55 years of age) elephants over a 12-month period for analysis of serum progestogens and prolactin. Females were categorized as normal cycling (regular 13- to 17-week cycles), irregular cycling (cycles longer or shorter than normal) or acyclic (baseline progestogens, <0.1 ng/ml throughout), and having Low/Normal (<14 or 18 ng/ml) or High (≥14 or 18 ng/ml) prolactin for Asian and African elephants, respectively. Rates of normal cycling, acyclicity and irregular cycling were 73.2, 22.5 and 4.2% for Asian, and 48.4, 37.9 and 13.7% for African elephants, respectively, all of which differed between species (P < 0.05). For African elephants, univariate assessment found that social isolation decreased and higher enrichment diversity increased the chance a female would cycle normally. The strongest multi-variable models included Age (positive) and Enrichment Diversity (negative) as important factors of acyclicity among African elephants. The Asian elephant data set was not robust enough to support multi-variable analyses of cyclicity status. Additionally, only 3% of Asian elephants were found to be hyperprolactinemic as compared to 28% of Africans, so predictive analyses of prolactin status were conducted on African elephants only. The strongest multi-variable model included Age (positive), Enrichment Diversity (negative), Alternate Feeding Methods (negative) and Social Group Contact (positive) as predictors of hyperprolactinemia. In summary, the incidence of ovarian cycle problems and hyperprolactinemia predominantly affects African elephants, and increases in social stability and feeding and enrichment diversity may have positive influences on hormone status. PMID:27416141

Reproductive Health Assessment of Female Elephants in North American Zoos and Association of Husbandry Practices with Reproductive Dysfunction in African Elephants (Loxodonta africana).

PubMed

Brown, Janine L; Paris, Stephen; Prado-Oviedo, Natalia A; Meehan, Cheryl L; Hogan, Jennifer N; Morfeld, Kari A; Carlstead, Kathy

2016-01-01

As part of a multi-institutional study of zoo elephant welfare, we evaluated female elephants managed by zoos accredited by the Association of Zoos and Aquariums and applied epidemiological methods to determine what factors in the zoo environment are associated with reproductive problems, including ovarian acyclicity and hyperprolactinemia. Bi-weekly blood samples were collected from 95 African (Loxodonta africana) and 75 Asian (Elephas maximus) (8-55 years of age) elephants over a 12-month period for analysis of serum progestogens and prolactin. Females were categorized as normal cycling (regular 13- to 17-week cycles), irregular cycling (cycles longer or shorter than normal) or acyclic (baseline progestogens, <0.1 ng/ml throughout), and having Low/Normal (<14 or 18 ng/ml) or High (≥14 or 18 ng/ml) prolactin for Asian and African elephants, respectively. Rates of normal cycling, acyclicity and irregular cycling were 73.2, 22.5 and 4.2% for Asian, and 48.4, 37.9 and 13.7% for African elephants, respectively, all of which differed between species (P < 0.05). For African elephants, univariate assessment found that social isolation decreased and higher enrichment diversity increased the chance a female would cycle normally. The strongest multi-variable models included Age (positive) and Enrichment Diversity (negative) as important factors of acyclicity among African elephants. The Asian elephant data set was not robust enough to support multi-variable analyses of cyclicity status. Additionally, only 3% of Asian elephants were found to be hyperprolactinemic as compared to 28% of Africans, so predictive analyses of prolactin status were conducted on African elephants only. The strongest multi-variable model included Age (positive), Enrichment Diversity (negative), Alternate Feeding Methods (negative) and Social Group Contact (positive) as predictors of hyperprolactinemia. In summary, the incidence of ovarian cycle problems and hyperprolactinemia predominantly affects African elephants, and increases in social stability and feeding and enrichment diversity may have positive influences on hormone status.

Lipids, cardiovascular disease, and oral contraceptives: a practical perspective.

PubMed

Upton, G V

1990-01-01

Figure 9 is an attempt to summate the influences of life-style on lipid parameters. Based on the work of Nikkila, it shows the source of the production of HDL and LDL, the factors that can affect these lipoprotein levels, and where in the cascade of lipoprotein metabolism these factors exert influence. The source of HDL production is the liver and the intestine. At this stage, diet, exercise, hormones, genetics, drugs, and certain disease states can affect HDL levels. Lecithin-cholesterol acyl transferase (LCAT) esterifies HDL-free cholesterol in plasma, and HDL3 is formed that in turn is transformed to HDL2. At the same time, VLDL from the gut and the liver will be converted, under the influence of LPL, to HDL2 and LDL. Thus HDL2 is being formed by the breakdown of VLDL and from the transformation of HDL3 to HDL2. Insulin, exercise, alcohol, fats, drugs, and diet affect lipoprotein lipase and consequently influence levels of LDL and HDL2 indirectly. Progestogens increase and estrogens decrease hepatic endothelial lipase, thus affecting the HDL2 concentration. It is at this point that combination OCs influence HDL2. The balance between estrogen and progestogen in a given contraceptive determines the extent and direction of HDL2 concentration. A separate pathway in the liver also catabolizes HDL2 and HDL3. LDL is generated partly from catabolism of VLDL and is partly secreted from the liver. The removal of LDL is mediated by receptors in both the liver and peripheral tissues. It is here that the Brown-Goldstein theory plays a major role. If LDL receptors are present in an insufficient number or are defective, then the C will accumulate and atherosclerosis may follow. Thus two key enzymes, LCAT and LPL, control the production of HDL2 and LDL, whereas a third enzyme, hepatic endothelial lipase, catabolizes HDL2.

A comparative 2-year study of the effects of sequential regimens of 1 mg 17beta-estradiol and trimegestone with a regimen containing estradiol valerate and norethisterone on the bleeding profile and endometrial safety in postmenopausal women.

PubMed

Koninckx, P R; Spielmann, D

2005-08-01

To compare the bleeding profiles and endometrial protection of two sequential regimens of 17beta-estradiol (17beta-E2) and trimegestone (TMG) with a sequential estradiol valerate (E2V)/norethisterone (NET) regimen. This was a randomized, double-blind, multicenter study conducted in eight countries in healthy, postmenopausal women with an intact uterus. A total of 1218 women were enrolled into the initial 1-year study (13 cycles), and subsequently 531 of these received treatment for a further year (26 cycles). Treatment regimens were 1 mg 17beta-E2 on days 1-14 and 1 mg 17beta-E2/0.125 mg TMG or 1 mg 17beta-E2/0.25 mg TMG on days 15-28, and 1 mg E2V on days 1-16 and 1 mg E2V/1 mg NET on days 17-28. Mean percentage of women reporting onset of withdrawal bleeding episodes during the week following discontinuation of progestogen was higher in the 1 mg 17beta-E2/0.25 mg TMG group than in the other two treatments, showing a more efficient progestogen effect on the endometrium and good predictability of bleeding onset with this treatment. The mean numbers and average lengths of bleeding episodes were similar in the three treatment groups. Overall, the bleeding profile was more favorable with 1 mg 17beta-E2/0.25 mg TMG than with the lower-dose TMG preparation. Both of the TMG regimens demonstrated a good protective effect on endometrial proliferation, with the 0.25 mg TMG dose showing a lower incidence of proliferative endometrium. The 1 mg 17beta-E2/0.25 mg TMG regimen showed an adequate protection of the endometrium, with an overall favorable bleeding profile.

Haemostatic effects of a new combined oral contraceptive, nomegestrol acetate/17β-estradiol, compared with those of levonorgestrel/ethinyl estradiol. A double-blind, randomised study.

PubMed

Gaussem, Pascale; Alhenc-Gelas, Martine; Thomas, Jean-Louis; Bachelot-Loza, Christilla; Remones, Veronique; Ali, Fouad Dali; Aiach, Martine; Scarabin, Pierre-Yves

2011-03-01

Use of oral contraceptives (OC) that combine a progestogen with synthetic ethinyl estradiol (EE) is associated with increased risk of venous thromboembolism. NOMAC/E2 is a new monophasic OC that combines nomegestrol acetate (NOMAC), a highly selective progestogen, with 17β-estradiol (E2). The study objective was to compare the effects on markers of haemostasis of NOMAC/E2 (2.5 mg/1.5 mg) versus the second-generation OC, levonorgestrel (LNG)/EE (100 μg/20 μg). Healthy women (age 18-38 years) received once-daily treatment for three consecutive 28-day cycles in a double-blind, randomised study: either NOMAC/E2 for 24 days with a four-day placebo interval (n=45) or LNG/EE for 21 days with a seven-day placebo interval (n=45) per cycle. Mean changes from baseline to end-of-treatment in coagulation markers, including prothrombin fragment 1+2 (primary endpoint), fibrinolysis markers and platelet functions were assessed. Mean prothrombin fragment 1+2 levels (primary endpoint) did not increase with NOMAC/E2 compared with LNG/EE ( -0.02 vs. +0.08 nM, p<0.01). Other significant differences between NOMAC/E2 and LNG/EE were mean changes in antithrombin (+0.3% vs. -4.4%, p<0.001), activated protein C resistance - normalised ratio (+0.20 vs. +0.46, p<0.01), D-dimer ( -53 vs. +43 ng/ml, p<0.001), plasminogen (+6% vs. +30%, p<0.0001) and plasminogen activator inhibitor-1 ( -3.1 vs. -8.0 ng/ml, p<0.001). There was no effect of either treatment on platelet aggregation. The NOMAC/E2 pill regimen has fewer adverse effects on blood biological coagulation and fibrinolysis markers than LNG/EE. This suggests that NOMAC/E2 could have a more favourable venous thromboembolism risk profile than LNG/EE; further epidemiological data are required to confirm this.

Influence of hormonal contraceptives and the occurrence of stroke: integrative review.

PubMed

Lima, Adman Câmara Soares; Martins, Larissa Castelo Guedes; Lopes, Marcos Venícios de Oliveira; Araújo, Thelma Leite de; Lima, Francisca Elisângela Teixeira; Aquino, Priscila de Souza; Moura, Escolástica Rejane Ferreira

2017-01-01

To identify scientific evidence regarding the influence of hormonal contraceptive use and the occurrence of stroke. Integrative review of the literature, through database search using the descriptors "contraceptive agents", "contraceptive devices", "contraceptives, Oral" and "Stroke". Original studies in Portuguese, Spanish and English, published in full and available online were included. Studies that did not answer our guiding questions and duplicated studies were excluded. Women using combined oral contraceptives have higher risk of stroke, even with a lower hormonal dosage and different types of progestogen, regardless of the duration of use. The use of contraceptives associated with smoking, hypertension, migraine, hypercholesterolemia, obesity and sedentary lifestyle increases the chance of stroke. Contraceptive patch and vaginal ring are associated to increased risk. Use of combined hormonal contraceptives, except for the injectable and the transdermal ones, increases the chance of occurrence of the event. Progestogen-only contraceptives were considered safe. Identificar evidências científicas acerca da influência do uso de anticoncepcionais hormonais na ocorrência do acidente vascular cerebral (AVC). Revisão integrativa da literatura, com pesquisa em bases de dados, utilizando os descritores "contraceptive agents", "contraceptive devices", "contraceptives, Oral" e "stroke". Foram incluídos artigos originais nos idiomas português, espanhol e inglês, publicados na íntegra e disponíveis eletronicamente. Foram excluídos artigos que não respondiam às questões norteadoras e repetidos. Usuárias de anticoncepcional oral combinado apresentam risco maior de AVC, mesmo com dosagem hormonal menor e diferentes tipos de progestágeno, independente do tempo de uso. A presença associada de tabagismo, hipertensão arterial, enxaqueca, hipercolesterolemia, obesidade e sedentarismo aumenta a chance desse desfecho. Adesivo anticoncepcional e anel vaginal são relacionados ao aumento desse risco. A exposição aos anticoncepcionais hormonais combinados aumenta a chance de ocorrência do evento, exceto o injetável e o transdérmico. Os exclusivos de progestágeno foram considerados seguros.

Ferrrate(VI) and freeze-thaw treatment for oxidation of hormones and inactivation of fecal coliforms in sludge.

PubMed

Diak, James; Örmeci, Banu

2017-04-01

This study examined the individual and combined effects of potassium ferrate(VI) additions and freeze-thaw conditioning for the treatment and dewatering of wastewater sludge in cold climates, with particular focus on the inactivation of fecal coliforms and oxidation of estrogens, androgens, and progestogens. The first phase of the study evaluated the effects of potassium ferrate(VI) pre-treatment followed by freeze-thaw at -20 °C using a low (0.5 g/L) and high (5.0 g/L) dose of potassium ferrate(VI). The results showed that pre-treatment of anaerobically digested sludge with 5 g/L of potassium ferrate(VI) reduced the concentration of fecal coliforms in the sludge cake to below 100 MPN/g DS. The second phase evaluated the ability of ferrate(VI) to oxidise selected hormones in sludge. Anaerobically digested sludge samples were spiked with 10 different hormones: estrone (E1), 17α-estradiol, 17β-estradiol (E2), estriol (E3), 17α-ethinylestradiol (EE2), equilin, mestranol, testosterone, norethindrone and norgestrel in two groups of low (3-75 ng/mL) and high (12-300 ng/L) concentration ranges of hormones. The samples were treated with either 0.5 or 1.0 g/L of potassium ferrate(VI), and hormone concentrations were measured again after treatment. Potassium ferrate(VI) additions as low as 1.0 g/L reduced the concentration of estrogens in sludge. Potassium ferrate(VI) additions of 0.5 and 1.0 g/L were less effective at reducing the concentrations of androgens and progestogens. Increasing ferrate(VI) dose would likely result in more substantial decreases in the concentrations of fecal coliforms and hormones. The results of this study indicate that the combined use of freeze-thaw and ferrate(VI) has the potential to provide a complete sludge treatment solution in cold regions.

Access to emergency hormonal contraception from community pharmacies and family planning clinics

PubMed Central

Lewington, Gaye; Marshall, Kay

2006-01-01

Aims To evaluate differences in the time taken to access progestogen-only emergency hormonal contraception (EHC) by young women from family planning (FP) or community pharmacy settings. Methods An observational study of 203 women requesting EHC from FP clinics and community pharmacies in South-west Kent Primary Care Trust (PCT) from December 2002 to October 2003. Results Access to EHC from community pharmacy was significantly faster than from FP clinics (16 h vs. 41 h, P < 0.001). Older teenagers tended to seek EHC more quickly and were more likely to have had a contraceptive failure rather than have used no contraception at all. Conclusion The results provide further support for pharmacist involvement in the supply of EHC. PMID:16669854

Drospirenone/ethinylestradiol: a review on efficacy and noncontraceptive benefits.

PubMed

Machado, Rogério Bonassi; Pompei, Luciano de Melo; Giribela, Arícia Galvão; Giribela, Cassiana Galvão

2011-01-01

Considerable advances have been made in the field of combined oral contraceptives since their introduction 50 years ago. This ongoing evolution has been focused on reducing the estrogen dose and synthesizing new progestogens. A recently launched combination of ethinylestradiol 20 µg and drospirenone 3 mg demonstrates the advantages of a lower estrogen dose with the antimineralocorticoid activity of drospirenone that is responsible for the drug's significant antiandrogenic and antimineralocorticoid effects, reflected clinically in lower rates of adverse events including less fluid retention. In addition to the drug's contraceptive efficacy, its effects on the skin and other classic noncontraceptive benefits, the ethinylestradiol 20 µg and drospirenone 3 mg combination has demonstrated highly satisfactory results in women with premenstrual dysphoric syndrome.

Exposure to the contraceptive progestin, gestodene, alters reproductive behavior, arrests egg deposition, and masculinizes development in the fathead minnow (Pimephales promelas)

USGS Publications Warehouse

Frankel, Tyler E.; Meyer, Michael T.; Kolpin, Dana W.; Gillis, Amanda B.; Alvarez, David A.; Orlando, Edward F.

2016-01-01

Endogenous progestogens and pharmaceutical progestins enter the environment through wastewater treatment plant effluent and agricultural field runoff. Lab studies demonstrate strong, negative exposure effects of these chemicals on aquatic vertebrate reproduction. Behavior can be a sensitive, early indicator of exposure to environmental contaminants associated with altered reproduction yet is rarely examined in ecotoxicology studies. Gestodene is a human contraceptive progestin and a potent activator of fish androgen receptors. Our objective was to test the effects of gestodene on reproductive behavior and associated egg deposition in the fathead minnow. After only 1 day, males exposed to ng/L of gestodene were more aggressive and less interested in courtship and mating, and exposed females displayed less female courtship behavior. Interestingly, 25% of the gestodene tanks contained a female that drove the male out of the breeding tile and displayed male-typical courtship behaviors toward the other female. Gestodene decreased or arrested egg deposition with no observed gonadal histopathology. Together, these results suggest that effects on egg deposition are primarily due to altered reproductive behavior. The mechanisms by which gestodene disrupts behavior are unknown. Nonetheless, the rapid and profound alterations of the reproductive biology of gestodene-exposed fish suggest that wild populations could be similarly affected.

Emergency Contraception: Awareness, Perception and Practice among Female Undergraduates in Imo State University, Southeastern Nigeria.

PubMed

Ojiyi, Ec; Anolue, Fc; Ejekunle, Sd; Nzewuihe, Ac; Okeudo, C; Dike, Ei; Ejikem, Ce

2014-11-01

Limited knowledge and practice of contraception is a global public health problem. Unintended pregnancies are the primary cause of induced abortion. When safe abortions are not available, as in Nigeria with restricted abortion laws, abortion can contribute significantly to maternal mortality and morbidity. Adequate information on the awareness and the use of emergency contraception is necessary for planning interventions in groups vulnerable to unwanted pregnancy. The aim of the following study is to access the awareness, perception and practice of emergency contraception among female undergraduates in Imo State University, South Eastern Nigeria. A questionnaire based cross-sectional survey using female undergraduates selected randomly from Imo State University, Owerri. A total of 700 students participated in the study. Awareness of emergency contraception was very high (85.1%) (596/700). The awareness was significantly higher amongst students in health related faculties than in the non-health related faculties (P = 0.01). The main sources of information were through friends (43.1%) (317/700) and lectures (22.1%) (192/700). High dose progestogen (postinor-2) was the most commonly known type of emergency contraception (70.8%) (422/596). Only 58.1% (346/596) of those who were aware of emergency contraception approved of their use. The major reasons given by the 41.9% (250/596) who disapproved of their use were religious reasons (50.4%) (126/250) and that they were harmful to health (49.2%) (123/250). Two-third (67%) (46 9/700) of the students were sexually active and only 39.9% (187/469) of them used emergency contraception. High dose progestogen (postinor-2) was again the most commonly used method (70.8%) (422/596). The most common situation in which emergency contraception was used was following unprotected sexual intercourse (45.5%) (85/144). Only 34.6% (206/596) of those who were aware of emergency contraception identified correctly the appropriate time interval for its effectiveness. Although the awareness of emergency contraception was high amongst female undergraduates, the attitude and practice are still poor. The inclusion of reproductive health education as part of the undergraduate school curriculum might help to change students' attitude toward emergency contraceptives.

The use of altrenogest to avoid hyperestrogenism after eCG-hCG ovulation induction in southern tigrina (Leopardus guttulus).

PubMed

Micheletti, Tatiane; Brown, Janine L; Walker, Susan L; Cubas, Zalmir S; Furtado, Priscila V; Putman, Sarah B; de Moraes, Wanderlei; de Oliveira, Marcos J; de Oliveira, Claudio A; Moreira, Nei

2015-09-01

The goal of this study was to optimize an ovulation induction protocol for use with artificial insemination in the southern tigrina (Leopardus guttulus). The specific aims were to report the efficacy of using altrenogest, an oral progestin (Regumate, MSD Animal Health, Merck Animal Health), to suppress ovarian activity and prevent follicular hyperstimulation and hyperestrogenism after the administration of exogenous eCG and hCG. To monitor ovarian responses, fecal estrogen and progestogen metabolites were quantified by enzyme immunoassay in females before and after intramuscular administration of 200-IU eCG and 150-IU hCG in two trials, 4 months apart. During the first trial, there was no use of altrenogest, only the eCG-hCG ovulation induction protocol. In the second trial, the ovulation induction protocol was preceded by the administration of oral altrenogest for 14 days (minimum of 0.192 mg per kg per day). Altrenogest administration resulted in a suppression of follicular activity in three out of six females before eCG-hCG administration on the basis of lower mean estrogen concentrations (P < 0.05). It also resulted in four out of six females presenting lower fecal estrogen metabolite concentrations (P < 0.05) after ovulation induction, and two out of six individuals showed a reduction (P < 0.05) in postovulatory fecal progestogen metabolite concentrations, all when compared to the same female's cycles without the progestin. Fecal estrogen metabolite concentrations were closer to baseline in 50% of these individuals after altrenogest and eCG-hCG treatments when compared to basal concentrations before gonadotropins without the use of altrenogest. This study reported that use of altrenogest in southern tigrina can suppress ovarian activity and avoid hyperestrogenism after administration of eCG and hCG treatment. However, not all females responded uniformly, so more studies are needed to increase the efficacy of ovulation induction for use with artificial insemination in this species. Copyright © 2015 Elsevier Inc. All rights reserved.

[The menopause and the skin (author's transl)].

PubMed

Aron-Brunetière, R

It is currently admitted that the skin and its appendages plays an important part in steroid metabolism, especially in genital androgens, estrogens and progestogens. This activity produces the cutaneous changes sometimes associated with the premenopause period : facial hyper-seborrhea, seborrhea of the scalp, loss of scalp hairs, increaed pilosity on the cheeks and upper lip, whether they occur spontaneously or after hormonal treatment. Following the menopause-onset a progressive decreases in hair growth, can be observed, especially in the axillary and pubic regions, with occasional diffuse alopecia, increase in degeneration of elastic tissue, and atrophy of the vaginal mucosa, in fact as some changes appearing in the skin show correlations with the hormonal changes, others appear to be more closely related to aging of the skin. Thus, hormonal therapy will not be able to treat efficiently all these disorders.

Evaluation of effects of an oral contraceptive containing ethinylestradiol combined with drospirenone on adrenal steroidogenesis in hyperandrogenic women with polycystic ovary syndrome.

PubMed

De Leo, Vincenzo; Morgante, Giuseppe; Piomboni, Paola; Musacchio, Maria Concetta; Petraglia, Felice; Cianci, Antonio

2007-07-01

To investigate whether the administration of an oral contraceptive containing the new antiandrogenic drospirenone is associated with reduced adrenal androgen synthesis in hyperandrogenic women with diagnosis of polycystic ovary syndrome. Drospirenone, an analogue of spironolactone and aldosterone antagonist, is a novel progestin under clinical development that is similar to the natural hormone progesterone, combining potent progestogenic with antimineralocorticoid and antiandrogenic activities. Prospective study. Healthy volunteers in University Department of Obstetrics and Gynecology. Fifteen women ages 18 to 28 years with the diagnosis of polycystic ovary syndrome. Three months of contraceptive use (30 mcg ethinylestradiol, 3 mg drospirenone). An adrenocorticotropic hormone test was performed before and after the study. Adrenal production of cortisol was unchanged after therapy with oral contraceptives. An interesting observation was reduced basal concentrations of androgens such as androstenedione, dehydroepiandrosterone sulfate, testosterone, and free testosterone during therapy. The ratios of the areas of substrates to products before and after oral contraceptive administration were compared for differences in 17alpha-hydroxylase (17-hydroxyprogesterone/progesterone) and 17,20-lyase (androstenedione/17-hydroxyprogesterone); activities were significantly reduced, indicating a reduction in the activities of these enzymes. The present results show for the first time that oral contraceptives containing drospirenone affect adrenal steroidogenesis by reducing synthesis and release of androgens in response to adrenocorticotropic hormone, leaving adrenal production of cortisol unchanged.

Non-contraceptive oestrogen-containing preparations for controlling symptoms of premenstrual syndrome.

PubMed

Naheed, Bushra; Kuiper, Jan Herman; Uthman, Olalekan A; O'Mahony, Fidelma; O'Brien, Patrick Michael Shaughn

2017-03-03

Premenstrual syndrome (PMS) is a psychological and somatic disorder of unknown aetiology, with symptoms typically including irritability, depression, mood swings, bloating, breast tenderness and sleep disturbances. About 3% to 10% of women who experience these symptoms may also meet criteria for premenstrual dysphoric disorder (PMDD). PMS symptoms recur during the luteal phase of the menstrual cycle and reduce by the end of menstruation. PMS results from ovulation and may be due to ovarian steroid interactions relating to neurotransmitter dysfunction. Premenstrual disorders have a devastating effect on women, their families and their work.Several treatment options have been suggested for PMS, including pharmacological and surgical interventions. The treatments thought to be most effective tend to fall into one of two categories: suppressing ovulation or correcting a speculated neuroendocrine anomaly.Transdermal oestradiol by patch, gel or implant effectively stops ovulation and the cyclical hormonal changes which produce the cyclical symptoms. These preparations are normally used for hormone therapy and contain lower doses of oestrogen than found in oral contraceptive pills. A shortened seven-day course of a progestogen is required each month for endometrial protection but can reproduce premenstrual syndrome-type symptoms in these women. To determine the effectiveness and safety of non-contraceptive oestrogen-containing preparations in the management of PMS. On 14 March 2016, we searched the following databases: the Cochrane Gynaecology and Fertility Group (CGF) Specialised Register; Cochrane Central Register of Studies (CRSO); MEDLINE; Embase; PsycINFO; CINAHL; ClinicalTrials.gov; metaRegister of Controlled trials (mRCT); and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) Search Portal. In addition, we checked the reference lists of articles retrieved. We included published and unpublished randomized placebo or active controlled trials on the efficacy of the use of non-contraceptive oestrogen-containing preparations in the management of premenstrual syndrome in women of reproductive age with PMS diagnosed by at least two prospective cycles without current psychiatric disorder. Two review authors independently selected studies, assessed risk of bias, extracted data on premenstrual symptoms and adverse effects and entered data into Review Manager 5 software. Where possible, intention-to-treat or modified intention-to-treat analysis was used. Studies were pooled using a fixed-effect model, analysing cross-over trials as parallel trials. Standardised mean differences (SMDs) with 95% confidence intervals (CIs) were calculated for premenstrual symptom scores. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated for dichotomous outcomes. The overall quality of the evidence was assessed using the GRADE working group methods. The search resulted in 524 potentially relevant articles. Five eligible randomized controlled trials (RCTs) were identified (305 women). Trials using oral tablets, transdermal patches and implants were identified. No trial used gels.One small cross-over trial (11 women, effective sample size 22 women considering cross-over trials) compared oral luteal-phase oestrogen versus placebo. Data were very low quality and unsuitable for analysis, but study authors reported that the intervention was ineffective and might aggravate the symptoms of PMS. They also reported that there were no adverse events.Three studies compared continuous oestrogen with progestogen versus placebo (with or without progestogen). These trials were of reasonable quality, although with a high risk of attrition bias and an unclear risk of bias due to potential carry-over effects in two cross-over trials. Continuous oestrogen had a small to moderate positive effect on global symptom scores (SMD -0.34, 95% CI -0.59 to -0.10, P = 0.005, 3 RCTs, 158 women, effective sample size 267 women, I² = 63%, very low quality evidence). The evidence was too imprecise to determine if the groups differed in withdrawal rates due to adverse effects (RR 0.64, 95% CI 0.26 to 1.58, P = 0.33, 3 RCTs, 196 women, effective sample size 284 women, I² = 0%, very low quality evidence). Similarly, the evidence was very imprecise in measures of specific adverse events, with large uncertainties around the true value of the relative risk. None of the studies reported on long-term risks such as endometrial cancer or breast cancer.One study compared patch dosage (100 vs 200 µg oestrogen, with progestogen in both arms) and had a high risk of performance bias, detection bias and attrition bias. The study did not find evidence that dosage affects global symptoms but there was much uncertainty around the effect estimate (SMD -1.55, 95% CI -8.88 to 5.78, P = 0.68, 1 RCT, 98 women, very low quality evidence). The evidence on rates of withdrawal for adverse events was too imprecise to draw any conclusions (RR 0.70, 95% CI 0.34 to 1.46, P = 0.34, 1 RCT, 107 women, low-quality evidence). However, it appeared that the 100 µg dose might be associated with a lower overall risk of adverse events attributed to oestrogen (RR 0.51, 95% Cl 0.26 to 0.99, P = 0.05, 1 RCT, 107 women, very low quality evidence) with a large uncertainty around the effect estimate.The overall quality of the evidence for all comparisons was very low, mainly due to risk of bias (specifically attrition), imprecision, and statistical and clinical heterogeneity. We found very low quality evidence to support the effectiveness of continuous oestrogen (transdermal patches or subcutaneous implants) plus progestogen, with a small to moderate effect size. We found very low quality evidence from a study based on 11 women to suggest that luteal-phase oral unopposed oestrogen is probably ineffective and possibly detrimental for controlling the symptoms of PMS. A comparison between 200 µg and 100 µg doses of continuous oestrogen was inconclusive with regard to effectiveness, but suggested that the lower dose was less likely to cause side effects. Uncertainty remains regarding safety, as the identified studies were too small to provide definite answers. Moreover, no included trial addressed adverse effects that might occur beyond the typical trial duration of 2-8 months. This suggests the choice of oestrogen dose and mode of administration could be based on an individual woman's preference and modified according to the effectiveness and tolerability of the chosen regimen.

A UHPLC-MS/MS method for profiling multifunctional steroids in human hair.

PubMed

Dong, Zhen; Wang, Caihong; Zhang, Jinlan; Wang, Zhe

2017-08-01

It is important to profile steroids in many physiological and pathological processes. Recently, hair has been used for the long-term measurement of endogenous steroid hormones. Analyzing hair has advantages of being noninvasive and time sequential compared with other bio-specimens. Liquid chromatography-mass spectrometry (LC-MS) techniques have been widely used over the past decades; however, it is challenging to profile estrogens in hair by LC-MS, and more comprehensive steroid profiling is required. In this paper, an ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed to simultaneously profile 28 multifunctional steroids, including corticosteroids (n = 6), estrogens (n = 13), androgens (n = 5) and progestogens (n = 4), in human scalp hair in a single run. To optimize the sample preparation procedure, we evaluated extraction time, post-incubation purification and hair fragment length; 30 mg hair samples were washed with hexane, cut into 5 mm pieces and incubated in methanol for 18 h at 25 °C. Methanol extraction derivatized using Girard P and dansyl chloride reagent was analyzed within 25 min using an automated injection program combined with a diverter valve switch and step analysis (AIDSA). The method was well validated in terms of linearity, limit of detection (LOD), limit of quantification (LOQ), precision, accuracy, matrix effect and recovery, and was successfully applied to a steroid profile from male and female hairs. Significant differences were observed between genders. In addition, steroids showed a declining trend from the proximal to more distal hair segments; thus, care should be taken when obtaining hair samples for analysis to account for this difference in steroid levels along the length of hair. Graphical Abstract The workflow of the estabished UHPLC-MS/MS method.

Activity of Protein Kinase C is Important for 3α,5α-THP’s Actions at Dopamine Type 1-like and/or GABAA receptors in the Ventral Tegmental Area for Lordosis of Rats

PubMed Central

Frye, Cheryl A.; Walf, Alicia A.

2008-01-01

In the ventral tegmental area, progestogens facilitate sexual receptivity of rodents via actions at dopamine type 1-like and/or γ-aminobutyric type A receptors and activation of downstream signal transduction molecules. In the present study, we investigated whether effects of progesterone’s metabolite, 3α,5α-THP, to enhance lordosis via actions at these receptors in the ventral tegmental area requires phospholipase C-dependent protein kinase C. The objective of this study was to test the hypothesis that: if progestogens’ actions through dopamine type 1-like and/or γ-aminobutyric type A receptors in the ventral tegmental area for lordosis require protein kinase C, then inhibiting protein kinase C in the ventral tegmental area should reduce 3α,5α-THP-facilitated lordosis and its enhancement by dopamine type 1-like or γ-aminobutyric type A receptor agonists. Ovariectomized, E2 (10 μg s.c. at hr 0)-primed rats were tested for their baseline lordosis responses and then received a series of three infusions to the ventral tegmental area: first, bisindolylmaleimide (75 nM/side) or vehicle; second, SKF38393 (100 ng/side), muscimol (100 ng/side), or vehicle; third, 3α,5α-THP (100, 200 ng) or vehicle. Rats were pre-tested for lordosis and motor behavior and then tested for lordosis after each infusion and 10 and 60 mins after the last infusion. Rats were tested for motor behavior following their last lordosis test. As has been previously demonstrated, 3α,5α-THP infusions to the ventral tegmental area increased lordosis and effects were further enhanced by infusions of SKF38393 and muscimol. Infusions of bisindolylmaleimide to the ventral tegmental area attenuated 3α,5α-THP-, SKF38393-, and/or muscimol-facilitated lordosis. Effects on lordosis were not solely due to changes in general motor behavior. Thus, 3α,5α-THP’s actions in the ventral tegmental area through membrane receptors may require activity of protein kinase C. PMID:18675324

The contraception needs of the perimenopausal woman.

PubMed

Hardman, Sarah M R; Gebbie, Ailsa E

2014-08-01

Perimenopausal women have low fertility but must still be advised to use contraception until natural sterility is reached if they are sexually active. Patterns of contraceptive use vary in different countries worldwide. Long-acting reversible contraceptive methods offer reliable contraception that may be an alternative to sterilisation. Hormonal methods confer significant non-contraceptive benefits, and each individual woman should weigh up the benefits and risks of a particular method. No method of contraception is contraindicated by age alone, although combined hormonal contraception and injectable progestogens are not recommended for women over the age of 50 years. The intrauterine system has particular advantages as a low-dose method of effective hormonal contraception, which also offers control of menstrual dysfunction and endometrial protection in women requiring oestrogen replacement. Condoms are recommended for personal protection against sexually transmitted infections in new relationships. Standard hormone replacement therapy is not a method of contraception. Copyright © 2014 Elsevier Ltd. All rights reserved.

Developmental profiles of progesterone receptor transcripts and molecular responses to gestagen exposure during Silurana tropicalis early development.

PubMed

Thomson, Paisley; Langlois, Valerie S

2018-05-18

Environmental gestagens are an emerging class of contaminants that have been recently measured in surface water and can interfere with reproduction in aquatic vertebrates. Gestagens include endogenous progestogens, such as progesterone (P4), which bind P4-receptors and have critically important roles in vertebrate physiology and reproduction. Gestagens also include synthetic progestins, which are components of human and veterinary drugs, such as melengestrol acetate (MGA). Endogenous progestogens are essential in the regulation of reproduction in mammalian species, but the role of P4 in amphibian larval development remains unclear. This project aims to understand the roles and the regulatory mechanisms of P4 in amphibians and to assess the consequences of exposures to environmental gestagens on the P4-receptor signaling pathways in frogs. Here, we established the developmental profiles of the P4 receptors: the intracellular progesterone receptor (ipgr), the membrane progesterone receptor β (mpgrβ), and the progesterone receptor membrane component 1 (pgrmc1) in Western clawed frog (Silurana tropicalis) embryos using real-time qPCR. P4-receptor mRNAs were detected throughout embryogenesis. Transcripts for ipgr and pgrmc1 were detected in embryos at Nieuwkoop and Faber (NF) stage 2 and 7, indicative of maternal transfer of mRNA. We also assessed the effects of P4 and MGA exposure in embryonic and early larval development. Endocrine responses were evaluated through transcript analysis of a suite of gene targets of interest, including: ipgr, mpgrβ, pgrmc1, androgen receptor (ar), estrogen receptor α (erα), follicle stimulating hormone β (fshβ), prolactin (prl), and the steroid 5-alpha reductase family (srd5α1, 2, and 3). Acute exposure (NF 12-46) to P4 caused a 2- to 5-fold change increase of ipgr, mpgrβ, pgrmc1, and ar mRNA levels at the environmentally relevant concentration of 195 ng/L P4. Acute exposure to MGA induced a 56% decrease of srd5α3 at 1140 ng/L MGA. We conclude that environmental exposure to P4 induced multiple endocrine-related transcript responses in amphibians; however, the differential responses of MGA suggest that the effects of MGA are not mediated through the classical P4 signaling pathway in S. tropicalis. Copyright © 2018 Elsevier Inc. All rights reserved.

Estrus resynchronization in ewes with unknown pregnancy status.

PubMed

Miranda, Vladinis O; Oliveira, Fernando C; Dias, Jenniffer H; Vargas Júnior, Sergio F; Goularte, Karina L; Sá Filho, Manoel F; Sá Filho, Ocilon G de; Baldassarre, Hernan; Vieira, Arnaldo D; Lucia, Thomaz; Gasperin, Bernardo G

2018-01-15

Although fixed-time artificial insemination (FTAI) protocols are available for sheep, estrus resynchronization has not been previously reported. The objectives of this study were to evaluate the effect of estrus resynchronization with exogenous progestogen on endogenous progesterone levels and to compare pregnancy rates after two consecutive estrus synchronizations in ewes. In Experiment 1, ewes (n = 20) received an intravaginal device (IVD) containing 60 mg medroxyprogesterone acetate (MPA) for 10 days. At the IVD withdrawal (D0), ewes received 250 IU eCG and were allocated into two treatments: either no further treatment (Control; n = 10) or estrus resynchronization (Resynch; n = 10) from D12 to D19. Serum progesterone (P4) levels did not differ at D12 and D19 (P > 0.05), but were greater at D15 for the Control compared with the Resynch group (P < 0.05). In experiment 2, ewes (n = 250) were submitted to a first synchronization protocol followed by estrus detection and either artificial insemination (AI) or natural mating (NM). Subsequently, ewes were divided into two groups: Control (n = 104): which received no further treatment and were bred by NM; and Resynch (n = 146): which were submitted to a second synchronization starting on D14 (first IVD withdrawal = D0) and to NM after second IVD withdrawal (D20). Cumulative pregnancy rates did not differ between the Control (67.3%, 70/104) and Resynch (62.3%, 91/146) groups. In a third experiment, ewes (n = 83) were bred by two consecutive FTAI within a 20-day interval. Pregnancy rates after the first (30.1%, 25/83) and the second FTAI (36.2%, 21/58) did not differ (P > 0.05). In conclusion, although exogenous progestogen supplementation reduced circulating levels of P4, pregnancy maintenance was unaffected. Estrus resynchronization in ewes is feasible, resulting in similar fertility after the first and the second services. The use of resynchronization coupled with artificial insemination using semen from genetically superior rams may potentially accelerate genetic improvement in sheep herds by allowing a higher differential selection compared with natural breeding. Copyright © 2017 Elsevier Inc. All rights reserved.

Activity of binary mixtures of drospirenone with progesterone and 17α-ethinylestradiol in vitro and in vivo.

PubMed

Rossier, Nadine Madeleine; Chew, Geraldine; Zhang, Kun; Riva, Francesco; Fent, Karl

2016-05-01

Despite potential exposure of aquatic organisms to mixtures of steroid hormones, very little is known on their joint activity in fish. Drospirenone (DRS) is a new synthetic progestin used in contraceptive pills in combination with 17α-ethinylestradiol (EE2). Here we systematically analyzed effects of DRS in binary mixtures with progesterone (P4) and EE2. First, we determined the in vitro activity of single compounds in recombinant yeast assays that express the human progesterone, androgen, or estrogen receptor, followed by determination of mixture activities of DRS and P4, DRS and EE2, as well as medroxyprogesterone acetate (MPA) and dydrogesterone (DDG). Mixtures of DRS and P4, as well as of DRS and EE2 showed additive progestogenic and androgenic activities. However, DDG and MPA showed non-additive progestogenic and androgenic activities. We then analyzed the in vivo activity of single compounds and mixtures of DRS and P4, as well as DRS and EE2, by assessing transcriptional changes of up to 14 selected target genes in zebrafish embryos at 48h post fertilization (hpf), and in eleuthero-embryos at 96hpf and 144hpf. DRS, P4, and EE2 led to significant transcriptional alteration of genes, including those encoding hormone receptors (pgr, esr1), a steroidogenic enzyme (hsd17b3), and estrogenic markers (vtg1, cyp19b), in particular at 144 hpf. In general, DRS showed stronger transcriptional changes than P4. In mixtures of DRS and P4, they were mainly non-additive (antagonistic interaction). In mixtures of DRS and EE2, transcriptional responses of esr1, vtg1 and cyp19b were dominated by EE2, suggesting an antagonistic interaction or independent action. Equi-effective mixtures of DRS and EE2, based on progesterone receptor transcripts, showed antagonistic interactions. Our data suggest that interactions in mixtures assessed in vitro in recombinant yeast cannot be translated to the in vivo situation. The receptor-based responses did not correspond well to the transcriptional responses in embryos which are much more complex due to the interplay between hormonal pathways, receptor crosstalk, and hormonal feedback loops. Copyright © 2016 Elsevier B.V. All rights reserved.

Female gonadal hormones and reproductive behaviors as key determinants of successful reproductive output of breeding whooping cranes (Grus americana)

USGS Publications Warehouse

Brown, Megan E; Converse, Sarah J.; Chandler, Jane N.; Shafer, Charles; Brown, Janine L; Keefer, Carol L; Songsasen, Nucharin

2016-01-01

Reproductive success of endangered whooping cranes (Grus americana) maintained ex situ is poor. As part of an effort to identify potential causes of poor reproductive success in a captive colony, we used non-invasive endocrine monitoring to assess gonadal and adrenal steroids of bird pairs with various reproductive outcomes and evaluated the relationships of hormones and behaviors to reproductive performance. Overall, reproductively successful (i.e., egg laying) females had significantly higher mean estrogen levels but lower mean progestogen concentrations than did unsuccessful females. Other hormones, including glucocorticoids and androgens, were not significantly different between successful and unsuccessful individuals. Observations of specific behaviors such as unison calling, marching, and the number of copulation attempts, along with overall time spent performing reproductive behaviors, were significantly higher in successful pairs. Our findings indicate that overall reproductive performance of whooping crane pairs is linked to female gonadal hormone excretion and reproductive behaviors, but not to altered adrenal hormone production.

Unanswered questions on ectopic pregnancy.

PubMed

Jonas, E G

1980-07-19

In a previous article (3 May, p. 1127), the British Medical Journal attempted to assess the demography of ectopic pregnancy and noted that a rise in incidence might lead to a better diagnosis of the condition. Cited as possible causes of ectopic pregnancy are pelvic sepsis and IUD usage. There is clinical confirmation of the relationship between pelvic sepsis and IUD usage. A review of the records of 325 consecutive patients diagnosed as having ectopic pregnancy in 4 large London Hospitals during the period 1967-79 revealed that PID (Pelvic Inflammatory Disease) was uncommon (11%). 12% of the remaining patients had IUDs and a further 2% were progestogen-only contraceptive failures. As regards the role of IUDs in ectopic pregnancy, failed intrauterine contraception is hypothesized to result in pregnancy, but with an incidence of ectopic, mainly tubal, implantation by reasons of disturbed ovum migration along the oviduct. The physiology of the human oviduct is not well known. Further research should be done on the many common aberations of human reproduction, iatrogenic and spontaneous.

Contraceptive options for women with premenstrual dysphoric disorder: current insights and a narrative review

PubMed Central

Lete, Iñaki; Lapuente, Oihane

2016-01-01

Premenstrual syndrome and its most severe form, premenstrual dysphoric disorder (PMDD), are two well-defined clinical entities that affect a considerable number of women. Progesterone metabolites and certain neurotransmitters, such as gamma-aminobutyric acid and serotonin, are involved in the etiology of this condition. Until recently, the only treatment for women with PMDD was psychoactive drugs, such as selective serotonin reuptake inhibitors. Several years ago, there has been evidence of the beneficial role of combined hormonal contraceptives in controlling PMDD symptoms. Oral combined hormonal contraceptives that contain drospirenone in a 24+4-day regimen are the only drugs that have been approved by US Food and Drug Administration for the treatment of PMDD, but there is scientific evidence that other agents, with other formulations and regimens, could also be effective for the treatment of this condition. However, it remains unclear whether the beneficial effect of combined hormonal contraceptives is associated with the type of estrogen or progestogen used or the treatment regimen. PMID:29386943

Female gonadal hormones and reproductive behaviors as key determinants of successful reproductive output of breeding whooping cranes (Grus americana).

PubMed

Brown, Megan E; Converse, Sarah J; Chandler, Jane N; Shafer, Charles; Brown, Janine L; Keefer, Carol L; Songsasen, Nucharin

2016-05-01

Reproductive success of endangered whooping cranes (Grus americana) maintained ex situ is poor. As part of an effort to identify potential causes of poor reproductive success in a captive colony, we used non-invasive endocrine monitoring to assess gonadal and adrenal steroids of bird pairs with various reproductive outcomes and evaluated the relationships of hormones and behaviors to reproductive performance. Overall, reproductively successful (i.e., egg laying) females had significantly higher mean estrogen levels but lower mean progestogen concentrations than did unsuccessful females. Other hormones, including glucocorticoids and androgens, were not significantly different between successful and unsuccessful individuals. Observations of specific behaviors such as unison calling, marching, and the number of copulation attempts, along with overall time spent performing reproductive behaviors, were significantly higher in successful pairs. Our findings indicate that overall reproductive performance of whooping crane pairs is linked to female gonadal hormone excretion and reproductive behaviors, but not to altered adrenal hormone production. Published by Elsevier Inc.

Simultaneous total occlusion of two coronary arteries associated with use of drospirenone-ethinyl estradiol (oral contraceptive).

PubMed

Atmaca, Hüsnü; Köprülü, Diyar; Kiriş, Tuncay; Zeren, Gönül; Şahin, İrfan

2018-01-01

Although the use of oral contraceptives is associated with an increased risk of venous thromboembolic disease, the risk of myocardial infarction (MI) is unclear. A new, third-generation contraceptive agent, drospirenone-ethinyl estradiol, which contains less estrogen and a new progestogen, drospirenone, in a different combination, has been considered more reliable in terms of risk of MI. However, there have been some cases of MI associated with the use of drospirenone-ethinyl estradiol, despite the protective effects of this oral contraceptive. In this report, a 33-year-old woman who had used drospirenone-ethinyl estradiol for 6 months was admitted with MI and symptoms of cardiogenic shock. Coronary angiography revealed the total occlusion of 2 coronary arteries and so percutaneous coronary intervention was performed. To the best of our knowledge, this is the first case report of simultaneous total occlusion of 2 coronary arteries associated with the use of drospirenone-ethinyl estradiol in the English-language medical literature.

Vaginal mucus from ewes treated with progestogen sponges affects quality of ram spermatozoa.

PubMed

Manes, Jorgelina; Ríos, Glenda; Fiorentino, María Andrea; Ungerfeld, Rodolfo

2016-03-15

The use of intravaginal sponges (IS) to synchronize estrous onset in ewes provokes vaginitis, an increase in the vaginal bacterial load, and growth of bacterial species that are not present during spontaneous estrous behavior. The objective of the study was to compare the functional sperm parameters after incubating it with mucus collected from the vagina of ewes during spontaneous estrus or estrous synchronized with IS. Pooled spermatozoa were co-incubated with: (1) vaginal mucus collected from ewes in spontaneous estrus; (2) vaginal mucus collected from ewes in estrus pretreated with progestogen-impregnated IS; (3) synthetic mucus; and (4) medium without mucus as a control group. Sperm samples were evaluated after incubating it for 30 and 90 minutes. The number of colony-forming units (CFUs/mL), pH, and osmolality were greater in the mucus collected from ewes treated with IS than from those untreated (P = 0.046; P < 0.0001, and P < 0.0001, respectively). The percentage of sperm with progressive motility was lower after incubation with vaginal mucus collected from estrous ewes treated with IS than in the other three treatments both, 30 and 90 minutes after incubation (P = 0.0009 and P < 0.0001, respectively). The sample incubated for 30 minutes with mucus from ewes treated with IS had a lower percentage of sperm with intact plasma membrane than all the other treatments (P < 0.0001). The percentage of sperm with functional membrane was significantly lower in the sample incubated for 30 minutes with vaginal mucus from ewes treated with IS than in the other three treatments (P < 0.0001). After 90 minutes, the percentage was still lower than that in the sample collected from ewes during their spontaneous estrus (P = 0.0005). The lowest percentages of sperm with acrosome damage were observed in sperm incubated with mucus collected from sheep in spontaneous estrus for 30 and 90 minutes (P < 0.0001 and P = 0.008, respectively). The percentage of apoptotic spermatozoa was greater in samples incubated during 30 minutes with vaginal mucus collected from ewes treated with IS than in the other three groups (P = 0.0005). The functionality and the viability of ram sperm is negatively affected by the cervical mucus of ewes pretreated with progestagen-impregnated IS used in estrous synchronization treatments. This may partially explain the decrease in conception rate obtained with treatments with IS. Copyright © 2016 Elsevier Inc. All rights reserved.

Hormone Replacement Therapy: Will it affect seizure control and AED levels?

PubMed Central

Harden, Cynthia L.

2008-01-01

Interest in the years of reproductive changes for women with epilepsy (WWE), specifically perimenopause, menopause and postmenopause has been emerging in the epilepsy community. This article discusses evidence for changes in seizure frequency during perimenopause and postmenopause. Further, a catamenial epilepsy pattern during the reproductive years may be a hallmark for the observed seizure frequency change during these years; that is, an increase at perimenopause but a decrease at menopause. This finding implies that a subset of WWE are particularly susceptible to endogenous reproductive hormonal changes. An adverse effect on seizure frequency with the use of hormone replacement therapy (HRT) during postmenopause for WWE was reported in questionnaires, and was later borne out in a clinical trial. The laboratory counterpart of this human trial, HRT in ovariectomized rodent seizure models, shows that estrogen and progesterone are neuroprotective and do not uniformly increase seizure frequency. Possible reasons for the discrepancy between “the lab and the clinic” are presented. Strategies for managing HRT in symptomatic postmenopausal WWE using estrogenic and progestogenic compounds that may be less likely to promote seizures are discussed. PMID:18187348

Update on the male hormonal contraceptive agents.

PubMed

Walton, Melanie; Anderson, Richard A

2004-09-01

There remains a need for new acceptable and effective male contraceptives to increase the choice for couples throughout the world. There have been no recent advances in available male contraceptive methods although a number of promising approaches have been identified, of which the hormonal approach is currently undergoing clinical investigation. In recent years the pace of research in this area has quickened significantly with increasing interest and now investment by the pharmaceutical industry. This is vital if the work undertaken so far by the public sector is to be transformed into a commercial reality. The hormonal approach is based on suppression of pituitary gonadotropin secretion resulting in a reversible reduction in spermatogenesis with azoospermia in all men being the ultimate aim. Without stimulation by luteinising hormone from the pituitary, testicular testosterone production also ceases. Therefore, androgen administration to restore physiological levels is an essential component of all male hormonal contraceptive regimes. Male hormonal contraceptives can consist of testosterone alone, or either a progestogen or gonadotropin-releasing hormone antagonist with 'add-back' testosterone. This article reviews the current state of progress in this field.

Bridging progestogens in pregnancy and pregnancy prevention

PubMed Central

Micks, Elizabeth; Raglan, Greta B; Schulkin, Jay

2015-01-01

Steroid hormones have been in use for more than a half a century as contraceptive agents, and only now are researchers elucidating the biochemical mechanisms of action and non-target effects. Progesterone and synthetic progestins, critical for women's health in the US and internationally, appear to have important effects on immune functioning and other diverse systems. Apart from the contraceptive world is a separate field that is devoted to understanding progesterone in other contexts. Based on research following a development timeline parallel to hormonal contraception, progesterone and 17-hydroxyprogesterone caproate are now administered to prevent preterm birth in high-risk pregnant women. Preterm birth researchers are similarly working to determine the precise biochemical actions and immunological effects of progesterone. Progesterone research in both areas could benefit from increased collaboration and bringing these two bodies of literature together. Progesterone, through actions on various hormone receptors, has lifelong importance in different organ systems and researchers have much to learn about this molecule from the combination of existing literatures, and from future studies that build on this combined knowledge base. PMID:26581227

Oral contraceptives and the prothrombin time.

PubMed

Pangrazzi, J; Roncaglioni, M C; Donati, M B

1980-02-02

Dr. De Teresa and others reported that mean prothrombin time ratio of 12 patients on long-term anticoagulation with warfarin was significantly higher when they were also taking oral contraceptives (OCs). A study of prothrombin complex activity was recently conducted in female rats treated with an estrogen-progestogen combination (lynestrenol 5 mg; mestranol 0.3 mg/kg body weight) which resulted in a 100% infertility in this species. After 1 treatment for only 1 estral cycle, OC-treated rats had a significantly longer Normotest clotting time (37.7+ or-0.5 sec) than control rats (31.0+or-0.4); the difference was even more notable after 10 cycles. Although this finding has not been reported in women on OCs, it may be that the estrogen-induced "lability" of the prothrombin complex occurs in humans only in special conditions, such as anticoagulation. Alternatively, liver dysfunction occurring among women on OCs may be responsible for reduced metabolism of warfarin, contributing to the effectiveness of the anticoagulation. Further pharmacology studies should be done to clarify the interaction between OCs and oral anticoagulants.

The impact of dydrogesterone supplementation on hormonal profile and progesterone-induced blocking factor concentrations in women with threatened abortion.

PubMed

Kalinka, Jarosław; Szekeres-Bartho, Julia

2005-04-01

The therapeutic value of progestogens in threatened abortion is still under debate. In the presence of sufficient progesterone levels during pregnancy, lymphocytes synthesize a mediator [progesterone-induced blocking factor (PIBF)] that is anti-abortive in mice. The aim of this study was to evaluate the effect of dydrogesterone on pregnancy outcome of threatened aborters. Twenty-seven threatened aborters were treated for 10 days with dydrogesterone (30-40 mg/day). Sixteen healthy pregnant controls received no treatment. Serum progesterone and estradiol concentrations as well as urine PIBF concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Pregnancy outcomes in dydrogesterone-treated threatened aborters did not statistically differ from those in healthy controls. Serum progesterone concentrations in control patients, but not those in threatened aborters increased as pregnancy progressed. Following dydrogesterone treatment, initially low PIBF concentrations of threatened aborters significantly increased (P = 0.001) to reach the PIBF level found in healthy controls. These data suggest that by inducing PIBF production, dydrogesterone might improve pregnancy success rates in threatened aborters. Copyright 2005 Blackwell Munksgaard.

A possible role of progesterone receptor in mouse oocyte in vitro fertilization regulated by norethisterone and its reduced metabolite.

PubMed

Flores-Herrera, Héctor; Díaz-Cervantes, Paola; De la Mora, Gustavo; Zaga-Clavellina, Verónica; Uribe-Salas, Felipe; Castro, Ivone

2008-12-01

The contraceptive effect of the progestogen norethisterone (NET) and its main metabolites 5alpha-NET and 3beta,5alpha-NET has been demonstrated in several species, and most studies have focused on the effects of these compounds in the uterus. We previously reported that 5alpha-NET inhibits the progesterone (P(4))-induced acrosome reaction in pig and mouse spermatozoa and induces severe morphological damage in two-cell fertilized mouse oocytes. The main goal of this study was to analyze the possible role of P(4) receptor (PR) in the effects of NET and 5alpha-NET on the oocyte fertilization process. Different steroid treatments were used with or without cumulus-enclosed oocytes. It was demonstrated that NET increases the percentage of fertilized oocytes in the same manner as P(4) does, while 5alpha-NET reduces the percentage of fertilized oocytes. This effect was not reversed by P(4) in the same concentrations. A possible molecular mechanism for the effects of 5alpha-NET may be through a PR localized in the oocyte plasma membrane.

Dydrogesterone does not reverse the cardiovascular benefits of percutaneous estradiol.

PubMed

Kuba, V M; Teixeira, M A M; Meirelles, R M R; Assumpção, C R L; Costa, O S

2013-02-01

To evaluate the influence of dydrogesterone on estimated cardiovascular risk of users of hormone replacement therapy (HRT) (with percutaneous 17β-estradiol in monotherapy and in combination with dydrogesterone) and HRT non-users through the Framingham score tool for a period of 2 years. Framingham scores were calculated from the medical records of patients treated for at least 2 years with 17β-estradiol alone or in combination with dydrogesterone, along with HRT non-users, through the analysis of patient medical records, followed for at least 2 years at Instituto Estadual de Diabetes e Endocrinologia Luiz Capriglione. Improvements in lipid profile, glucose and blood pressure levels, which reduced the estimated cardiovascular risk, were observed in the 17β-estradiol group. Similar changes were observed in the users of 17β-estradiol + dydrogesterone, suggesting that this progestogen does not attenuate the effects caused by 17β-estradiol. Both HRT groups showed a reduction in their Framingham score. In contrast to data from other HRT investigations on cardiovascular risk, these formulations proved to be safe, even in the first year of use.

Why use of dienogest for the first contraceptive pill with estradiol?

PubMed

Mueck, Alfred O; Seeger, Harald; Bühling, Kai J

2010-02-01

Dienogest (DNG) has the essential properties of an effective progestogen for use in a new contraceptive pill using estradiol valerate as estrogenic component -- it inhibits ovulation and protects against endometrial proliferation. DNG is a derivative of norethisterone (NET), but has a cyanomethyl- instead of an ethinyl-group in C17 position which may offer a variety of benefits regarding hepatic effects. The similarity to NET is reflected in the high endometriotropy and in similar pharmacokinetics like short plasma half-live and high bioavailability. However, DNG also elicits properties of progesterone derivatives like neutrality in metabolic and cardiovascular system and considerable antiandrogenic activity, the latter increased by lack of binding to SHBG as specific property of DNG. It has no glucocorticoid and antimineralocorticoid activity and has no antiestrogenic activity with the consequence that possible beneficial estradiol effects should not be antagonized. This may be of special importance for the tolerability and safety of the first pill with estradiol valerate instead of ethinylestradiol, although well-designed postmarketing studies are still ongoing to demonstrate what can be expected on the basis of pharmacology.

Dysmenorrhoea.

PubMed

Latthe, Pallavi Manish; Champaneria, Rita

2014-10-21

Dysmenorrhoea may begin soon after the menarche, after which it often improves with age; or it may originate later in life, after the onset of an underlying causative condition. Dysmenorrhoea is common, and in up to 20% of women it may be severe enough to interfere with daily activities. We conducted a systematic review and aimed to answer the following clinical question: What are the effects of pharmacological treatments for primary dysmenorrhoea? We searched: Medline, Embase, The Cochrane Library, and other important databases up to December 2013 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We found eight studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. In this systematic review, we present information relating to the effectiveness and safety of the following interventions: contraceptives (combined oral), non-steroidal anti-inflammatory drugs (NSAIDs), progestogens (intrauterine), and simple analgesics (aspirin, paracetamol) .

Action against contraceptive implant threatened.

PubMed

Dyer, C

1995-08-19

Norplant provides contraception over a five-year period through the gradual subcutaneous release of the progestogen levonorgestrel. It has been on the US market since 1991 and available in Great Britain since 1993. Already the subject of group legal actions in several US states, Norplant may soon be the target of lawyers in Britain for litigation. The lawyers allege that insertion of the implant under the skin of the upper arm by untrained doctors has led to painful and difficult removals and left women with scarred arms. Moreover, insufficient warning has been given about possible side effects such as mood swings and continuous vaginal bleeding. Hoechst Roussel, marketer of the implant in Britain, however, argues that only doctors trained in Norplant insertion and removal should attempt either procedure. Removal will be problematic only if preceded by a problem insertion. Hoechst Roussel recently advised gynecologists, in writing, not to attempt to extract the implant unless they are trained in the removal technique. By British law, the application of a drug product once approved for general release to general practitioners and family planning doctors cannot be restricted by a pharmaceutical company.

Effects of contraceptive agents on drug metabolism in various animal species.

PubMed Central

Briatico, G; Guiso, G; Jori, A; Ravazzani, C

1976-01-01

The effect on liver microsomal enzyme activity of three steroid contraceptive drug (SCD) combinations was compared in rats, mice and guinea-pigs. Lynestrenol plus mestranol, norethisterone plus mestranol and norethynodrel plus mestranol were given orally for 4 consecutive days (acute treatment) or 30 days (chronic treatment) at various doses eliciting an experimentally controlled antifertility activity which varied in its extent. In rats and mice all the combined treatments (with the exception of norethynodrel plus mestranol in mice) were active as inducers of liver microsomal enzymes. This induction seems to be mediated mainly by the progestogenic compounds. Oestrogens showed a very poor effect bordering on significance only in a few cases. No effect on liver microsomal protein or cytochrome P 450 concentration was obtained after treatment with doses capable of increasing the microsomal enzyme activity. The activity of the liver microsomal enzymes did not appear to be reduced immediately (2 h) after the last administration of the SCD given during 4 or 30 days. Contraceptive treatments at doses capable of eliciting complete antifertility activity were inactive on liver microsomal enzyme activity in guinea-pigs. PMID:987822

Current understanding on pharmacokinetics, clinical efficacy and safety of progestins for treating pain associated to endometriosis.

PubMed

Barra, Fabio; Scala, Carolina; Ferrero, Simone

2018-04-01

Endometriosis is a chronic estrogen and progestogen responsive inflammatory disease associated with pain symptoms and infertility. The medical therapy of endometriosis aims to induce decidualization within the hormonally dependent ectopic endometrium, and it is often administered to ameliorate women' pain symptoms or to prevent post-surgical disease recurrence. A variety of progestins have been used in monotherapy for the medical management of women with endometriosis. Areas covered: This review aims to offer the reader a complete overview of pharmacokinetic (PK) and clinical efficacy of progestins for the treatment of endometriosis. Expert opinion: Each progestin has a distinct PK parameters and pharmacodynamics affinity not only for progesterone receptor, but also for other steroid receptors, such as estrogen, androgen, and glucocorticoid. Moreover, progestins can also be delivered in different formulations. All these characteristics influence their final biological effect. Randomized, controlled, non-blinded studies support the use of oral progestin-only treatment for pelvic pain associated with endometriosis. Currently, the only two progestins approved by Food and Drug Administration (FDA) for the treatment of endometriosis are norethindrone acetate (NETA) and depot medroxyprogesterone acetate (DMPA).

The consequences of exposure to mixtures of chemicals: Something from 'nothing' and 'a lot from a little' when fish are exposed to steroid hormones.

PubMed

Thrupp, Tara J; Runnalls, Tamsin J; Scholze, Martin; Kugathas, Subramaniam; Kortenkamp, Andreas; Sumpter, John P

2018-04-01

Ill-defined, multi-component mixtures of steroidal pharmaceuticals are present in the aquatic environment. Fish are extremely sensitive to some of these steroids. It is important to know how fish respond to these mixtures, and from that knowledge develop methodology that enables accurate prediction of those responses. To provide some of the data required to reach this objective, pairs of fish were first exposed to five different synthetic steroidal pharmaceuticals (one estrogen, EE2; one androgen, trenbolone; one glucocorticoid, beclomethasone dipropionate; and two progestogens, desogestrel and levonorgestrel) and concentration-response data on egg production obtained. Based on those concentration-response relationships, a five component mixture was designed and tested twice. Very similar effects were observed in the two experiments. The mixture inhibited egg production in an additive manner predicted better by the model of Independent Action than that of Concentration Addition. Our data provide a reference case for independent action in an in vivo model. A significant combined effect was observed when each steroidal pharmaceutical in the mixture was present at a concentration which on its own would produce no statistically significant effect (something from 'nothing'). Further, when each component was present in the mixture at a concentration expected to inhibit egg production by between 18% (Beclomethasone diproprionate) and 40% (trenbolone), this mixture almost completely inhibited egg production: a phenomenon we term 'a lot from a little'. The results from this proof-of-principle study suggest that multiple steroids present in the aquatic environment can be analysed for their potential combined environmental risk. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Challenges and Opportunities for Testing Students Who Are Deaf or Hard of Hearing: Information for Educators on Creating Test Equity. Test Equity Considerations: Schools

ERIC Educational Resources Information Center

PEPNet-West, 2010

2010-01-01

For most students, test taking is a challenge. For students who are deaf or hard of hearing, classroom quizzes, tests, and exams are even more challenging. Standardized tests--The SAT, ACT, state proficiency tests, No Child Left Behind annual tests, and psychoeducational evaluations--present additional challenges for students who are deaf or hard…

Aqueous exposure to the progestin, levonorgestrel, alters anal fin development and reproductive behavior in the eastern mosquitofish (Gambusia holbrooki)

USGS Publications Warehouse

Frankel, Tyler E.; Meyer, Michael T.; Orlando, Edward F.

2016-01-01

Endogenous progestogens are important regulators of vertebrate reproduction. Synthetic progestins are components of human contraceptive and hormone replacement pharmaceuticals. Both progestogens and progestins enter the environment through a number of sources, and have been shown to cause profound effects on reproductive health in various aquatic vertebrates. Progestins are designed to bind human progesterone receptors, but they also have been shown to strongly activate androgen receptors in fish. Levonorgestrel (LNG) activates fish androgen receptors and induces development of male secondary sex characteristics in females of other species. Although behavior has been postulated to be a sensitive early indicator of exposure to certain environmental contaminants, no such research on the reproductive behavior of gestagen-exposed fish has been conducted to date. The goal of our study was to examine the exposure effects of a human contraceptive progestin, LNG, on the reproductive development and behavior of the viviparous eastern mosquitofish (Gambusia holbrooki). Internal fertilization is a requisite characteristic of viviparous species, and is enabled by an androgen driven elongation of the anal fin into the male gonopodium (i.e., phallus). In this study, we exposed adult mosquitofish to ethanol (EtOH control), 10 ng/L, and 100 ng/L LNG for 8 d using a static replacement exposure design. After 8 d, a subset of males and females from each treatment were examined for differences in the 4:6 anal fin ratio. In addition, paired social interaction trials were performed using individual control males and control females or females treated 10 ng/L or 100 ng/L LNG. Female mosquitofish exposed to LNG were masculinized as evidenced by the elongation of the anal fin rays, a feature normal to males and abnormal to females. LNG caused significant increases in the 4:6 anal fin ratios of female mosquitofish in both the 10 ng/L and 100 ng/L treatments, although these differences were not significant between the two treatments. LNG caused significant increases in the 4:6 anal fin ratio of males exposed to 100 ng/L, with no effects observed in the 10 ng/L treatment. In addition, the reproductive behavior of control males paired with female mosquitofish exposed to 100 ng/L LNG was also altered, for these males spent more time exhibiting no reproductive behavior, had decreased attending behavior, and a lower number of gonopodial thrusts compared to control males paired to control female mosquitofish. Given the rapid effects on both anal fin morphology and behavior observed in this study, the mosquitofish is an excellent sentinel species for the detection of exposure to LNG and likely other 19-nortestosterone derived contraceptive progestins in the environment.

Vaginal progesterone, but not 17α-hydroxyprogesterone caproate, has antiinflammatory effects at the murine maternal-fetal interface

PubMed Central

Furcron, Amy-Eunice; Romero, Roberto; Plazyo, Olesya; Unkel, Ronald; Xu, Yi; Hassan, Sonia S.; Chaemsaithong, Piya; Mahajan, Arushi; Gomez-Lopez, Nardhy

2016-01-01

OBJECTIVE Progestogen (vaginal progesterone or 17-alpha-hydroxyprogesterone caproate [17OHP-C]) administration to patients at risk for preterm delivery is widely used for the prevention of preterm birth (PTB). The mechanisms by which these agents prevent PTB are poorly understood. Progestogens have immunomodulatory functions; therefore, we investigated the local effects of vaginal progesterone and 17OHP-C on adaptive and innate immune cells implicated in the process of parturition. STUDY DESIGN Pregnant C57BL/6J mice received vaginal progesterone (1 mg per 200 μL, n = 10) or Replens (control, 200 μL, n = 10) from 13 to 17 days postcoitum (dpc) or were subcutaneously injected with 17OHP-C (2 mg per 100 μL, n = 10) or castor oil (control, 100 μL, n = 10) on 13, 15, and 17 dpc. Decidual and myometrial leukocytes were isolated prior to term delivery (18.5 dpc) for immunophenotyping by flow cytometry. Cervical tissues were collected to determine matrix metalloproteinase (MMP)-9 activity by in situ zymography and visualization of collagen content by Masson’s trichrome staining. Plasma concentrations of progesterone, estradiol, and cytokines (interferon [IFN]-γ, interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, KC/GRO, and tumor necrosis factor-α) were quantified by enzyme-linked immunosorbent assays. Pregnant mice pretreated with vaginal progesterone or Replens were injected with 10 μg of an endotoxin on 16.5 dpc (n = 10 each) and monitored via infrared camera until delivery to determine the effect of vaginal progesterone on the rate of PTB. RESULTS The following results were found: (1) vaginal progesterone, but not 17OHP-C, increased the proportion of decidual CD4+ T-regulatory cells; (2) vaginal progesterone, but not 17OHP-C, decreased the proportion of decidual CD8+CD25+Foxp3+ T cells and macrophages; (3) vaginal progesterone did not cause an M1→M2 macrophage polarization but reduced the proportion of myometrial IFNγ+ neutrophils and cervical active MMP-9-positive neutrophils and monocytes; (4) 17OHP-C did not reduce the proportion of myometrial IFNy-positive neutrophils; however, it increased the abundance of cervical active MMP-9-positive neutrophils and monocytes; (5) vaginal progesterone immune effects were associated with reduced systemic concentrations of IL-1β but not with alterations in progesterone or estradiol concentrations; and (6) vaginal progesterone pretreatment protected against endotoxin-induced PTB (effect size 50%, P = .008). CONCLUSION Vaginal progesterone, but not 17OHP-C, has local antiinflammatory effects at the maternal-fetal interface and the cervix and protects against endotoxin-induced PTB. PMID:26264823

Correlation of in vitro challenge testing with consumer use testing for cosmetic products.

PubMed Central

Brannan, D K; Dille, J C; Kaufman, D J

1987-01-01

An in vitro microbial challenge test has been developed to predict the likelihood of consumer contamination of cosmetic products. The challenge test involved inoculating product at four concentrations (30, 50, 70, and 100%) with microorganisms known to contaminate cosmetics. Elimination of these microorganisms at each concentration was followed over a 28-day period. The test was used to classify products as poorly preserved, marginally preserved, or well preserved. Consumer use testing was then used to determine whether the test predicted the risk of actual consumer contamination. Products classified by the challenge test as poorly preserved returned 46 to 90% contaminated after use. Products classified by the challenge test as well preserved returned with no contamination. Marginally preserved products returned with 0 to 21% of the used units contaminated. As a result, the challenge test described can be accurately used to predict the risk of consumer contamination of cosmetic products. PMID:3662517

Diagnosis of penicillin allergy revisited: the value of case history, skin testing, specific IgE and prolonged challenge.

PubMed

Hjortlund, J; Mortz, C G; Skov, P S; Bindslev-Jensen, C

2013-08-01

Skin testing in duplicate, correlation between case history of immediate and nonimmediate reactions and challenge outcome and prolonged oral treatment with penicillin in the diagnostic evaluation of allergic reactions to β-lactam antibiotics, mimicking real-life situations, have only been addressed in few studies. A total of 342 patients suspected of having β-lactam allergy were investigated according to the European Network for Drug Allergy (ENDA) guidelines and patients found to be negative in the ENDA program were supplemented with a 7-day oral treatment with penicillin. Skin testing with penicillins was performed in duplicate. Patients with case histories of reactions to other β-lactams were also subsequently challenged with the culprit drug. Nineteen patients were IgE-sensitized to penicillin. Then, intracutaneous tests (ICTs) were performed, in which 35 patients tested positive for allergy, 21 with delayed and 14 with immediate reactions. Only three patients tested positive for the major (PPL) and/or minor (MDM) penicillin determinants, all being positive for penicillin G in ICT. The remaining 291 patients were challenged with penicillin: 10 tested positive in single-dose challenge and 23 tested positive in the 7-day challenge. A total of 17 of 78 patients with a negative penicillin challenge tested positive during challenges with other β-lactams. We found no correlation between case histories of immediate and nonimmediate reactions and reaction time during challenge. The data suggest that case history is often insufficient to discriminate between immediate reactors and nonimmediate reactors. A 7-day challenge with the culprit β-lactam may yield more positive reactions than the accepted one- or 2-day challenge. Interpretation of skin testing should be made with caution. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Testing Scientific Software: A Systematic Literature Review.

PubMed

Kanewala, Upulee; Bieman, James M

2014-10-01

Scientific software plays an important role in critical decision making, for example making weather predictions based on climate models, and computation of evidence for research publications. Recently, scientists have had to retract publications due to errors caused by software faults. Systematic testing can identify such faults in code. This study aims to identify specific challenges, proposed solutions, and unsolved problems faced when testing scientific software. We conducted a systematic literature survey to identify and analyze relevant literature. We identified 62 studies that provided relevant information about testing scientific software. We found that challenges faced when testing scientific software fall into two main categories: (1) testing challenges that occur due to characteristics of scientific software such as oracle problems and (2) testing challenges that occur due to cultural differences between scientists and the software engineering community such as viewing the code and the model that it implements as inseparable entities. In addition, we identified methods to potentially overcome these challenges and their limitations. Finally we describe unsolved challenges and how software engineering researchers and practitioners can help to overcome them. Scientific software presents special challenges for testing. Specifically, cultural differences between scientist developers and software engineers, along with the characteristics of the scientific software make testing more difficult. Existing techniques such as code clone detection can help to improve the testing process. Software engineers should consider special challenges posed by scientific software such as oracle problems when developing testing techniques.

Testing Scientific Software: A Systematic Literature Review

PubMed Central

Kanewala, Upulee; Bieman, James M.

2014-01-01

Context Scientific software plays an important role in critical decision making, for example making weather predictions based on climate models, and computation of evidence for research publications. Recently, scientists have had to retract publications due to errors caused by software faults. Systematic testing can identify such faults in code. Objective This study aims to identify specific challenges, proposed solutions, and unsolved problems faced when testing scientific software. Method We conducted a systematic literature survey to identify and analyze relevant literature. We identified 62 studies that provided relevant information about testing scientific software. Results We found that challenges faced when testing scientific software fall into two main categories: (1) testing challenges that occur due to characteristics of scientific software such as oracle problems and (2) testing challenges that occur due to cultural differences between scientists and the software engineering community such as viewing the code and the model that it implements as inseparable entities. In addition, we identified methods to potentially overcome these challenges and their limitations. Finally we describe unsolved challenges and how software engineering researchers and practitioners can help to overcome them. Conclusions Scientific software presents special challenges for testing. Specifically, cultural differences between scientist developers and software engineers, along with the characteristics of the scientific software make testing more difficult. Existing techniques such as code clone detection can help to improve the testing process. Software engineers should consider special challenges posed by scientific software such as oracle problems when developing testing techniques. PMID:25125798

New protocol of clomiphene citrate treatment in women with hypothalamic amenorrhea.

PubMed

Borges, Lavinia Estrela; Morgante, Giuseppe; Musacchio, Maria Concetta; Petraglia, Felice; De Leo, Vincenzo

2007-06-01

To determine if a new protocol of administration of clomiphene citrate (CC) is effective in menstrual cycle recovery in women with hypothalamic secondary amenorrhea. This was an open-label study. Patients comprised a group of eight women with secondary amenorrhea. Interventions. An oral preparation containing CC (50 mg/day) was administered for 5 days followed by a double dose (100 mg/day) for another 5 days, initiated on day 3 after estrogen/progestogen-induced withdrawal bleeding. If ovulation and vaginal bleeding occurred, treatment continued in the two next months with 100 mg/day from day 3 to day 7 day of the cycle. Cycle control was evaluated at each visit, when patients recorded bleeding patterns and tablet intake. Data on the intensity and duration of bleeding were collected. Six patients responded to the first cycle of CC administration, resuming normal menstrual cycles. The other two patients failed to menstruate after the first 10 days of treatment with CC and repeated the same protocol. After the second administration, these two women also had normal menstrual bleeding. The present data show that this new protocol of CC treatment may be useful to restore normal menstrual cycles in young women with hypothalamic amenorrhea.

Advances in pharmacologic strategies for cancer cachexia.

PubMed

Madeddu, Clelia; Mantovani, Giovanni; Gramignano, Giulia; Macciò, Antonio

2015-01-01

Cancer cachexia is a severe inflammatory metabolic syndrome accounting for fatigue, an impairment of normal activities and, eventually, death. The loss of muscle mass associated with body weight loss is the main feature of this syndrome. The present review aims to describe the advances in the pharmacological approaches for cancer cachexia, highlighting the impact on weight loss, muscle wasting and related outcomes. Among the pharmacological agents, attention should yet be given to the currently most widely studied drugs, such as progestogens and NSAIDs. Emerging drugs, such as ghrelin and selective androgen receptor modulators, have obtained promising results in recent randomized clinical trials. Larger sample sizes and more robust data on the effectiveness of anti-cytokine agents are needed. Any pharmacological approach to counteract cancer cachexia should always be associated with an adequate caloric intake, obtained by diet or through enteral or parenteral supplementation, if indicated. Finally, we can currently state that a combined approach that simultaneously targets the fundamental pathways involved in the pathogenesis of cancer cachexia is likely to be the most effective in terms of improvements in body weight as well as muscle wasting, function, physical performance and quality of life.

Mini-pill in lactating women.

PubMed

Canto, T E; Vera, L; Polanco, L E; Colven, C E

1989-06-01

A non-comparative study of the progestogen-only oral contraceptive, norgestrel 0.075 mg, in breast-feeding women was conducted at the Centro de Investigaciones Regionales, Merida, Yucatan, Mexico. The study was designed to evaluate the overall acceptability and contraceptive efficacy of norgestrel in breast-feeding women. This report includes a survey of 200 women, all of whom were less than 26 weeks postpartum at admission; 113 were interval patients and 87 were postpartum. Follow-up visits were scheduled at 2, 6 and 12 months after admission. Overall, women experienced an increase in intermenstrual bleeding, amenorrhea, vaginal discharge and breast discomfort. The discontinuation rate at 12 months was 32.5 and the corresponding lost to follow-up rate was 22.5; this is a measure of acceptability. The 12-month life-table rate for pregnancy was 3.4 with a standard error of 2.0. Three women discontinued use of the mini-pill due to accidental pregnancy. One pregnancy was attributed to user failure and the woman conceived 9 months after entering into the study; the other two were attributed to method failure, one woman conceived 3 months after admission and the other conceived 6 months after admission.

Increased expression of progesterone receptor membrane component 1 is associated with aggressive phenotype and poor prognosis in ER-positive and negative breast cancer.

PubMed

Ruan, Xiangyan; Zhang, Ying; Mueck, Alfred O; Willibald, Marina; Seeger, Harald; Fehm, Tanja; Brucker, Sara; Neubauer, Hans

2017-02-01

Expression of progesterone receptor membrane component 1 (PGRMC1) has been shown to be higher in breast cancer than normal tissue. We have previously shown that certain progestogens strongly stimulate proliferation of breast cancer cells overexpressing PGRMC1, and therefore hypothesize that PGRMC1 may play a critical role in breast cancer progression. Because little information is available if expression of PGRMC1 is also associated with worse prognosis for breast cancer patients, in this study we investigated the clinicopathologic significance of PGRMC1 expression in breast cancer tissue. Expression of PGRMC1 was analyzed by immunohistochemical staining of primary tumor tissues obtained from 69 breast cancer patients. A labeling score was developed, and results were correlated with tumor size, lymph node metastasis, and clinical outcome. Overexpression of PGRMC1 is correlating with larger tumor size and lymph node metastasis. Kaplan-Meier survival curves indicate that patients with PGRMC1 tumors have poorer disease-free and overall survival independent from the estrogen receptor status than breast cancer patients with PGRMC1 tumors. Our findings suggest that the expression of PGRMC1 might be useful for predicting prognosis in patients with breast cancer.

Medroxyprogesterone acetate-treated human, primary endometrial epithelial cells reveal unique gene expression signature linked to innate immunity and HIV-1 susceptibility.

PubMed

Woods, Matthew W; Zahoor, Muhammad Atif; Dizzell, Sara; Verschoor, Chris P; Kaushic, Charu

2018-01-01

Medroxyprogesterone acetate (MPA), a progestin-based hormonal contraceptive designed to mimic progesterone, has been linked to increased human immunodeficiency virus (HIV-1) susceptibility. Genital epithelial cells (GECs) form the mucosal lining of the female genital tract (FGT) and provide the first line of protection against HIV-1. The impact of endogenous sex hormones or MPA on the gene expression profile of GECs has not been comprehensively documented. Using microarray analysis, we characterized the transcriptional profile of primary endometrial epithelial cells grown in physiological levels of E2, P4, and MPA. Each hormone treatment altered the gene expression profile of GECs in a unique manner. Interestingly, although MPA is a progestogen, the gene expression profile induced by it was distinct from P4. MPA increased gene expression of genes related to inflammation and cholesterol synthesis linked to innate immunity and HIV-1 susceptibility. The analysis of gene expression profiles provides insights into the effects of sex hormones and MPA on GECs and allows us to posit possible mechanisms of the MPA-mediated increase in HIV-1 acquisition. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Recommendations for provoked challenge urine testing.

PubMed

Ruha, Anne-Michelle

2013-12-01

"Urine mobilization test," "challenge test," and "provoked urine test" are all terms used to describe the administration of a chelating agent to a person prior to collection of their urine to test for metals. There is no standard, validated challenge test. Despite recommendations by professional and government organizations against the use of provoked urine testing, the tests are still commonly used and recommended by some practitioners. Challenge testing utilizes a variety of chelating agents, including dimercaptosuccinic acid (DMSA), dimercaptopropanesulfonate (DMPS), and ethylenediaminetetraacetic acid (EDTA). The agents are given by a variety of routes of administration, doses used are inconsistent, and urine collection procedures vary. Additional problems with challenge tests include comparison of results to inappropriate reference ranges and creatinine correction of urine obtained within hours of chelator administration. Human volunteer studies demonstrate that mercury is detected in the urine of most people even in the absence of known exposure or chelator administration, and that urinary mercury excretion rises after administration of a chelator, regardless of exposure history and in an unpredictable fashion. Studies also demonstrate that challenge testing fails to reveal a "body burden" of mercury due to remote exposure. Chelating agents have been associated with adverse reactions. Current evidence does not support the use of DMPS, DMSA, or other chelation challenge tests for the diagnosis of metal toxicity. Since there are no established reference ranges for provoked urine samples in healthy subjects, no reliable evidence to support a diagnostic value for the tests, and potential harm, these tests should not be utilized.

In Vitro Gluten Challenge Test for Celiac Disease Diagnosis.

PubMed

Khalesi, Maryam; Jafari, Seyed Ali; Kiani, Mohammadali; Picarelli, Antonio; Borghini, Raffaele; Sadeghi, Ramin; Eghtedar, Alireza; Ayatollahi, Hosein; Kianifar, Hamid R

2016-02-01

The in vitro gluten challenge test is an important diagnostic modality in celiac disease (CD), especially in patients who begin treatment with a gluten-free diet before adequate diagnostic workup or in cases with atypical CD. Available literature was reviewed regarding the accuracy of the in vitro gluten challenge test for CD diagnosis. MEDLINE, Scopus, and Google Scholar were searched, and studies that used serology and bowel biopsy as the criterion standard for diagnosis were included in our study. Data on authors, publication year, characteristics of the patient and control groups, patients' diet, duration of the gluten challenge test, histology findings, endomysial antibody (EMA) and anti-tissue transglutaminase (tTG) levels, CD markers, and intercellular cell adhesion molecule-1, and human leukocyte antigens before and after the gluten challenge test were extracted. Overall, 15 studies were included in this meta-analysis. Pooled sensitivity %/specificity % was 84/99 for EMA after the challenge, 52/96 for EMA without the challenge, 95.5/98.3 for anti-tTG after the challenge, and 95.1/98.3 for anti-tTG without the challenge test. Sensitivity/specificity for immunological markers were 89/97 for the percentage of CD25⁺-lamina propria lymphocytes, 96/91 for the percentage of CD3⁺-lamina propria lymphocytes, and 96.1/85.7 for the percentage of intercellular cell adhesion molecule-1-lamina propria lymphocytes. The factors that increased the sensitivity of EMA were longer test duration, and the evaluation of patients on a gluten-containing diet or short-term gluten-free diet. The in vitro gluten challenge test can be a useful part of the diagnostic workup of CD, rather than only a model to evaluate its mechanisms.

Challenging Tasks: What Happens When Challenging Tasks Are Used in Mixed Ability Middle School Mathematics Classrooms?

ERIC Educational Resources Information Center

Perkins, Karen

2016-01-01

The topics of decimals and polygons were taught to two classes by using challenging tasks, rather than the more conventional textbook approach. Students were given a pre-test and a post-test. A comparison between the two classes on the pre- and post-test was made. Prior to teaching through challenging tasks, students were surveyed about their…

Awareness of Individual Cardiovascular Risk Factors and Self-Perception of Cardiovascular Risk in Women.

PubMed

Monsuez, Jean-Jacques; Pham, Tai; Karam, Nicole; Amar, Laurence; Chicheportiche-Ayache, Corinne; Menasché, Philippe; Desnos, Michel; Dardel, Paul; Weill, Isabelle

2017-09-01

Cardiovascular risk factors (CVRFs) self-perception by women may be inaccurate. A questionnaire was completed anonymously Online by women who self-reported their personal CVRF levels including age, weight, contraceptive use, menopausal status, smoking, diet and physical activities. Self-perceived risk was matched to actual cardiovascular risk according to the Framingham score. Among 5,240 young and middle-aged women with a high educational level, knowledge of personal CVRFs increased with age, from 51-90% for blood pressure (BP), 22-45% for blood glucose and 15-47% for blood cholesterol levels, between 30 and 65 years, respectively. This knowledge was lower for smoking compared with nonsmoking women: 62.5% vs. 74.5% for BP (P < 0.001), 22.7% vs. 33.8% for blood glucose (P < 0.001), 21.9% vs. 32.0% for cholesterol levels (P < 0.001). Knowledge of BP level was reduced among women using an estrogen-progestogen contraception (56.8% vs. 62.1%, P = 0.0031) and even more reduced among smokers (52.2%, P < 0.001). Conversely, women with leisure-time physical or sportive activity (60.5%), were less overweight or obese (22.4% vs. 34.2%, P < 0.001). They reported better knowledge of BP (72.4% vs. 68.3%, P < 0.001), blood cholesterol (31.1% vs. 26.4%, P < 0.001) and glucose levels (32.7% vs. 27.8%, P < 0.001). Self-perceived cardiovascular risk was rated low by 1,279 (20.4%), moderate by 3,710 (63.3%) and high by 893 (16.3%) women. Among 3,386 women tested using the Framingham score, 40.8% were at low, 25.2% at moderate and 33.8% at high risk. Knowledge of CVRFs and self-perception of individual risk are inaccurate in women. Educational interventions should be emphasized. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

A comparative study of Cyclofem and depot medroxyprogesterone acetate (DMPA) effects on endometrial vasculature.

PubMed

Simbar, Masoumeh; Tehrani, Fahimeh Ramezani; Hashemi, Zeinab; Zham, Hananeh; Fraser, Ian S

2007-10-01

The most common reason for discontinuation of long-acting progestogen-only contraceptives is irregular bleeding following local endometrial vascular changes. To reduce unpredictable bleeding episodes among depot medroxyprogesterone acetate (DMPA) users, the combined injectable contraceptive, Cyclofem, was offered as an alternative. However, there is a gap in our knowledge about the effects of Cyclofem on the endometrial vasculature and patterns of bleeding. This study aimed to compare the effects of Cyclofem and DMPA on endometrial vascular density, endometrial histology and pattern of bleeding. Sixty-eight healthy women with regular menstrual bleeding and seeking injectable long-acting contraceptives were recruited. Two endometrial samples (before and 3 to 6 months after initial exposure to DMPA or Cyclofem) were collected from each participant. The samples were stained using an immunohistochemical method and anti-CD34 to visualise the endometrial vasculature. Endometrial vascular density was assessed using standard techniques. Sixty-eight women were randomly assigned to Cyclofem (38 women) or DMPA (30 women). Endometrial vascular density was 149.3 +/- 6.7 (mean +/- SD)/mm(2) before injection. This significantly decreased to 132.4 +/- 12.2 after DMPA use, and from 151.9 +/- 5.8 to 131.8 +/- 12.8 vessels/mm(2) following Cyclofem use (paired t-test, p <0.05). However, there was no significant difference between endometrial vascular density during treatment with Cyclofem or DMPA. Total bleeding days in the first and second 3-month time intervals were 28 +/- 23 and 18 +/- 12 days in DMPA users and 22 +/- 14 and 16 +/- 9 days in Cyclofem users, respectively, Spotting was the most common type of bleeding experienced, and atrophic endometrium was the most common histological pattern observed in both groups. This study demonstrated that both Cyclofem and DMPA use are associated with decreased endometrial vascular density and atrophic endometrium, in addition to irregular bleeding, mainly spotting. There was no significant difference in bleeding patterns or endometrial findings observed for these two injectable contraceptives in Iranian women.

Managing Challenges in a Multi Contractor Project

NASA Technical Reports Server (NTRS)

King, Ron

2011-01-01

The presentation provides a project description, describes the integrated product team, and review project challenges. The challenges include programmatic, technical, basic drop tests, heavy drop tests, C-17 envelope expansion, and Ares I-X.

A retrospective comparison of false negative skin test rates in penicillin allergy, using pencilloyl-poly-lysine and minor determinants or Penicillin G, followed by open challenge.

PubMed

Rosenfield, Lana; Kalicinsky, Chrystyna; Warrington, Richard

2015-01-01

A history of penicillin allergy in patients is common, but only 10-15 % are truly allergic. While the gold standard for diagnosing penicillin allergy is challenge, it is not recommended that this be done without first carrying out diagnostic skin testing. This is carried out with the major determinant benzylpenicilloyl (PPL) and the minor determinant mixture (MDM), consisting of penilloate, penicilloate and Penicillin G. However, since availability of the MDM is limited, Penicillin G alone has been used. A retrospective chart review was carried out on patients tested for penicillin allergy in the Clinical Immunology and Allergy Clinic at the Health Sciences Centre, Winnipeg, Canada between 2005 and 2013. A total of 521 patients charts were reviewed, of whom 240 had skin testing, ImmunoCap(®) for IgE to Penicillin G and V and had oral challenges with penicillin, amoxicillin or cloxacillin. 17/240 (7.5 %) were skin test positive, 8 to PPL, 4 to MDM and 5 to Penicillin G. One was also positive on ImmunoCap(®) testing. Three patients had negative skin tests but weakly positive ImmunoCap(®). 222 patients with negative skin tests and serological tests were challenged. Of these, 12 patients reacted to challenge. Three of the challenges were equivocal. Of the nine patients with definite positive challenges, three were tested with Penicillin G and six with MDM. Therefore the false negative rates for testing were 2.3 % with PPL and Penicillin G and 6.97 % for PPL and MDM. The difference was not significant (p = 0.0856). In this group of patients with a history of penicillin allergy tested with the major determinant of benzyl penicillin and either MDM or Penicillin G, there was no difference in the rate of false negative testing, based on oral penicillin challenges. Therefore, Penicillin G can be safely used as an alternative to MDM in diagnosing penicillin allergy.

Prediction of challenge test results by flour-specific IgE and skin prick test in symptomatic bakers.

PubMed

van Kampen, V; Rabstein, S; Sander, I; Merget, R; Brüning, T; Broding, H C; Keller, C; Müsken, H; Overlack, A; Schultze-Werninghaus, G; Walusiak, J; Raulf-Heimsoth, M

2008-07-01

Wheat and rye flours are among the most important allergens causing occupational asthma. Usually, the diagnosis of baker's asthma is based on inhalation challenge tests with flours. To evaluate the relevance of flour-specific serum immunoglobulin E (IgE) and skin prick test (SPT) in the diagnosis of baker's asthma and to define flour-specific IgE concentrations and wheal sizes that allow a prediction of the outcome of challenge testing. Bronchial and nasal challenge tests with wheat (rye) flour were performed in 71 (95) symptomatic bakers. Determinations of flour-specific IgE as well as SPTs were performed in all subjects. Analyses included the calculation of sensitivity, specificity, positive (PPV) and negative predictive values (NPV) at different IgE concentrations and different wheal sizes, and receiver-operating characteristics (ROC) plots with the challenge result as gold standard. Thirty-seven bakers were positive in the challenge with wheat flour, while 63 were positive with rye flour. Depending on the flour-specific IgE concentrations (wheal size), PPV was 74-100% (74-100%) for wheat and 82-100% (91-100%) for rye flour, respectively. The minimal cut-off values with a PPV of 100% were 2.32 kU/l (5.0 mm) for wheat flour and 9.64 kU/l (4.5 mm) for rye flour. The shapes of the ROC plots were similar for wheat and rye flour. High concentrations of flour-specific IgE and clear SPT results in symptomatic bakers are good predictors for a positive challenge test. Challenge tests with flours may be avoided in strongly sensitized bakers.

Skin testing and oral penicillin challenge in patients with a history of remote penicillin allergy.

PubMed

Goldberg, Arnon; Confino-Cohen, Ronit

2008-01-01

Penicillin administration is usually contraindicated in penicillin-allergic patients with positive skin test results. To examine whether penicillin oral challenge for patients with a history of remote non-life-threatening allergic reaction to penicillin can be well tolerated irrespective of skin test results. In a prospective open-label trial, 8,702 individuals were screened between November 1998 and January 2000. Of 687 patients with a non-life-threatening allergic reaction to penicillin, occurring longer than 3 years earlier, 169 were enrolled. Regardless of the response to penicillin skin testing, patients received the usual 1-day dosage of penicillin and amoxicillin, on 2 separate occasions. Two to 6 years later, a follow-up was conducted to assess the outcomes of further penicillin administration. A total of 272 combined skin tests and oral challenges were performed on 169 patients. Among 137 challenges with a positive skin test result and 135 patients with a negative skin test result, 9 (6.6%) and 5 (3.7%) (P = .29), respectively, developed a mild rash to oral challenge. At follow-up, 2 to 6 years afterward, 3 of 55 patients (5.5%) who were given a full treatment course of penicillin developed a mild skin eruption. Positive penicillin skin test results for patients with a remote history of non-life-threatening allergic reaction to penicillin were not associated with a greater prevalence of adverse reactions to oral challenge with penicillin than negative results. Because skin testing is considered the gold standard and the safest method for predicting tolerance to penicillin administration, oral penicillin challenge may be used as a diagnostic method only in these specific patients when skin testing is not feasible.

A synthetic kisspeptin analog that triggers ovulation and advances puberty

PubMed Central

Decourt, C.; Robert, V.; Anger, K.; Galibert, M.; Madinier, J.-B.; Liu, X.; Dardente, H.; Lomet, D.; Delmas, A. F.; Caraty, A.; Herbison, A. E.; Anderson, G. M; Aucagne, V.; Beltramo, M.

2016-01-01

The neuropeptide kisspeptin and its receptor, KiSS1R, govern the reproductive timeline of mammals by triggering puberty onset and promoting ovulation by stimulating gonadotrophin-releasing hormone (GnRH) secretion. To overcome the drawback of kisspeptin short half-life we designed kisspeptin analogs combining original modifications, triazole peptidomimetic and albumin binding motif, to reduce proteolytic degradation and to slow down renal clearance, respectively. These analogs showed improved in vitro potency and dramatically enhanced pharmacodynamics. When injected intramuscularly into ewes (15 nmol/ewe) primed with a progestogen, the best analog (compound 6, C6) induced synchronized ovulations in both breeding and non-breeding seasons. Ovulations were fertile as demonstrated by the delivery of lambs at term. C6 was also fully active in both female and male mice but was completely inactive in KiSS1R KO mice. Electrophysiological recordings of GnRH neurons from brain slices of GnRH-GFP mice indicated that C6 exerted a direct excitatory action on GnRH neurons. Finally, in prepubertal female mice daily injections (0.3 nmol/mouse) for five days significantly advanced puberty. C6 ability to trigger ovulation and advance puberty demonstrates that kisspeptin analogs may find application in the management of livestock reproduction and opens new possibilities for the treatment of reproductive disorders in humans. PMID:27245315

Advances in pharmacotherapy for treating endometriosis.

PubMed

Tafi, Emanuela; Leone Roberti Maggiore, Umberto; Alessandri, Franco; Bogliolo, Stefano; Gardella, Barbara; Vellone, Valerio Gaetano; Grillo, Federica; Mastracci, Luca; Ferrero, Simone

2015-01-01

Endometriosis is an estrogen-dependent chronic disease requiring long-term therapy. Therefore, the choice of medical treatment should be based on efficacy, preference of patients, incidence and severity of adverse effects and cost. This review briefly summarizes the currently available medical treatment for endometriosis. The treatments most recently proposed for endometriosis will be described in detail, including gonadotropin-releasing hormone (GnRH) antagonists, aromatase inhibitors (AIs) and the flexible extended combined oral contraceptive. The oral contraceptive pill and progestogens allow for the treatment of the majority of patients with endometriosis. The flexible extended dosing regimen, containing drospirenone and ethinylestradiol, may be particularly useful in patients suffering severe dysmenorrhea and improving the adherence and compliance with treatment. GnRH agonists may be used in patients resistant to first-line therapy; up to now, limited data are available on the use of GnRH antagonist (such as elagolix) in patients with endometriosis. AIs should be regarded as experimental therapies and used only in patients with symptoms resistant to other therapies; however, the use of these drugs is limited by the possibility to administer the treatment for short-term periods only (6 months) and, similarly to GnRH antagonists, by the high incidence of adverse effects, requiring the use of add-back therapy.

Pituitary, ovarian and additional contraceptive effects of an estradiol-based combined oral contraceptive: results of a randomized, open-label study.

PubMed

Endrikat, Jan; Parke, Susanne; Trummer, Dietmar; Serrani, Marco; Duijkers, Ingrid; Klipping, Christine

2013-02-01

The estrogen step-down/progestogen step-up 28-day estradiol valerate/dienogest (E(2)V/DNG) oral contraceptive effectively inhibits ovulation; however, limited data are available regarding its effects on estradiol (E2), progesterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) or its additional extraovarian contraceptive effects. In this secondary analysis, 100 women received E(2)V 3 mg on days 1-2, E(2)V 2 mg/DNG 2 mg on days 3-7, E(2)V 2 mg/DNG 3 mg on days 8-24, E(2)V 1 mg on days 25-26 and placebo on days 27-28 for one treatment cycle. Measures included the presence/absence of cervical mucus; endometrial thickness; and serum E2, progesterone, and gonadotropin levels. E2, progesterone, LH and FSH levels did not exhibit the typical ovulatory increase and remained relatively stable during the cycle. E(2)V/DNG reduced mean maximal endometrial thickness and proportion of women with visible cervical mucus. All parameters returned to pretreatment levels during the posttreatment cycle. E(2)V/DNG provides extraovarian contraceptive effects (reducing endometrial thickness and cervical mucus production) in addition to inhibiting ovulation, assuring contraceptive efficacy. Copyright © 2013 Elsevier Inc. All rights reserved.

Effects of chronic treatment with cyclooxygenase inhibitor, indomethacin on oral contraceptive-induced high blood pressure in female rats.

PubMed

Olatunji, L A; Soladoye, A O

2010-03-01

The present study sought to investigate the effects of prostaglandins synthesis inhibition with indomethacin on blood pressure, heart rate, cardiac weight, plasma electrolytes and cardiovascular responses to arterial baroreceptor stimulation in Oral contraceptive (OC) treated female Sprague-Dawley rats. Oral administration of synthetic oestrogen, ethinyl oestradiol in combination with progestogen, norgestrel for ten weeks significantly increased blood pressure and cardiac weight compared with those of the control rats. Concomitant treatment with indomethacin significantly abrogated increase in blood pressure but did not affect the increase in cardiac weight induced by OC. Heart rate, plasma sodium and potassium concentrations were not affected by OC and/or indomethacin treatment. OC treatment did not alter sympathetic-mediated pressor and tachycardiac responses caused by bilateral carotid baroreceptors unloading. However, these responses were significantly attenuated by indomethacin treatment. These results demonstrated that rat model of OC-induced high blood pressure developed cardiac hypertrophy that is not associated with altered sympathetic-mediated cardiovascular responses to arterial baroreceptor stimulation. The finding that indomethacin prevented OC-induced high blood pressure, but not associated cardiac hypertrophy implies that synthesis of prostaglandins may be an important determinant of OC-induced hypertension, while associated cardiac hypertrophy may not be pressure overload-dependent.

Mechanism of action of the levonorgestrel-releasing intrauterine system in the treatment of heavy menstrual bleeding.

PubMed

Cihangir, Uzunçakmak; Ebru, Akbay; Murat, Ekin; Levent, Yaşar

2013-11-01

To assess the efficacy and adverse effects, and reveal the effective pathway of the levonorgestrel-releasing intrauterine system (LNG-IUS) in the treatment of heavy menstrual bleeding. In a prospective single-center study in Istanbul, Turkey, the LNG-IUS was inserted in 60 patients diagnosed with heavy menstrual bleeding between January 2008 and June 2010. Menstrual bleeding pattern, coagulation parameters, uterine arterial blood flow, endometrial thickness, and uterine and ovarian volumes were assessed pre-insertion, and at 6 and 12months. Forty-nine women completed the study. When compared with pre-insertion values, the LNG-IUS led to improvements in hemoglobin and marked decreases in visual bleeding scores, endometrial thickness, and fibrinogen levels (P<0.001); platelet count, international normalized ratio, prothrombin time, activated partial thromboplastin time, and uterine volume also decreased (P<0.05). No significant change in ovarian volumes, or uterine artery resistive and pulsatility indices was observed at 6 or 12months compared with pre-insertion values. The decline in menstrual blood loss among LNG-IUS users was associated with local progestogenic effects and aggravation of intrinsic and extrinsic coagulation pathways. Although the LNG-IUS is a highly effective method for treating heavy menstrual bleeding, care must be taken when a patient has thromboembolic risk factors. © 2013.

The use of contraception for patients after bariatric surgery.

PubMed

Ostrowska, Lucyna; Lech, Medard; Stefańska, Ewa; Jastrzębska-Mierzyńska, Marta; Smarkusz, Joanna

2016-01-01

Obesity in women of reproductive age is a serious concern regarding reproductive health. In many cases of infertility in obese women, reduction of body weight may lead to spontaneous pregnancy, without the need for more specific methods of treatment. Bariatric surgery is safe and is the most effective method for body weight reduction in obese and very obese patients. In practice there are two bariatric techniques; gastric banding, which leads to weight loss through intake restriction, and gastric bypass, leads to weight loss through food malabsorption. Gastric bypass surgery (the more frequently performed procedure), in most cases, leads to changes in eating habits and may result in vomiting, diarrhea and rapid body mass reduction. There are reliable data describing the continuous increase in the number of women who are trying to conceive, or are already pregnant, following bariatric surgery. Most medical specialists advise women to avoid pregnancy within 12-18 months after bariatric surgery. This allows for time to recover sufficiency from the decreased absorption of nutrients caused by the bariatric surgery. During this period there is a need for the use of reliable contraception. As there is a risk for malabsorption of hormones taken orally, the combined and progestogen-only pills are contraindicated, and displaced by non-oral hormonal contraception or non-hormonal methods, including intrauterine devices and condoms.

Transition in Pediatric and Adolescent Hypogonadal Girls: Gynecological Aspects, Estrogen Replacement Therapy, and Contraception.

PubMed

Tønnes Pedersen, Anette; Cleemann, Line; Main, Katharina M; Juul, Anders

2018-01-01

Hypogonadism may be suspected if puberty is delayed. Pubertal delay may be caused by a normal physiological variant, by primary ovarian insufficiency (Turner syndrome), or reflect congenital hypogonadotropic hypogonadism (HH; genetic) or acquired HH (brain lesions). Any underlying chronic disease like inflammatory bowel disease, celiac disease, malnutrition (anorexia or orthorexia), or excessive physical activity may also result in functional HH. Thus, girls with delayed puberty should be evaluated for an underlying pathology before any treatment, including oral contraception, is initiated. Estrogen replacement is important and natural 17β-estradiol, preferably transdermally, is the preferred choice, whereas the oral route can be used as an alternative depending on patient preference and compliance. Sexual activity is often delayed in the hypogonadal adolescent girl. In the adolescent hypogonadal girl, hormone replacement therapy (HRT) most likely has been initiated at the time she becomes sexually active. If a risk of unwanted pregnancy cannot be ruled out, there is a need to consider contraception. This consideration does not contradict the principles of HRT but can be included as a part of the substitution, e.g. oral contraceptives containing 17β-estradiol or a progestogen intrauterine device combined with continuous 17β-estradiol (transdermal or oral). © 2018 S. Karger AG, Basel.

Effects of the mycotoxin deoxynivalenol on steroidogenesis and apoptosis in granulosa cells.

PubMed

Guerrero-Netro, Hilda M; Chorfi, Younès; Price, Christopher A

2015-06-01

Mycotoxins can reduce fertility and development in livestock, notably in pigs and poultry, although the effect of most mycotoxins on reproductive function in cattle has not been established. One major mycotoxin, deoxynivalenol (DON), not only targets immune cells and activates the ribotoxic stress response (RSR) involving MAPK activation, but also inhibits oocyte maturation in pigs. In this study, we determined the effect of DON on bovine granulosa cell function using a serum-free culture system. Addition of DON inhibited estradiol and progesterone secretion, and reduced levels of mRNA encoding estrogenic (CYP19A1) but not progestogenic (CYP11A1 and STAR) proteins. Cell apoptosis was increased by DON, which also increased FASLG mRNA levels. The mechanism of action of DON was assessed by western blotting and PCR experiments. Addition of DON rapidly and transiently increased phosphorylation of MAPK3/1, and resulted in a more prolonged phosphorylation of MAPK14 (p38) and MAPK8 (JNK). Activation of these pathways by DON resulted in time- and dose-dependent increases in abundance of mRNA encoding the transcription factors FOS, FOSL1, EGR1, and EGR3. We conclude that DON is deleterious to granulosa cell function and acts through a RSR pathway. © 2015 Society for Reproduction and Fertility.

Asthma control in patients on fixed dose combination evaluated with mannitol challenge test.

PubMed

Romberg, Kerstin A M; Berggren, Anna-Carin; Bjermer, Leif

2014-02-01

Asthma is often difficult to control and it is likely that not all patients are optimally treated. This study aimed to explore asthma control in adults receiving fixed dose combination (FDC) therapy. Control of asthma was assessed using the mannitol challenge test as a monitoring tool to see if this would give additional information compared to the asthma control test (ACT). The study was an open-label, prospective study on 98 adults prescribed with FDC therapies for at least three months. 74 patients considered that their asthma was well controlled. However, 60 patients had a positive mannitol challenge test (PD15 < 635 mg), and when those with a positive response to the short-acting β2-agonist (≥15%) after the mannitol challenge test were included, this increased to 64 patients (65%). Exploratory analysis determined that the spirometry parameters; FEV1/FVC and FEV1% of predicted, were statistically significant predictors of a positive mannitol challenge test. Co-morbid conditions such as concomitant upper airway involvement or eczema did not predict mannitol reactivity. Although most patients rated their asthma as well controlled, many provided a positive mannitol challenge test, suggesting the presence of underlying inflammation, despite treatment with fixed dose combination therapy. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Rapid diagnostic tests for malaria

PubMed Central

Daily, Jennifer; Hotte, Nora; Dolkart, Caitlin; Cunningham, Jane; Yadav, Prashant

2015-01-01

Abstract Maintaining quality, competitiveness and innovation in global health technology is a constant challenge for manufacturers, while affordability, access and equity are challenges for governments and international agencies. In this paper we discuss these issues with reference to rapid diagnostic tests for malaria. Strategies to control and eliminate malaria depend on early and accurate diagnosis. Rapid diagnostic tests for malaria require little training and equipment and can be performed by non-specialists in remote settings. Use of these tests has expanded significantly over the last few years, following recommendations to test all suspected malaria cases before treatment and the implementation of an evaluation programme to assess the performance of the malaria rapid diagnostic tests. Despite these gains, challenges exist that, if not addressed, could jeopardize the progress made to date. We discuss recent developments in rapid diagnostic tests for malaria, highlight some of the challenges and provide suggestions to address them. PMID:26668438

Challenge of COPD: Getting Tested

MedlinePlus

... please turn JavaScript on. Feature: The Challenge of COPD Getting Tested Past Issues / Fall 2014 Table of Contents Getting Tested Everyone at risk for COPD who has cough, sputum production, or shortness of ...

Skin testing only with penicillin G in children with a history of penicillin allergy.

PubMed

Picard, Matthieu; Paradis, Louis; Bégin, Philippe; Paradis, Jean; Des Roches, Anne

2014-07-01

The absence of commercially available penicilloyl-polylysine (PPL) for most of the last decade severely hampered the practice of penicillin allergy evaluation because skin testing without PPL is reported to have a poor negative predictive value (NPV). To determine the safety and NPV of skin testing without PPL using only penicillin G followed by a 3-dose graded challenge to the incriminated penicillin in children with a history of penicillin allergy. Patients evaluated for a history of penicillin allergy at the CHU Sainte-Justine Allergy Clinic between December 2006 and December 2009 were skin tested only with penicillin G and underwent a 3-dose graded challenge to the culprit penicillin if the skin test result was negative. Among 563 patients skin tested to penicillin G, 185 (33%) had a positive skin test result. These patients had a shorter interval between the initial reaction and skin testing compared with patients with a negative skin test result (P = .03). A total of 375 of 378 patients (99%) with a negative skin test result were challenged and 18 (4.8%) reacted, translating into a NPV of 95.2% (95% confidence interval [CI], 92.5%-97.1%). Three of 17 patients with a history of anaphylaxis and a negative skin test result reacted to challenge (NPV, 82.4%; 95% CI, 59.0-93.8%). All challenge reactions were mild and resolved promptly with treatment. Among children with a history of penicillin allergy, skin testing only with penicillin G followed by a 3-dose graded challenge to the incriminated penicillin is safe and yields a good NPV. This approach could be useful when PPL is unavailable. Copyright © 2014 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

WLCG scale testing during CMS data challenges

NASA Astrophysics Data System (ADS)

Gutsche, O.; Hajdu, C.

2008-07-01

The CMS computing model to process and analyze LHC collision data follows a data-location driven approach and is using the WLCG infrastructure to provide access to GRID resources. As a preparation for data taking, CMS tests its computing model during dedicated data challenges. An important part of the challenges is the test of the user analysis which poses a special challenge for the infrastructure with its random distributed access patterns. The CMS Remote Analysis Builder (CRAB) handles all interactions with the WLCG infrastructure transparently for the user. During the 2006 challenge, CMS set its goal to test the infrastructure at a scale of 50,000 user jobs per day using CRAB. Both direct submissions by individual users and automated submissions by robots were used to achieve this goal. A report will be given about the outcome of the user analysis part of the challenge using both the EGEE and OSG parts of the WLCG. In particular, the difference in submission between both GRID middlewares (resource broker vs. direct submission) will be discussed. In the end, an outlook for the 2007 data challenge is given.

A comparison of skin prick tests, intradermal skin tests, and specific IgE in the diagnosis of mouse allergy.

PubMed

Sharma, Hemant P; Wood, Robert A; Bravo, Andrea R; Matsui, Elizabeth C

2008-04-01

Mouse sensitization is assessed by using skin testing and serum levels of mouse allergen-specific IgE (m-IgE). However, it is unknown whether a positive skin test response or m-IgE result accurately identifies those with clinically relevant mouse sensitization. We sought to compare skin testing and m-IgE measurement in the diagnosis of mouse allergy. Sixty-nine mouse laboratory workers underwent skin prick tests (SPTs), intradermal tests (IDTs), and serum IgE measurements to mouse allergen, followed by nasal challenge to increasing concentrations of mouse allergen. Challenge response was assessed by nasal symptom score. Thirty-eight women and 31 men with a mean age of 30 years were studied. Forty-nine workers reported mouse-related symptoms, of whom 10 had positive m-IgE results and 12 had positive SPT responses. Fifteen had negative SPT responses but positive IDT responses. Positive nasal challenges were observed in 70% of workers with positive m-IgE results, 83% of workers with positive SPT responses, 33% of workers with negative SPT responses/positive IDT responses, and 0% of workers with negative IDT responses. SPTs performed best, having the highest positive and negative predictive values. Among participants with a positive challenge result, those with a positive SPT response or m-IgE result had a significantly lower challenge threshold than those with a positive IDT response (P = .01). Workers with a positive challenge result were more likely to have an increase in nasal eosinophilia after the challenge compared with those with a negative challenge result (P = .03). SPTs perform best in discriminating patients with and without mouse allergy. Mouse-specific IgE and IDTs appear to be less useful than SPTs in the diagnosis of mouse allergy.

42 CFR 410.18 - Diabetes screening tests.

Code of Federal Regulations, 2010 CFR

2010-10-01

... this subpart are met: (1) Fasting blood glucose test. (2) Post-glucose challenges including, but not...-pregnant adults, a 2-hour post glucose challenge test alone. (3) Other tests as determined by the Secretary... 42 Public Health 2 2010-10-01 2010-10-01 false Diabetes screening tests. 410.18 Section 410.18...

42 CFR 410.18 - Diabetes screening tests.

Code of Federal Regulations, 2014 CFR

2014-10-01

... this subpart are met: (1) Fasting blood glucose test. (2) Post-glucose challenges including, but not...-pregnant adults, a 2-hour post glucose challenge test alone. (3) Other tests as determined by the Secretary... 42 Public Health 2 2014-10-01 2014-10-01 false Diabetes screening tests. 410.18 Section 410.18...

42 CFR 410.18 - Diabetes screening tests.

Code of Federal Regulations, 2012 CFR

2012-10-01

... this subpart are met: (1) Fasting blood glucose test. (2) Post-glucose challenges including, but not...-pregnant adults, a 2-hour post glucose challenge test alone. (3) Other tests as determined by the Secretary... 42 Public Health 2 2012-10-01 2012-10-01 false Diabetes screening tests. 410.18 Section 410.18...

42 CFR 410.18 - Diabetes screening tests.

Code of Federal Regulations, 2013 CFR

2013-10-01

... this subpart are met: (1) Fasting blood glucose test. (2) Post-glucose challenges including, but not...-pregnant adults, a 2-hour post glucose challenge test alone. (3) Other tests as determined by the Secretary... 42 Public Health 2 2013-10-01 2013-10-01 false Diabetes screening tests. 410.18 Section 410.18...

42 CFR 410.18 - Diabetes screening tests.

Code of Federal Regulations, 2011 CFR

2011-10-01

... this subpart are met: (1) Fasting blood glucose test. (2) Post-glucose challenges including, but not...-pregnant adults, a 2-hour post glucose challenge test alone. (3) Other tests as determined by the Secretary... 42 Public Health 2 2011-10-01 2011-10-01 false Diabetes screening tests. 410.18 Section 410.18...

Cost-effectiveness of various methods of diagnosing hypersensitivity to Alternaria.

PubMed

Escudero, A I; Sánchez-Guerrero, I M; Mora, A M; Soriano, V; López, J D; García, F J; Negro, J M; Hernández, J; Pagán, J A

1993-01-01

This study was undertaken for two reasons: 1) It is more difficult to diagnose hypersensitivity to molds than to other allergens, so an evaluation of diagnostic tests was needed. 2) Alternaria is the principal cause of mold sensitization in our area. Sixty-six patients (20 +/- 4 years) were selected and divided into two groups. Group A was made up of patients with rhinitis and/or asthma due to Alternaria sensitization. Group B consisted of patients sensitized to other allergens and patients with nonrespiratory allergic disorders. Skin tests (prick and intradermal), challenge tests (conjunctival, nasal, and bronchial), and specific IgE determination were performed for all patients. A biologically standardized extract of Alternaria tenuis (Alergia e Inmunología Abelló, S. A., Madrid, Spain) obtained from a single batch was used for all tests. Our diagnostic criterion was a clinical history of rhinitis or asthma that coincided with the results of nasal/bronchial challenge. The diagnostic value of the other tests was compared to this criterion. In the group of rhinitic patients, skin tests and conjunctival challenge were more sensitive than specific IgE determination. In asthmatic patients, the most sensitive techniques were nasal and conjunctival challenges, followed by prick and intradermal skin tests, and, lastly, serum specific IgE determination. When rhinitis and asthma were considered jointly, the most sensitive test was conjunctival challenge, followed by skin-prick and intradermal tests. All tests had the same specificity, regardless of disorder. Nasal challenge was positive in all patients. Skin tests are easy to perform, cheap, non-traumatic for the patient, and sufficiently specific and sensitive for the diagnosis of Alternaria hypersensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Drug Testing Programs Face Snags and Legal Challenges.

ERIC Educational Resources Information Center

Cowart, Virginia S.

1988-01-01

A description of the problems that occurred with attempts to conduct drug tests at the 1987 Pan American games leads to a discussion of the legal challenges to drug testing and the need to establish a clear, effective, and fair policy for drug tests of athletes. (CB)

Oral challenge test with sodium metabisulfite in steroid-dependent asthmatic patients.

PubMed

Prieto, L; Juyol, M; Paricio, A; Martínez, M A; Palop, J; Castro, J

1988-01-01

Oral challenge tests were carried out with sodium metabisulfite solution doses of 0.5, 1, 10, 25, 50 mg and encapsulated doses of 100 and 200 mg, as well as with lactose-placebo, on 44 non-atopic patients with steroid-dependent bronchial asthma, without clinical evidence of intolerance to these agents. Only those patients with an acceptable and not very labile pulmonary function were tested. A single-blind challenge protocol was performed in 22 patients (sodium metabisulfite solutions at pH 2.2 to 2.6) and the positive responses were confirmed by double-blind challenge. The other 22 were tested directly in a double-blind manner (pH4). Initially, 6/44 presented a positive reaction. However, a careful analysis and the confirmation by double-blind challenge of the positive responses obtained with the single-blind test, allowed us to identify 4 false positive responses. Thus, the true prevalence of sulfite sensitivity in our population is 4.5%. A patient with intolerance to sulfite agents also suffered aspirin-induced asthma. The labile tendency of the pulmonary function of the asthmatic patients may have contributed to some false positive reactions and probably explain the very high prevalence found in some studies. It does not appear that the variations of pH decisively influence the result of the challenge test.

Swimming endurance of bull trout, lake trout, arctic char, and rainbow trout following challenge with Renibacterium salmoninarum

USGS Publications Warehouse

Jones, D.T.; Moffitt, C.M.

2004-01-01

We tested the swimming endurance of juvenile bull trout Salvelinus confluentus, lake trout S. namaycush, Arctic char S. alpinus, and rainbow trout Oncorhynchus mykiss at 9??C and 15??C to determine whether sublethal infection from a moderate challenge of Renibacterium salmoninarum administered months before testing affected the length of time fish could maintain a swimming speed of 5-6 body lengths per second in an experimental flume. Rainbow trout and Arctic char swam longer in trials than did bull trout or lake trout, regardless of challenge treatment. When we tested fish 14-23 weeks postchallenge, we found no measurable effect of R. salmoninarum on the swimming endurance of the study species except for bull trout, which showed a mixed response. We conducted additional trials with bull trout 5-8 weeks postchallenge to determine whether increasing the challenge dose would affect swimming endurance and hematocrit. In those tests, bull trout with clinical signs of disease and those exposed to the highest challenge doses had significantly reduced swimming endurance compared with unchallenged control fish. Fish hematocrit levels measured at the end of all swimming endurance tests varied among species and between test temperatures, and patterns were not always consistent between challenged and control fish.

Dissociation between history and challenge in patients with physical urticaria.

PubMed

Komarow, Hirsh D; Arceo, Sarah; Young, Michael; Nelson, Celeste; Metcalfe, Dean D

2014-01-01

Physical urticaria is a subtype of chronic urticaria induced by a physical stimulus. To evaluate the consistency between a history of physical urticaria and results of challenge testing. Seventy-six subjects, ages 3 to 77 years old, were referred with the diagnosis of a physical urticaria and were evaluated by using challenge testing directed toward the presenting diagnosis, yet included other stimuli based on history. The majority of subjects were tested to 3 or more stimuli, thus 294 provocation tests were performed. Fifty-seven subjects were surveyed for the status of their physical urticaria at least 1 year after initial evaluation. Of the 76 subjects with a positive history of a physical urticaria, 38% (n = 29) were challenge negative to the presenting diagnosis. Eight subjects within the challenge negative group reacted positively to additional testing, thus 28% (n = 21) remained negative to all challenge testing, which allowed discontinuation of medications and avoidance behavior. A negative challenge result was less likely with subjects who presented with cold-induced urticaria (25%), delayed pressure urticaria (25%), and dermatographism (29%), yet more common with cholinergic (65%) and solar urticaria (67%). A 1-year follow-up survey of 57 subjects was consistent with initial results. Nineteen of this subgroup were rechallenged for the presenting diagnosis, and the outcome was unchanged in 17 subjects and, in 2 subjects the urticaria had resolved. The diagnosis by history of a physical urticaria should be verified by testing whenever possible and particularly if the condition is judged as severe and thus requires both significant life-style changes and pharmacologic intervention. Published by Elsevier Inc.

Using a gluten oral food challenge protocol to improve diagnosis of wheat-dependent exercise-induced anaphylaxis.

PubMed

Brockow, Knut; Kneissl, Daniel; Valentini, Luzia; Zelger, Otto; Grosber, Martine; Kugler, Claudia; Werich, Martina; Darsow, Ulf; Matsuo, Hiroaki; Morita, Eishin; Ring, Johannes

2015-04-01

Oral wheat plus cofactors challenge tests in patients with wheat-dependent exercise-induced anaphylaxis (WDEIA) produce unreliable results. We sought to confirm WDEIA diagnosis by using oral gluten flour plus cofactors challenge, to determine the amount of gluten required to elicit symptoms, and to correlate these results with plasma gliadin levels, gastrointestinal permeability, and allergologic parameters. Sixteen of 34 patients with a history of WDEIA and ω5-gliadin IgE underwent prospective oral challenge tests with gluten with or without cofactors until objective symptoms developed. Gluten reaction threshold levels, plasma gliadin concentrations, gastrointestinal permeability, sensitivities and specificities for skin prick tests, and specific IgE levels were ascertained in patients and 38 control subjects. In 16 of 16 patients (8 female and 8 male patients; age, 23-76 years), WDEIA was confirmed by challenges with gluten alone (n = 4) or gluten plus cofactors (n = 12), including 4 patients with previous negative wheat challenge results. Higher gluten doses or acetylsalicylic acid (ASA) plus alcohol instead of physical exercise were cofactors in 2 retested patients. The cofactors ASA plus alcohol and exercise increased plasma gliadin levels (P < .03). Positive challenge results developed after a variable period of time at peak or when the plateau plasma gliadin level was attained. Positive plasma gliadin threshold levels differed by greater than 100-fold and ranged from 15 to 2111 pg/mL (median, 628 pg/mL). The clinical history, IgE gliadin level, and baseline gastrointestinal level were not predictive of the outcomes of the challenge tests. The challenge-confirmed sensitivity and specificity of gluten skin prick tests was 100% and 96%, respectively. Oral challenge with gluten alone or along with ASA and alcohol is a sensitive and specific test for the diagnosis of WDEIA. Exercise is not an essential trigger for the onset of symptoms in patients with WDEIA. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Critical evaluation of the EU-technical guidance on shelf-life studies for L. monocytogenes on RTE-foods: a case study for smoked salmon.

PubMed

Vermeulen, A; Devlieghere, F; De Loy-Hendrickx, A; Uyttendaele, M

2011-01-31

In November 2008, a technical guidance document on the challenge test protocol was published by the EU CRL (Community of Reference Laboratory) for L. monocytogenes. This document describes the practical aspects on the execution of a challenge test in order to comply to the EU Commission regulation N° 2073/2005 on microbiological criteria for foodstuff. In this guideline two approaches are specified. On the one hand challenge tests, based on actual data measurements at the beginning and end of the shelf-life of products stored under reasonably foreseen T-profile, are described. On the other hand, growth potential is calculated by predictive models using a validated maximum specific growth rate. The present study evaluates the two above mentioned approaches on cold smoked salmon, a typical risk product for L. monocytogenes. The focus is on: (i) the relative importance of intrabatch versus interbatch variability, (ii) the concept of a simple challenge test based on actual data at start and end of shelf life versus a modelling approach and (iii) the interpretation of challenge tests. Next to this, available tertiary models were used to estimate the growth potential of these products based on their initial physicochemical characteristics. From the results it could be concluded that in some batches considerable intrabatch variability was obtained. In general, however, the interbatch variability was significantly higher than intrabatch variability. Concerning the two above mentioned methods for challenge tests, it can be stated that the first approach (simple challenge test) can be set up rather rapidly and is cost-effective for SMEs (small and medium enterprises) but provides only a single isolated outcome. This implies that challenge tests should be redone if changes occur in composition or production process. The second (modelling) approach, using extended challenge tests to establish growth parameters needs larger set ups and more complicated data analysis, which makes them more expensive. Using available tertiary models has the major advantage that the most important intrinsic and extrinsic factors can be included for the prediction of the growth parameter. It was clear that product specific models, taking into account the interaction effects with background flora, performed the best. Regarding the challenge tests, it can be concluded that the best approach to choose will depend on the particular context as in the end both approaches will lead to the same conclusion. Copyright © 2010 Elsevier B.V. All rights reserved.

KSC-2009-6487

NASA Image and Video Library

2009-11-19

CAPE CANAVERAL, Fla. – At the Astronaut Hall of Fame near NASA’s Kennedy Space Center in Florida, Patrick Simpkins, director of Engineering at Kennedy, tries out a pair of space gloves for their dexterity and flexibility in a glove box at the 2009 Astronaut Glove Challenge, part of NASA’s Centennial Challenges Program. Looking over his shoulder is Kennedy Director Bob Cabana. The nationwide competition focused on developing improved pressure suit gloves for astronauts to use while working in space. During the challenge, the gloves were submitted to burst tests, joint force tests and tests to measure their dexterity and strength during operation in a glove box which simulates the vacuum of space. Centennial Challenges is NASA’s program of technology prizes for the citizen-inventor. The winning prize for the Glove Challenge is $250,000 provided by the Centennial Challenges Program. Photo credit: NASA/Kim Shiflett

KSC-2009-6488

NASA Image and Video Library

2009-11-19

CAPE CANAVERAL, Fla. – At the Astronaut Hall of Fame near NASA’s Kennedy Space Center in Florida, participants in the 2009 Astronaut Glove Challenge, part of NASA’s Centennial Challenges Program, pose for a group portrait. In the center of the front row are the winners, Ted Southern of Brooklyn, N.Y., at left, and Peter Homer of Southwest Harbor, Maine. The nationwide competition focused on developing improved pressure suit gloves for astronauts to use while working in space. During the challenge, the gloves were submitted to burst tests, joint force tests and tests to measure their dexterity and strength during operation in a glove box which simulates the vacuum of space. Centennial Challenges is NASA’s program of technology prizes for the citizen-inventor. The winning prize for the Glove Challenge is $250,000 provided by the Centennial Challenges Program. Photo credit: NASA/Kim Shiflett

Some considerations on the safety evaluation of nonviral microbial pesticides

PubMed Central

Shadduck, J. A.

1983-01-01

The tactics and rationale of maximum challenge safety tests for nonviral microbial pesticides have been reviewed. Maximum challenge tests and a tier approach to data collection for regulatory purposes offer the best opportunities to detect the acute effects of entomopathogenic organisms in mammals. Premature condemnation of promising organisms that are based on incomplete results of maximum challenge tests must be avoided. Further investigations should be conducted on the role of mammalian immune response in resistance to entomopathogenic organisms and on the value of medium- or long-term exposure tests. PMID:6601535

Developments in Test Facility and Data Networking for the Altitude Test Stand at the John C. Stennis Space Center: A General Overview

NASA Technical Reports Server (NTRS)

Hebert, Phillip W.

2008-01-01

NASA/SSC's Mission in Rocket Propulsion Testing Is to Acquire Test Performance Data for Verification, Validation and Qualification of Propulsion Systems Hardware: Accurate, Reliable, Comprehensive, and Timely. Data Acquisition in a Rocket Propulsion Test Environment Is Challenging: a) Severe Temporal Transient Dynamic Environments; b) Large Thermal Gradients; c) Vacuum to high pressure regimes. A-3 Test Stand Development is equally challenging with respect to accommodating vacuum environment, operation of a CSG system, and a large quantity of data system and control channels to determine proper engine performance as well as Test Stand operation. SSC is currently in the process of providing modernized DAS, Control Systems, Video, and network systems for the A-3 Test Stand to overcome these challenges.

Automated Source-Code-Based Testing of Object-Oriented Software

NASA Astrophysics Data System (ADS)

Gerlich, Ralf; Gerlich, Rainer; Dietrich, Carsten

2014-08-01

With the advent of languages such as C++ and Java in mission- and safety-critical space on-board software, new challenges for testing and specifically automated testing arise. In this paper we discuss some of these challenges, consequences and solutions based on an experiment in automated source- code-based testing for C++.

Bronchial hyperresponsiveness testing in athletes of the Swiss Paralympic team

PubMed Central

2013-01-01

Background The aim of this study was to assess airway hyperresponsiveness to eucapnic voluntary hyperventilation and dry powder mannitol challenge in athletes aiming to participate at the Paralympic Games 2008 in Beijing, especially in athletes with spinal cord injury. Methods Forty-four athletes with a disability (27 with paraplegia (group 1), 3 with tetraplegia (group 2) and 14 with other disabilities such as blindness or single limb amputations (group 3) performed spirometry, skin prick testing, measurement of exhaled nitric oxide, eucapnic voluntary hyperventilation challenge test (EVH) and mannitol challenge test (MCT). A fall in FEV1 of ≥10% in either challenge test was deemed positive for exercise-induced bronchoconstriction. Results Fourteen (32%) athletes were atopic and 7 (16%) had a history of physician-diagnosed asthma. Absolute lung function values were significantly lower in patients of group 1 and 2 compared to group 3. Nine (20%) athletes were positive to EVH (8 paraplegics, 1 tetraplegic), and 8 (18%) athletes were positive to MCT (7 paraplegics, 1 tetraplegic). Fourteen (22.7%) subjects were positive to at least one challenge; only three athletes were positive to both tests. None of the athletes in group 3 had a positive test. Both challenge tests showed a significant association with physician-diagnosed asthma status (p = 0.0001). The positive and negative predictive value to diagnose physician-diagnosed asthma was 89% and 91% for EHV, and 75% and 86% for MCT, respectively. Conclusion EVH and MCT can be used to identify, but especially exclude asthma in Paralympic athletes. PMID:23845126

Multi-parameter comparison of a standardized mixed meal tolerance test in healthy and type 2 diabetic subjects: the PhenFlex challenge.

PubMed

Wopereis, Suzan; Stroeve, Johanna H M; Stafleu, Annette; Bakker, Gertruud C M; Burggraaf, Jacobus; van Erk, Marjan J; Pellis, Linette; Boessen, Ruud; Kardinaal, Alwine A F; van Ommen, Ben

2017-01-01

A key feature of metabolic health is the ability to adapt upon dietary perturbations. Recently, it was shown that metabolic challenge tests in combination with the new generation biomarkers allow the simultaneous quantification of major metabolic health processes. Currently, applied challenge tests are largely non-standardized. A systematic review defined an optimal nutritional challenge test, the "PhenFlex test" (PFT). This study aimed to prove that PFT modulates all relevant processes governing metabolic health thereby allowing to distinguish subjects with different metabolic health status. Therefore, 20 healthy and 20 type 2 diabetic (T2D) male subjects were challenged both by PFT and oral glucose tolerance test (OGTT). During the 8-h response time course, 132 parameters were quantified that report on 26 metabolic processes distributed over 7 organs (gut, liver, adipose, pancreas, vasculature, muscle, kidney) and systemic stress. In healthy subjects, 110 of the 132 parameters showed a time course response. Patients with T2D showed 18 parameters to be significantly different after overnight fasting compared to healthy subjects, while 58 parameters were different in the post-challenge time course after the PFT. This demonstrates the added value of PFT in distinguishing subjects with different health status. The OGTT and PFT response was highly comparable for glucose metabolism as identical amounts of glucose were present in both challenge tests. Yet the PFT reports on additional processes, including vasculature, systemic stress, and metabolic flexibility. The PFT enables the quantification of all relevant metabolic processes involved in maintaining or regaining homeostasis of metabolic health. Studying both healthy subjects and subjects with impaired metabolic health showed that the PFT revealed new processes laying underneath health. This study provides the first evidence towards adopting the PFT as gold standard in nutrition research.

Extending the Challenge-Hindrance Model of Occupational Stress: The Role of Appraisal

ERIC Educational Resources Information Center

Webster, Jennica R.; Beehr, Terry A.; Love, Kevin

2011-01-01

Interest regarding the challenge-hindrance occupational stress model has increased in recent years, however its theoretical foundation has not been tested. Drawing from the transactional theory of stress, this study tests the assumptions made in past research (1) that workload and responsibility are appraised as challenges and role ambiguity and…

KSC-2009-6491

NASA Image and Video Library

2009-11-19

CAPE CANAVERAL, Fla. – At the Astronaut Hall of Fame near NASA’s Kennedy Space Center in Florida, Anna Heiney, a Public Affairs support writer with Abacus Technology at Kennedy, tries out a pair of space gloves for their dexterity and flexibility in a glove box at the 2009 Astronaut Glove Challenge, part of NASA’s Centennial Challenges Program. Looking over his shoulder is Kennedy Director Bob Cabana. The nationwide competition focused on developing improved pressure suit gloves for astronauts to use while working in space. During the challenge, the gloves were submitted to burst tests, joint force tests and tests to measure their dexterity and strength during operation in a glove box which simulates the vacuum of space. Centennial Challenges is NASA’s program of technology prizes for the citizen-inventor. The winning prize for the Glove Challenge is $250,000 provided by the Centennial Challenges Program. Photo credit: NASA/Kim Shiflett

Testing Universal Design of a Public Media Website with Diverse Users.

PubMed

Chen, Weiqin; Kessel, Siri; Sanderson, Norun C; Tatara, Naoe

2016-01-01

Testing with users can identify more issues than other testing methods. Many researchers have argued for the importance of user testing in Universal Design. However, testing Universal Design with diverse users poses many challenges. In this paper we will share our experience with testing the Universal Design of a public media website with real users. We discuss the challenges faced and lessons learned in the process.

Mannitol challenge testing for asthma in a community cohort of young adults.

PubMed

White, Elisha C; de Klerk, Nicholas; Hantos, Zoltan; Priston, Monique; Hollams, Elysia M; James, Alan; Sly, Peter D; Holt, Patrick G; Hall, Graham L

2017-05-01

Mannitol challenge testing is an established tool for clinical asthma diagnosis, and can be performed outside of specialized respiratory laboratories. Despite applicability in both clinical and non-clinical populations, with different pre-test asthma probabilities, differences in diagnostic properties have not been well explored. This study aimed to quantify the diagnostic utility of mannitol challenge testing for asthma in a community cohort and a symptomatic wheezing subset of this cohort. During the 22-year follow-up of the Western Australian Pregnancy (Raine) Cohort, 772 participants (384 males) completed mannitol challenge and skin prick testing and respiratory health questionnaires, of whom 148 reporting wheeze in the past 12 months were included in a wheezing subset. Responsiveness to mannitol had low sensitivity (19%) and high specificity (97%) to identify current asthma in the complete cohort, with positive and negative predictive values (PPV and NPV) of 45% and 92%, respectively. Within the wheezing subset, sensitivity (19%) and specificity (94%) remained similar, but PPV increased to 79%, and NPV decreased to 52%. Our findings support previously reported high specificity and good PPV for mannitol challenge testing in symptomatic wheezing populations, and highlight the need for caution when interpreting mannitol test results in non-clinical populations. © 2016 Asian Pacific Society of Respirology.

New validated recipes for double-blind placebo-controlled low-dose food challenges.

PubMed

Winberg, Anna; Nordström, Lisbeth; Strinnholm, Åsa; Nylander, Annica; Jonsäll, Anette; Rönmark, Eva; West, Christina E

2013-05-01

Double-blind placebo-controlled food challenges are considered the most reliable method to diagnose or rule out food allergy. Despite this, there are few validated challenge recipes available. The present study aimed to validate new recipes for low-dose double-blind placebo-controlled food challenges in school children, by investigating whether there were any sensory differences between the active materials containing cow's milk, hen's egg, soy, wheat or cod, and the placebo materials. The challenge materials contained the same hypoallergenic amino acid-based product, with or without added food allergens. The test panels consisted of 275 school children, aged 8-10 and 14-15 yr, respectively, from five Swedish schools. Each participant tested at least one recipe. Standardized blinded triangle tests were performed to investigate whether any sensory differences could be detected between the active and placebo materials. In our final recipes, no significant differences could be detected between the active and placebo materials for any challenge food (p > 0.05). These results remained after stratification for age and gender. The taste of challenge materials was acceptable, and no unfavourable side effects related to test materials were observed. In summary, these new validated recipes for low-dose double-blinded food challenges contain common allergenic foods in childhood; cow's milk, hen's egg, soy, wheat and cod. All test materials contain the same liquid vehicle, which facilitates preparation and dosing. Our validated recipes increase the range of available recipes, and as they are easily prepared and dosed, they may facilitate the use of double-blind placebo-controlled food challenges in daily clinical practice. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

Can conjunctival provocation test facilitate the diagnosis of food allergy in children?

PubMed

Krane Kvenshagen, B; Jacobsen, M; Halvorsen, R

2010-01-01

Food allergy is common in children, occurring in 5-7.5%. The diagnosis may, however, be difficult. Elevated IgE or positive skin prick test to a food allergen is often considered proof of allergy, but may represent sensitisation without clinical manifestations. For a precise diagnosis oral challenge is necessary, but this is often not performed because of risk of serious allergic reactions. The aim of this study was to evaluate whether conjunctival provocation test would facilitate the diagnosis of IgE-mediated food allergy. One hundred and forty-nine children with 174 possible diagnoses of food allergy were included. General examination, skin prick test and specific IgE were performed, as well as conjunctival provocation test of the suspected food allergen. Open food challenges and double-blind placebo controlled tests were performed in order to diagnose possible food allergy. Forty-six children with strongly positive conjunctival reactions (rubor, itching, oedema) to fifty food allergens were all proven to have allergy to the food in question. The children with negative conjunctival provocation tests showed no allergic reactions when challenged. We find that a strongly positive conjunctival reaction to a food allergen correlates well with true allergy. An oral challenge should be carefully performed. With a negative conjunctival test an oral challenge may safely be performed. Copyright © 2009 SEICAP. Published by Elsevier Espana. All rights reserved.

Bronchial reactions to exposure to welding fumes.

PubMed Central

Contreras, G R; Chan-Yeung, M

1997-01-01

OBJECTIVES: To study the airway response and its mechanism to welding fumes in six welders with respiratory symptoms. METHODS: Methacholine and welding challenge tests were carried out. The concentration of welding fumes during the exposure test was measured. On two subjects who developed bronchoconstricition to welding challenge, additional tests were carried out including prick, patch, and inhalation challenges with metal salt solutions. RESULTS: Three subjects developed immediate bronchial reaction to exposure to welding fume; one to mild steel and stainless steel welding, another to mild steel and galvanised welding, and one only to galvanised welding. They all had a moderate to pronounced degree of non-specific bronchial hyperresponsiveness. The concentration of fumes during welding tests, particularly to galvanised welding, was high. An inhalation challenge test with zinc chloride salt solution in two subjects who reacted to galvanised welding was negative. Prick and patch tests with zinc chloride were also negative. CONCLUSION: The airway response to welding in these subjects is non-specific and is due to irritation rather than to sensitisation. PMID:9538358

Bronchial reactions to exposure to welding fumes.

PubMed

Contreras, G R; Chan-Yeung, M

1997-11-01

To study the airway response and its mechanism to welding fumes in six welders with respiratory symptoms. Methacholine and welding challenge tests were carried out. The concentration of welding fumes during the exposure test was measured. On two subjects who developed bronchoconstricition to welding challenge, additional tests were carried out including prick, patch, and inhalation challenges with metal salt solutions. Three subjects developed immediate bronchial reaction to exposure to welding fume; one to mild steel and stainless steel welding, another to mild steel and galvanised welding, and one only to galvanised welding. They all had a moderate to pronounced degree of non-specific bronchial hyperresponsiveness. The concentration of fumes during welding tests, particularly to galvanised welding, was high. An inhalation challenge test with zinc chloride salt solution in two subjects who reacted to galvanised welding was negative. Prick and patch tests with zinc chloride were also negative. The airway response to welding in these subjects is non-specific and is due to irritation rather than to sensitisation.

Sensitization to Food Additives in Patients with Allergy: A Study Based on Skin Test and Open Oral Challenge.

PubMed

Moghtaderi, Mozhgan; Hejrati, Zinatosadat; Dehghani, Zahra; Dehghani, Faranak; Kolahi, Niloofar

2016-06-01

There has been a great increase in the consumption of various food additives in recent years. The purpose of this study was to identify the incidence of sensitization to food additives by using skin prick test in patients with allergy and to determine the concordance rate between positive skin tests and oral challenge in hypersensitivity to additives. This cross-sectional study included 125 (female 71, male 54) patients aged 2-76 years with allergy and 100 healthy individuals. Skin tests were performed in both patient and control groups with 25 fresh food additives. Among patients with allergy, 22.4% showed positive skin test at least to one of the applied materials. Skin test was negative to all tested food additives in control group. Oral food challenge was done in 28 patients with positive skin test, in whom 9 patients showed reaction to culprit (Concordance rate=32.1%). The present study suggested that about one-third of allergic patients with positive reaction to food additives showed positive oral challenge; it may be considered the potential utility of skin test to identify the role of food additives in patients with allergy.

Radiation Test Challenges for Scaled Commerical Memories

NASA Technical Reports Server (NTRS)

LaBel, Kenneth A.; Ladbury, Ray L.; Cohn, Lewis M.; Oldham, Timothy

2007-01-01

As sub-100nm CMOS technologies gather interest, the radiation effects performance of these technologies provide a significant challenge. In this talk, we shall discuss the radiation testing challenges as related to commercial memory devices. The focus will be on complex test and failure modes emerging in state-of-the-art Flash non-volatile memories (NVMs) and synchronous dynamic random access memories (SDRAMs), which are volatile. Due to their very high bit density, these device types are highly desirable for use in the natural space environment. In this presentation, we shall discuss these devices with emphasis on considerations for test and qualification methods required.

The space shuttle ascent vehicle aerodynamic challenges configuration design and data base development

NASA Technical Reports Server (NTRS)

Dill, C. C.; Young, J. C.; Roberts, B. B.; Craig, M. K.; Hamilton, J. T.; Boyle, W. W.

1985-01-01

The phase B Space Shuttle systems definition studies resulted in a generic configuration consisting of a delta wing orbiter, and two solid rocket boosters (SRB) attached to an external fuel tank (ET). The initial challenge facing the aerodynamic community was aerodynamically optimizing, within limits, this configuration. As the Shuttle program developed and the sensitivities of the vehicle to aerodynamics were better understood the requirements of the aerodynamic data base grew. Adequately characterizing the vehicle to support the various design studies exploded the size of the data base to proportions that created a data modeling/management challenge for the aerodynamicist. The ascent aerodynamic data base originated primarily from wind tunnel test results. The complexity of the configuration rendered conventional analytic methods of little use. Initial wind tunnel tests provided results which included undesirable effects from model support tructure, inadequate element proximity, and inadequate plume simulation. The challenge to improve the quality of test results by determining the extent of these undesirable effects and subsequently develop testing techniques to eliminate them was imposed on the aerodynamic community. The challenges to the ascent aerodynamics community documented are unique due to the aerodynamic complexity of the Shuttle launch. Never before was such a complex vehicle aerodynamically characterized. The challenges were met with innovative engineering analyses/methodology development and wind tunnel testing techniques.

Noninvasive Fetal ECG: the PhysioNet/Computing in Cardiology Challenge 2013.

PubMed

Silva, Ikaro; Behar, Joachim; Sameni, Reza; Zhu, Tingting; Oster, Julien; Clifford, Gari D; Moody, George B

2013-03-01

The PhysioNet/CinC 2013 Challenge aimed to stimulate rapid development and improvement of software for estimating fetal heart rate (FHR), fetal interbeat intervals (FRR), and fetal QT intervals (FQT), from multichannel recordings made using electrodes placed on the mother's abdomen. For the challenge, five data collections from a variety of sources were used to compile a large standardized database, which was divided into training, open test, and hidden test subsets. Gold-standard fetal QRS and QT interval annotations were developed using a novel crowd-sourcing framework. The challenge organizers used the hidden test subset to evaluate 91 open-source software entries submitted by 53 international teams of participants in three challenge events, estimating FHR, FRR, and FQT using the hidden test subset, which was not available for study by participants. Two additional events required only user-submitted QRS annotations to evaluate FHR and FRR estimation accuracy using the open test subset available to participants. The challenge yielded a total of 91 open-source software entries. The best of these achieved average estimation errors of 187bpm 2 for FHR, 20.9 ms for FRR, and 152.7 ms for FQT. The open data sets, scoring software, and open-source entries are available at PhysioNet for researchers interested on working on these problems.

Economic challenges associated with tuberculosis diagnostic development

PubMed Central

Hanrahan, Colleen F.; Shah, Maunank

2015-01-01

Tuberculosis remains a global health crisis in part due to underdiagnosis. Technological innovations are needed to improve diagnostic test accuracy and reduce the reliance on expensive laboratory infrastructure. However, there are significant economic challenges impeding the development and implementation of new diagnostics. The aim of this piece is to examine the current state of TB diagnostics, outline the unmet needs for new tests, and detail the economic challenges associated with development of new tests from the perspective of developers, policy makers and implementers. PMID:24766367

Economic challenges associated with tuberculosis diagnostic development.

PubMed

Hanrahan, Colleen F; Shah, Maunank

2014-08-01

Tuberculosis remains a global health crisis in part due to underdiagnosis. Technological innovations are needed to improve diagnostic test accuracy and reduce the reliance on expensive laboratory infrastructure. However, there are significant economic challenges impeding the development and implementation of new diagnostics. The aim of this piece is to examine the current state of TB diagnostics, outline the unmet needs for new tests, and detail the economic challenges associated with development of new tests from the perspective of developers, policy makers and implementers.

Universal penetration test apparatus with fluid penetration sensor

DOEpatents

Johnson, Phillip W.; Stampfer, Joseph F.; Bradley, Orvil D.

1999-01-01

A universal penetration test apparatus for measuring resistance of a material to a challenge fluid. The apparatus includes a pad saturated with the challenge fluid. The apparatus includes a compression assembly for compressing the material between the pad and a compression member. The apparatus also includes a sensor mechanism for automatically detecting when the challenge fluid penetrates the material.

KSC-2009-6474

NASA Image and Video Library

2009-11-19

CAPE CANAVERAL, Fla. – This newly designed glove, one of the entries in the 2009 Astronaut Glove Challenge, undergoes a joint force test the 2009 Astronaut Glove Challenge, part of NASA’s Centennial Challenges Program, at the Astronaut Hall of Fame near NASA’s Kennedy Space Center in Florida. The nationwide competition focused on developing improved pressure suit gloves for astronauts to use while working in space. During the challenge, inventors tested the gloves to measure dexterity and strength during operation in a glove box which simulates the vacuum of space. Centennial Challenges is NASA’s program of technology prizes for the citizen-inventor. The winning prize for the Glove Challenge is $250,000 provided by the Centennial Challenges Program. Photo credit: NASA/Kim Shiflett

ERS technical standard on bronchial challenge testing: general considerations and performance of methacholine challenge tests.

PubMed

Coates, Allan L; Wanger, Jack; Cockcroft, Donald W; Culver, Bruce H; Diamant, Zuzana; Gauvreau, Gail; Hall, Graham L; Hallstrand, Teal S; Horvath, Ildiko; de Jongh, Frans H C; Joos, Guy; Kaminsky, David A; Laube, Beth L; Leuppi, Joerg D; Sterk, Peter J

2017-05-01

This international task force report updates general considerations for bronchial challenge testing and the performance of the methacholine challenge test. There are notable changes from prior recommendations in order to accommodate newer delivery devices. Rather than basing the test result upon a methacholine concentration (provocative concentration (PC 20 ) causing a 20% fall in forced expiratory volume in 1 s (FEV 1 )), the new recommendations base the result upon the delivered dose of methacholine causing a 20% fall in FEV 1 (provocative dose (PD 20 )). This end-point allows comparable results from different devices or protocols, thus any suitable nebuliser or dosimeter may be used, so long as the delivery characteristics are known. Inhalation may be by tidal breathing using a breath-actuated or continuous nebuliser for 1 min (or more), or by a dosimeter with a suitable breath count. Tests requiring maximal inhalations to total lung capacity are not recommended because the bronchoprotective effect of a deep breath reduces the sensitivity of the test. Copyright ©ERS 2017.

Prevalence and challenge tests of Listeria monocytogenes in Belgian produced and retailed mayonnaise-based deli-salads, cooked meat products and smoked fish between 2005 and 2007.

PubMed

Uyttendaele, M; Busschaert, P; Valero, A; Geeraerd, A H; Vermeulen, A; Jacxsens, L; Goh, K K; De Loy, A; Van Impe, J F; Devlieghere, F

2009-07-31

Processed ready-to-eat (RTE) foods with a prolonged shelf-life under refrigeration are at risk products for listeriosis. This manuscript provides an overview of prevalence data (n=1974) and challenge tests (n=299) related to Listeria monocytogenes for three categories of RTE food i) mayonnaise-based deli-salads (1187 presence/absence tests and 182 challenge tests), ii) cooked meat products (639 presence/absence tests and 92 challenge tests), and iii) smoked fish (90 presence/absence tests and 25 challenge tests), based on data records obtained from various food business operators in Belgium in the frame of the validation and verification of their HACCP plans over the period 2005-2007. Overall, the prevalence of L. monocytogenes in these RTE foods in the present study was lower compared to former studies in Belgium. For mayonnaise-based deli-salads, in 80 out of 1187 samples (6.7%) the pathogen was detected in 25 g. L. monocytogenes positive samples were often associated with smoked fish deli-salads. Cooked meat products showed a 1.1% (n=639) prevalence of the pathogen. For both food categories, numbers per gram never exceeded 100 CFU. L. monocytogenes was detected in 27.8% (25/90) smoked fish samples, while 4/25 positive samples failed to comply to the 100 CFU/g limit set out in EU Regulation 2073/2005. Challenge testing showed growth potential in 18/182 (9.9%) deli-salads and 61/92 (66%) cooked meat products. Nevertheless, both for deli-salads and cooked meat products, appropriate product formulation and storage conditions based upon hurdle technology could guarantee no growth of L. monocytogenes throughout the shelf-life as specified by the food business operator. Challenge testing of smoked fish showed growth of L. monocytogenes in 12/25 samples stored for 3-4 weeks at 4 degrees C. Of 45 (non-inoculated) smoked fish samples (13 of which were initially positive in 25 g) which were subjected to shelf-life testing, numbers exceeded 100 CFU/g in only one sample after storage until the end of shelf-life. Predictive models, dedicated to and validated for a particular food category, taking into account the inhibitory effect of various factors in hurdle technology, provided predictions of growth potential of L. monocytogenes corresponding to observed growth in challenge testing. Based on the combined prevalence data and growth potential, mayonnaise-based deli-salads and cooked meat products can be classified as intermediate risk foods, smoked fish as a high risk food.

Evaluation of preservative efficacy in pharmaceutical products: the use of psychrotolerant, low-nutrient preferring microbes in challenge tests.

PubMed

Charnock, C; Otterholt, E

2012-10-01

Preservative efficacy in medicines is typically investigated using challenge tests. In such tests, the product is artificially contaminated with a high concentration of standard bacterial and fungal test strains such as Pseudomonas aeruginosa and Candida albicans. The rate and extent of reductions in inoculum viability over a specified period forms the basis for acceptance/rejection of preservative efficacy. None of the strains named for inclusion in the challenge test outlined in the European Pharmacopoeia are associated with the contamination of high-quality water used in pharmaceutical production. Alpha- and Betaproteobacteria are easily the most common microbes in waters intended for pharmaceutical production. In addition, none of the standard test strain panel prefer low-nutrient, dilute conditions or grow at or around refrigeration temperatures. This is important because the water activity and nutrient content of medicines can vary greatly and medicines are often stored cold. We investigate the relevance of these factors when testing preservative efficacy by including other strains in challenge tests. Psychrotolerant, low-nutrient preferring strains (Beta- and Alphaproteobacteria and a yeast) were isolated from pristine waters. These were compared in challenge tests with C. albicans and P. aeruginosa using different storage temperatures. Pharmaceutical products differing widely in water-content, pH and preservative systems were included in the study. Regardless of the type of medicine tested C. albicans always showed superior survival characteristics to the yeast isolate (Cryptococcus terricola). One of the three screened bacterial strains (a Sphingomonas sp.) survived significantly better than P. aeruginosa in all but one product tested. However, the results for all products taken together cannot easily be explained by reference to this strain's psychrotolerancy or its preference for dilute, low-nutrient environments. This study supports previous work indicating that the inclusion of wild-type test strains, in this instance strains that are suited to survival in high-quality waters, improves preservative efficacy tests. Use of a Sphingomonas sp. isolated from a pristine water as a challenge test strain, gave a more stringent indication of preservative efficacy in a wide range of pharmaceuticals than did P. aeruginosa. © 2012 Blackwell Publishing Ltd.

A study of myocardial perfusion in patients with panic disorder and low risk coronary artery disease after 35% CO2 challenge.

PubMed

Fleet, Richard; Foldes-Busque, Guillaume; Grégoire, Jean; Harel, François; Laurin, Catherine; Burelle, Denis; Lavoie, Kim

2014-01-01

We have previously reported that 35% CO2 challenge induced myocardial ischemia in 81% of coronary artery disease (CAD) patients with comorbid panic disorder (PD) and previous positive nuclear exercise stress tests. However, it is yet unclear whether this is the case among CAD patients with PD and normal nuclear exercise stress test results. We hypothesized that a potent mental stressor such as a panic challenge among CAD patients with PD would also induce ischemia in patients with normal exercise stress tests. Forty-one coronary artery disease patients with normal nuclear exercise stress tests (21 patients with PD and 20 without PD) were submitted to a well-established panic challenge test (with 1 vital capacity inhalation of a gas mixture containing 35% CO2 and 65% O2) and injected with Tc-99m-tetrofosmin (Myoview), upon inhalation. Single photon emission computed tomography imaging was used to assess per-panic challenge reversible myocardial ischemia and HR, BP, and a 12 lead ECG was continuously measured during the procedure. Fifty-eight percent of panic disorder patients (12/21) had a panic attack during the panic challenge vs 15% (3/20) of controls (p=0.005). Only 10% of patients in each group displayed myocardial ischemia per panic challenge. These findings suggest that panic attacks among panic disorder patients with lower-risk coronary artery disease may not confer a risk for myocardial ischemia. © 2013.

Effect of oral contraceptives on markers of hyperandrogenism and SHBG in women with polycystic ovary syndrome.

PubMed

De Leo, Vincenzo; Di Sabatino, Alessandra; Musacchio, Maria C; Morgante, Giuseppe; Scolaro, Valeria; Cianci, Antonio; Petraglia, Felice

2010-09-01

This randomized study's aim was to compare the effect of four oral contraceptives (OCs) containing 30 mcg of ethinylestradiol (EE) and different progestogens [drospirenone, (DRSP), chlormadinone acetate (CMA), desogestrel (DSG), gestodene (GSD)] on biochemical and hormonal parameters of hyperandrogenism and sex hormone-binding globulin (SHBG) in women with polycystic ovary syndrome (PCOS). Forty women with PCOS (age 16-35 years) were recruited and randomly assigned to one of four treatment groups of 10 women each, treated, respectively, with 3 mg DRSP/30 mcg EE (Yasmin, Bayer Shering), 2 mg CMA/30 mcg EE (Belara, Grunenthal), 75 mcg GSD/30 mcg EE (Minulet, Wyeth Lederle) and 150 mcg DSG/30 mcg EE (Practil 21, Organon Italia). Blood samples were obtained on day 6-8 of the control cycle and day 6-8 of the third treatment cycle for assay of the following hormones: androsteredione (A), total testosterone (T), free T, SHBG, dehydroepiandrosterone sulphate (DHEAS). In all groups, mean concentrations of free T, total T and A dropped by 40-60%, and concentrations of DHEAS dropped by 20-50%. Formulations with DRSP and CMA caused a greater reduction of androgens and a progressive increase in serum concentrations of SHBG than those with DSG and GSD. Clinical studies need to be performed to determine effects of these OCs upon clinical signs of hyperandrogenism. Copyright 2010 Elsevier Inc. All rights reserved.

The impact of dydrogesterone supplementation on serum cytokine profile in women with threatened abortion.

PubMed

Kalinka, Jarosław; Radwan, Michał

2006-02-01

The role of increased Th1 cytokine expression in pregnancy failure has been questioned recently. The therapeutic value of progestogens in threatened abortion (TA) is still debated. The aim of this prospective study was to compare serum cytokine [tumor necrosis factor (TNF)-alpha, interleukin (IL)-12 and IL-10] concentrations in women with TA to those in women with normal pregnancy and to evaluate the impact of dydrogesterone supplementation in the former group on cytokine concentration. Twenty-seven threatened aborters were treated for 10 days with dydrogesterone (30-40 mg/day). Sixteen healthy pregnant controls received no treatment. Serum cytokine concentrations were measured twice in both groups by enzyme-linked immunosorbent assay. Mean serum concentrations of Th1- and Th2-type cytokines in women with TA did not differ from those in women with normal pregnancy at first and second sampling. After dydrogesterone supplementation, mean TNF-alpha/IL-10 ratio changed from 1.08 to 1.75 while IL-12/IL-10 ratio remained almost the same (0.56-0.61) in the threatened aborters group and did not differ from those in healthy women. The results of this study indicate that peripheral cytokine production in threatened aborters does not differ from that observed among healthy pregnant women. The protective effect of dydrogesterone supplementation in threatened aborters is manifested via restoring progesterone-induced blocking factor concentration rather than controlling cytokine production.

Progesterone Receptors: Form and Function in Brain

PubMed Central

Brinton, Roberta Diaz; Thompson, Richard F.; Foy, Michael R.; Baudry, Michel; Wang, JunMing; Finch, Caleb E; Morgan, Todd E.; Stanczyk, Frank Z.; Pike, Christian J.; Nilsen, Jon

2008-01-01

Emerging data indicate that progesterone has multiple non-reproductive functions in the central nervous system to regulate cognition, mood, inflammation, mitochondrial function, neurogenesis and regeneration, myelination and recovery from traumatic brain injury. Progesterone-regulated neural responses are mediated by an array of progesterone receptors (PR) that include the classic nuclear PRA and PRB receptors and splice variants of each, the seven transmembrane domain 7TMPRβ and the membrane-associated 25-Dx PR (PGRMC1). These PRs induce classic regulation of gene expression while also transducing signaling cascades that originate at the cell membrane and ultimately activate transcription factors. Remarkably, PRs are broadly expressed throughout the brain and can be detected in every neural cell type. The distribution of PRs beyond hypothalamic borders, suggests a much broader role of progesterone in regulating neural function. Despite the large body of evidence regarding progesterone regulation of reproductive behaviors and estrogen-inducible responses as well as effects of progesterone metabolite neurosteroids, much remains to be discovered regarding the functional outcomes resulting from activation of the complex array of PRs in brain by gonadally and / or glial derived progesterone. Moreover, the impact of clinically used progestogens and developing selective PR modulators for targeted outcomes in brain is a critical avenue of investigation as the non-reproductive functions of PRs have far-reaching implications for hormone therapy to maintain neurological health and function throughout menopausal aging. PMID:18374402

The history of hormone therapy use and recent controversy related to heart disease and breast cancer arising from prevention trial outcomes.

PubMed

Alexander, Ivy M

2012-01-01

The reasons for hormone therapy use have changed dramatically over time from being very popular for the purpose of preserving youth in women to menopause-related symptom management, disease prevention, and now back to menopause-related symptom management. Over time, several important risks associated with the use of hormone therapy have become evident, causing dramatic reductions in the use of hormone therapy for periods of time following identification of these risks. Most recently, randomized controlled prevention trials that evaluated hormone therapy for the purpose of reducing or preventing coronary heart disease among women have found that hormone therapy is associated with increased rather than decreased risks for coronary heart disease. The most recent of these trials again identified increased risks for breast cancer associated with estrogen plus progestogen therapy. The evolving evidence base from these randomized controlled prevention trials is complicated and in some cases contradictory. Specifically, the data suggest that the timing of when hormone therapy is initiated once a woman is postmenopausal may influence her risk for developing heart disease and breast cancer. In this article, contradictory evidence is carefully sifted so risks and benefits can be weighed by clinicians when partnering with women to individualize decisions about using hormone therapy. © 2012 by the American College of Nurse-Midwives.

Comparison of progesterone and glucocorticoid receptor binding and stimulation of gene expression by progesterone, 17-alpha hydroxyprogesterone caproate (17-OHPC), and related progestins

PubMed Central

Attardi, Barbara J.; Zeleznik, Anthony; Simhan, Hyagriv; Chiao, Jye Ping; Mattison, Donald R; Caritis, Steve N

2007-01-01

Condensation 17-hydroxyprogesterone caproate is not better than progesterone in binding to progesterone or glucocorticoid receptors or eliciting gene expression in progesterone responsive genes. Comparison of progesterone and glucocorticoid receptor binding and stimulation of gene expression by progesterone, 17-alpha hydroxyprogesterone caproate (17-OHPC), and related progestins. Objective To determine whether the reduction in premature birth attributable to 17-OHPC occurs because of a greater affinity for progesterone (PR) or glucocorticoid (GR) receptors or by enhanced stimulation of progestogen responsive genes when compared with progesterone. Study Design We performed competitive steroid hormone receptor binding assays using cytosols expressing either recombinant human PR-A (rhPR-A) or B (rhPR-B) or rabbit uterine or thymic cytosols. We used four different carcinoma cell lines to assess transactivation of reporter genes or induction of alkaline phosphatase. Results Relative binding affinity of 17-OHPC for rhPR-B, rhPR-A and rabbit PR was 26–30% that of progesterone. Binding of progesterone to rabbit thymic GR was weak. 17-OHPC was comparable to progesterone in eliciting gene expression in all cell lines studied. Conclusions Binding to PR, GR or expression of progesterone-responsive genes is no greater with 17-OHPC than with progesterone. Other mechanisms must account for the beneficial effect of 17-OHPC on preterm birth rates. PMID:18060946

Ozone oxidation of pharmaceuticals, endocrine disruptors and pesticides during drinking water treatment.

PubMed

Broséus, R; Vincent, S; Aboulfadl, K; Daneshvar, A; Sauvé, S; Barbeau, B; Prévost, M

2009-10-01

This study investigates the oxidation of pharmaceuticals, endocrine disrupting compounds and pesticides during ozonation applied in drinking water treatment. In the first step, second-order rate constants for the reactions of selected compounds with molecular ozone (k(O3)) were determined in bench-scale experiments at pH 8.10: caffeine (650+/-22M(-1)s(-1)), progesterone (601+/-9M(-1)s(-1)), medroxyprogesterone (558+/-9M(-1)s(-1)), norethindrone (2215+/-76M(-1)s(-1)) and levonorgestrel (1427+/-62M(-1)s(-1)). Compared to phenolic estrogens (estrone, 17beta-estradiol, estriol and 17alpha-ethinylestradiol), the selected progestogen endocrine disruptors reacted far slower with ozone. In the second part of the study, bench-scale experiments were conducted with surface waters spiked with 16 target compounds to assess their oxidative removal using ozone and determine if bench-scale results would accurately predict full-scale removal data. Overall, the data provided evidence that ozone is effective for removing trace organic contaminants from water with ozone doses typically applied in drinking water treatment. Ozonation removed over 80% of caffeine, pharmaceuticals and endocrine disruptors within the CT value of about 2 mg min L(-1). As expected, pesticides were found to be the most recalcitrant compounds to oxidize. Caffeine can be used as an indicator compound to gauge the efficacy of ozone treatment.

[Customization of hormonal contraception].

PubMed

DE Leo, Vincenzo; Cianci, Antonio; DI Carlo, Costantino; Cappelli, Valentina; Fruzzetti, Franca

2018-02-01

In the last few years new oral contraceptives have been marketed showing a better safety profile for women. They are the result of important changes made to the old compounds. As far as the estrogenic component, with the aim of decreasing side effects, the dose of ethinyl estradiol has been reduced and synthetic estrogens have been replaced by natural estradiol, further improving the safety profile. Also the progestin component in the last years has been changed in terms of dose, endocrine and metabolic characteristics. Levonorgestrel is an androgenic progestin, but now there is the possibility of choosing progestins without androgenic effect (gestodene and desogestrel) or progestins with antiandrogenic effect (cyproterone acetate, dienogest, drospirenone, chlormadinone acetate), very useful in patients with hyperandrogenism. Some of these progestins, like Drospirenone, represented the real held contributing, because of its antimineralcorticoid action, to reduce an important side effect like fluid retention; moreover there is the possibility to choose products with high progestogen effect on endometrium (dienogest, nomegestrole acetate), resulting very effective in women with abnormal uterine bleedings. Also the regimens of administration have been changed, by shortening or eliminating the tablet-free period; in this way the women may avoid premenstrual symptoms. The oral is not the only route of administration, but today there are alternative routes like transdermal, transvaginal, intrauterine and subcutaneous, reducing gastro-intestinal interferences and possible mistakes in pill intake.

A multicenter phase IIb study of a novel combination of intramuscular androgen (testosterone decanoate) and oral progestogen (etonogestrel) for male hormonal contraception.

PubMed

Hay, Cathy J; Brady, Brian M; Zitzmann, Michael; Osmanagaoglu, Kaan; Pollanen, Pasi; Apter, Dan; Wu, Frederick C W; Anderson, Richard A; Nieschlag, Eberhard; Devroey, Paul; Huhtaniemi, Ilpo; Kersemaekers, Wendy M

2005-04-01

The effect of a novel combination of oral etonogestrel (ENG) and im testosterone decanoate (TD) on suppression of gonadotropins and spermatogenesis as a potential lead for male contraception was investigated. Healthy male volunteers were randomized into two groups receiving 300 microg ENG daily and 400 mg TD every 4 (n = 55) or 6 (n = 57) wk for 48 wk. At wk 48, all men except one in the 6-wk group suppressed sperm concentration to less than 1 million/ml. Faster suppression occurred in the 4-wk group. Gonadotropins were suppressed in both groups and most consistently in the 4-wk group. During treatment, trough testosterone levels increased into the normal range in the 4-wk group but remained just below normal in the 6-wk group. All peak levels were within the normal range. After treatment cessation, recovery of sperm counts and gonadotropins to normal levels occurred in both groups. Minor effects on weight and cholesterol were noted. Fourteen subjects withdrew because of an adverse event with those possibly related to the study medication reported more frequently in the 6-wk group (nine vs. one). In conclusion, the combination of 300 microg ENG with 400 mg TD every 4 wk was superior in terms of efficacy, hormone profiles, and safety. This represents a promising approach to male hormonal contraception.

Food allergy in infants and children: clinical evaluation and management.

PubMed

Levy, Y; Kornbroth, B; Ofer, I; Garty, B Z; Danon, Y L

1994-12-01

A total of 122 infants and children up to age 17 (69 males and 53 females) who were referred for food allergy to the Pediatric Allergy and Clinical Immunology Unit were evaluated by complete history, emphasizing the implicated foods, clinical presentation and involvement of various organ systems, physical examination, and prick skin tests to food allergens. Fourteen infants with a history of egg white allergy and positive skin tests to egg white also underwent skin tests (prick and intradermal in 1:100 dilution) to measles-mumps-rubella (MMR) vaccine; 35 children under 3 years old had 41 oral challenges with the suspected foods; and 9 children over 3 years old had 12 oral challenges with the suspected foods. We found that cow milk/humanized milk formula, egg white, soybean, and peanut are the main allergenic foods in the pediatric population. Thirteen children had 13 positive oral challenges: 12 to cow milk/humanized milk formula and one to egg white. Symptoms reproduced by oral challenges included urticarial and erythematous rash, conjunctival itching, angioedema, abdominal pain, vomiting, diarrhea, and rhinorrhea. No anaphylactic shock was reported. Negative skin test has an excellent predictive accuracy for negative oral challenge with the suspected food in children > 3 years old. The negative predictive accuracy of cow milk skin test in children < 3 years was 73%. Positive skin test is not a good predictor of a clinical reaction to food. Oral food challenge performed cautiously in a medical setting is the "gold standard" for diagnosis. MMR vaccine can be safely administered to infants with egg white allergy after skin tests with the vaccine are performed.

Principles of Work Sample Testing. Volume I: A Non-Empirical Taxonomy of Test Uses; Volume II: Evaluation of Personnel Testing Programs; Volume III: Construction and Evaluation of Work Sample Tests; Volume IV: Generalizability.

ERIC Educational Resources Information Center

Guion, Robert M.; Ironson, Gail H.

Challenges to classical psychometric theory are examined in the context of a broader range of fundamental, derived, and intuitive measurements in psychology; the challenges include content-referenced testing, latent trait theory, and generalizability theory. A taxonomy of psychological measurement is developed, based on: (1) purposes of…

9 CFR 113.309 - Bovine Parainfluenza3 Vaccine.

Code of Federal Regulations, 2011 CFR

2011-01-01

...-challenge for serum antibody studies. (6) Satisfactory Test Criteria: (i) All virus isolations attempts... develop antibody titers of 1:32 or greater by day 6 ±2 days post-challenge. (8) A sequential test... parainfluenza, susceptible calves shall be used as test animals (20 vaccinates and five controls). Blood samples...

9 CFR 113.309 - Bovine Parainfluenza3 Vaccine.

Code of Federal Regulations, 2014 CFR

2014-01-01

...-challenge for serum antibody studies. (6) Satisfactory Test Criteria: (i) All virus isolations attempts... develop antibody titers of 1:32 or greater by day 6 ±2 days post-challenge. (8) A sequential test... parainfluenza, susceptible calves shall be used as test animals (20 vaccinates and five controls). Blood samples...

9 CFR 113.309 - Bovine Parainfluenza3 Vaccine.

Code of Federal Regulations, 2013 CFR

2013-01-01

...-challenge for serum antibody studies. (6) Satisfactory Test Criteria: (i) All virus isolations attempts... develop antibody titers of 1:32 or greater by day 6 ±2 days post-challenge. (8) A sequential test... parainfluenza, susceptible calves shall be used as test animals (20 vaccinates and five controls). Blood samples...

Advanced Electronics Technologies: Challenges for Radiation Effects Testing, Modeling, and Mitigation

NASA Technical Reports Server (NTRS)

LaBel, Kenneth A.; Cohn, Lewis M.

2005-01-01

Emerging Electronics Technologies include: 1) Changes in the commercial semiconductor world; 2) Radiation Effects Sources (A sample test constraint); and 3) Challenges to Radiation Testing and Modeling: a) IC Attributes-Radiation Effects Implication b) Fault Isolation c) Scaled Geometry d) Speed e) Modeling Shortfall f) Knowledge Status

Increasing HIV testing among African immigrants in ireland: challenges and opportunities.

PubMed

Adedimeji, Adebola A; Asibon, Aba; O'Connor, Gerard; Carson, Richard; Cowan, Ethan; McKinley, Philip; Leider, Jason; Mallon, Patrick; Calderon, Yvette

2015-02-01

In 2012, immigrants constitute 63% of new cases of heterosexually transmitted HIV among individuals born outside Ireland. Current strategies to encourage testing can be ineffective if immigrants perceive them as culturally insensitive. We obtained qualitative data to explore challenges to voluntary HIV-testing for immigrants in Ireland. Content analysis was undertaken to identify and describe pertinent themes. Widespread beliefs that HIV is primarily a disease of African immigrants were identified as challenges that constrain access to testing and care. The organization and location of testing services, attitude of health workers, and beliefs regarding mandatory HIV-testing for immigrants seeking access to welfare benefits were also identified. Immigrants in Ireland encounter a variety of structural, cultural and personal constraints to HIV testing. Opportunities exist in the Irish Health system to increase testing among immigrants through greater acknowledgement of cultural sensitivities of immigrant groups.

Affordable Electro-Magnetic Interference (EMI) Testing on Large Space Vehicles

NASA Technical Reports Server (NTRS)

Aldridge, Edward; Curry, Bruce; Scully, Robert

2015-01-01

Objective: Perform System-Level EMI testing of the Orion Exploration Flight Test-1 (EFT-1) spacecraft in situ in the Kennedy Space Center's Neil Armstrong Operations & Checkout (O&C) Facility in 6 days. The only way to execute the system-level EMI testing and meet this schedule challenge was to perform the EMI testing in situ in the Final Assembly & System Test (FAST) Cell in a reverberant mode, not the direct illumination mode originally planned. This required the unplanned construction of a Faraday Cage around the vehicle and FAST Cell structure. The presence of massive steel platforms created many challenges to developing an efficient screen room to contain the RF energy and yield an effective reverberant chamber. An initial effectiveness test showed marginal performance, but improvements implemented afterward resulted in the final test performing surprisingly well! The paper will explain the design, the challenges, and the changes that made the difference in performance!

Laboratory Information Systems in Molecular Diagnostics: Why Molecular Diagnostics Data are Different.

PubMed

Lee, Roy E; Henricks, Walter H; Sirintrapun, Sahussapont J

2016-03-01

Molecular diagnostic testing presents new challenges to information management that are yet to be sufficiently addressed by currently available information systems for the molecular laboratory. These challenges relate to unique aspects of molecular genetic testing: molecular test ordering, informed consent issues, diverse specimen types that encompass the full breadth of specimens handled by traditional anatomic and clinical pathology information systems, data structures and data elements specific to molecular testing, varied testing workflows and protocols, diverse instrument outputs, unique needs and requirements of molecular test reporting, and nuances related to the dissemination of molecular pathology test reports. By satisfactorily addressing these needs in molecular test data management, a laboratory information system designed for the unique needs of molecular diagnostics presents a compelling reason to migrate away from the current paper and spreadsheet information management that many molecular laboratories currently use. This paper reviews the issues and challenges of information management in the molecular diagnostics laboratory.

Universal penetration test apparatus with fluid penetration sensor

DOEpatents

Johnson, P.W.; Stampfer, J.F.; Bradley, O.D.

1999-02-02

A universal penetration test apparatus is described for measuring resistance of a material to a challenge fluid. The apparatus includes a pad saturated with the challenge fluid. The apparatus includes a compression assembly for compressing the material between the pad and a compression member. The apparatus also includes a sensor mechanism for automatically detecting when the challenge fluid penetrates the material. 23 figs.

KSC-2009-6494

NASA Image and Video Library

2009-11-19

CAPE CANAVERAL, Fla. - At the Astronaut Hall of Fame near NASA’s Kennedy Space Center in Florida, the winners of the 2009 Astronaut Glove Challenge, part of NASA’s Centennial Challenges Program, pose for a group photograph with their friends, family and the event organizers. From left are Caroline Homer and her father, Peter Homer, winner of the $250,000 first prize; Alan Hayes, chairman of Volanz Aerospace Inc.; Andy Petro, manager of NASA Centennial Challenges; Ted Southern, winner of the $100,000 second prize; his friend and glove tester Amy Miller; and Paul Secor, Secor Strategies LLC. The nationwide competition focused on developing improved pressure suit gloves for astronauts to use while working in space. During the challenge, the gloves were submitted to burst tests, joint force tests and tests to measure their dexterity and strength during operation in a glove box which simulates the vacuum of space. Centennial Challenges is NASA’s program of technology prizes for the citizen-inventor. The winning prize for the Glove Challenge is $250,000 provided by the Centennial Challenges Program. Photo credit: NASA/Kim Shiflett

Evaluation of colonoscopic allergen provocation as a diagnostic tool in dogs with proven food hypersensitivity reactions.

PubMed

Allenspach, K; Vaden, S L; Harris, T S; Gröne, A; Doherr, M G; Griot-Wenk, M E; Bischoff, S C; Gaschen, F

2006-01-01

To evaluate the colonoscopic allergen provocation (COLAP) test as a new tool for the diagnosis of IgE-mediated food allergy. Oral food challenges as well as COLAP testing were performed in a colony of nine research dogs with proven immediate-type food allergic reactions. In addition, COLAP was performed in five healthy dogs. When compared with the oral challenge test, COLAP accurately determined 18 of 23 (73 per cent) positive oral challenge reactions (73 per cent) in dogs with food allergies and was negative in the healthy dogs. The accuracy of this new test may be higher than that for gastric sensitivity testing. Therefore, COLAP holds promise as a new test to confirm the diagnosis of suspect IgE-mediated food allergy in dogs.

Validation of sterilizing grade filtration.

PubMed

Jornitz, M W; Meltzer, T H

2003-01-01

Validation consideration of sterilizing grade filters, namely 0.2 micron, changed when FDA voiced concerns about the validity of Bacterial Challenge tests performed in the past. Such validation exercises are nowadays considered to be filter qualification. Filter validation requires more thorough analysis, especially Bacterial Challenge testing with the actual drug product under process conditions. To do so, viability testing is a necessity to determine the Bacterial Challenge test methodology. Additionally to these two compulsory tests, other evaluations like extractable, adsorption and chemical compatibility tests should be considered. PDA Technical Report # 26, Sterilizing Filtration of Liquids, describes all parameters and aspects required for the comprehensive validation of filters. The report is a most helpful tool for validation of liquid filters used in the biopharmaceutical industry. It sets the cornerstones of validation requirements and other filtration considerations.

Development and validation of challenge materials for double-blind, placebo-controlled food challenges in children.

PubMed

Vlieg-Boerstra, Berber J; Bijleveld, Charles M A; van der Heide, Sicco; Beusekamp, Berta J; Wolt-Plompen, Saskia A A; Kukler, Jeanet; Brinkman, Joep; Duiverman, Eric J; Dubois, Anthony E J

2004-02-01

The use of double-blind, placebo-controlled food challenges (DBPCFCs) is considered the gold standard for the diagnosis of food allergy. Despite this, materials and methods used in DBPCFCs have not been standardized. The purpose of this study was to develop and validate recipes for use in DBPCFCs in children by using allergenic foods, preferably in their usual edible form. Recipes containing milk, soy, cooked egg, raw whole egg, peanut, hazelnut, and wheat were developed. For each food, placebo and active test food recipes were developed that met the requirements of acceptable taste, allowance of a challenge dose high enough to elicit reactions in an acceptable volume, optimal matrix ingredients, and good matching of sensory properties of placebo and active test food recipes. Validation was conducted on the basis of sensory tests for difference by using the triangle test and the paired comparison test. Recipes were first tested by volunteers from the hospital staff and subsequently by a professional panel of food tasters in a food laboratory designed for sensory testing. Recipes were considered to be validated if no statistically significant differences were found. Twenty-seven recipes were developed and found to be valid by the volunteer panel. Of these 27 recipes, 17 could be validated by the professional panel. Sensory testing with appropriate statistical analysis allows for objective validation of challenge materials. We recommend the use of professional tasters in the setting of a food laboratory for best results.

Food-additive-induced urticaria: a survey of 838 patients with recurrent chronic idiopathic urticaria.

PubMed

Di Lorenzo, Gabriele; Pacor, Maria Luisa; Mansueto, Pasquale; Martinelli, Nicola; Esposito-Pellitteri, Maria; Lo Bianco, Claudia; Ditta, Vito; Leto-Barone, Maria Stefania; Napoli, Nicola; Di Fede, Gaetana; Rini, Giovambattista; Corrocher, Roberto

2005-11-01

Recurrent chronic idiopathic urticaria (RCIU) is a common skin condition that affects 0.1-3% of the population in the USA and Europe and accounts for nearly 75% of all 'ordinary' chronic urticaria (CU) cases. We studied 838 consecutive patients with RCIU referred to hospital between 1998 and 2003. Patients with known causes of CU were excluded. Clinical history, physical examination, and symptom diaries were evaluated during two periods, a diet-free period (1 week) and a food-additive-free diet (FAFD) period (4 weeks), respectively, and two double-blind placebo-controlled (DBPC) challenges of six food additives were administered. The first DBPC challenge included a mixture of the six food additives (DBPCmixed) given to all patients. The second DBPC challenge comprised the single food additives, administered at increasing doses (DBPCsingle) to patients with a positive DBPCmixed test and 105 patients with a negative DBPCmixed test, as a control. The DBPCmixed challenge was positive in 116 patients. None of the 105 control patients had a positive DBPCsingle test. Only 31 DBPCsingle tests were positive in patients with positive DBPCmixed challenge. Twenty-four of the 116 patients showing a positive DBPCmixed challenge also had a positive DBPCsingle result. Our results confirmed that food additive hypersensitivity reactions occurred in few RCIU patients using DBPCsingle challenge. The combination of the results of FAFD and DBPCmixed challenge seems to be of considerable practical interest for allergists, internists and dermatologists, rather than the data of clinical history and the results of DBPCsingle challenge, in patients with RCIU. Copyright (c) 2005 S. Karger AG, Basel.

Occupational asthma induced by cephalosporins.

PubMed

Sastre, J; Quirce, S; Novalbos, A; Lluch-Bernal, M; Bombín, C; Umpiérrez, A

1999-05-01

A 20-yr-old pharmaceutical worker who developed attacks of shortness of breath and wheezing 9 months after beginning work on a process in which cefadroxil powder was bottled or encapsulated will be described. Skin test with cefaxodril was negative. Baseline spirometry and methacholine inhalation test were normal. A controlled bronchial challenge test was carried out in a closed-circuit system with assessment of respirable dust concentration. Exposure to cefadroxil powder at a mean concentration of 10 mg x m(-3) for 10 min elicited an isolated immediate asthmatic response, but no response was observed to control challenge with lactose. Single-blind oral challenge test with amoxicillin up to 500 mg was well tolerated, whereas the oral challenge with cephalexin (25 mg) elicited an immediate asthmatic response. This patient had developed occupational asthma caused by inhalation of cefadroxil as confirmed by specific inhalation test. Since she tolerated oral amoxicillin, a synthetic penicillin with the side-chain identical to that of cefadroxil, it seems that she may be sensitized to the dihydrothiazine ring of cephalosporins.

Eosinophilic airway disease in a patient with a negative skin prick test, but a positive patch test with platinum salts--implications for medical surveillance.

PubMed

Merget, Rolf; Fartasch, Manigé; Sander, Ingrid; Van Kampen, Vera; Raulf, Monika; Brüning, Thomas

2015-09-01

We present the case of a 52-year-old woman with a topic dermatitis since adolescence who developed work-related hand eczema, cough and runny nose 12 years after she had started working as a laboratory technician at a precious metals refinery. While skin prick test with sodium hexachloroplatinate (SPTPt ) was negative, patch testing with ammonium tetrachloroplatinate was positive after 24, 48, 72, and 96 hr. Inhalation challenge with sodium hexachloroplatinate yielded cough, mild shortness of breath, and a maximal decrease of FEV1 of 8% from baseline 24 hr after the challenge. Significant increases of bronchial hyperresponsiveness, exhaled nitric monoxide and sputum eosinophils were documented after the challenge. We conclude that eosinophilic airway disease due to platinum salts may occur in SPTPt negative subjects. Both, patch testing and inhalation challenge with platinum salts should be considered in SPT negative subjects with occupational exposure to precious metal salts and work-related allergic symptoms. © 2015 Wiley Periodicals, Inc.

USDA regulatory guidelines and practices for veterinary Leptospira vaccine potency testing.

PubMed

Srinivas, G B; Walker, A; Rippke, B

2013-09-01

Batch-release potency testing of leptospiral vaccines licensed by the United States Department of Agriculture (USDA) historically was conducted through animal vaccination-challenge models. The hamster vaccination-challenge assay was Codified in 1974 for bacterins containing Leptospira pomona, Leptospira icterohaemorrhagiae, and Leptospira canicola, and in 1975 for bacterins containing Leptospira grippotyphosa. In brief, 10 hamsters are vaccinated with a specified dilution of bacterin. After a holding period, the vaccinated hamsters, as well as nonvaccinated controls, are challenged with virulent Leptospira and observed for mortality. Eighty percent of vaccinated hamsters must survive in the face of a valid challenge. The high cost of the Codified tests, in terms of monetary expense and animal welfare, prompted the Center for Veterinary Biologics (CVB) to develop ELISA alternatives for them. Potency tests for other serogroups, such as Leptospira hardjo-bovis, that do not have Codified requirements for potency testing continue to be examined on a case-by-case basis. Published by Elsevier Ltd.

A Structured Career Intervention Program for Academically Challenged Students

ERIC Educational Resources Information Center

Salleh, Amla; Abdullah, Syed Mohamad; Mahmud, Zuria; Ghavifekr, Simin; Ishak, Noriah

2013-01-01

A study was carried out to test the effects of a 2-week structured intervention program on academically challenged students' career development. A quasi-experimental study was designed using pre-tests, post-tests, and a control group approach to examine the effects of the intervention program. Data were collected from both the experimental and…

Computer-Based Signing Accommodations: Comparing a Recorded Human with an Avatar

ERIC Educational Resources Information Center

Russell, Michael; Kavanaugh, Maureen; Masters, Jessica; Higgins, Jennifer; Hoffmann, Thomas

2009-01-01

Many students who are deaf or hard-of-hearing are eligible for a signing accommodation for state and other standardized tests. The signing accommodation, however, presents several challenges for testing programs that attempt to administer tests under standardized conditions. One potential solution for many of these challenges is the use of…

Continuing challenges for computer-based neuropsychological tests.

PubMed

Letz, Richard

2003-08-01

A number of issues critical to the development of computer-based neuropsychological testing systems that remain continuing challenges to their widespread use in occupational and environmental health are reviewed. Several computer-based neuropsychological testing systems have been developed over the last 20 years, and they have contributed substantially to the study of neurologic effects of a number of environmental exposures. However, many are no longer supported and do not run on contemporary personal computer operating systems. Issues that are continuing challenges for development of computer-based neuropsychological tests in environmental and occupational health are discussed: (1) some current technological trends that generally make test development more difficult; (2) lack of availability of usable speech recognition of the type required for computer-based testing systems; (3) implementing computer-based procedures and tasks that are improvements over, not just adaptations of, their manually-administered predecessors; (4) implementing tests of a wider range of memory functions than the limited range now available; (5) paying more attention to motivational influences that affect the reliability and validity of computer-based measurements; and (6) increasing the usability of and audience for computer-based systems. Partial solutions to some of these challenges are offered. The challenges posed by current technological trends are substantial and generally beyond the control of testing system developers. Widespread acceptance of the "tablet PC" and implementation of accurate small vocabulary, discrete, speaker-independent speech recognition would enable revolutionary improvements to computer-based testing systems, particularly for testing memory functions not covered in existing systems. Dynamic, adaptive procedures, particularly ones based on item-response theory (IRT) and computerized-adaptive testing (CAT) methods, will be implemented in new tests that will be more efficient, reliable, and valid than existing test procedures. These additional developments, along with implementation of innovative reporting formats, are necessary for more widespread acceptance of the testing systems.

Safely diagnosing clinically significant penicillin allergy using only penicilloyl-poly-lysine, penicillin, and oral amoxicillin.

PubMed

Macy, Eric; Ngor, Eunis W

2013-01-01

Penicillin skin testing is rarely used to undiagnose penicillin "allergy" in the United States, partially because of concern that commercially available materials are inadequate. We determined whether skin testing with only commercially available penicilloyl-poly-lysine and penicillin followed by an oral amoxicillin challenge, if skin test-negative, can safely identify clinically significant penicillin allergy. Five hundred sequential persons with positive history of penicillin "allergy" were evaluated by skin testing with penicilloyl-poly-lysine and penicillin between June 8, 2010, and March 29, 2012. All persons with negative skin tests were given an oral amoxicillin challenge and observed for 1 hour. Persons undergoing penicillin allergy testing were representative of all health plan members with penicillin allergy. Only 4 persons (0.8%; 95% CI, 0.32%-2.03%) had a positive skin test result. Only 4 persons (0.8%; 95% CI, 0.32%-2.03%) had an acute objective oral amoxicillin challenge reaction. Fifteen persons (3.0%; 95% CI, 1.83%-4.98%) had subjective oral challenge reactions, either acute transient itching or dizziness. All were women and 11 (73.3%) had multiple drug intolerance syndrome. None had severe reactions or objective signs. These were not considered to be positive challenge reactions. Sixty-eight subjects (13.6%) who were negative on testing were exposed to 88 courses of penicillins during 90 days of follow-up. New reactions were reported after 4 courses (4.5%), 3 (75%) occurring in subjects with multiple drug intolerance syndrome. Penicillin skin testing, using only penicilloyl-poly-lysine and penicillin, followed by oral amoxicillin challenge, if negative, can safely identify clinically significant IgE-mediated penicillin allergy in patients who use health care in the United States at this time. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

New Mass Properties Engineers Aerospace Ballasting Challenge Facilitated by the SAWE Community

NASA Technical Reports Server (NTRS)

Cutright, Amanda; Shaughnessy, Brendan

2010-01-01

The discipline of Mass Properties Engineering tends to find the engineers; not typically vice versa. In this case, two engineers quickly found their new responsibilities deep in many aspects of mass properties engineering and required to meet technical challenges in a fast paced environment. As part of NASA's Constellation Program, a series of flight tests will be conducted to evaluate components of the new spacecraft launch vehicles. One of these tests is the Pad Abort 1 (PA-1) flight test which will test the Launch Abort System (LAS), a system designed to provide escape for astronauts in the event of an emergency. The Flight Test Articles (FTA) used in this flight test are required to match mass properties corresponding to the operational vehicle, which has a continually evolving design. Additionally, since the structure and subsystems for the Orion Crew Module (CM) FTA are simplified versions of the final product, thousands of pounds of ballast are necessary to achieve the desired mass properties. These new mass properties engineers are responsible for many mass properties aspects in support of the flight test, including meeting the ballasting challenge for the CM Boilerplate FTA. SAWE expert and experienced mass properties engineers, both those that are directly on the team and many that supported via a variety of Society venues, significantly contributed to facilitating the success of addressing this particular mass properties ballasting challenge, in addition to many other challenges along the way. This paper discusses the details regarding the technical aspects of this particular mass properties challenge, as well as identifies recommendations for new mass properties engineers that were learned from the SAWE community along the way.

Increased anti-Mullerian hormone levels and ovarian size in a subgroup of women with functional hypothalamic amenorrhea: further identification of the link between polycystic ovary syndrome and functional hypothalamic amenorrhea.

PubMed

Carmina, Enrico; Fruzzetti, Franca; Lobo, Roger A

2016-06-01

Functional hypothalamic amenorrhea is a disorder characterized by cessation of menstrual cycles in the absence of organic disease. In most patients, it occurs in adult life after a stressful event and may be related to a condition of mild chronic energy deprivation. The endocrine pattern is characterized by low estrogen levels with an absent response to a progestogen challenge test and low-normal gonadotropin levels. A few studies have shown that some of these women may have some features of polycystic ovary syndrome; these features include an increased androgen response to gonadotropins, increased anti-Mullerian hormone levels, and altered ovarian morphology or increased ovarian size. These findings suggest a link between these 2 completely different disorders: functional hypothalamic amenorrhea and polycystic ovary syndrome. The importance of the possible coexistence of these disorders in some women is important for follow-up of these women and in their treatment if they desire to become pregnant. To determine whether a subgroup of well-characterized women with functional hypothalamic amenorrhea may have the coexistence of polycystic ovary syndrome. Retrospective analysis of women with functional hypothalamic amenorrhea. Forty consecutive patients and 28 normal age-matched control patients were studied. Blood was obtained for serum anti-Mullerian hormone, androgens, and other hormone levels and all women had ovarian ultrasonographic measurements. In the entire group of women with functional hypothalamic amenorrhea, anti-Mullerian hormone and ovarian volume were greater than in control patients. In 13 patients (32.5%), anti-Mullerian hormone was elevated (>4.7 ng/mL, levels consistent with polycystic ovary syndrome) and in this group, ovarian volume was significantly greater than in the remaining patients with functional hypothalamic amenorrhea. Four of the 13 women with functional hypothalamic amenorrhea who had elevated anti-Mullerian hormone levels (10%), also had ovarian volume ≥10 cc (consistent with polycystic ovarian syndrome). In these patients all studied androgens were in the upper normal range or slightly elevated despite low-normal gonadotropins; mean total testosterone was significantly greater than in the other patients with increased anti-Mullerian hormone values with normal ovarian size (P<.05.) Six other women with functional hypothalamic amenorrhea who had increased anti-Mullerian hormone also had isolated elevations of some androgen levels, but mean testosterone and ovarian size were normal. As many as 10% of women with functional hypothalamic amenorrhea may have the coexistence of polycystic ovary syndrome. Because no signs or symptoms of this disorder were reported by these women before the appearance of the amenorrhea, it does not seem to be a coincidental relationship. The possibility that functional hypothalamic amenorrhea favors the appearance of polycystic ovary syndrome or more likely, that a mild (ovulatory) phenotype of polycystic ovary syndrome predisposes to the development of functional hypothalamic amenorrhea should be considered. Possible mechanisms are unclear and need to be investigated but may involve common vulnerabilities such as psychologic and mood disturbances. Copyright © 2016 Elsevier Inc. All rights reserved.

Short communication: estrus synchronization using progestogens or cloprostenol in tropical hair sheep.

PubMed

Alavez Ramírez, Alejandro; Arroyo Ledezma, Jaime; Montes Pérez, Ruben; Zamora Bustillos, Roberto; Navarrete Sierra, Luis Fernando; Magaña Sevilla, Hector

2014-12-01

The objective of the experiment was to compare the use of a PGF2α analogue (Cloprostenol) IM, with an intravaginal progestagen sponge, flurogestone acetate (FGA), and equine chorionic gonadotropin (eCG) IM application protocol. A total of 30 cyclical hair ewes (54.07 ± 0.5 kg live weight, body condition score 3.5 ± 0.5, and age 3 ± 1 years) were used. For the control group ewes (n = 15), intravaginal sponges (IS) impregnated with 20 mg of FGA were inserted for 12 days with 500 IU of eCG IM at sponges withdrawal. For the PG group ewes (Treatment group n = 15), two injections of Cloprostenol (75 mcg) were given 12 days apart. The presence of estrus was detected using two rams with 8 h interval beginning at the end of the treatment. Progesterone concentrations in blood were measured by solid phase radioimmunoassay. A student's t test was performed to analyze the duration of estrus and the interval between the ends of the treatment and the onset of estrus (ET-OE) presentation. Progesterone levels were compared with two-way ANOVA, with treatment, and day of menstrual cycle as fixed factors. Treatment costs ratio was calculated by dividing the total costs of FGA IS application between total costs of Cloprostenol application. Significant differences (P < 0.05) were found in the (ET-OE) interval and estrus duration. For the control group, estrus was presented at 30 + 8.2 h; in treatment group, at 44 h after the last application, duration of estrus was 54.9 + 8.34 h, and 41 + 1.83 h for the control and treatment group, pregnancy rates were 53.3 and 60.0 %, respectively. Significant differences (P < 0.001) were found from days 9 to 13 on Progesterone levels in both treatments. Treatment costs of Cloprostenol protocol were 2.63 cheaper than FGA including disposable material, biological products, and labor. It was concluded that Cloprostenol could be an effective tool in estrus synchronization in hair sheep in tropical areas.

Increasing age influences uterine integrity, but not ovarian function or oocyte quality, in the cheetah (Acinonyx jubatus).

PubMed

Crosier, Adrienne E; Comizzoli, Pierre; Baker, Tom; Davidson, Autumn; Munson, Linda; Howard, JoGayle; Marker, Laurie L; Wildt, David E

2011-08-01

Although the cheetah (Acinonyx jubatus) routinely lives for more than 12 yr in ex situ collections, females older than 8 yr reproduce infrequently. We tested the hypothesis that reproduction is compromised in older female cheetahs due to a combination of disrupted gonadal, oocyte, and uterine function/integrity. Specifically, we assessed 1) ovarian response to gonadotropins; 2) oocyte meiotic, fertilization, and developmental competence; and 3) uterine morphology in three age classes of cheetahs (young, 2-5 yr, n = 17; prime, 6-8 yr, n = 8; older, 9-15 yr, n = 9). Ovarian activity was stimulated with a combination of equine chorionic gonadotropin and human chorionic gonadotropin (hCG), and fecal samples were collected for 45 days before gonadotropin treatment and for 30 days after oocyte recovery by laparoscopy. Twenty-six to thirty hours post-hCG, uterine morphology was examined by ultrasound, ovarian follicular size determined by laparoscopy, and aspirated oocytes assessed for nuclear status or inseminated in vitro. Although no influence of age on fecal hormone concentrations or gross uterine morphology was found (P > 0.05), older females produced fewer (P < 0.05) total antral follicles and oocytes compared to younger counterparts. Regardless of donor age, oocytes had equivalent (P > 0.05) nuclear status and ability to reach metaphase II and fertilize in vitro. A histological assessment of voucher specimens revealed an age-related influence on uterine tissue integrity, with more than 87% and more than 56% of older females experiencing endometrial hyperplasia and severe pathologies, respectively. Our collective findings reveal that lower reproductive success in older cheetahs appears to be minimally influenced by ovarian and gamete aging and subsequent dysfunction. Rather, ovaries from older females are responsive to gonadotropins, produce normative estradiol/progestogen concentrations, and develop follicles containing oocytes with the capacity to mature and be fertilized. A more likely cause of reduced fertility may be the high prevalence of uterine endometrial hyperplasia and related pathologies. The discovery that a significant proportion of oocytes from older females have developmental capacity in vitro suggests that in vitro fertilization and embryo transfer may be useful for "rescuing" the genome of older, nonreproductive cheetahs.

Immediate hypersensitivity to iodinated contrast media: diagnostic accuracy of skin tests and intravenous provocation test with low dose.

PubMed

Sesé, L; Gaouar, H; Autegarden, J-E; Alari, A; Amsler, E; Vial-Dupuy, A; Pecquet, C; Francès, C; Soria, A

2016-03-01

The diagnosis of HSR to iodinated contrast media (ICM) is challenging based on clinical history and skin tests. This study evaluates the negative predictive value (NPV) of skin tests and intravenous provocation test (IPT) with low-dose ICM in patients with suspected immediate hypersensitivity reaction (HSR) to ICM. Thirty-seven patients with suspected immediate hypersensitivity reaction to ICM were included retrospectively. Skin tests and a single-blind placebo-controlled intravenous provocation test (IPT) with low-dose iodinated contrast media (ICM) were performed. Skin tests with ICM were positive in five cases (one skin prick test and five intradermal test). Thirty-six patients were challenged successfully by IPT, and only one patient had a positive challenge result, with a grade I reaction by the Ring and Messmer classification. Ten of 23 patients followed up by telephone were re-exposed to a negative tested ICM during radiologic examination; two experienced a grade I immediate reaction. For immediate hypersensitivity reaction to ICM, the NPV for skin tests and IPT with low dose was 80% (95% CI 44-97%). © 2016 John Wiley & Sons Ltd.

Experimental intramammary inoculation with Mycoplasma bovis in vaccinated and unvaccinated cows: effect on milk production and milk quality.

PubMed Central

Boothby, J T; Jasper, D E; Thomas, C B

1986-01-01

The effect of vaccination on milk production was evaluated in vaccinated and control cows experimentally challenged in two of four quarters with live Mycoplasma bovis. During the first three weeks after experimental challenge, six of eight unchallenged quarters on vaccinated cows and seven of eight unchallenged quarters on control cows became infected. Most of these quarters secreted normal milk, with negative California Mastitis Test scores and maintained normal milk production throughout most of the study (although some quarters on control cows remained infected). All challenged quarters became infected, had strong California Mastitis Test reactions, and had a drastic (greater than 85%) loss in milk production. Thereafter, four of eight challenged quarters on control cows remained infected, had mostly positive California Mastitis Test scores, produced mostly normal-appearing milk, and recovered some productive capabilities. By the end of the study no M. bovis could be recovered from challenged quarters on vaccinated cows and the milk appeared mostly normal. The California Mastitis Test scores on these quarters, however, remained elevated and milk production remained very low. PMID:3756674

Predicting hypoxaemia during flights in children with cystic fibrosis

PubMed Central

Buchdahl, R; Babiker, A; Bush, A; Cramer, D

2001-01-01

BACKGROUND—We have previously suggested that it is possible to predict oxygen desaturation during flight in children with cystic fibrosis and chronic lung disease by non-invasive measurement of oxygen saturation following inhalation of 15% oxygen—the pre-flight hypoxic challenge. This study reports on the results of measurements over 5years.
METHODS—The study comprised a pre-flight hypoxic challenge measuring oxygen saturation by finger tip pulse oximetry (SpO2) during tidal breathing of 15% oxygen in nitrogen and spirometric testing 1 month before the flight followed by SpO2 measurements during intercontinental flights to and from holidays abroad with children in wake and sleep states.
RESULTS—Pre-flight tests were completed on 87 children with cystic fibrosis. Desaturation of <90% occurred in 10 children at some stage during the flight, three of whom received supplementary oxygen. Using a cut off SpO2 of 90%, the pre-flight hypoxic challenge correctly predicted desaturation in only two of these children. The sensitivity and specificity of the pre-flight hypoxic challenge were 20% and 99%, respectively, compared with 70% and 96% for spirometric tests (using a cut off for forced expiratory volume in 1 second (FEV1) of <50% predicted). Overall, pre-flight spirometric tests were a better predictor of desaturation during flight with the area under the Receiver Operating Characteristic (ROC) curve of 0.89 compared with 0.73 for the hypoxic challenge test.
CONCLUSIONS—In this group of subjects pre-flight spirometric testing was a better predictor of desaturation during flight than the pre-flight hypoxic challenge.

 PMID:11641514

Levodopa-Induced Changes in Electromyographic Patterns in Patients with Advanced Parkinson’s Disease

PubMed Central

Ruonala, Verneri; Pekkonen, Eero; Airaksinen, Olavi; Kankaanpää, Markku; Karjalainen, Pasi A; Rissanen, Saara M

2018-01-01

Levodopa medication is the most efficient treatment for motor symptoms of Parkinson’s disease (PD). Levodopa significantly alleviates rigidity, rest tremor, and bradykinesia in PD. The severity of motor symptoms can be graded with UPDRS-III scale. Levodopa challenge test is routinely used to assess patients’ eligibility to deep-brain stimulation (DBS) in PD. Feasible and objective measurements to assess motor symptoms of PD during levodopa challenge test would be helpful in unifying the treatment. Twelve patients with advanced PD who were candidates for DBS treatment were recruited to the study. Measurements were done in four phases before and after levodopa challenge test. Rest tremor and rigidity were evaluated using UPDRS-III score. Electromyographic (EMG) signals from biceps brachii and kinematic signals from forearm were recorded with wireless measurement setup. The patients performed two different tasks: arm isometric tension and arm passive flexion–extension. The electromyographic and the kinematic signals were analyzed with parametric, principal component, and spectrum-based approaches. The principal component approach for isometric tension EMG signals showed significant decline in characteristics related to PD during levodopa challenge test. The spectral approach on passive flexion–extension EMG signals showed a significant decrease on involuntary muscle activity during the levodopa challenge test. Both effects were stronger during the levodopa challenge test compared to that of patients’ personal medication. There were no significant changes in the parametric approach for EMG and kinematic signals during the measurement. The results show that a wireless and wearable measurement and analysis can be used to study the effect of levodopa medication in advanced Parkinson’s disease. PMID:29459845

The challenge of developmentally appropriate care: predictive genetic testing in young people for familial adenomatous polyposis.

PubMed

Duncan, Rony E; Gillam, Lynn; Savulescu, Julian; Williamson, Robert; Rogers, John G; Delatycki, Martin B

2010-03-01

Predictive genetic tests for familial adenomatous polyposis (FAP) are routinely offered to young people during early adolescence. While this is not controversial, due to the medical benefit conferred by the test, it is nonetheless challenging as a consequence of the stage of life of the young people, and the simultaneous involvement of multiple family members. Despite these challenges, it is possible to ensure that the test is offered in such a way that it actively acknowledges and facilitates young people's developing autonomy and psychosocial well-being. In this paper we present findings from ten in-depth interviews with young people who have undergone predictive genetic testing for FAP (four male, six female; five gene-positive, five gene-negative; aged 10-17 years at the time of their predictive test; aged 12-25 years at the time of their research interview). We present five themes that emerged from the interviews which highlight key ethical challenges associated with such testing. These are: (1) the significance of the test; (2) young people's lack of involvement in the decision to be tested; (3) young people's limited understanding; (4) provision of the blood test at the first visit; and (5) group testing of family members. We draw on these themes to make eight recommendations for future practice. Together, these recommendations highlight the importance of providing developmentally appropriate care to young people undergoing predictive genetic testing for FAP.

Repeated Challenge Studies: A Comparison of Union-Intersection Testing with Linear Modeling.

ERIC Educational Resources Information Center

Levine, Richard A.; Ohman, Pamela A.

1997-01-01

Challenge studies can be used to see whether there is a causal relationship between an agent of interest and a response. An approach based on union-intersection testing is presented that allows researchers to examine observations on a single subject and test the hypothesis of interest. An application using psychological data is presented. (SLD)

Wireless Instrumentation Systems for Flight Testing at NASA AFRC

NASA Technical Reports Server (NTRS)

Hang, Richard

2017-01-01

NASA Armstrong Flight Research Center is revolutionizing its traditional wired instrumentation systems with wireless technologies. This effort faces many technical challenges, such as spectrum compliance, time synchronization, power distribution and airworthiness. This presentation summarizes NASA AFRC's flight test capabilities with current conventional instrumentation methodology and highlights the technical challenges of wireless systems used for flight test research applications.

Radiation Testing on State-of-the-Art CMOS: Challenges, Plans, and Preliminary Results

NASA Technical Reports Server (NTRS)

LaBel, Kenneth A.; Cohn, Lewis M.

2009-01-01

At GOMAC 2007 and 2008, we discussed a variety of challenges for radiation testing of modern semiconductor devices and technologies [1, 2]. In this presentation, we provide more specific details in this on-going investigation focusing on out-of-the-box lessons observed for providing radiation effects assurances as well as preliminary test results.

Immunologic responses against hydrolyzed soy protein in dogs with experimentally induced soy hypersensitivity.

PubMed

Puigdemont, Anna; Brazís, Pilar; Serra, Montserrat; Fondati, Alessandra

2006-03-01

To assess whether dogs with experimentally induced type I hypersensitivity against soy protein would respond to soy hydrolysate and develop cutaneous or gastrointestinal tract reactions after intradermal and oral challenge exposure. 12 naïve Beagle pups (9 sensitized and 3 control dogs). 9 dogs were sensitized against soy protein by administration of allergens during a 90-day period. After the sensitization period, serum concentrations of soy-specific IgE were determined and an intradermal test was performed to confirm the dogs were sensitized against soy protein. An intradermal challenge test and an oral challenge test with native and hydrolyzed soy protein were conducted on 6 sensitized and 2 control dogs. High serum concentrations of soy-specific IgE and positive results for the intradermal test were observed for the 9 sensitized dogs after completion of the sesitization process. Sensitized dogs challenge exposed with hydrolyzed soy protein had a reduced inflammatory response after intradermal injection and no clinical response after an oral challenge exposure, compared with responses after intradermal and oral challenge exposure with native soy protein. Soy-sensitized dogs did not respond to oral administration of hydrolyzed soy protein. Thus, hydrolyzed soy protein may be useful in diets formulated for the management of dogs with adverse reactions to food.

The current preference for the immuno-analytical ELISA method for quantitation of steroid hormones (endocrine disruptor compounds) in wastewater in South Africa.

PubMed

Manickum, Thavrin; John, Wilson

2015-07-01

The availability of national test centers to offer a routine service for analysis and quantitation of some selected steroid hormones [natural estrogens (17-β-estradiol, E2; estrone, E1; estriol, E3), synthetic estrogen (17-α-ethinylestradiol, EE2), androgen (testosterone), and progestogen (progesterone)] in wastewater matrix was investigated; corresponding internationally used chemical- and immuno-analytical test methods were reviewed. The enzyme-linked immunosorbent assay (ELISA) (immuno-analytical technique) was also assessed for its suitability as a routine test method to quantitate the levels of these hormones at a sewage/wastewater treatment plant (WTP) (Darvill, Pietermaritzburg, South Africa), over a 2-year period. The method performance and other relevant characteristics of the immuno-analytical ELISA method were compared to the conventional chemical-analytical methodology, like gas/liquid chromatography-mass spectrometry (GC/LC-MS), and GC-LC/tandem mass spectrometry (MSMS), for quantitation of the steroid hormones in wastewater and environmental waters. The national immuno-analytical ELISA technique was found to be sensitive (LOQ 5 ng/L, LOD 0.2-5 ng/L), accurate (mean recovery 96%), precise (RSD 7-10%), and cost-effective for screening and quantitation of these steroid hormones in wastewater and environmental water matrix. A survey of the most current international literature indicates a fairly equal use of the LC-MS/MS, GC-MS/MS (chemical-analytical), and ELISA (immuno-analytical) test methods for screening and quantitation of the target steroid hormones in both water and wastewater matrix. Internationally, the observed sensitivity, based on LOQ (ng/L), for the steroid estrogens E1, E2, EE2, is, in decreasing order: LC-MSMS (0.08-9.54) > GC-MS (1) > ELISA (5) (chemical-analytical > immuno-analytical). At the national level, the routine, unoptimized chemical-analytical LC-MSMS method was found to lack the required sensitivity for meeting environmental requirements for steroid hormone quantitation. Further optimization of the sensitivity of the chemical-analytical LC-tandem mass spectrometry methods, especially for wastewater screening, in South Africa is required. Risk assessment studies showed that it was not practical to propose standards or allowable limits for the steroid estrogens E1, E2, EE2, and E3; the use of predicted-no-effect concentration values of the steroid estrogens appears to be appropriate for use in their risk assessment in relation to aquatic organisms. For raw water sources, drinking water, raw and treated wastewater, the use of bioassays, with trigger values, is a useful screening tool option to decide whether further examination of specific endocrine activity may be warranted, or whether concentrations of such activity are of low priority, with respect to health concerns in the human population. The achievement of improved quantitation limits for immuno-analytical methods, like ELISA, used for compound quantitation, and standardization of the method for measuring E2 equivalents (EEQs) used for biological activity (endocrine: e.g., estrogenic) are some areas for future EDC research.

Reducing animal experimentation in foot-and-mouth disease vaccine potency tests.

PubMed

Reeve, Richard; Cox, Sarah; Smitsaart, Eliana; Beascoechea, Claudia Perez; Haas, Bernd; Maradei, Eduardo; Haydon, Daniel T; Barnett, Paul

2011-07-26

The World Organisation for Animal Health (OIE) Terrestrial Manual and the European Pharmacopoeia (EP) still prescribe live challenge experiments for foot-and-mouth disease virus (FMDV) immunogenicity and vaccine potency tests. However, the EP allows for other validated tests for the latter, and specifically in vitro tests if a "satisfactory pass level" has been determined; serological replacements are also currently in use in South America. Much research has therefore focused on validating both ex vivo and in vitro tests to replace live challenge. However, insufficient attention has been given to the sensitivity and specificity of the "gold standard"in vivo test being replaced, despite this information being critical to determining what should be required of its replacement. This paper aims to redress this imbalance by examining the current live challenge tests and their associated statistics and determining the confidence that we can have in them, thereby setting a standard for candidate replacements. It determines that the statistics associated with the current EP PD(50) test are inappropriate given our domain knowledge, but that the OIE test statistics are satisfactory. However, it has also identified a new set of live animal challenge test regimes that provide similar sensitivity and specificity to all of the currently used OIE tests using fewer animals (16 including controls), and can also provide further savings in live animal experiments in exchange for small reductions in sensitivity and specificity. Copyright © 2011 Elsevier Ltd. All rights reserved.

Opportunities and strategies to further reduce animal use for Leptospira vaccine potency testing.

PubMed

Walker, A; Srinivas, G B

2013-09-01

Hamsters are routinely infected with virulent Leptospira for two purposes in the regulation of biologics: the performance of Codified potency tests and maintenance of challenge culture for the Codified potency tests. Options for reducing animal use in these processes were explored in a plenary lecture at the "International Workshop on Alternative Methods for Leptospira Vaccine Potency Testing: State of the Science and the Way Forward" held at the Center for Veterinary Biologics in September 2012. The use of validated in vitro potency assays such as those developed by the U.S. Department of Agriculture for Leptospira (L.) canicola, Leptospira grippotyphosa, Leptospira pomona, and Leptospira icterohaemorrhagiae rather than the Codified hamster vaccination-challenge assay was encouraged. Alternatives such as reduced animal numbers in the hamster vaccination-challenge testing were considered for problematic situations. Specifically, the merits of sharing challenge controls, reducing group sizes, and eliminating animals for concurrent challenge dose titration were assessed. Options for maintaining virulent, stable cultures without serial passage through hamsters or with decreased hamster use were also discussed. The maintenance of virulent Leptospira without the use of live animals is especially difficult since a reliable means to maintain virulence after multiple in vitro passages has not yet been identified. Published by Elsevier Ltd.

Evaluation of Food Allergy in Children by Skin Prick Tests with Commercial Extracts and Fresh Foods, Specific IgE and, Open Oral Food Challenge-Our Five Years Experience in Food Allergy Work-up.

PubMed

Zivanovic, Mirjana; Atanasković-Marković, Marina; Medjo, Biljana; Gavrović-Jankulović, Marija; Smiljanić, Katarina; Tmušić, Vladimir; Djurić, Vojislav

2017-04-01

IgE- mediated food allergy affects 6-8% of children. Our study aimed to define the correlations between the results obtained with skin prick tests (SPTs) using commercial extracts and fresh foods, and the correlations between these result and those obtained with specific IgE (sIgE) and/ or challenge. Children aged from 2 months to 6 years were recruited prospectively. Overall 571 children were positive to one food. In all children we performed  SPT using commercial extracts of suspected food and fresh foods and sIgE. If SPT and sIgE test results did not correspond to the history, we performed open oral food challenge. Sensitivity of SPT with commercial extracts for all tested food was poor (3-35%), while  sensitivity of fresh food skin prick tests (FFSPT) was excellent (50-100%), and showed correlation with open oral food challenge (p<0.001). Our results suggest that fresh food extracts are more effective in detecting sensitization and with levels of sIgE greater than class 3 could predict clinical reactivity, without the need for potentially hazardous food challenges.

Microbiological Challenge Testing for Listeria Monocytogenes in Ready-to-Eat Food: A Practical Approach.

PubMed

Spanu, Carlo; Scarano, Christian; Ibba, Michela; Pala, Carlo; Spanu, Vincenzo; De Santis, Enrico Pietro Luigi

2014-12-09

Food business operators (FBOs) are the primary responsible for the safety of food they place on the market. The definition and validation of the product's shelf-life is an essential part for ensuring microbiological safety of food and health of consumers. In the frame of the Regulation (EC) No 2073/2005 on microbiological criteria for foodstuffs, FBOs shall conduct shelf-life studies in order to assure that their food does not exceed the food safety criteria throughout the defined shelf-life. In particular this is required for ready-to-eat (RTE) food that supports the growth of Listeria monocytogenes . Among other studies, FBOs can rely on the conclusion drawn by microbiological challenge tests. A microbiological challenge test consists in the artificial contamination of a food with a pathogen microorganism and aims at simulating its behaviour during processing and distribution under the foreseen storage and handling conditions. A number of documents published by international health authorities and research institutions describes how to conduct challenge studies. The authors reviewed the existing literature and described the methodology for implementing such laboratory studies. All the main aspects for the conduction of L. monocytogenes microbiological challenge tests were considered, from the selection of the strains, preparation and choice of the inoculum level and method of contamination, to the experimental design and data interpretation. The objective of the present document is to provide an exhaustive and practical guideline for laboratories that want to implement L. monocytogenes challenge testing on RTE food.

Microbiological Challenge Testing for Listeria Monocytogenes in Ready-to-Eat Food: A Practical Approach

PubMed Central

Scarano, Christian; Ibba, Michela; Pala, Carlo; Spanu, Vincenzo; De Santis, Enrico Pietro Luigi

2014-01-01

Food business operators (FBOs) are the primary responsible for the safety of food they place on the market. The definition and validation of the product’s shelf-life is an essential part for ensuring microbiological safety of food and health of consumers. In the frame of the Regulation (EC) No 2073/2005 on microbiological criteria for foodstuffs, FBOs shall conduct shelf-life studies in order to assure that their food does not exceed the food safety criteria throughout the defined shelf-life. In particular this is required for ready-to-eat (RTE) food that supports the growth of Listeria monocytogenes. Among other studies, FBOs can rely on the conclusion drawn by microbiological challenge tests. A microbiological challenge test consists in the artificial contamination of a food with a pathogen microorganism and aims at simulating its behaviour during processing and distribution under the foreseen storage and handling conditions. A number of documents published by international health authorities and research institutions describes how to conduct challenge studies. The authors reviewed the existing literature and described the methodology for implementing such laboratory studies. All the main aspects for the conduction of L. monocytogenes microbiological challenge tests were considered, from the selection of the strains, preparation and choice of the inoculum level and method of contamination, to the experimental design and data interpretation. The objective of the present document is to provide an exhaustive and practical guideline for laboratories that want to implement L. monocytogenes challenge testing on RTE food. PMID:27800369

Allergy to cow's milk proteins: what contribution does hypersensitivity in skin tests have to this diagnosis?

PubMed

Costa, Aldo José Fernandes; Sarinho, Emanuel Sávio Cavalcanti; Motta, Maria Eugênia Farias Almeida; Gomes, Priscila Nogueira; de Oliveira de Melo, Sabrina Maria; da Silva, Giselia Alves Pontes

2011-02-01

Food allergy is an immunologically mediated adverse reaction to food protein. Cow's milk protein allergy (CMPA) is the most frequent type and is the one that is most difficult to diagnose. This study had the objective of analyzing the accuracy of hypersensitivity and specific IgE skin tests among children with CMPA and predominantly gastrointestinal clinical manifestations. The participants in this study were 192 children aged one and five (median of 2 yr). Among these, 122 underwent open oral challenge to the suspected food. After evaluating the sensitivity, specificity and positive and negative predictive values (respectively, PPV and NPV) of skin and specific IgE tests in relation to the gold standard (open oral challenge); all the children underwent the skin prick test (SPT), specific IgE test and atopy patch test (APT) for cow's milk, eggs, wheat and peanuts and the open oral challenge for the food to which the child was sensitive or had suspected sensitivity. Presence of food allergy was confirmed for 50 children (40.9%). Among these cases, 44/50 (88%) were of allergy to cow's milk protein. Children who presented a positive response to an oral challenge to cow's milk protein were considered to be cases, while the controls were children with negative response. Twenty-two of the 44 cases (50.0%) presented symptoms within the first 4 h after the challenge. The SPT presented 31.8% sensitivity, 90.3% specificity, 66.7% PPV and 68.4% NPV. The APT presented 25.0% sensitivity, 81.9% specificity, 45.8% PPV and 64.1% NPV. The specific IgE test presented, respectively, 20.5%, 88.9%, 52.9% and 64.6%. Despite the operational difficulty and the possible exposure risk, oral challenge is the best method for diagnosing CMPA, because of the low sensitivity and PPV of skin and specific IgE tests. © 2011 John Wiley & Sons A/S.

Implementation Considerations for Multisite Clinical Trials with Cognitive Neuroscience Tasks

PubMed Central

Keefe, Richard S. E.; Harvey, Philip D.

2008-01-01

Multisite clinical trials aimed at cognitive enhancement across various neuropsychiatric conditions have employed standard neuropsychological tests as outcome measures. While these tests have enjoyed wide clinical use and have proven reliable and predictive of functional disability, a number of implementation challenges have arisen when these tests are used in clinical trials. These issues are likely to be magnified in future studies when cognitive neuroscience (CN) procedures are explored in these trials, because in their current forms CN procedures are less standardized and more difficult to teach and monitor. For multisite trials, we anticipate that the most challenging issues will include assuring tester competence, monitoring tester performance, specific challenges with complex assessment methods, and having resources available for adequate monitoring of data quality. Suggestions for overcoming these implementation challenges are offered. PMID:18495645

Anticipating the Ethical Challenges of Psychiatric Genetic Testing.

PubMed

Appelbaum, Paul S; Benston, Shawna

2017-07-01

Genetic testing for mental illness is likely to become increasingly prevalent as the science behind it is refined. This article identifies anticipated ethical challenges for patients, psychiatrists, and genetic counselors and makes recommendations for addressing them. Many of the ethical challenges of psychiatric genetic testing are likely to stem from failures to comprehend the nature and implications of test results. Recent studies have identified gaps in the knowledge base of psychiatrists and genetic counselors, which limit their abilities to provide patients with appropriate education. A small number of studies have demonstrated the value of counseling in empowering patients to deal with relevant genetic information. Psychiatrists and other health professionals must be able to assist patients and families in making informed decisions about genetic testing and interpreting test results. Filling their knowledge gaps on these issues will be a critical step towards meeting these responsibilities.

Lessons in the Design and Characterization Testing of the Semi-Span Super-Sonic Transport (S4T) Wind-Tunnel Model

NASA Technical Reports Server (NTRS)

2012-01-01

This paper focuses on some of the more challenging design processes and characterization tests of the Semi-Span Super-Sonic Transport (S4T)-Active Controls Testbed (ACT). The model was successfully tested in four entries in the National Aeronautics and Space Administration Langley Transonic Dynamics Tunnel to satisfy the goals and objectives of the Fundamental Aeronautics Program Supersonic Project Aero-Propulso-Servo-Elastic effort. Due to the complexity of the S4T-ACT, only a small sample of the technical challenges for designing and characterizing the model will be presented. Specifically, the challenges encountered in designing the model include scaling the Technology Concept Airplane to model scale, designing the model fuselage, aileron actuator, and engine pylons. Characterization tests included full model ground vibration tests, wing stiffness measurements, geometry measurements, proof load testing, and measurement of fuselage static and dynamic properties.

Development of an objective gene expression panel as an alternative to self-reported symptom scores in human influenza challenge trials.

PubMed

Muller, Julius; Parizotto, Eneida; Antrobus, Richard; Francis, James; Bunce, Campbell; Stranks, Amanda; Nichols, Marshall; McClain, Micah; Hill, Adrian V S; Ramasamy, Adaikalavan; Gilbert, Sarah C

2017-06-08

Influenza challenge trials are important for vaccine efficacy testing. Currently, disease severity is determined by self-reported scores to a list of symptoms which can be highly subjective. A more objective measure would allow for improved data analysis. Twenty-one volunteers participated in an influenza challenge trial. We calculated the daily sum of scores (DSS) for a list of 16 influenza symptoms. Whole blood collected at baseline and 24, 48, 72 and 96 h post challenge was profiled on Illumina HT12v4 microarrays. Changes in gene expression most strongly correlated with DSS were selected to train a Random Forest model and tested on two independent test sets consisting of 41 individuals profiled on a different microarray platform and 33 volunteers assayed by qRT-PCR. 1456 probes are significantly associated with DSS at 1% false discovery rate. We selected 19 genes with the largest fold change to train a random forest model. We observed good concordance between predicted and actual scores in the first test set (r = 0.57; RMSE = -16.1%) with the greatest agreement achieved on samples collected approximately 72 h post challenge. Therefore, we assayed samples collected at baseline and 72 h post challenge in the second test set by qRT-PCR and observed good concordance (r = 0.81; RMSE = -36.1%). We developed a 19-gene qRT-PCR panel to predict DSS, validated on two independent datasets. A transcriptomics based panel could provide a more objective measure of symptom scoring in future influenza challenge studies. Trial registration Samples were obtained from a clinical trial with the ClinicalTrials.gov Identifier: NCT02014870, first registered on December 5, 2013.

High-Stakes Testing in the Warm Heart of Africa: The Challenges and Successes of the Malawi National Examinations Board

ERIC Educational Resources Information Center

Chakwera, Elias; Khembo, Dafter; Sireci, Stephen G.

2004-01-01

In the United States, tests are held to high standards of quality. In developing countries such as Malawi, psychometricians must deal with these same high standards as well as several additional pressures such as widespread cheating, test administration difficulties due to challenging landscapes and poor resources, difficulties in reliably scoring…

Measuring Ability, Speed, or Both? Challenges, Psychometric Solutions, and What Can Be Gained from Experimental Control

ERIC Educational Resources Information Center

Goldhammer, Frank

2015-01-01

The main challenge of ability tests relates to the difficulty of items, whereas speed tests demand that test takers complete very easy items quickly. This article proposes a conceptual framework to represent how performance depends on both between-person differences in speed and ability and the speed-ability compromise within persons. Related…

Practical challenges related to point of care testing.

PubMed

Shaw, Julie L V

2016-04-01

Point of care testing (POCT) refers to laboratory testing that occurs near to the patient, often at the patient bedside. POCT can be advantageous in situations requiring rapid turnaround time of test results for clinical decision making. There are many challenges associated with POCT, mainly related to quality assurance. POCT is performed by clinical staff rather than laboratory trained individuals which can lead to errors resulting from a lack of understanding of the importance of quality control and quality assurance practices. POCT is usually more expensive than testing performed in the central laboratory and requires a significant amount of support from the laboratory to ensure the quality testing and meet accreditation requirements. Here, specific challenges related to POCT compliance with accreditation standards are discussed along with strategies that can be used to overcome these challenges. These areas include: documentation of POCT orders, charting of POCT results as well as training and certification of individuals performing POCT. Factors to consider when implementing connectivity between POCT instruments and the electronic medical record are also discussed in detail and include: uni-directional versus bidirectional communication, linking patient demographic information with POCT software, the importance of positive patient identification and considering where to chart POCT results in the electronic medical record.

Current limitations and recommendations to improve testing for the environmental assessment of endocrine active substances

EPA Science Inventory

In this paper existing regulatory frameworks and test systems for assessing potential endocrine-active chemicals are described, and associated challenges discussed, along with proposed approaches to address these challenges. Regulatory frameworks vary somewhat across organizatio...

The diagnosis of Brazil nut allergy using history, skin prick tests, serum-specific immunoglobulin E and food challenges.

PubMed

Ridout, S; Matthews, S; Gant, C; Twiselton, R; Dean, T; Arshad, S H

2006-02-01

Allergy to Brazil nut is a relatively common nut allergy and can be fatal. However, the evidence is lacking regarding the best approach to its diagnosis. We sought to determine the relative merits of history, skin prick testing, measurement of serum-specific IgE and challenge in the diagnosis of Brazil nut allergy. Fifty-six children and adults with a history of an allergic reaction to Brazil nut or evidence of sensitization were investigated by questionnaire (n=56), skin prick tests (SPTs) (n=53), measurement of serum-specific IgE to Brazil nut (n=54) and double-blind, placebo-controlled labial, and if necessary oral, challenges (n=19). Brazil nut allergy occurred in highly atopic individuals of any age with a strong family history of atopy. In 24 of 56 (43%), the history of an immediate reaction was sufficient to make a diagnosis with confidence and an oral challenge was considered unsafe. Of the 19 subjects undertaking the 'gold standard' test of a double-blind, placebo-controlled, food challenge, all six subjects with a SPT of at least 6 mm had a positive challenge and all three subjects with a SPT of 0 mm had a negative challenge. In the remaining 10 (53%) subjects, where SPT was between 1 and 5 mm and serum-specific IgE was less than 3.5 kU/L, an oral challenge was performed resulting in three positive and seven negative challenges. A combination of history, SPT and serum-specific IgE was adequate in achieving a diagnosis in the majority (77%) patients with suspected Brazil nut allergy. However, a doubtful history with SPT between 1 and 5 mm, or a serum-specific IgE less than 3.5 kU/L may require an oral challenge to help determine the risk of a Brazil nut allergic reaction.

The space shuttle launch vehicle aerodynamic verification challenges

NASA Technical Reports Server (NTRS)

Wallace, R. O.; Austin, L. D.; Hondros, J. G.; Surber, T. E.; Gaines, L. M.; Hamilton, J. T.

1985-01-01

The Space Shuttle aerodynamics and performance communities were challenged to verify the Space Shuttle vehicle (SSV) aerodynamics and system performance by flight measurements. Historically, launch vehicle flight test programs which faced these same challenges were unmanned instrumented flights of simple aerodynamically shaped vehicles. However, the manned SSV flight test program made these challenges more complex because of the unique aerodynamic configuration powered by the first man-rated solid rocket boosters (SRB). The analyses of flight data did not verify the aerodynamics or performance preflight predictions of the first flight of the Space Transportation System (STS-1). However, these analyses have defined the SSV aerodynamics and verified system performance. The aerodynamics community also was challenged to understand the discrepancy between the wind tunnel and flight defined aerodynamics. The preflight analysis challenges, the aerodynamic extraction challenges, and the postflight analyses challenges which led to the SSV system performance verification and which will lead to the verification of the operational ascent aerodynamics data base are presented.

Bronchial provocation tests in clinical practice.

PubMed

Borges, Marcos de Carvalho; Ferraz, Erica; Vianna, Elcio Oliveira

2011-01-01

Bronchial hyperresponsiveness, which consists of an exaggerated response of the airways to bronchoconstrictor stimuli, is one of the main characteristics of asthma, presented in nearly all asthmatic patients. Bronchial hyperresponsiveness may also be present in other diseases, such as allergic rhinitis, chronic obstructive pulmonary disease, cystic fibrosis, heart failure and respiratory infection, and with some medications, such as β-blockers. Bronchial provocation tests (also known as bronchial challenges) are used to evaluate bronchial responsiveness. These tests have become increasingly used over the last 20 years, with the development and validation of accurate, safe and reproducible tests, and with the publication of well-detailed protocols. Several stimuli can be used in a bronchial challenge, and they are classified as direct and indirect stimuli. There are many indications for a bronchial challenge. In this review, we discuss the main differences between direct and indirect stimuli, and the use of bronchial challenges in clinical practice, especially for confirming diagnoses of asthma, exercise-induced bronchoconstriction and cough-variant asthma, and for use among elite-level athletes.

Sesame allergy: role of specific IgE and skin-prick testing in predicting food challenge results.

PubMed

Permaul, Perdita; Stutius, Lisa M; Sheehan, William J; Rangsithienchai, Pitud; Walter, Jolan E; Twarog, Frank J; Young, Michael C; Scott, Jordan E; Schneider, Lynda C; Phipatanakul, Wanda

2009-01-01

There are conflicting data regarding the diagnostic value of sesame-specific IgE and sesame skin test. Currently, there are no established thresholds that predict clinical reactivity. We examined the correlation of sesame ImmunoCAP and skin-prick test (SPT) results with oral challenge outcomes in children suspected of having a sesame food allergy. We conducted a retrospective chart review of children, aged 2-12 years, receiving a sesame ImmunoCAP level, SPT, and food challenge from January 2004 to August 2008 at Children's Hospital Boston and affiliated allergy clinics. Food challenges were conducted in cases of questionable clinical history or a negative ImmunoCAP and/or negative SPT despite a convincing history. Thirty-three oral sesame challenges were conducted. Of the 33 challenges performed, 21% (n = 7) failed and 79% (n = 26) passed. A sesame-specific IgE level of > or = 7 kU(A)/L showed specificity of >90%. An SPT wheal size of > or = 6 mm showed specificity of >90%. Receiver operator characteristic (ROC) curve analysis for sesame-specific IgE revealed an area under the curve (AUC) of 0.56. ROC curve analysis for SPT wheal size revealed an AUC of 0.67. To our knowledge, this study represents the largest number of sesame challenges performed to evaluate the diagnostic value of both sesame-specific IgE and SPT. Based on our sample, both tests are not good predictors of true sesame allergy as determined by an oral challenge. We were unable to establish a threshold with a 95% positive predictive value for both sesame-specific IgE and SPT.

Patch Test Negative Generalized Dermatitis.

PubMed

Spiker, Alison; Mowad, Christen

2016-01-01

Allergic contact dermatitis is a common condition in dermatology. Patch testing is the criterion standard for diagnosis. However, dermatitis is not always caused by an allergen, and patch testing does not identify a culprit in every patient. Generalized dermatitis, defined as eczematous dermatitis affecting greater than 3 body sites, is often encountered in dermatology practice, especially patch test referral centers. Management for patients with generalized dermatitis who are patch test negative is challenging. The purpose of this article is to outline an approach to this challenging scenario and summarize the paucity of existing literature on patch test negative generalized dermatitis.

Comparison of spike and aerosol challenge tests for the recovery of viable influenza virus from non-woven fabrics.

PubMed

Zuo, Zhili; de Abin, Martha; Chander, Yogesh; Kuehn, Thomas H; Goyal, Sagar M; Pui, David Y H

2013-09-01

To experimentally determine the survival kinetics of influenza virus on personal protective equipment (PPE) and to evaluate the risk of virus transfer from PPE, it is important to compare the effects on virus recovery of the method used to contaminate the PPE with virus and the type of eluent used to recover it. Avian influenza virus (AIV) was applied as a liquid suspension (spike test) and as an aerosol to three types of non-woven fabrics [polypropylene (PP), polyester (PET), and polyamide (Nylon)] that are commonly used in the manufacture of PPE. This was followed by virus recovery using eight different eluents (phosphate-buffered saline, minimum essential medium, and 1.5% or 3.0% beef extract at pH 7, 8, or 9). For spike tests, no statistically significant difference was found in virus recovery using any of the eluents tested. Hydrophobic surfaces (PP and PET) yielded higher spiked virus recovery than hydrophilic Nylon. From all materials, the virus recovery was much lower in aerosol challenge tests than in spike tests. Significant differences were found in the recovery of viable AIV from non-woven fabrics between spike and aerosol challenge tests. The findings of this study demonstrate the need for realistic aerosol challenge tests rather than liquid spike tests in studies of virus survival on surfaces where airborne transmission of influenza virus may get involved. © 2013 John Wiley & Sons Ltd.

sIgE Ana o 1, 2 and 3 accurately distinguish tolerant from allergic children sensitized to cashew nuts.

PubMed

van der Valk, J P M; Gerth van Wijk, R; Vergouwe, Y; Steyerberg, E W; Reitsma, M; Wichers, H J; Savelkoul, H F J; Vlieg-Boerstra, B; de Groot, H; Dubois, A E J; de Jong, N W

2017-01-01

The double-blind, placebo-controlled food challenge test (DBPCFC) is the gold standard in cashew nut allergy. This test is costly, time consuming and not without side effects. Analysis of IgE reactivity to cashew nut components may reduce the need for food challenge tests. In a prospective and multicentre study, children with suspected cashew nut allergy underwent a DBPCFC with cashew nut. Specific IgE to cashew nut and to the components Ana o 1, 2 and 3 were determined. A skin prick test (SPT) with cashew nut extract was performed. The association between the outcome of the food challenge test and specific IgE to Ana o 1, 2 and 3 was assessed with logistic regression analyses, unadjusted and adjusted for other diagnostic variables. Discriminative ability was quantified with a concordance index (c). A total of 173 children (103 boys, 60%) with a median age of 9 years were included. About 79% had a positive challenge test outcome. A steep rise in the risk of a positive challenge was observed for specific IgE to each individual component Ana o 1, 2 and 3 with estimated risks up to approximately 100%. Median values of Ana o 1, 2, 3 were 1.29 kU/l (range 0-100 kU/l), 4.77 kU/l (range 0-100 kU/l) and 8.33 kU/l (range 0-100 kU/l) respectively and varied significantly (p < 0.001). Specific IgE to Ana o 1, 2 and 3 was better distinguished between cashew-allergic and tolerant children (c = 0.87, 0.85 and 0.89, respectively) than specific IgE to cashew nut or SPT (c = 0.76 and 0.83, respectively). The major cashew nut allergens Ana o 1, 2 and 3 are each individually predictive for the outcome of food challenge tests in cashew-allergic children. © 2016 John Wiley & Sons Ltd.

Modeling and design of challenge tests: Inflammatory and metabolic biomarker study examples.

PubMed

Gabrielsson, Johan; Hjorth, Stephan; Vogg, Barbara; Harlfinger, Stephanie; Gutierrez, Pablo Morentin; Peletier, Lambertus; Pehrson, Rikard; Davidsson, Pia

2015-01-25

Given the complexity of pharmacological challenge experiments, it is perhaps not surprising that design and analysis, and in turn interpretation and communication of results from a quantitative point of view, is often suboptimal. Here we report an inventory of common designs sampled from anti-inflammatory, respiratory and metabolic disease drug discovery studies, all of which are based on animal models of disease involving pharmacological and/or patho/physiological interaction challenges. The corresponding data are modeled and analyzed quantitatively, the merits of the respective approach discussed and inferences made with respect to future design improvements. Although our analysis is limited to these disease model examples, the challenge approach is generally applicable to the vast majority of pharmacological intervention studies. In the present five Case Studies results from pharmacodynamic effect models from different therapeutic areas were explored and analyzed according to five typical designs. Plasma exposures of test compounds were assayed by either liquid chromatography/mass spectrometry or ligand binding assays. To describe how drug intervention can regulate diverse processes, turnover models of test compound-challenger interaction, transduction processes, and biophase time courses were applied for biomarker response in eosinophil count, IL6 response, paw-swelling, TNFα response and glucose turnover in vivo. Case Study 1 shows results from intratracheal administration of Sephadex, which is a glucocorticoid-sensitive model of airway inflammation in rats. Eosinophils in bronchoalveolar fluid were obtained at different time points via destructive sampling and then regressed by the mixed-effects modeling. A biophase function of the Sephadex time course was inferred from the modeled eosinophil time courses. In Case Study 2, a mouse model showed that the time course of cytokine-induced IL1β challenge was altered with or without drug intervention. Anakinra reversed the IL1β induced cytokine IL6 response in a dose-dependent manner. This Case Study contained time courses of test compound (drug), challenger (IL1β) and cytokine response (IL6), which resulted in high parameter precision. Case Study 3 illustrates collagen-induced arthritis progression in the rat. Swelling scores (based on severity of hind paw swelling) were used to describe arthritis progression after the challenge and the inhibitory effect of two doses of an orally administered test compound. In Case Study 4, a cynomolgus monkey model for lipopolysaccharide LPS-induced TNFα synthesis and/or release was investigated. This model provides integrated information on pharmacokinetics and in vivo potency of the test compounds. Case Study 5 contains data from an oral glucose tolerance test in rats, where the challenger is the same as the pharmacodynamic response biomarker (glucose). It is therefore convenient to model the extra input of glucose simultaneously with baseline data and during intervention of a glucose-lowering compound at different dose levels. Typically time-series analyses of challenger- and biomarker-time data are necessary if an accurate and precise estimate of the pharmacodynamic properties of a test compound is sought. Erosion of data, resulting in the single-point assessment of drug action after a challenge test, should generally be avoided. This is particularly relevant for situations where one expects time-curve shifts, tolerance/rebound, impact of disease, or hormetic concentration-response relationships to occur. Copyright © 2014 Elsevier B.V. All rights reserved.

The Challenge Course Experience Questionnaire: A Facilitator's Assessment Tool

ERIC Educational Resources Information Center

Schary, David P.; Waldron, Alexis L.

2017-01-01

Challenge course programs influence a variety of psychological, social, and educational outcomes. Yet, many challenges exist when measuring challenge course outcomes like logistical constraints and a lack of specific assessment tools. This study piloted and tested an assessment tool designed for facilitators to measure participant outcomes in…

Expressive communication of children with autism: the use of challenging behaviour.

PubMed

Chiang, Hsu-Min

2008-11-01

There is a lack of empirical research investigating challenging behaviour in children with autism with severe speech impairments in naturalistic settings. The aim of the present study was to investigate challenging behaviour among Australian and Taiwanese children with autism who are non-verbal or have limited speech (i.e. less than five functional words) in school settings and to address the following questions: (1) What are the communicative characteristics (e.g. communicative functions, partners, activities and partner's responses) of challenging behaviour? (2) Do sample characteristics (e.g. age, severity of autism, adaptive behaviour level, the use of graphic symbols, the use of non-symbolic acts, the use of speech) associate with the amount of challenging behaviour? (3) Do cultural differences exist in communicative variables of challenging behaviour? Naturalistic observations were used to investigate challenging behaviour in children with autism. A total of 32 (17 Australian and 15 Taiwanese) children with autism who were non-verbal or had limited speech participated in the current study and each participant was videotaped for 2 h during his/her everyday school routines. Sixteen out of 32 children had challenging behaviour. Challenging behaviour was used for requesting and rejecting communicative functions. A paired-samples t-test revealed that no significant differences existed in the frequency of occurrence between request and reject. Challenging behaviour was directed to adults and peers. A paired-samples t-test revealed that challenging behaviour was directed to adults significantly more frequently than to peers. Communicative partners showed different responses (e.g. deny, no response, delivered, removed, acknowledge) to challenging behaviour. A repeated-measures analysis of variance (ANOVA) revealed a main effect for partner response. Deny was the most common response. Challenging behaviour occurred across a variety of classroom activities (e.g. academic activities, morning circle, morning tea, lunch, free time). A repeated-measures ANOVA revealed a main effect for activity. Challenging behaviour occurred most often during academic activities. A set of correlation analyses indicated a significant correlation existed between the use of graphic symbols and the amount of challenging behaviour. A series of Mann-Whitney U-tests revealed significant differences between Australian and Taiwanese children on the amount of challenging behaviour, communicative functions and partners. A Chi-squared test revealed that there were significantly more Australian children with autism who displayed challenging behaviour than Taiwanese children. The current study shows that a high proportion of children with autism with severe speech impairments used challenging behaviour as a form of expressive communication in their school environments. The findings from the present study may have implications for practitioners who work with children with autism.

Effect of hormone therapy on lean body mass, falls, and fractures: Six-year results from the Women’s Health Initiative Hormone Trials

PubMed Central

Bea, Jennifer W.; Zhao, Qiuhong; Cauley, Jane A.; LaCroix, Andrea Z.; Bassford, Tamsen; Lewis, Cora E.; Jackson, Rebecca D.; Tylavsky, Frances A.; Chen, Zhao

2010-01-01

Objective Loss of lean body mass with aging may contribute to falls and fractures. The objective of this analysis was to determine if taking postmenopausal hormone therapy (HT: estrogen plus progestogen therapy, EPT or estrogen therapy alone, ET) favorably affects age-related changes in lean body mass and if these changes partially account for decreased falls or fractures with HT. Methods Participants randomly assigned to either EPT (n=543) or control (n=471) and ET (n= 453) or control (n= 474) and receiving dual-energy X-ray absorptiometry (DXA) scans to estimate body composition during the Women’s Health Initiative (WHI) were evaluated. Falls and fracture occurrence were obtained by annual self-report. Fractures were confirmed by clinical chart review. Results At 6yrs post-randomization, lean body mass was not different between HT and control groups. Although lean body mass positively influenced BMD, independent of HT status, the preserved lean body mass observed in the HT arms in the first 3 years did not significantly contribute to models evaluating HT influence on falls and fractures between years 3 and 6. Women taking at least 80% of their medication in the HT arms demonstrated fewer falls compared to placebo; this difference was not attributable to change in lean body mass. Conclusions Despite early preservation of lean body mass with HT (3years), HT did not ameliorate long-term (6 years) loss in lean body mass with aging. PMID:20689466

The 2012 Hormone Therapy Position Statement of The North American Menopause Society

PubMed Central

2012-01-01

Objective This position statement aimed to update the evidence-based position statement published by The North American Menopause Society (NAMS) in 2010 regarding recommendations for hormone therapy (HT) for postmenopausal women. This updated position statement further distinguishes the emerging differences in the therapeutic benefit-risk ratio between estrogen therapy (ET) and combined estrogen-progestogen therapy (EPT) at various ages and time intervals since menopause onset. Methods An Advisory Panel of expert clinicians and researchers in the field of women’s health was enlisted to review the 2010 NAMS position statement, evaluate new evidence, and reach consensus on recommendations. The Panel’s recommendations were reviewed and approved by the NAMS Board of Trustees as an official NAMS position statement. Results Current evidence supports the use of HT for perimenopausal and postmenopausal women when the balance of potential benefits and risks is favorable for the individual woman. This position statement reviews the effects of ET and EPT on many aspects of women’s health and recognizes the greater safety profile associated with ET. Conclusions Recent data support the initiation of HT around the time of menopause to treat menopause-related symptoms and to prevent osteoporosis in women at high risk of fracture. The more favorable benefit-risk ratio for ET allows more flexibility in extending the duration of use compared with EPT, where the earlier appearance of increased breast cancer risk precludes a recommendation for use beyond 3 to 5 years. PMID:22367731

Pathophysiology of premenstrual syndrome and premenstrual dysphoric disorder.

PubMed

Rapkin, Andrea J; Akopians, Alin L

2012-06-01

Premenstrual syndrome (PMS) and premenstrual dysphoric disorder are triggered by hormonal events ensuing after ovulation. The symptoms can begin in the early, mid or late luteal phase and are not associated with defined concentrations of any specific gonadal or non-gonadal hormone. Although evidence for a hormonal abnormality has not been established, the symptoms of the premenstrual disorders are related to the production of progesterone by the ovary. The two best-studied and relevant neurotransmitter systems implicated in the genesis of the symptoms are the GABArgic and the serotonergic systems. Metabolites of progesterone formed by the corpus luteum of the ovary and in the brain bind to a neurosteroid-binding site on the membrane of the gamma-aminobutyric acid (GABA) receptor, changing its configuration, rendering it resistant to further activation and finally decreasing central GABA-mediated inhibition. By a similar mechanism, the progestogens in some hormonal contraceptives are also thought to adversely affect the GABAergic system. The lowering of serotonin can give rise to PMS-like symptoms and serotonergic functioning seems to be deficient by some methods of estimating serotonergic activity in the brain; agents that augment serotonin are efficacious and are as effective even if administered only in the luteal phase. However, similar to the affective disorders, PMS is ultimately not likely to be related to the dysregulation of individual neurotransmitters. Brain imaging studies have begun to shed light on the complex brain circuitry underlying affect and behaviour and may help to explicate the intricate neurophysiological foundation of the syndrome.

Risk of venous thrombosis in users of hormonal contraceptives in German gynaecological practices: a patient database analysis.

PubMed

Ziller, M; Ziller, V; Haas, G; Rex, J; Kostev, K

2014-02-01

Recent studies showed differences in the risk of venous thrombosis between different combined hormonal contraceptives. Database studies comprising large cohorts can add relevant aspects from daily clinical practice. The purpose of this study was to evaluate different progestogen in combination with ethinylestradiol on the risk of venous thrombosis in Germany. Computerized data from 68,168 contraceptive users in gynecological practices throughout Germany (Disease Analyzer Database) were analyzed. The adjusted odds ratios for risk of thrombosis were estimated in users of different oral contraceptive (OC) formulations relative to users of levonorgestrel-containing preparations. In total, 38 (0.06 %) of the 68,168 contraceptive users had a recorded diagnosis of thrombosis within 365 days after the initial prescription. The adjusted risk was 1.95 for desogestrel (95 % CI 0.52-7.29), 2.97 for dienogest (95 % CI 0.96-9.24), 1.57 for drospirenone (95 % CI 0.46-5.38), 2.54 for chlormadinone (95 % CI 0.72-9.04), and 3.24 for norgestimate (95 % CI 0.59-17.75) compared to levonorgestrel. None of those findings reached statistical significance. The maximum absolute increase versus levonorgestrel was 6 cases per 10,000 women (n.s.). The study shows the low incidence rates of thrombosis in OC users. Since there is no significant difference, this study does not confirm an increased risk but shows only a tendency for this risk of third- and fourth-generation OC versus levonorgestrel-containing products.

The effect of ethinylestradiol-containing contraceptives on the serum concentration of olanzapine and N-desmethyl olanzapine.

PubMed

Haslemo, Tore; Refsum, Helge; Molden, Espen

2011-04-01

To investigate the potential interaction between olanzapine, a CYP1A2 substrate, and ethinylestradiol-containing contraceptives (ECC). The study was carried out at a routine therapeutic drug monitoring service. To identify patients who were co-administered ECC or other contraceptives, a questionnaire was sent to the physician who ordered serum monitoring of olanzapine for women aged 18-40 years during an 18 month period. The physicians were asked to provide information about contraceptive use and smoking habits. When questionnaires were returned by the physicians, the respective serum concentration data were included in the analysis. Patients were stratified into users of ECC, progestogen-based contraceptives (PBC) or no contraceptives. Dose-adjusted serum concentrations of olanzapine and the metabolite N-desmethyl olanzapine were compared between the subgroups. A total of 149 patients were included in the study (10 ECC users and 10 PBC users). In users of ECC, we found no differences in serum concentrations of olanzapine, but significantly lower concentrations of the CYP1A2-mediated metabolite N-desmethyl olanzapine compared with users of PBC (P = 0.019) and non-contraceptive users (P = 0.012). The present study confirms that ECC exhibit CYP1A2-inhibitory properties in terms of significantly lower exposure of N-desmethyl olanzapine. However, the inhibition does not provide clinically relevant changes in serum concentrations of olanzapine. © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.

The use of hormonal treatments to improve reproductive performance of anestrous beef cattle in tropical climates.

PubMed

Baruselli, P S; Reis, E L; Marques, M O; Nasser, L F; Bó, G A

2004-07-01

Most of the world's bovine herd is found in tropical regions. Bos indicus predominates, due to their adaptation to the climate and management conditions. Anestrous is the main factor that negatively affects reproductive performance of animals bred in these regions of the globe. Several factors affect postpartum anestrous, including suckling and maternal-offspring bond, and pre- and postpartum nutritional status. The short duration of estrus and the tendency to show estrus during the night, greatly affect the efficiency of artificial insemination (AI) programs in B. indicus cattle managed in tropical areas. Several restricted suckling or weaning procedures (temporary or permanent), and hormonal treatments have been used to induce ovulation and cyclicity in postpartum cows. Most hormonal treatments are based on progesterone/progestogen (P4) releasing devices associated with estradiol benzoate (EB), or a combination of GnRH/PGF(2alpha)/GnRH (Ovsynch). Treatments with GnRH/PGF(2alpha)/GnRH has presented inconsistent results, probably due to the variable number of cows in anestrous. Treatments using P4 devices and EB have resulted in apparently more consistent results than Ovsynch programs in B. indicus cattle; however, pregnancy rates are low in herds presenting high anestrous rates and moderate to low body condition. The addition of an eCG treatment at the time of device removal, which increased plasma progesterone concentrations and pregnancy rates in anestrous postpartum suckled B. indicus cows, may be useful to improve reproductive performance of beef cattle in tropical climates.

A case-control study of hormonal exposures as etiologic factors for ALS in women: Euro-MOTOR.

PubMed

Rooney, James P K; Visser, Anne E; D'Ovidio, Fabrizio; Vermeulen, Roel; Beghi, Ettore; Chio, Adriano; Veldink, Jan H; Logroscino, Giancarlo; van den Berg, Leonard H; Hardiman, Orla

2017-09-19

To investigate the role of hormonal risk factors for amyotrophic lateral sclerosis (ALS) among women from 3 European countries. ALS cases and matched controls were recruited over 4 years in Ireland, Italy, and the Netherlands. Hormonal exposures, including reproductive history, breastfeeding, contraceptive use, hormonal replacement therapy, and gynecologic surgical history, were recorded with a validated questionnaire. Logistic regression models adjusted for age, education, study site, smoking, alcohol, and physical activity were used to determine the association between female hormones and ALS risk. We included 653 patients and 1,217 controls. Oral contraceptive use was higher among controls (odds ratio [OR] 0.65, 95% confidence interval [CI] 0.51-0.84), and a dose-response effect was apparent. Hormone replacement therapy (HRT) was associated with a reduced risk of ALS only in the Netherlands (OR = 0.57, 95% CI 0.37-0.85). These findings were robust to sensitivity analysis, but there was some heterogeneity across study sites. This large case-control study across 3 different countries has demonstrated an association between exogenous estrogens and progestogens and reduced odds of ALS in women. These results are at variance with previous findings, which may be partly explained by differential regulatory, social, and cultural attitudes toward pregnancy, birth control, and HRT across the countries included. Our results indicate that hormonal factors may be important etiologic factors in ALS; however, a full understanding requires further investigation. © 2017 American Academy of Neurology.

Progesterone and Nestorone promote myelin regeneration in chronic demyelinating lesions of corpus callosum and cerebral cortex

PubMed Central

el-Etr, Martine; Rame, Marion; Boucher, Celine; Ghoumari, Abdel; Kumar, Narender; Liere, Philippe; Pianos, Antoine; Schumacher, Michael; Sitruk-Ware, Regine

2014-01-01

Multiple Sclerosis affects mainly women and consists in intermittent or chronic damages to the myelin sheaths, focal inflammation and axonal degeneration. Current therapies are limited to immunomodulators and anti-inflammatory drugs, but there is no efficient treatment for stimulating the endogenous capacity of myelin repair. Progesterone and synthetic progestins have been shown in animal models of demyelination to attenuate myelin loss, reduce clinical symptoms severity, modulate inflammatory responses and partially reverse the age-dependent decline in remyelination. Moreover, progesterone has been demonstrated to promote myelin formation in organotypic cultures of cerebellar slices. In the present study, we show that progesterone and the synthetic 19-nor-progesterone derivative Nestorone® promote the repair of severe chronic demyelinating lesions induced by feeding cuprizone to female mice for up to 12 weeks. Progesterone and Nestorone increase the density of NG2+ oligodendrocyte progenitor cells and CA II+ mature oligodendrocytes and enhance the formation of myelin basic protein (MBP)- and proteolipid protein (PLP)-immunoreactive myelin. However, while demyelination in response to cuprizone was less marked in corpus callosum than in cerebral cortex, remyelination appeared earlier in the former. The remyelinating effect of progesterone was progesterone receptor (PR)-dependent, as it was absent in PR knockout mice. Progesterone and Nestorone also decreased (but did not suppress) neuroinflammatory responses, specifically astrocyte and microglial cell activation. Therefore, some progestogens are promising therapeutic candidates for promoting the regeneration of myelin. PMID:25092805

Comparison of the effects of chlormadinone acetate versus drospirenone containing oral contraceptives on metabolic and hormonal parameters in women with PCOS for a period of two-year follow-up.

PubMed

Yildizhan, Recep; Gokce, Anik Ilhan; Yildizhan, Begum; Cim, Numan

2015-05-01

A randomized trial to compare the effects of two oral contraceptive pills containing either chlormadinone acetate or drospirenone as the progestogen, in women with PCOS for a period of two-year follow-up. Group A received ethinyl-estradiol 0.03 mg + drospirenone 3 mg (EE + DRSP; n = 56) and Group B received ethinyl-estradiol 0.03 mg + chlormadinone acetate 2 mg (EE + CMA; n = 50). Clinical, hormonal and biochemical parameters were compared at baseline, 6 months, 12 months and 24 months. The increase in total cholesterol and hsCRP levels was statistically significantly higher at 6, 12 and 24 months in Group B when compared with Group A. The change in the high-density lipoprotein cholesterol level at the 24 months of treatment was statistically significantly higher in Group A. Group A has a significantly higher reduction in FAI at 6 and 24 months, in FGS at 6, 12 and 24 months and in HOMA-IR index at 12 and 24 months when compared with Group B. Drospirenone containing combined oral contraceptive (COC) is found to have more favorable effects on lipid profiles, hsCRP levels, insulin resistance and hyperandrogenism when compared with the CMA containing COC and appears to be more beneficial for the long-term cardiovascular and metabolic aspects of PCOS.

Drospirenone/ethinylestradiol 3mg/20microg (24/4 day regimen): a review of its use in contraception, premenstrual dysphoric disorder and moderate acne vulgaris.

PubMed

Fenton, Caroline; Wellington, Keri; Moen, Marit D; Robinson, Dean M

2007-01-01

Drospirenone 3mg with ethinylestradiol 20microg (Yaz) is a low-dose combined oral contraceptive (COC) administered in a regimen of 24 days of active tablets followed by a short hormone-free interval (4 days; 24/4 regimen). Drospirenone, unlike other synthetic progestogens used in COCs, is a 17alpha-spirolactone derivative and a 17alpha-spironolactone analogue with antimineralocorticoid and antiandrogenic properties. Drospirenone/ethinylestradiol 3mg/20microg (24/4) is approved in the US for the prevention of pregnancy in women, for the treatment of the symptoms of premenstrual dysphoric disorder (PMDD) and for the treatment of moderate acne vulgaris in women who wish to use an oral contraceptive for contraception.Drospirenone/ethinylestradiol 3mg/20microg (24/4) provided 99% contraceptive protection over 1 year of treatment in two large studies. The same treatment regimen over three treatment cycles also significantly improved the emotional and physical symptoms associated with PMDD, and improved moderate acne vulgaris over six treatment cycles in double-blind trials. It was generally well tolerated, with adverse events generally typical of those experienced with other COCs and which were most likely to occur in the first few cycles. Clinical trials indicate that drospirenone/ethinylestradiol 3mg/20microg (24/4) is a good long-term contraceptive option, and additionally offers relief of symptoms that characterise PMDD and has a favourable effect on moderate acne vulgaris.

Risks and benefits of hormone therapy: has medical dogma now been overturned?

PubMed

Shapiro, S; de Villiers, T J; Pines, A; Sturdee, D W; Baber, R J; Panay, N; Stevenson, J C; Mueck, A O; Burger, H G

2014-06-01

In an integrated overview of the benefits and risks of menopausal hormone therapy (HT), the Women's Health Initiative (WHI) investigators have claimed that their 'findings … do not support use of this therapy for chronic disease prevention'. In an accompanying editorial, it was claimed that 'the WHI overturned medical dogma regarding menopausal [HT]'. To evaluate those claims. Epidemiological criteria of causation were applied to the evidence. A 'global index' purporting to summarize the overall benefit versus the risk of HT was not valid, and it was biased. For coronary heart disease, an increased risk in users of estrogen plus progestogen (E + P), previously reported by the WHI, was not confirmed. The WHI study did not establish that E+ P increases the risk of breast cancer; the findings suggest that unopposed estrogen therapy (ET) does not increase the risk, and may even reduce it. The findings for stroke and pulmonary embolism were compatible with an increased risk, and among E+ P users there were credible reductions in the risk of colorectal and endometrial cancer. For E+ P and ET users, there were credible reductions in the risk of hip fracture. Under 'worst case' and 'best case' assumptions, the changes in the incidence of the outcomes attributable to HT were minor. Over-interpretation and misrepresentation of the WHI findings have damaged the health and well-being of menopausal women by convincing them and their health professionals that the risks of HT outweigh the benefits.

D3R grand challenge 2015: Evaluation of protein-ligand pose and affinity predictions

NASA Astrophysics Data System (ADS)

Gathiaka, Symon; Liu, Shuai; Chiu, Michael; Yang, Huanwang; Stuckey, Jeanne A.; Kang, You Na; Delproposto, Jim; Kubish, Ginger; Dunbar, James B.; Carlson, Heather A.; Burley, Stephen K.; Walters, W. Patrick; Amaro, Rommie E.; Feher, Victoria A.; Gilson, Michael K.

2016-09-01

The Drug Design Data Resource (D3R) ran Grand Challenge 2015 between September 2015 and February 2016. Two targets served as the framework to test community docking and scoring methods: (1) HSP90, donated by AbbVie and the Community Structure Activity Resource (CSAR), and (2) MAP4K4, donated by Genentech. The challenges for both target datasets were conducted in two stages, with the first stage testing pose predictions and the capacity to rank compounds by affinity with minimal structural data; and the second stage testing methods for ranking compounds with knowledge of at least a subset of the ligand-protein poses. An additional sub-challenge provided small groups of chemically similar HSP90 compounds amenable to alchemical calculations of relative binding free energy. Unlike previous blinded Challenges, we did not provide cognate receptors or receptors prepared with hydrogens and likewise did not require a specified crystal structure to be used for pose or affinity prediction in Stage 1. Given the freedom to select from over 200 crystal structures of HSP90 in the PDB, participants employed workflows that tested not only core docking and scoring technologies, but also methods for addressing water-mediated ligand-protein interactions, binding pocket flexibility, and the optimal selection of protein structures for use in docking calculations. Nearly 40 participating groups submitted over 350 prediction sets for Grand Challenge 2015. This overview describes the datasets and the organization of the challenge components, summarizes the results across all submitted predictions, and considers broad conclusions that may be drawn from this collaborative community endeavor.

D3R Grand Challenge 2015: Evaluation of Protein-Ligand Pose and Affinity Predictions

PubMed Central

Gathiaka, Symon; Liu, Shuai; Chiu, Michael; Yang, Huanwang; Stuckey, Jeanne A; Kang, You Na; Delproposto, Jim; Kubish, Ginger; Dunbar, James B.; Carlson, Heather A.; Burley, Stephen K.; Walters, W. Patrick; Amaro, Rommie E.; Feher, Victoria A.; Gilson, Michael K.

2017-01-01

The Drug Design Data Resource (D3R) ran Grand Challenge 2015 between September 2015 and February 2016. Two targets served as the framework to test community docking and scoring methods: (i) HSP90, donated by AbbVie and the Community Structure Activity Resource (CSAR), and (ii) MAP4K4, donated by Genentech. The challenges for both target datasets were conducted in two stages, with the first stage testing pose predictions and the capacity to rank compounds by affinity with minimal structural data; and the second stage testing methods for ranking compounds with knowledge of at least a subset of the ligand-protein poses. An additional sub-challenge provided small groups of chemically similar HSP90 compounds amenable to alchemical calculations of relative binding free energy. Unlike previous blinded Challenges, we did not provide cognate receptors or receptors prepared with hydrogens and likewise did not require a specified crystal structure to be used for pose or affinity prediction in Stage 1. Given the freedom to select from over 200 crystal structures of HSP90 in the PDB, participants employed workflows that tested not only core docking and scoring technologies, but also methods for addressing water-mediated ligand-protein interactions, binding pocket flexibility, and the optimal selection of protein structures for use in docking calculations. Nearly 40 participating groups submitted over 350 prediction sets for Grand Challenge 2015. This overview describes the datasets and the organization of the challenge components, summarizes the results across all submitted predictions, and considers broad conclusions that may be drawn from this collaborative community endeavor. PMID:27696240

In vitro Alternative Methodologies for Central Nervous System Assessment: A Critique using Nanoscale Materials as an Example.

EPA Science Inventory

Identifying the potential health hazards to the central nervous system of a new family of materials presents many challenges. Whole-animal toxicity testing has been the tradition, but in vitro methods have been steadily gaining popularity. There are numerous challenges in testing...

Radiation Testing, Characterization and Qualification Challenges for Modern Microelectronics and Photonics Devices and Technologies

NASA Technical Reports Server (NTRS)

LaBel, Kenneth A.; Cohn, Lewis M.

2008-01-01

At an earlier conference we discussed a selection of the challenges for radiation testing of modern semiconductor devices focusing on state-of-the-art CMOS technologies. In this presentation, we extend this discussion focusing on the following areas: (1) Device packaging, (2) Evolving physical single even upset mechanisms, (3) Device complexity, and (4) the goal of understanding the limitations and interpretation of radiation testing results.

Validation of the cephalosporin intradermal skin test for predicting immediate hypersensitivity: a prospective study with drug challenge.

PubMed

Yoon, S-Y; Park, S Y; Kim, S; Lee, T; Lee, Y S; Kwon, H-S; Cho, Y S; Moon, H-B; Kim, T-B

2013-07-01

Cephalosporin is a major offending agent in terms of drug hypersensitivity along with penicillin. Cephalosporin intradermal skin tests (IDTs) have been widely used; however, their validity for predicting immediate hypersensitivity has not been studied. This study aimed to determine the predictive value of cephalosporin intradermal skin testing before administration of the drug. We prospectively conducted IDTs with four cephalosporins, one each of selected first-, second-, third-, or fourth-generation cephalosporins: ceftezol; cefotetan or cefamandole; ceftriaxone or cefotaxime; and flomoxef, respectively, as well as with penicillin G. After the skin test, whatever the result, one of the tested cephalosporins was administered intravenously and the patient was carefully observed. We recruited 1421 patients who required preoperative cephalosporins. Seventy-four patients (74/1421, 5.2%) were positive to at least one cephalosporin. However, none of responders had immediate hypersensitivity reactions after a challenge dose of the same or different cephalosporin, which were positive in the skin test. Four patients who suffered generalized urticaria and itching after challenge gave negative skin tests for the corresponding drug. The IDT for cephalosporin had a sensitivity of 0%, a specificity of 97.5%, a negative predictive value of 99.7%, and a positive predictive value (PPV) of 0%, when challenged with the same drugs that were positive in the skin test. Routine skin testing with a cephalosporin before its administration is not useful for predicting immediate hypersensitivity because of the extremely low sensitivity and PPV of the skin test (CRIS registration no. KCT0000455). © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Challenges of Cold Conditioning and Static Testing the Second Ares Demonstration Motor (DM-2)

NASA Technical Reports Server (NTRS)

Quinn, Shyla; Davis, Larry C.

2011-01-01

On August 31, 2010, a five-segment demonstration motor (DM) for the Ares program was successfully tested. A series of demonstration motors (DMs) will be tested in different conditioned environments to confirm they meet their design specifications. The second demonstration motor (DM-2) was the first cold motor. The motor needed to be subjected to sub-freezing temperatures for two months so that its internal propellant mean bulk temperature (PMBT) was approximately 40 F. Several challenges had to be overcome to make this a successful test. One challenge was to condition four field joints to get the O-rings approximately 32 F. This would be done by applying conditioning shrouds to externally cool each field joint after the test bay was pulled off. The purpose of this conditioning was to validate the new O-ring design and allow joint heaters to be eliminated. Another challenge was maintaining temperature requirements for components in the nozzle vectoring system. A separate heating system was used to warm these components during cold conditioning. There were 53 test objectives that required 764 channels of data to be recorded; 460 were specific to DM-2. This instrumentation had to be installed prior to conditioning, which meant the baseline process and timeline had to be modified to meet this time critical schedule.

Emerging Resistance, New Antimicrobial Agents  …  but No Tests! The Challenge of Antimicrobial Susceptibility Testing in the Current US Regulatory Landscape.

PubMed

Humphries, R M; Hindler, J A

2016-07-01

Accurate and timely performance of antimicrobial susceptibility testing (AST) by the clinical laboratory is paramount to combating antimicrobial resistance. The ability of laboratories in the United States to effectively perform ASTs is challenged by several factors. Some, such as new resistance mechanisms and the associated evolution of testing recommendations and breakpoints, are inevitable. Others are entirely man-made. These include unnecessarily strict US Food and Drug Administration (FDA) limitations on how commercial AST systems can be used for diagnostic testing, the absence of up-to-date performance data on these systems, and the lack of commercially available FDA-cleared tests for newer antimicrobial agents or for older agents with updated breakpoints. This viewpoint will highlight contemporary AST challenges faced by the clinical laboratory, and propose some solutions. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Challenges to Integrating Pharmacogenetic Testing into Medication Therapy Management

PubMed Central

Allen LaPointe, Nancy M.; Moaddeb, Jivan

2015-01-01

Background Some have proposed the integration of pharmacogenetic (PGx) testing into medication therapy management (MTM) to enable further refinement of treatment(s) to reduce risk of adverse responses and improve efficacy. PGx testing involves the analysis of genetic variants associated with therapeutic or adverse response and may be useful in enhancing the ability to identify ineffective and/or harmful drugs or drug combinations. This “enhanced” MTM might also reduce patient concerns about side effects and increase confidence that the medication is effective, addressing two key factors that impact patient adherence - concern and necessity. However, the feasibility and effectiveness of the integration of PGx testing into MTM in clinical practice has not yet been determined. Objectives In this paper, we consider some of the challenges to the integration and delivery of PGx testing in MTM services. What is already known about this subject While the addition of pharmacogenetic testing has been suggested, little literature exists exploring the challenges or feasibility of doing so. PMID:25803768

Aerodynamic challenges of ALT

NASA Technical Reports Server (NTRS)

Hooks, I.; Homan, D.; Romere, P. O.

1985-01-01

The approach and landing test (ALT) of the Space Shuttle Orbiter presented a number of unique challenges in the area of aerodynamics. The purpose of the ALT program was both to confirm the use of the Boeing 747 as a transport vehicle for ferrying the Orbiter across the country and to demonstrate the flight characteristics of the Orbiter in its approach and landing phase. Concerns for structural fatigue and performance dictated a tailcone be attached to the Orbiter for ferry and for the initial landing tests. The Orbiter with a tailcone attached presented additional challenges to the normal aft sting concept of wind tunnel testing. The landing tests required that the Orbiter be separated from the 747 at approximately 20,000 feet using aerodynamic forces to fly the vehicles apart. The concept required a complex test program to determine the relative effects of the two vehicles on each other. Also of concern, and tested, was the vortex wake created by the 747 and the means for the Orbiter to avoid it following separation.

Validation of novel recipes for double-blind, placebo-controlled food challenges in children and adults.

PubMed

Vlieg-Boerstra, B J; Herpertz, I; Pasker, L; van der Heide, S; Kukler, J; Jansink, C; Vaessen, W; Beusekamp, B J; Dubois, A E J

2011-07-01

In double-blind, placebo-controlled food challenges (DBPCFCs), the use of challenge materials in which blinding is validated is a prerequisite for obtaining true blinded conditions during the test procedure. Therefore, the aim of this study was to enlarge the available range of validated recipes for DBPCFCs to facilitate oral challenge tests in all age groups, including young children, while maximizing the top dose in an acceptable volume. Recipes were developed and subsequently validated by a panel recruited by a matching sensory test. The best 30% of candidates were selected to participate in sensory testing using the paired comparison test. For young children, three recipes with cow's milk and one recipe with peanut could be validated which may be utilized in DBPCFCs. For children older than 4 years and adults, one recipe with egg, two with peanut, one with hazelnut, and one with cashew nut were validated for use in DBPCFCs. All recipes contained larger amounts of allergenic foods than previously validated. These recipes increase the range of validated recipes for use in DBPCFCs in adults and children. © 2011 John Wiley & Sons A/S.

Expanding Access to Malaria Diagnosis through Retail Shops in Western Kenya: What Do Shop Workers Think?

PubMed

Rusk, Andria; Goodman, Catherine; Naanyu, Violet; Koech, Beatrice; Obala, Andrew; O'Meara, Wendy Prudhomme

2013-01-01

Background. The common symptoms of malaria reduce the specificity of clinical diagnosis. Presumptive treatment is conventional but can lead to overdiagnosis of malaria, delay of appropriate treatment, overprescription of antimalarials, and drug resistance. Routine use of diagnostic tests can address many of these concerns. Though treatment is often procured from retailers, there is low availability of rapid diagnostic tests for malaria (MRDTs), a simple, inexpensive, and accurate diagnostic solution. We know little about the challenges to expanding access to diagnostics through these outlets. Methods. To understand the perceptions of the benefits and challenges to selling rapid diagnostic tests for malaria, we conducted focus group discussions with antimalarial retailers who serve the residents of the Webuye Health and Demographic Surveillance Site in western Kenya. Results. Medicine retailers perceived MRDTs to be beneficial to their customers and businesses but also included cost, fear of the tests, risks of self-treatment, and regulatory concerns among the challenges to using and selling MRDTs. Conclusion. MRDTs represent a viable approach to increase access to malaria diagnostic testing. Medicine retailers are eager for MRDTs to be made available to them. However, certain challenges remain to implementation in retail outlets and should be addressed in advance.

Nonclinical safety testing of biopharmaceuticals--Addressing current challenges of these novel and emerging therapies.

PubMed

Brennan, Frank R; Baumann, Andreas; Blaich, Guenter; de Haan, Lolke; Fagg, Rajni; Kiessling, Andrea; Kronenberg, Sven; Locher, Mathias; Milton, Mark; Tibbitts, Jay; Ulrich, Peter; Weir, Lucinda

2015-10-01

Non-clinical safety testing of biopharmaceuticals can present significant challenges to human risk assessment with these often innovative and complex drugs. Hot Topics in this field were discussed recently at the 4th Annual European Biosafe General Membership meeting. In this feature article, the presentations and subsequent discussions from the main sessions are summarized. The topics covered include: (i) wanted versus unwanted immune activation, (ii) bi-specific protein scaffolds, (iii) use of Pharmacokinetic (PK)/Pharmacodynamic (PD) data to impact/optimize toxicology study design, (iv) cytokine release and challenges to human translation (v) safety testing of cell and gene therapies including chimeric antigen receptor T (CAR-T) cells and retroviral vectors and (vi) biopharmaceutical development strategies encompassing a range of diverse topics including optimizing entry of monoclonal antibodies (mAbs) into the brain, safety testing of therapeutic vaccines, non-clinical testing of biosimilars, infection in toxicology studies with immunomodulators and challenges to human risk assessment, maternal and infant anti-drug antibody (ADA) development and impact in non-human primate (NHP) developmental toxicity studies, and a summary of an NC3Rs workshop on the future vision for non-clinical safety assessment of biopharmaceuticals. Copyright © 2015 Elsevier Inc. All rights reserved.

The after breakfast 50-g, 1-hour glucose challenge test in urban Mexican pregnant women: its sensitivity and specificity evaluated by three diagnostic criteria for gestational diabetes mellitus.

PubMed

Espinosa de los Monteros, A; Parra, A; Hidalgo, R; Zambrana, M

1999-04-01

To study the sensitivity and specificity of the 50-g, 1-hour gestational glucose challenge test performed 1 to 2 hours after a non-standardized home breakfast in urban Mexican women by using three different gestational diabetes mellitus diagnostic criteria. Four hundred and forty-five consecutive women of 24-28 weeks gestation were studied. The glucose challenge test was performed in the fed state and a week later a fasting 100-g, 3-hours oral glucose tolerance test was carried out in all of them. Duplicate serum glucose concentrations were determined by a glucose-oxidase method. Sensitivity and specificity were calculated using three different diagnostic criteria for gestational diabetes mellitus. The glucose challenge test performed as indicated, with a cutoff of 7.8 mmol/L, had 88-89% sensitivity and 85-87% specificity when using as diagnostic criteria those proposed by the National Diabetes Data Group and by Carpenter & Coustan; by using Sacks et al. criteria, the values were 82% and 88%, respectively. Considering only pregnant women > or = 25 years of age, the sensitivity increased to 92% with the National Diabetes Data Group criteria. Pregnant women < 25 years of age had significantly lower blood glucose values than those with age > or = 25 years during the glucose tolerance test. For the general group the sensitivity of the glucose challenge test performed 1 to 2 hours after breakfast was similar, based on the National Diabetes Data Group and the Carpenter & Coustan's diagnostic criteria for gestational diabetes mellitus. However, when pregnant women > or = 25 years of age were considered, the use of the former criteria yielded a slightly better sensitivity.

The predictive value of specific immunoglobulin E levels in serum for the outcome of the development of tolerance in cow's milk allergy.

PubMed

Martorell, A; García Ara, M C; Plaza, A M; Boné, J; Nevot, S; Echeverria, L; Alonso, E; Garde, J

2008-01-01

Immunoglobulin E-mediated allergy to cow's milk protein (CMP) tends to subside over years of follow-up. The gold standard for detecting such allergy has been the oral challenge test. The development of some other test for determining the correct timing of the oral challenge test would avoid unnecessary patient discomfort. The aim of this study was to determine whether monitoring cow's milk (CM) specific IgE levels over time can be used as a predictor for determining when patients develop clinical tolerance. A prospective 4-year follow-up study was made of 170 patients with IgE-mediated allergy to CMP, involving periodic evaluations (12, 18, 24, 36 and 48 months) with the determination of casein and CM specific IgE on each visit, along with CM challenge testing. ROC curves were used to analyse the sensitivity, specificity and predictive values of the casein and CM specific IgE levels versus the challenge test outcomes at the different moments of follow-up. In the course of follow-up, 140 infants (82 %) became tolerant. Specific IgE levels to CM: 2.58, 2.5, 2.7, 2.26, 5 kU(A)/l and to casein: 0.97, 1.22, 3, 2.39, 2.73 kU(A)/l, respectively, predicted clinical reactivity (greatest diagnostic efficiency values) at the different analysed moments of follow-up (12, 18, 24, 36 and 48 months). Quantification of CMP specific IgE is a useful test for diagnosing symptomatic allergy to CM in the paediatric population, and could eliminate the need to perform oral challenges tests in a significant number of children.

Mud crab susceptibility to disease from white spot syndrome virus is species-dependent.

PubMed

Somboonna, Naraporn; Mangkalanan, Seksan; Udompetcharaporn, Attasit; Krittanai, Chartchai; Sritunyalucksana, Kallaya; Flegel, Tw

2010-11-20

Based on a report for one species (Scylla serrata), it is widely believed that mud crabs are relatively resistant to disease caused by white spot syndrome virus (WSSV). We tested this hypothesis by determining the degree of susceptibility in two species of mud crabs, Scylla olivacea and Scylla paramamosain, both of which were identified by mitochondrial 16 S ribosomal gene analysis. We compared single-dose and serial-dose WSSV challenges on S. olivacea and S. paramamosain. In a preliminary test using S. olivacea alone, a dose of 1 × 106 WSSV copies/g gave 100% mortality within 7 days. In a subsequent test, 17 S. olivacea and 13 S. paramamosain were divided into test and control groups for challenge with WSSV at 5 incremental, biweekly doses starting from 1 × 104 and ending at 5 × 106 copies/g. For 11 S. olivacea challenged, 3 specimens died at doses between 1 × 105 and 5 × 105 copies/g and none died for 2 weeks after the subsequent dose (1 × 106 copies/g) that was lethal within 7 days in the preliminary test. However, after the final challenge on day 56 (5 × 106 copies/g), the remaining 7 of 11 S. olivacea (63.64%) died within 2 weeks. There was no mortality in the buffer-injected control crabs. For 9 S. paramamosain challenged in the same way, 5 (55.56%) died after challenge doses between 1 × 104 and 5 × 105 copies/g, and none died for 2 weeks after the challenge dose of 1 × 106 copies/g. After the final challenge (5 × 106 copies/g) on day 56, no S. paramamosain died during 2 weeks after the challenge, and 2 of 9 WSSV-infected S. paramamosain (22.22%) remained alive together with the control crabs until the end of the test on day 106. Viral loads in these survivors were low when compared to those in the moribund crabs. S. olivacea and S. paramamosain show wide variation in response to challenge with WSSV. S. olivacea and S. paramamosain are susceptible to white spot disease, and S. olivacea is more susceptible than S. paramamosain. Based on our single-challenge and serial challenge results, and on previous published work showing that S. serrata is relatively unaffected by WSSV infection, we propose that susceptibility to white spot disease in the genus Scylla is species-dependent and may also be dose-history dependent. In practical terms for shrimp farmers, it means that S. olivacea and S. paramamosain may pose less threat as WSSV carriers than S. serrata. For crab farmers, our results suggest that rearing of S. serrata would be a better choice than S. paramamosain or S. olivacea in terms of avoiding losses from seasonal outbreaks of white spot disease.

Diagnostic accuracy of patch test in children with food allergy.

PubMed

Caglayan Sozmen, Sule; Povesi Dascola, Carlotta; Gioia, Edoardo; Mastrorilli, Carla; Rizzuti, Laura; Caffarelli, Carlo

2015-08-01

The gold standard test for confirming whether a child has clinical hypersensitivity reactions to foods is the oral food challenge. Therefore, there is increasing interest in simpler diagnostic markers of food allergy, especially in children, to avoid oral food challenge. The goal of this study was to assess the diagnostic accuracy of atopy patch test in comparison with oral food challenge. We investigated 243 children (mean age, 51 months) referred for evaluation of suspected egg or cow's milk allergy. Skin prick test and atopy patch test were carried out, and after a 2 weeks elimination diet, oral food challenge was performed. Two hundred and forty-three children underwent OFC to the suspected food. We found clinically relevant food allergies in 40 (65%) children to egg and in 22 (35%) to cow's milk. The sensitivity of skin prick test for both milk and egg was 92%, specificity 91%, positive predictive value 35%, and negative predictive value of 93%. Sensitivity, specificity, positive predictive value, and negative predictive value of atopy patch test for both milk and egg were 21%, 73%, 20%, and 74%, respectively. Our study suggests that there is insufficient evidence for the routine use of atopy patch test for the evaluation of egg and cow's milk allergy. OFC remains gold standard for the diagnosis of egg and milk allergy even in the presence of high costs in terms of both time and risks during application. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Symptoms, Diagnosis, and Treatment of Cow's Milk Allergy.

PubMed

Vandenplas, Yvan; Marchand, Johan; Meyns, Lien

2015-01-01

The diagnosis and management of cow's milk allergy (CMA) is a topic of debate because there are no specific symptoms and reliable diagnostic tests. Literature was searched using databases to find original papers and reviews on this topic. A "challenge test" is still recommended as the most specific and sensitive diagnostic test, although a positive challenge test does not proof the involvement of the immune system. Only in the rare case of anaphylaxis, the challenge tests is not recommended. The Cow's Milk Symptom Score (CoMiSS) is an awareness tool for health care professionals to better recognize symptoms caused by the ingestion of cow's milk, but still needs validation. Today, the recommended diagnostic approach consists of an elimination diet with an extensive cow's milk based hydrolysate, followed by a challenge test. Amino acid based formula is reserved for the severe cases. Rice hydrolysates are gaining popularity, because they have been shown to be effective, have a better acceptability, and to be cheaper than the extensive cow's milk based hydrolysates. Soy infant formula may offer an additional alternative option as reviews concluded that about 10-15% of infants allergic to cow's milk will also react to soy. Gastro-intestinal microbiota manipulation may be of additional benefit in the treatment of CMA. The development of rice hydrolysates challenge the use of Today, extensive cow's milk based extensive hydrolysates remain the first option for the majority of patients and amino acid formula for the most severe cases. Rice hydrolysates and soy infant formula are considered as second choice options.

Occupational asthma due to turpentine in art painter--case report.

PubMed

Dudek, Wojciech; Wittczak, Tomasz; Swierczyńska-Machura, Dominika; Walusiak-Skorupa, Jolanta; Pałczyński, Cezary

2009-01-01

Turpentine is a fluid obtained by distillation of wood resins containing mixture of terpens. It can act as an irritant and sensitiser. Most common health problem among workers exposed to turpentine is contact dermatitis. Little is know about turpentine to cause type I hypersensitivity reaction. We present a case of a 27-year old art painter using turpentine as a thinner for oil-based paints. She developed asthmatic reactions after 5 years of working with turpentine. A number of clinical procedures were performed, including clinical examination, routine laboratory tests, total serum IgE, skin prick tests to common aeroallergens, metal salts, oil-based paints and balsamic turpentine, resting spirometry test, histamine challenge, and a single-blind, placebo-controlled specific inhalation challenge with balsamic turpentine. Clinical findings and laboratory test results were normal but a significant bronchial hyperreactivity was found. During the specific challenge, dyspnoea and decreased forced expiratory volume (FEV1) were observed in late phase of asthmatic reaction. An increased proportion of eosinophils in induced sputum could also be noted 24 h after the challenge. Positive clinical response to the specific challenge as well as the morphological changes found in induced sputum served as the basis for diagnosing occupational asthma. To our knowledge, this is the first well-documented case of turpentine-induced occupational asthma.

Approach to evaluation and management of a patient with multiple food allergies.

PubMed

Bird, J Andrew

2016-01-01

Diagnosing food allergy is often challenging, and validated testing modalities are mostly limited to immunoglobulin E (IgE)-mediated reactions to foods. Use of food-specific IgE tests and skin prick tests in individuals without a history that supports an IgE-mediated reaction to the specific food being tested diminishes the predictive capabilities of the test. To review the literature regarding evaluation of patients with a concern for multiple food allergies and to demonstrate an evidence-based approach to diagnosis and management. A literature search was performed and articles identified as relevant based on the search terms "food allergy," "food allergy diagnosis," "skin prick test," "serum IgE test," "oral food challenge", and "food allergy management." Patients at risk of food allergy are often misdiagnosed and appropriate evaluation of patients with concern for food allergy includes taking a thorough diet history and reaction history, performing specific tests intentionally and when indicated, and conducting an oral food challenge in a safe environment by an experienced provider when test results are inconclusive. An evidence-based approach to diagnosing and managing a patient at risk of having a life-threatening food allergy is reviewed.

Decision making about healthcare-related tests and diagnostic test strategies. Paper 2: a review of methodological and practical challenges.

PubMed

Mustafa, Reem A; Wiercioch, Wojtek; Cheung, Adrienne; Prediger, Barbara; Brozek, Jan; Bossuyt, Patrick; Garg, Amit X; Lelgemann, Monika; Büehler, Diedrich; Schünemann, Holger J

2017-12-01

In this first of a series of five articles, we provide an overview of how and why healthcare-related tests and diagnostic strategies are currently applied. We also describe how our findings can be integrated with existing frameworks for making decisions that guide the use of healthcare-related tests and diagnostic strategies. We searched MEDLINE, references of identified articles, chapters in relevant textbooks, and identified articles citing classic literature on this topic. We provide updated frameworks for the potential roles and applications of tests with suggested definitions and practical examples. We also discuss study designs that are commonly used to assess tests' performance and the effects of tests on people's health. These designs include diagnostic randomized controlled trials and retrospective validation. We describe the utility of these and other currently suggested designs, which questions they can answer and which ones they cannot. In addition, we summarize the challenges unique to decision-making resulting from the use of tests. This overview highlights current challenges in the application of tests in decision-making in healthcare, provides clarifications, and informs the proposed solutions. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparison of diagnostic validity of mannitol and methacholine challenges and relationship to clinical status and airway inflammation in steroid-naïve asthmatic patients.

PubMed

Porpodis, Konstantinos; Domvri, Kalliopi; Kontakiotis, Theodoros; Fouka, Evangelia; Kontakioti, Eirini; Zarogoulidis, Konstantinos; Papakosta, Despina

2017-06-01

The purpose of this study was to demonstrate and compare the diagnostic validity of two bronchial challenges and to investigate their correlation with patient clinical status, atopy and inflammation markers. Eighty-eight patients, 47 women and 41 men, mean age 38.56 ± 16.73 years who presented with asthma related symptoms and were not on any anti-asthma medication, were challenged with mannitol and methacholine on separate days. Medical history regarding asthmatic symptoms, physical examination, skin prick tests and FeNO levels were also assessed. The clinical diagnosis of asthma was based on bronchodilator reversibility test. Sixty-seven patients were diagnosed with asthma and 21 without asthma. Both methacholine (P < 0.014) and mannitol (P < 0.000) challenges were significant in diagnosing asthma. The positive/negative predictive value was 93.33%/41.86% for methacholine, 97.72%/45.45% for mannitol and 97.05%/45.45%. for both methods assessed together. Worthy of note that 22% of asthmatics had both tests negative. There was a negative correlation between PC20 of methacholine and the FeNO level P < 0.001, and positive with the PD15 of mannitol P < 0.001 and the pre-test FEV 1 % pred P < 0.005, whereas PD15 of mannitol was negatively correlated with the FeNO level P < 0.001. Furthermore, dyspnea was the only asthmatic symptom associated with FeNO level P < 0.035 and the positivity of mannitol P < 0.014 and methacholine P < 0.04. Both challenge tests were equivalent in diagnosing asthma. Nevertheless, specificity appeared to be slightly higher in mannitol challenge.

Acanthamoeba: An Overview of the Challenges to the Development of a Consensus Methodology of Disinfection Efficacy Testing for Contact Lens Care Products.

PubMed

Brocious, Jeffrey; Tarver, Michelle E; Hampton, Denise; Eydelman, Malvina

2018-04-24

With the increasing incidence of more pathogens that can cause microbial keratitis (MK), it is necessary to periodically reassess disinfection multipurpose solutions testing requirements to ensure that relevant organisms to challenge them are being used. Current testing protocols have included common pathogens such as Pseudomonas aeruginosa, Staphylococcus aureus, Serratia marcescens, Candida albicans, and Fusarium solani but have omitted less common pathogens such as Acanthamoeba. Specifically, Acanthamoeba sp. has recently been identified as a prevalent cause of MK in certain countries. Developing an appropriate protocol for this unique organism presents a challenge, given its two distinct life stages, methods to grow the organism, encystment techniques, and many other parameters that can affect testing outcomes. Therefore, the appropriate combination of these parameters is crucial to developing a protocol that ensures consistent, accurate results. The FDA has recognized the importance of establishing a standardized testing protocol for this pathogen and embarked on research efforts to provide a recommended testing protocol for testing contact lens care products.

In vivo screening of candidate pretreatment compounds against cyanide using mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kiser, R.C.; Olson, C.T.; Menton, R.G.

1993-05-13

An in vivo screening procedure was established at Battelle's Medical Research and Evaluation Facility (MREF) to evaluate the efficacy of candidate pretreatment compounds in mice challenged with the blood agent, sodium cyanide (NaCN). Male albino mice of ICR outbred stock weighing between 22.5 and 27.5 g are challenged by intramuscular (i.m.) injection, at a volume of 0.5 mL/kg, of a dose of NaCN twice the LD50 of untreated mice as determined on that day of testing. Candidate drugs are tested at fractions of their LD50 or their limit of solubility in the most optimum vehicle and given intraperitoneally (i.p.) tomore » separate groups of mice at either 60 or 15 min prior to NaCN challenge. Sodium thiosulfate (1000 mg/kg)/sodium nitrite (100 mg/kg) controls are injected i.p. only at 60 min prior to challenge. A test compound is deemed effective if, at any of three concentrations tested, or at either pretreatment time, it is statistically more efficacious in preventing lethality than is a negative control substance (candidate compound vehicle).« less

Reversible obstructive sleep apnea caused by occupational exposure to guar gum dust.

PubMed

Leznoff, A; Haight, J S; Hoffstein, V

1986-05-01

This report describes a case of reversible obstructive sleep apnea caused by occupational exposure to an inhaled allergen, guar gum powder. The patient, a pet food plant employee, also experienced severe cough, rhinitis, and conjunctivitis. Skin tests confirmed the specific guar allergy. Pharyngeal cross-sectional area was smaller than normal. Pulmonary function studies, histamine challenge tests, nasal air-flow resistance measurements, and nocturnal polysomnography were performed on 3 separate occasions: while the patient was working at his usual occupation, at the end of a 3-wk holiday, and after a guar dust challenge in an inhalation chamber. Pulmonary function and histamine challenge tests were consistently normal. At the time of the initial tests, nasal resistance was elevated, and nocturnal polysomnography revealed obstructive sleep apnea. After absence from work, obstructive sleep apnea resolved, and the nasal resistance returned to normal. After challenge with guar gum dust, the patient developed increased resistance to nasal air flow, and obstructive sleep apnea reappeared. This case demonstrates that allergy can cause reversible obstructive sleep apnea and that occupational exposure should be considered in the assessment of patients with this disease.

Developing a modified preservative efficacy testing approach as a predictive tool for the evaluation of preservative systems in liquid home care products under variable test conditions.

PubMed

Hoyt, Anne L; Bushman, Don; Lewis, Nathan; Faber, Robert

2012-01-01

How can a formulator have confidence that a preservative system will perform as expected under adverse conditions? Extreme conditions that can lead to the development of "off odors" in the product can be a serious challenge for companies providing home care products in the global market. Formulation and stability testing occur under controlled parameters that simulate limited environmental conditions and microbial challenges are typically performed with a standard inoculum level. While this is an acceptable and dependable process, it does not necessarily assess how well a preservative system can perform under extreme environmental conditions or against unusually high levels of bacterial challenges. This is especially true when formulations are diluted and stored by the end-user. By modifying microbial challenge testing of a liquid dishwashing product to include unexpected dilution schemes, increased microbial assaults, and elevated temperatures, a pattern of preservative efficacy was established. The resulting approach proved to be a useful tool when developing use directions, recommended dilution levels, the overall surfactant system, preservative type, and storage restrictions.

An evaluation of short-term corticosteroid response in perennial allergic rhinitis using histamine and adenosine monophosphate nasal challenge

PubMed Central

Wilson, Andrew M; Sims, Erika J; Orr, Linda C; Robb, Fiona; Lipworth, Brian J

2003-01-01

Aims To evaluate the role of AMP nasal challenge as a measure of short-term treatment response in patients receiving intranasal corticosteroids. Adenosine monophosphate (AMP) challenge has been shown to be a good inflammatory surrogate in the lower airways, but it has not been properly evaluated as a nasal challenge test. Methods Fourteen patients with perennial allergic rhinitis (PAR) were randomized to receive 2 weeks treatment with placebo (PL) or 200 µg intranasal mometasone furoate (MF) once daily in a randomized single-blind crossover study. AMP (25–800 mg ml−1) and histamine (0.25–8 mg ml−1) nasal challenge testing were performed after each treatment period with 30% decrease in minimal cross-sectional area (MCA). Domiciliary symptom data were collected. Results There was a significant (P < 0.05) improvement in PC30 MCA and nasal volume with AMP but not with histamine comparing MF vs PL. This amounted to a 2.8 (95% CI 1.5, 4.0) and 0.7 (95% CI −0.5, 1.9) doubling-dose change for AMP and histamine challenges, respectively. There were significant (P < 0.05) improvements in nasal symptoms and quality of life. Conclusions AMP nasal challenge using acoustic rhinometry may be a useful test to assess short-term treatment response in patient with PAR. PMID:12680883

Toxcast and the Use of Human Relevant In Vitro Exposures ...

EPA Pesticide Factsheets

The path for incorporating new approach methods and technologies into quantitative chemical risk assessment poses a diverse set of scientific challenges. These challenges include sufficient coverage of toxicological mechanisms to meaningfully interpret negative test results, development of increasingly relevant test systems, computational modeling to integrate experimental data, putting results in a dose and exposure context, characterizing uncertainty, and efficient validation of the test systems and computational models. The presentation will cover progress at the U.S. EPA in systematically addressing each of these challenges and delivering more human-relevant risk-based assessments. This abstract does not necessarily reflect U.S. EPA policy. Presentation at the British Toxicological Society Annual Congress on ToxCast and the Use of Human Relevant In Vitro Exposures: Incorporating high-throughput exposure and toxicity testing data for 21st century risk assessments .

Inventory of college challenges for ethnic minority students: psychometric properties of a new instrument in Chinese Americans.

PubMed

Ying, Yu-Wen; Lee, Peter Allen; Tsai, Jeanne L

2004-11-01

The Inventory of College Challenges for Ethnic Minority Students (ICCEMS) is a newly developed instrument that assesses challenges faced by ethnic minority college students across a range of cultural, academic, social, and practical domains. The present study tested the ICCEMS among Chinese American students in an attempt to identify its factor structure and assess its psychometric properties. A total of 13 factor domains emerged. The Cronbach's alpha and 1-month test-retest reliability of the subscales and the overall scale supported their reliability. Both criterion and construct validities were also demonstrated. Chinese American college students faced the greatest challenges in terms of unclear career direction and academic demands. 2004 APA

In vivo diagnosis of allergic diseases--allergen provocation tests.

PubMed

Agache, I; Bilò, M; Braunstahl, G-J; Delgado, L; Demoly, P; Eigenmann, P; Gevaert, P; Gomes, E; Hellings, P; Horak, F; Muraro, A; Werfel, T; Jutel, M

2015-04-01

The allergen challenge test has been the mainstay of diagnosis of allergic diseases for a long time since it offers a direct proof of the clinical relevance of a particular allergen for the allergic disease symptoms and severity. Standardisation and availability for daily practice (including safety issues) are still to be refined but most of the challenge tests have safely crossed the border from research tools to diagnostic tests available for daily practice for a well trained clinical staff. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The association between socio-demographic marginalization and plasma glucose levels at diagnosis of gestational diabetes.

PubMed

Sampson, L; Dasgupta, K; Ross, N A

2014-12-01

We examined the association between socio-demographic marginalization and plasma glucose levels at diagnosis of gestational diabetes in a multi-ethnic and socio-economically diverse patient group. Medical charts at a Toronto gestational diabetes clinic were reviewed for women with a recorded pregnancy between 1 March 2006 and 26 April 2011. One-hour 50-g glucose challenge test values and postal code data were abstracted. Postal codes were merged with 2006 Canadian census data to compute neighbourhood-level ethnic concentration (% recent immigrants, % visible minorities) and material deprivation (% low education, % low income, single-parent households). We compared women in the highest neighbourhood quintiles for both ethnic concentration and material deprivation with all other women to explore an association between marginalization and diagnostic glucose levels. Multivariate regression models of glucose challenge test values and insulin prescription were adjusted for age, prior gestational diabetes, parity and diabetes family history. Among 531 patients with complete glucose challenge test data (mean 11.94 mmol/l, sd 1.83), those in the most marginalized neighbourhoods had 0.43 mmol/l higher glucose challenge test values (95% CI 0.08-0.78) compared with the rest of the study population. Other factors associated with higher glucose challenge test values were prior gestational diabetes (0.59 mmol/l increment, 95% CI 0.19-0.99) and diabetes family history (0.32 mmol/l increment, 95% CI -0.01 to 0.66). Each additional 1 mmol/l glucose challenge test result was associated with an increased likelihood of being prescribed insulin (odds ratio 1.33, 95% CI 1.17-1.51). Women living in the most materially deprived and ethnically concentrated neighbourhoods have higher glucose levels at diagnosis of gestational diabetes. They may need close monitoring for timely initiation of insulin. © 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.

Evaluation of the filtration performance of NIOSH-approved N95 filtering facepiece respirators by photometric and number-based test methods.

PubMed

Rengasamy, Samy; Miller, Adam; Eimer, Benjamin C

2011-01-01

N95 particulate filtering facepiece respirators are certified by measuring penetration levels photometrically with a presumed severe case test method using charge neutralized NaCl aerosols at 85 L/min. However, penetration values obtained by photometric methods have not been compared with count-based methods using contemporary respirators composed of electrostatic filter media and challenged with both generated and ambient aerosols. To better understand the effects of key test parameters (e.g., particle charge, detection method), initial penetration levels for five N95 model filtering facepiece respirators were measured using NaCl aerosols with the aerosol challenge and test equipment employed in the NIOSH respirator certification method (photometric) and compared with an ultrafine condensation particle counter method (count based) for the same NaCl aerosols as well as for ambient room air particles. Penetrations using the NIOSH test method were several-fold less than the penetrations obtained by the ultrafine condensation particle counter for NaCl aerosols as well as for room particles indicating that penetration measurement based on particle counting offers a more difficult challenge than the photometric method, which lacks sensitivity for particles < 100 nm. All five N95 models showed the most penetrating particle size around 50 nm for room air particles with or without charge neutralization, and at 200 nm for singly charged NaCl monodisperse particles. Room air with fewer charged particles and an overwhelming number of neutral particles contributed to the most penetrating particle size in the 50 nm range, indicating that the charge state for the majority of test particles determines the MPPS. Data suggest that the NIOSH respirator certification protocol employing the photometric method may not be a more challenging aerosol test method. Filter penetrations can vary among workplaces with different particle size distributions, which suggests the need for the development of new or revised "more challenging" aerosol test methods for NIOSH certification of respirators.

Positive Skin Test or Specific IgE to Penicillin Does Not Reliably Predict Penicillin Allergy.

PubMed

Tannert, Line Kring; Mortz, Charlotte Gotthard; Skov, Per Stahl; Bindslev-Jensen, Carsten

According to guidelines, patients are diagnosed with penicillin allergy if skin test (ST) result or specific IgE (s-IgE) to penicillin is positive. However, the true sensitivity and specificity of these tests are presently not known. To investigate the clinical relevance of a positive ST result and positive s-IgE and to study the reproducibility of ST and s-IgE. A sample of convenience of 25 patients with positive penicillin ST results, antipenicillin s-IgE results, or both was challenged with their culprit penicillin. Further 19 patients were not challenged, but deemed allergic on the basis of a recent anaphylactic reaction or delayed reactions to skin testing. Another sample of convenience of 18 patients, 17 overlapping with the 25 challenged, with initial skin testing and s-IgE (median, 25; range, 3-121), months earlier (T -1 ), was repeat skin tested and had s-IgE measured (T 0 ), and then skin tested and had s-IgE measured 4 weeks later (T 1 ). Only 9 (36%) of 25 were challenge positive. There was an increased probability of being penicillin allergic if both ST result and s-IgE were positive at T 0 . Positive ST result or positive s-IgE alone did not predict penicillin allergy. Among the 18 patients repeatedly tested, 46.2% (12 of 25) of positive ST results at T -1 were reproducibly positive at T 0 . For s-IgE, 54.2% (14 of 24) positive measurements were still positive at T 0 and 7 converted to positive at T 1 . The best predictor for a clinically significant (IgE-mediated) penicillin allergy is a combination of a positive case history with simultaneous positive ST result and s-IgE or a positive challenge result. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

National Transonic Facility status

NASA Technical Reports Server (NTRS)

Mckinney, L. W.; Bruce, W. E., Jr.; Gloss, B. B.

1989-01-01

The National Transonic Facility (NTF) was operational in a combined checkout and test mode for about 3 years. During this time there were many challenges associated with movement of mechanical components, operation of instrumentation systems, and drying of insulation in the cryogenic environment. Most of these challenges were met to date along with completion of a basic flow calibration and aerodynamic tests of a number of configurations. Some of the major challenges resulting from cryogenic environment are reviewed with regard to hardware systems and data quality. Reynolds number effects on several configurations are also discussed.

Design evolution of the orbiter reaction control subsystem

NASA Technical Reports Server (NTRS)

Taeber, R. J.; Karakulko, W.; Belvins, D.; Hohmann, C.; Henderson, J.

1985-01-01

The challenges of space shuttle orbiter reaction control subsystem development began with selection of the propellant for the subsystem. Various concepts were evaluated before the current Earth storable, bipropellant combination was selected. Once that task was accomplished, additional challenges of designing the system to satisfy the wide range of requirements dictated by operating environments, reusability, and long life were met. Verification of system adequacy was achieved by means of a combination of analysis and test. The studies, the design efforts, and the test and analysis techniques employed in meeting the challenges are described.

Turbines, Wind Tunnels, and Teamwork: The 2017 Collegiate Wind Competition Technical Challenge

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

Ten college teams put their turbines to the test at the U.S. Department of Energy’s 2017 Collegiate Wind Competition Technical Challenge, held April 20–22 at the National Wind Technology Center (NWTC). The competition showcased a wide variety of turbine designs and highlighted the competitors’ brilliance, agility, and ingenuity. College students weren’t the only future wind energy experts at the NWTC that weekend: elementary and middle school students tested their turbines—crafted creatively from materials like soda bottles and aluminum foil—in the Colorado KidWind Challenge.

Temperature-mediated differences in bacterial kidney disease expression and survival in Renibacterium salmoninarum-challenged bull trout and other salmonids

USGS Publications Warehouse

Jones, D.T.; Moffitt, C.M.; Peters, K.K.

2007-01-01

Resource managers considering restoration and reconnection of watersheds to protect and enhance threatened populations of bull trout Salvelinus confluentus have little information about the consequences of bacterial kidney disease (BKD) caused by Renibacterium salmoninarum. To better understand the response of bull trout to R. salmoninarum challenge, we conducted several laboratory experiments at two water temperatures. The extent, severity, and lethality of BKD in bull trout were compared with those of similarly challenged lake trout S. namaycush, Arctic char S. alpinus, Chinook salmon Oncorhynchus tshawytscha, and rainbow trout O. mykiss. The lethal dose of bacterial cells necessary to induce 50% mortality (LD50) was 10-fold lower at the 15??C challenge than at the 9??C challenge. Of the species tested, bull trout were relatively resistant to BKD, Arctic char were the most susceptible among Salvelinus species, and Chinook salmon were the most susceptible among Oncorhynchus species tested. Mean time to death was more rapid for all fish tested at 15??C than for fish challenged at 9??C. These results suggest that infection of bull trout with BKD likely poses a low risk to successful restoration of threatened populations. ?? Copyright by the American Fisheries Society 2007.

Effect of lactose on oro-cecal transit in lactose digesters and maldigesters.

PubMed

He, T; Priebe, M G; Welling, G W; Vonk, R J

2006-10-01

The transit time of the small intestine, in addition to lactase activity, may influence lactose digestion and thus play a role in the occurrence of lactose intolerance. The objectives of this study were to investigate the effect of lactose on the oro-cecal transit time (OCTT) in lactose digesters and maldigesters as well as the possible mechanisms underlying these effects. Twenty-eight Chinese subjects and 16 Dutch subjects underwent one glucose and one lactose challenge in two single-blinded tests. Twenty of the Chinese subjects without complaints after the challenge then underwent another lactose challenge. A 6-h symptom score (SSC) was recorded, breath-hydrogen concentration was measured and OCTT after consumption of glucose and lactose was determined with the lactose-[13C] ureide breath test. The lactose digestion index (LDI) was determined in both the Dutch and 20 Chinese subjects with the 13C/2H-glucose test. Lactose digesters (n = 13) and maldigesters (n = 20) were classified based on the results of the LDI and the breath-hydrogen test. The OCTT after the lactose and glucose challenges did not differ in the digesters, whereas in the maldigesters the OCTT, after the lactose challenge, was shorter than that after glucose. There was no difference in OCTT after the glucose challenge between the maldigesters and the digesters. However, the OCTT after the lactose challenge in the maldigesters was shorter than that in the digesters. The LDI of the digesters was significantly higher than that of the maldigesters. The OCTT after the lactose challenge was not correlated to the LDI in the maldigesters nor in the digesters. Based on the SSC after the one glucose and two lactose challenges, a tolerant (n = 7) and an intolerant (n = 5) group were classified in the Chinese subjects. The two groups did not differ in their LDI or OCTT after the lactose challenge. The OCTT after the lactose challenge was not correlated to the SSC or the LDI. Lactose triggers a faster oro-cecal transit in lactose maldigesters, but not in digesters. However, this could not be explained by intestinal distension resulting from the osmotic load posed by maldigested lactose, and thus suggests a direct effect of lactose on intrinsic factors regulating intestinal motility.

Report of a consultation on the optimization of clinical challenge trials for evaluation of candidate blood stage malaria vaccines, 18-19 March 2009, Bethesda, MD, USA.

PubMed

Moorthy, V S; Diggs, C; Ferro, S; Good, M F; Herrera, S; Hill, A V; Imoukhuede, E B; Kumar, S; Loucq, C; Marsh, K; Ockenhouse, C F; Richie, T L; Sauerwein, R W

2009-09-25

Development and optimization of first generation malaria vaccine candidates has been facilitated by the existence of a well-established Plasmodium falciparum clinical challenge model in which infectious sporozoites are administered to human subjects via mosquito bite. While ideal for testing pre-erythrocytic stage vaccines, some researchers believe that the sporozoite challenge model is less appropriate for testing blood stage vaccines. Here we report a consultation, co-sponsored by PATH MVI, USAID, EMVI and WHO, where scientists from all institutions globally that have conducted such clinical challenges in recent years and representatives from regulatory agencies and funding agencies met to discuss clinical malaria challenge models. Participants discussed strengthening and harmonizing the sporozoite challenge model and considered the pros and cons of further developing a blood stage challenge possibly better suited for evaluating the efficacy of blood stage vaccines. This report summarizes major findings and recommendations, including an update on the Plasmodium vivax clinical challenge model, the prospects for performing experimental challenge trials in malaria endemic countries and an update on clinical safety data. While the focus of the meeting was on the optimization of clinical challenge models for evaluation of blood stage candidate malaria vaccines, many of the considerations are relevant for the application of challenge trials to other purposes.

Integration and Testing Challenges of Small, Multiple Satellite Missions: Experiences From The Space Technology 5 Project

NASA Technical Reports Server (NTRS)

Sauerwein, Timothy A.; Gostomski, Thomas

2007-01-01

This brief presentation describes the mechanical and electrical integration activities and environmental testing challenges of the Space Technology 5 (ST5) Project. Lessons learned during this process are highlighted, including performing mechanical activities serially to gain efficiency through repetition and performing electrical activities based on the level of subsystem expertise available.

A Framework for Evidence-Based Licensure of Adaptive Autonomous Systems

DTIC Science & Technology

2016-03-01

insights gleaned to DoD. The autonomy community has identified significant challenges associated with test, evaluation verification and validation of...licensure as a test, evaluation, verification , and validation (TEVV) framework that can address these challenges. IDA found that traditional...language requirements to testable (preferably machine testable) specifications • Design of architectures that treat development and verification of

Toxcast and the Use of Human Relevant In Vitro Exposures: Incorporating High-Throughput Exposure and Toxicity Testing Data for 21st Century Risk Assessments (British Toxicological Society Annual Congress)

EPA Science Inventory

The path for incorporating new approach methods and technologies into quantitative chemical risk assessment poses a diverse set of scientific challenges. These challenges include sufficient coverage of toxicological mechanisms to meaningfully interpret negative test results, dev...

Operational challenges in delivering CD4 diagnostics in sub-Saharan Africa.

PubMed

Thairu, L; Katzenstein, D; Israelski, D

2011-07-01

Access to reliable and low cost CD4 T-cell enumeration to stage illness and monitor anti-retroviral therapy remains elusive in resource-limited settings. We report challenges in delivering CD4 testing using the microcapillary Fluorescence-Activated Cell Sorter (FACS) methodology (Guava EasyCD4 instrument Guava Technologies, Hayward) in Burkina Faso and Zimbabwe. Resources, instruments, reagents, and training were provided to local laboratories within the existing infrastructure and data on CD4 were collected from routine laboratory testing. Challenges encountered included frequent instrument breakdown; poor manufacturer maintenance; difficulties in managing reagent stocks; high technician turnover; reliance on antiquated data management systems; redundant service provision; and lack of repeat testing in male HIV+ patients and in patients with higher CD4 counts after initial staging. While adopting newer, less expensive technologies such as fluorescent platforms and point of care tests can facilitate access to lower cost CD4 testing, our experience suggests that supply chain, corporate commitment to implementation, and community factors also require consideration.

The safety of the H1N1 influenza A vaccine in egg allergic individuals.

PubMed

Greenhawt, Matthew J; Chernin, Anna S; Howe, Laura; Li, James T; Sanders, Georgiana

2010-11-01

The safety of H1N1 vaccine is unknown in egg allergic (EA) recipients. To establish the safety of administering H1N1 vaccine and to evaluate the predictability of H1N1 skin testing in EA patients. In a controlled, prospective trial, H1N1 skin testing and vaccination was compared between EA patients (n = 105) and non-EA controls (n = 19). Those with negative H1N1 skin test results received a full H1N1 dose; those with a positive skin test result received a graded challenge (10%, 90%). Booster vaccine, if required, was given as a single dose from a different lot without prior testing. Prick and intradermal test results were positive in 3 (2.4%) of 124 and 41 (33.1%) of 124 study participants, respectively. Forty-one individuals received a 2-step graded vaccine challenge, including 13 of 25 with a history of egg anaphylaxis. No significant allergic reactions resulted from either method of vaccination or from subsequent booster doses. All study participants received the H1N1 vaccine without significant allergic reactions. Skin testing is unnecessary and does not predict vaccine tolerance. All study participants who received a graded challenge tolerated a single dose booster from a different, untested lot, including 7 individuals with a history of egg-induced anaphylaxis. We recommend administration of H1N1 vaccine to EA children without prior skin testing or graded challenge dosing. Copyright © 2010 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Clinical application of pharmacogenetics: focusing on practical issues.

PubMed

Chang, Matthew T; McCarthy, Jeanette J; Shin, Jaekyu

2015-01-01

Recent large-scale genetic-based studies have transformed the field of pharmacogenetics to identify, characterize and leverage genetic information to inform patient care. Genetic testing can be used to alter drug selection, optimize drug dosing and prevent unnecessary adverse events. As precision medicine becomes the mainstay in the clinic, it becomes critical for clinicians to utilize pharmacogenetics to guide patient care. One primary challenge is identifying patients where genetic tests that can potentially impact patient care. To address this challenge, our review highlights many practical issues clinicians may encounter: identifying candidate patients and clinical laboratories for pharmacogenetic testing, selecting highly curated resources to help asses test validity, reimbursing costs of pharmacogenetic tests, and interpreting of pharmacogenetic test results.

Occupational asthma caused by samba (Triplochiton scleroxylon) wood dust in a professional maker of wooden models of airplanes: a case study.

PubMed

Krawczyk-Szulc, Patrycja; Wiszniewska, Marta; Pałczyński, Cezary; Nowakowska-Świrta, Ewa; Kozak, Anna; Walusiak-Skorupa, Jolanta

2014-06-01

Wood dust is a known occupational allergen that may induce, in exposed workers, respiratory diseases including asthma and allergic rhinitis. Samba (obeche, Triplochiton scleroxylon) is a tropical tree, which grows in West Africa, therefore, Polish workers are rarely exposed to it. This paper describes a case of occupational asthma caused by samba wood dust. The patient with suspicion of occupational asthma due to wood dust was examined at the Department of Occupational Diseases and Clinical Toxicology in the Nofer Institute of Occupational Medicine. Clinical evaluation included: analysis of occupational history, skin prick tests (SPT) to common and occupational allergens, determination of serum specific IgE to occupational allergens, serial spirometry measurements, metacholine challenge test and specific inhalation challenge test with samba dust SPT and specific serum IgE assessment revealed sensitization to common and occupational allergens including samba. Spirometry measurements showed mild obstruction. Metacholine challenge test revealed a high level of bronchial hyperactivity. Specific inhalation challenge test was positive and cellular changes in nasal lavage and induced sputum confirmed allergic reaction to samba. IgE mediated allergy to samba wood dust was confirmed. This case report presents the first documented occupational asthma and rhinitis due to samba wood dust in wooden airplanes model maker in Poland.

Expanding Access to Malaria Diagnosis through Retail Shops in Western Kenya: What Do Shop Workers Think?

PubMed Central

Koech, Beatrice; Obala, Andrew; O'Meara, Wendy Prudhomme

2013-01-01

Background. The common symptoms of malaria reduce the specificity of clinical diagnosis. Presumptive treatment is conventional but can lead to overdiagnosis of malaria, delay of appropriate treatment, overprescription of antimalarials, and drug resistance. Routine use of diagnostic tests can address many of these concerns. Though treatment is often procured from retailers, there is low availability of rapid diagnostic tests for malaria (MRDTs), a simple, inexpensive, and accurate diagnostic solution. We know little about the challenges to expanding access to diagnostics through these outlets. Methods. To understand the perceptions of the benefits and challenges to selling rapid diagnostic tests for malaria, we conducted focus group discussions with antimalarial retailers who serve the residents of the Webuye Health and Demographic Surveillance Site in western Kenya. Results. Medicine retailers perceived MRDTs to be beneficial to their customers and businesses but also included cost, fear of the tests, risks of self-treatment, and regulatory concerns among the challenges to using and selling MRDTs. Conclusion. MRDTs represent a viable approach to increase access to malaria diagnostic testing. Medicine retailers are eager for MRDTs to be made available to them. However, certain challenges remain to implementation in retail outlets and should be addressed in advance. PMID:23766923

Clinical history as a predictor of penicillin skin test outcome.

PubMed

Wong, Benjamin B L; Keith, Paul K; Waserman, Susan

2006-08-01

Up to 10% of the population reports an "allergy" to penicillin, whereas approximately 1.1% has positive penicillin skin test results. Where penicillin skin tests are unavailable, some have advocated using history to decide whether to use a penicillin-related antibiotic. To determine if clinical history predicts penicillin skin test results. Retrospective medical record review of 94 consecutive patients who had previously taken penicillin referred for penicillin allergy. Case histories were taken, penicillin skin tests performed, and an oral challenge recommended if skin test results were negative. Of 91 cases studied, the average patient age was 27 years (range, 6 months to 82 years; 36% female). Fifty-two (57%) experienced hives as their main adverse reaction. Sixteen (18%) had at least 1 positive test result. Of this group, 9 had hives as their main symptom, whereas 1 had respiratory problems and 1 had angioedema. Most patients with positive skin test results had experienced their reaction at least 3 years ago. Regression analysis showed that age, sex, and clinical history, including type of reaction, time of reaction after penicillin ingestion, or time since the last reaction, were not associated with skin test positivity. Seventy-two (96%) of the 75 patients who had negative skin test results underwent oral challenge. Seventy had negative challenge results. The negative predictive value of a negative penicillin skin test result was 97%. Clinical history was not predictive of subsequent penicillin skin test results.

Entry, Descent, and Landing Mission Design for the Crew Exploration Vehicle Thermal Protection System Qualification Flight Test

NASA Technical Reports Server (NTRS)

Ivanov, Mark; Strauss, William; Maddock, Robert

2007-01-01

The TORCH team was challenged to generate the lowest cost mission design solution that meets the CEV aerothermal test objectives on a sub-scale flight article. The test objectives resulted from producing representative lunar return missions and observing the aerothermal envelopes of select surface locations on the CEV. From these aerothermal envelopes, two test boxes were established: one for high shear and one for high radiation. The unique and challenging trajectory design objective for the flight test was to fly through these aerothermal boxes in shear, pressure, heat flux, and radiation while also not over testing. These test boxes, and the max aerothermal limits, became the driving requirements for defining the mission design.

Economic evaluations of point of care testing strategies for active tuberculosis.

PubMed

Zwerling, Alice; Dowdy, David

2013-06-01

Point of care (POC) diagnostics are often hailed as having the potential to transform tuberculosis (TB) control efforts. However, POC testing is better conceptualized as a system of diagnosis and treatment, not simply a test that can provide rapid, deployable results. Economic evaluations may help decision makers allocate scarce resources for TB control, but evaluations of POC testing face unique challenges that include evaluating the full diagnostic system, incorporating implementation costs, translating diagnostic results into health and accounting for downstream treatment costs. For economic evaluations to reach their full potential as decision-making tools for POC testing in TB, these challenges must be understood and addressed.

AGONIST-MEDIATED AIRWAY CHALLENGE: CARDIOPULMONARY INTERACTIONS MODULATE GAS EXCHANGE AND RECOVERY

EPA Science Inventory

ABSTRACT
To better understand the early phase response (0-60 minutes) to airway challenge, we examined cardiopulmonary reactions during ovalbumin (OVA), histamine, and methacholine aerosol challenge tests in guinea pigs. Propranolol and 100% O2 were used to modify the reacti...

Improving Gram stain proficiency in hospital and satellite laboratories that do not have microbiology.

PubMed

Guarner, Jeannette; Street, Cassandra; Matlock, Margaret; Cole, Lisa; Brierre, Francoise

2017-03-01

Consolidation of laboratories has left many hospitals and satellite laboratories with minimal microbiologic testing. In many hospitals and satellite laboratories, Gram stains on primary specimens are still performed despite difficultly in maintaining proficiency. To maintain Gram stain proficiency at a community 450-bed hospital with an active emergency room we designed bimonthly challenges that require reporting Gram staining and morphology of different organisms. The challenges consist of five specimens prepared by the reference microbiology laboratory from cultures and primary specimens. Twenty to 23 medical laboratory scientists participate reading the challenges. Results from the challenges are discussed with each medical laboratory scientists. In addition, printed images from the challenges are presented at huddle to add microbiology knowledge. On the first three challenges, Gram staining was read correctly in 71%-77% of the time while morphology 53%-66%. In the last six challenges correct answers for Gram stain were 77%-99% while morphology 73%-96%. We observed statistically significant improvement when reading Gram stains by providing frequent challenges to medical laboratory scientists. The clinical importance of Gram stain results is emphasized during huddle presentations increasing knowledge and motivation to perform the test for patients.

Influence of Mechanical and Chemical Degradation in the Surface Roughness, Gloss, and Color of Microhybrid Composites.

PubMed

Lemos, Cleidiel Aa; Mauro, Silvio J; Dos Santos, Paulo H; Briso, Andre Lf; Fagundes, Ticiane C

2017-04-01

The aim of this study was to investigate the association of different degradations on the roughness, gloss, and color changes of microhybrid composites. Ten specimens were prepared for Charisma, Amelogen Plus, Point 4, and Opallis resins. Surfaces were polished and baseline measurements of roughness, gloss, and color were recorded. Specimens were then submitted to chemical and mechanical challenges, and the specimens were reevaluated. Roughness and gloss were analyzed by Kruskal -Wallis and Dunn's test (p < 0.05). Color change (ΔE) was analyzed by one-way analysis of variance and Tukey's tests (p < 0.05). The initial and final data were compared using the Wilcoxon test (p < 0.05). Spearman test checked the correlation between the roughness and gloss (p < 0.05). Regarding surface roughness and gloss, there was no difference between composites before challenges. However, all composites showed a significant increase of roughness after challenges, with highest values for Charisma. The gloss was influenced by challenges, evidencing the best gloss for Point 4. Charisma showed the highest value of color change. There was no correlation between surface roughness and gloss for the initial analysis, and after the challenges. Composites were influenced by association of challenges, and Charisma showed the highest changes for roughness, gloss, and color. The type of composite resin influenced the properties of materials, which are surface roughness, gloss, and color change. The dentist should be aware of the performance of different brands, to choose the correct required composite resin for each type of patient or region to be restored.

Fish allergy in atopic children.

PubMed

Peng, Y H; Shyur, S D; Chang, C L; Lai, C L; Chu, S H; Wu, W C; Wu, C Y

2001-12-01

The prevalence of fish allergy among 11 atopic children with elevated levels of specific immunoglobulin (Ig) E for cod was determined. None of the children had a history of fish allergy. All of the children had asthma and allergic rhinitis and 5 of them had also atopic dermatitis. The children underwent allergy skin tests (codfish, tuna, catfish, salmon, flounder, and bass), specific IgE tests (salmon, trout, tuna, eel, and mackerel), and food challenge tests. Skin tests in cod-specific IgE-positive children were positive for codfish in 4 children, tuna in 2, catfish in 2, salmon in 6, flounder in one, and bass in 2. Three children had elevated specific IgE for salmon, 5 for trout, 8 for tuna, 4 for eel, and 4 for mackerel. Oral fish challenge with 10 g of fish did not result in positive reaction in any of the children. In conclusion, a positive food challenge test provided the only definitive confirmation of fish allergy, whereas positive allergy skin tests or positive specific IgE tests were less reliable. Skin tests and in vitro specific IgE assays were not correlated with clinical symptoms of fish allergy, and the results of these 2 tests did not correlate with each other in this study.

Increased fall risk is associated with elevated co-contraction about the ankle during static balance challenges in older adults.

PubMed

Nelson-Wong, Erika; Appell, Ryan; McKay, Mike; Nawaz, Hannah; Roth, Joanna; Sigler, Robert; Third, Jacqueline; Walker, Mark

2012-04-01

Falls are a leading contributor to disability in older adults. Increased muscle co-contraction in the lower extremities during static and dynamic balance challenges has been associated with aging, and also with a history of falling. Co-contraction during static balance challenges has not been previously linked with performance on clinical tests designed to ascertain fall risk. The purpose of this study was to investigate the relationship between co-contraction about the ankle during static balance challenges with fall risk on a commonly used dynamic balance assessment, the Four Square Step Test (FSST). Twenty-three volunteers (mean age 73 years) performed a series of five static balance challenges (Romberg eyes open/closed, Sharpened Romberg eyes open/closed, and Single Leg Standing) with continuous electromyography (EMG) of bilateral tibialis anterior and gastrocnemius muscles. Participants then completed the FSST and were categorized as 'at-risk' or 'not-at-risk' to fall based on a cutoff time of 12 s. Co-contraction was quantified with co-contraction index (CCI). CCI during narrow base conditions was positively correlated with time to complete FSST. High CCIs during all static balance challenges with the exception of Romberg stance with eyes closed were predictive of being at-risk to fall based on FSST time, odds ratio 19.3. The authors conclude that co-contraction about the ankle during static balance challenges can be predictive of performance on a dynamic balance test.

Addressing the Analytic Challenges of Cross-Sectional Pediatric Pneumonia Etiology Data.

PubMed

Hammitt, Laura L; Feikin, Daniel R; Scott, J Anthony G; Zeger, Scott L; Murdoch, David R; O'Brien, Katherine L; Deloria Knoll, Maria

2017-06-15

Despite tremendous advances in diagnostic laboratory technology, identifying the pathogen(s) causing pneumonia remains challenging because the infected lung tissue cannot usually be sampled for testing. Consequently, to obtain information about pneumonia etiology, clinicians and researchers test specimens distant to the site of infection. These tests may lack sensitivity (eg, blood culture, which is only positive in a small proportion of children with pneumonia) and/or specificity (eg, detection of pathogens in upper respiratory tract specimens, which may indicate asymptomatic carriage or a less severe syndrome, such as upper respiratory infection). While highly sensitive nucleic acid detection methods and testing of multiple specimens improve sensitivity, multiple pathogens are often detected and this adds complexity to the interpretation as the etiologic significance of results may be unclear (ie, the pneumonia may be caused by none, one, some, or all of the pathogens detected). Some of these challenges can be addressed by adjusting positivity rates to account for poor sensitivity or incorporating test results from controls without pneumonia to account for poor specificity. However, no classical analytic methods can account for measurement error (ie, sensitivity and specificity) for multiple specimen types and integrate the results of measurements for multiple pathogens to produce an accurate understanding of etiology. We describe the major analytic challenges in determining pneumonia etiology and review how the common analytical approaches (eg, descriptive, case-control, attributable fraction, latent class analysis) address some but not all challenges. We demonstrate how these limitations necessitate a new, integrated analytical approach to pneumonia etiology data. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Addressing the Analytic Challenges of Cross-Sectional Pediatric Pneumonia Etiology Data

PubMed Central

Feikin, Daniel R.; Scott, J. Anthony G.; Zeger, Scott L.; Murdoch, David R.; O’Brien, Katherine L.; Deloria Knoll, Maria

2017-01-01

Abstract Despite tremendous advances in diagnostic laboratory technology, identifying the pathogen(s) causing pneumonia remains challenging because the infected lung tissue cannot usually be sampled for testing. Consequently, to obtain information about pneumonia etiology, clinicians and researchers test specimens distant to the site of infection. These tests may lack sensitivity (eg, blood culture, which is only positive in a small proportion of children with pneumonia) and/or specificity (eg, detection of pathogens in upper respiratory tract specimens, which may indicate asymptomatic carriage or a less severe syndrome, such as upper respiratory infection). While highly sensitive nucleic acid detection methods and testing of multiple specimens improve sensitivity, multiple pathogens are often detected and this adds complexity to the interpretation as the etiologic significance of results may be unclear (ie, the pneumonia may be caused by none, one, some, or all of the pathogens detected). Some of these challenges can be addressed by adjusting positivity rates to account for poor sensitivity or incorporating test results from controls without pneumonia to account for poor specificity. However, no classical analytic methods can account for measurement error (ie, sensitivity and specificity) for multiple specimen types and integrate the results of measurements for multiple pathogens to produce an accurate understanding of etiology. We describe the major analytic challenges in determining pneumonia etiology and review how the common analytical approaches (eg, descriptive, case-control, attributable fraction, latent class analysis) address some but not all challenges. We demonstrate how these limitations necessitate a new, integrated analytical approach to pneumonia etiology data. PMID:28575372

Challenger Anniversary Resource Tape

NASA Technical Reports Server (NTRS)

1996-01-01

This commemorative video marks the tenth anniversary, January 28, 1986, of the ninth Challenger flight and the seven astronauts onboard who died when the Challenger exploded 73 seconds into flight. The flight crew was comprised of Cmdr. Francis R. Scobee, Pilot Michael J. Smith, and Mission Specialists Judith A. Resnik, Ellison S. Onizuka, Ronald E. McNair, Gregory Jarvis (Hughes Aircraft representative), and S. Christie McAuliffe (teacher). The flight crew is shown performing preflight training, physiological tests, environmental tests, press conferences, prelaunch activities, and launch activities. The Challenger explosion is shown from both the launch site and from the control center. Various rescue operations, news coverage, and shots of the wreckage after salvage are also presented. President Ronald Reagan is shown giving a tribute at the memorial service for the flight crew. The video ends with a flyby salute and pictures of each of the members of the Challenger.

Glucose screening tests during pregnancy

MedlinePlus

Oral glucose tolerance test - pregnancy; OGTT - pregnancy; Glucose challenge test - pregnancy; Gestational diabetes - glucose screening ... first step, you will have a glucose screening test: You DO NOT need to prepare or change ...

Assessing Academic Challenges for Their Contribution to Cognitive Development.

ERIC Educational Resources Information Center

McCormick, David F.; Whittington, M. Susie

2000-01-01

Challenges (assignments, activities, tests) incorporated into agriculture classes were evaluated using Bloom's Taxonomy. The cognitive level varied by course and type of activity. Effectiveness depended on selecting challenges appropriate for the material, requiring higher-order thinking, and rewarding students for work at higher cognitive levels.…

[CHALLENGES IN THE DIAGNOSIS OF CUSHING'S SYNDROME IN THE MODERN ERA].

PubMed

Saiegh, Leonard; Sheikh-Ahmad, Mohammad; Reut, Maria; Jubran, Yousef; Shechner, Carmela

2015-12-01

Cushing's syndrome results from prolonged and excessive exposure to medically prescribed corticosteroids, or from excess endogenous cortisol secretion. When endogenous cortisol secretion is suspected, several screening tests are conducted in order to confirm or to rule out the diagnosis. In recent years, as the cut-off point of cortisol concentration on the 1 mg overnight dexamethasone suppression test was lowered, the prevalence of Cushing's syndrome has increased, and more cases of mild syndromes, with negative results on one or more screening tests, have increasingly been reported. In this paper, we will describe the various screening tests used for Cushing's syndrome, and will discuss their degree of sensitivity in the diagnosis of mild cases. We conclude that, in cases of mild syndromes, the sensitivity of some tests appears to be notably lower than has been reported. Until recently, the major challenge has been to distinguish between pseudo-Cushing's states and Cushing's syndrome. Today, however, the challenge has become to avoid misdiagnosis of mild cases, presenting with normal results on some screening tests. The sensitivity of urinary free cortisol seems to be lower than previously reported. Therefore, we recommend not to rely solely on this test in ruling out Cushing's syndrome.

Development of Cryogenic Engine for GSLV MkIII: Technological Challenges

NASA Astrophysics Data System (ADS)

Praveen, RS; Jayan, N.; Bijukumar, KS; Jayaprakash, J.; Narayanan, V.; Ayyappan, G.

2017-02-01

Cryogenic engine capable of delivering 200 kN thrust is being developed for the first time in the country by ISRO for powering the upper stage of GSLV Mk-III, the next generation launch vehicle of ISRO capable of launching four tonne class satellites to Geo-synchronous Transfer Orbit(GTO). Development of this engine started a decade ago when various sub-systems development and testing were taken up. Starting with injector element development, the design, realization and testing of the major sub-systems viz the gas generator, turbopumps, start-up system and thrust chamber have been successfully done in a phased manner before conducting a series of developmental tests in the integrated engine mode. Apart from the major sub-systems, many critical components like the igniter, control components etc were independently developed and qualified. During the development program many challenges were faced in almost all areas of propulsion engineering. Systems engineering of the engine was another key challenge in the realization. This paper gives an outlook on various technological challenges faced in the key areas related to the engine development, insight to the solutions and measures taken to overcome the challenges.

Fast Magnetotail Reconnection: Challenge to Global MHD Modeling

NASA Astrophysics Data System (ADS)

Kuznetsova, M. M.; Hesse, M.; Rastaetter, L.; Toth, G.; de Zeeuw, D.; Gombosi, T.

2005-05-01

Representation of fast magnetotail reconnection rates during substorm onset is one of the major challenges to global MHD modeling. Our previous comparative study of collisionless magnetic reconnection in GEM Challenge geometry demonstrated that the reconnection rate is controlled by ion nongyrotropic behavior near the reconnection site and that it can be described in terms of nongyrotropic corrections to the magnetic induction equation. To further test the approach we performed MHD simulations with nongyrotropic corrections of forced reconnection for the Newton Challenge setup. As a next step we employ the global MHD code BATSRUS and test different methods to model fast magnetotail reconnection rates by introducing non-ideal corrections to the induction equation in terms of nongyrotropic corrections, spatially localized resistivity, or current dependent resistivity. The BATSRUS adaptive grid structure allows to perform global simulations with spatial resolution near the reconnection site comparable with spatial resolution of local MHD simulations for the Newton Challenge. We select solar wind conditions which drive the accumulation of magnetic field in the tail lobes and subsequent magnetic reconnection and energy release. Testing the ability of global MHD models to describe magnetotail evolution during substroms is one of the elements of science based validation efforts at the Community Coordinated Modeling Center.

Student Design Challenges in Capillary Flow

NASA Technical Reports Server (NTRS)

Stocker, Dennis P.; Wollman, Andrew; Hall, Nancy R.; Weislogel, Mark; DeLombard, Richard

2016-01-01

For some grade 8-12 students, capillary flow has bridged the gap between the classroom and research facility, from normal gravity to microgravity. In the past four years, NASA and the Portland State University (PSU) have jointly challenged students to design test cells, using Computer-Aided Design (CAD), to study capillary action in microgravity as PSU has done on the International Space Station (ISS). Using the student-submitted CAD drawings, the test cells were manufactured by PSU and tested in their 2.1-second drop tower. The microgravity results were made available online for student analysis and reporting. Over 100 such experiments have been conducted, where there has been participation from 15 states plus a German school for the children of U.S. military personnel. In 2016, a related NASA challenge was held in partnership with the ASGSR, again, based on the research conducted by PSU. In this challenge, grade 9-12 students designed and built devices using capillary action to launch droplets as far as possible in NASAs 2.2 Second Drop Tower. Example results will be presented by students at this conference. The challenges engage students in ISS science and technology and can inspire them to pursue technical careers.

Simulating New Drop Test Vehicles and Test Techniques for the Orion CEV Parachute Assembly System

NASA Technical Reports Server (NTRS)

Morris, Aaron L.; Fraire, Usbaldo, Jr.; Bledsoe, Kristin J.; Ray, Eric; Moore, Jim W.; Olson, Leah M.

2011-01-01

The Crew Exploration Vehicle Parachute Assembly System (CPAS) project is engaged in a multi-year design and test campaign to qualify a parachute recovery system for human use on the Orion Spacecraft. Test and simulation techniques have evolved concurrently to keep up with the demands of a challenging and complex system. The primary simulations used for preflight predictions and post-test data reconstructions are Decelerator System Simulation (DSS), Decelerator System Simulation Application (DSSA), and Drop Test Vehicle Simulation (DTV-SIM). The goal of this paper is to provide a roadmap to future programs on the test technique challenges and obstacles involved in executing a large-scale, multi-year parachute test program. A focus on flight simulation modeling and correlation to test techniques executed to obtain parachute performance parameters are presented.

Challenges and solutions for high-volume testing of silicon photonics

NASA Astrophysics Data System (ADS)

Polster, Robert; Dai, Liang Yuan; Oikonomou, Michail; Cheng, Qixiang; Rumley, Sebastien; Bergman, Keren

2018-02-01

The first generation of silicon photonic products is now commercially available. While silicon photonics possesses key economic advantages over classical photonic platforms, it has yet to become a commercial success because these advantages can be fully realized only when high-volume testing of silicon photonic devices is made possible. We discuss the costs, challenges, and solutions of photonic chip testing as reported in the recent research literature. We define and propose three underlying paradigms that should be considered when creating photonic test structures: Design for Fast Coupling, Design for Minimal Taps, and Design for Parallel Testing. We underline that a coherent test methodology must be established prior to the design of test structures, and demonstrate how an optimized methodology dramatically reduces the burden when designing for test, by reducing the needed complexity of test structures.

ACToR – Aggregated Computational Toxicology Resource ...

EPA Pesticide Factsheets

This presentation reviews the US EPAs reaction to the challenge of the NRC on the future of toxicity testing through the development of the ACTor Project and the ToxRef database. This presentation reviews the US EPAs reaction to the challenge of the NRC on the future of toxicity testing through the development of the ACTor Project and the ToxRef database.

Limited Knowledge of Fraction Representations Differentiates Middle School Students with Mathematics Learning Disability (Dyscalculia) versus Low Mathematics Achievement

ERIC Educational Resources Information Center

Mazzocco, Michele M. M.; Myers, Gwen F.; Lewis, Katherine E.; Hanich, Laurie B.; Murphy, Melissa M.

2013-01-01

Fractions pose significant challenges for many children, but for some children those challenges persist into high school. Here we administered a fractions magnitude comparison test to 122 children, from Grades 4 to 8, to test whether their knowledge of fractions typically learned early in the sequence of formal math instruction (e.g., fractions…

Exit Exams, High-Stakes Testing, and Students with Disabilities: A Persistent Challenge

ERIC Educational Resources Information Center

Yell, Mitchell L.; Katsiyannis, Antonis; Collins, James C.; Losinski, Mickey

2012-01-01

The demands for accountability in education have led to an increase in high-stakes testing practices in public schools. Accountability can be seen at the high school level in the use of exit examinations (hereafter "exit exams") that students must pass to receive a diploma and graduate from high school. One of the most challenging issues…

Using Mathematics-Curriculum Based Measures to Predict Outcomes on the Mathematics Portion of the Mississippi Curriculum Test, Second Edition

ERIC Educational Resources Information Center

Hogan-Samuel, Eutrophia Lenora

2012-01-01

The nation is challenged with improving the mathematics achievement of its students. No Child Left Behind holds schools, districts, and states accountable for improving student achievement. Because high stakes tests are given at the end of the school year, schools are presented with the challenging task of developing or purchasing reliable…

Cross-protection between experimental anti-leptospirosis bacterins

PubMed Central

Dib, Cristina Corsi; Gonçales, Amane Paldês; de Morais, Zenaide Maria; de Souza, Gisele Oliveira; Miraglia, Fabiana; Abreu, Patricia Antonia Estima; Vasconcellos, Silvio Arruda

2014-01-01

We investigated the existence of cross-protection between two anti-leptospirosis monovalent experimental bacterins produced with two strains of Leptospira serogroup Pomona: Fromm strain of serovar Kennewicky, isolated from pigs in the United States, and strain GR6 of serovar Pomona isolated from pigs in Brazil. Both were added of aluminum hydroxide as an adjuvant. Experimental bacterins were tested with the hamster potency test in order to assess protection provided against the disease and against the establishment of kidney infection. Controls were polyvalent commercial vaccine produced with Leptospira strains isolated outside Brazil, which included a representative of Pomona serovar, or Sorensen solution added of aluminum hydroxide adjuvant. The challenge was performed with cross-strains of serogroup Pomona tested in accordance with international standards established for the potency test. After 21 days of the challenge, survivors were killed to evaluate the condition of Leptospira renal carrier. Experimental bacterins protected hamsters against homologous and heterologous strains, demonstrating the existence of cross-protection. The commercial vaccine protected the hamsters challenged with both strains, but there was a high proportion of animals diagnosed as renal carriers when the challenge was performed with strain GR6, isolated from pigs in Brazil. PMID:25477946

Replacement of fishmeal by spirulina Arthrospira platensis affects growth, immune related-gene expression in gibel carp (Carassius auratus gibelio var. CAS III), and its challenge against Aeromonas hydrophila infection.

PubMed

Cao, Shenping; Zhang, Peiyu; Zou, Tao; Fei, Shuzhan; Han, Dong; Jin, Junyan; Liu, Haokun; Yang, Yunxia; Zhu, Xiaoming; Xie, Shouqi

2018-05-15

The present study examined the effect of dietary spirulina, Arthrospira platensis on growth performance, blood physiological indices, immune-related gene expressions and resistance of juvenile gibel carp against Aeromonas hydrophila infection. Four isonitrogenous (360 g kg -1 ) and isolipidic (90 g kg -1 ) diets were formulated with containing different levels of spirulina powder of 0 g (SP0, the control diet), 3.38 g (SP3.38), 6.76 g (SP6.76) and 13.52 g (SP13.52) per 100 g diet to replace 0%, 25%, 50% and 100% of fishmeal protein, respectively. And each diet was randomly assigned to triplicate tanks (150-L capacity per each) and each tank was stocked with 22 fish (15.37 ± 0.06 g). Fish were fed one of the tested diets up to satiation twice a day for 46 days. A challenge test was carried out after the feeding trial by injecting Aeromonas hydrophila intraperitoneally for 7 days. The results showed that fish growth, feeding rate in groups SP3.38 and SP6.76 were significantly higher than those of groups SP0 and SP13.52 (P < 0.05). Feed efficiency and protein retention rate had no significant difference among all tested groups. Plasma superoxide dismutase and phagocyte activity of blood leukocytes significantly increased in the spirulina-fed fish groups at 12-h post the bacterial challenge (P < 0.05). Both pre and post challenge test, plasma lysozyme activities in spirulina-fed groups were significantly higher than that in the control group (P < 0.05). Plasma malondialdehyde got the lowest value in the SP13.52 group before and after the challenge test. The transcriptional levels of TLR2 (Toll like receptor 2), myeloid differentiation factor 88 (MyD88), Toll/IL-1 receptor domain-containing adaptor protein (TIRAP), interleukin-1β (IL-1β) and tumor necrosis factor-α1 (TNF-α1) in spleen and kidney significantly increased post the bacterial challenge compared to the pre challenge. And the relative expressions of the immune-related genes of spirulina-fed fish groups were higher than those of the control group before and after the challenge test. The 7-day cumulative survival rate after the bacterial challenge was highest in the SP3.38 group (P < 0.05). The present results indicated that low dietary inclusion of spirulina significantly enhanced the immune response of gibel carp partly through TLR2 pathway and 3.38% of dietary spirulina was recommended for the juveniles based on the growth and immune response. Copyright © 2018. Published by Elsevier Ltd.

Having Fun and Accepting Challenges Are Natural Instincts: Jigsaw Puzzles to Challenge Students and Test Their Abilities While Having Fun!

ERIC Educational Resources Information Center

Rodenbaugh, Hanna R.; Lujan, Heidi L.; Rodenbaugh, David W.; DiCarlo, Stephen E.

2014-01-01

Because jigsaw puzzles are fun, and challenging, students will endure and discover that persistence and grit are rewarded. Importantly, play and fun have a biological place just like sleep and dreams. Students also feel a sense of accomplishment when they have completed a puzzle. Importantly, the reward of mastering a challenge builds confidence…

Caffeine challenge test and panic disorder: a systematic literature review.

PubMed

Vilarim, Marina Machado; Rocha Araujo, Daniele Marano; Nardi, Antonio Egidio

2011-08-01

This systematic review aimed to examine the results of studies that have investigated the induction of panic attacks and/or the anxiogenic effect of the caffeine challenge test in patients with panic disorder. The literature search was performed in PubMed, Biblioteca Virtual em Saúde and the ISI Web of Knowledge. The words used for the search were caffeine, caffeine challenge test, panic disorder, panic attacks and anxiety disorder. In total, we selected eight randomized, double-blind studies where caffeine was administered orally, and none of them controlled for confounding factors in the analysis. The percentage of loss during follow-up ranged between 14.3% and 73.1%. The eight studies all showed a positive association between caffeine and anxiogenic effects and/or panic disorder.

Use of Genetic Testing for Primary Immunodeficiency Patients.

PubMed

Heimall, Jennifer R; Hagin, David; Hajjar, Joud; Henrickson, Sarah E; Hernandez-Trujillo, Hillary S; Tan, Yuval; Kobrynski, Lisa; Paris, Kenneth; Torgerson, Troy R; Verbsky, James W; Wasserman, Richard L; Hsieh, Elena W Y; Blessing, Jack J; Chou, Janet S; Lawrence, Monica G; Marsh, Rebecca A; Rosenzweig, Sergio D; Orange, Jordan S; Abraham, Roshini S

2018-04-01

Genetic testing plays a critical role in diagnosis for many primary immunodeficiency diseases. The goals of this report are to outline some of the challenges that clinical immunologists face routinely in the use of genetic testing for patient care. In addition, we provide a review of the types of genetic testing used in the diagnosis of PID, including their strengths and limitations. We describe the strengths and limitations of different genetic testing approaches for specific clinical contexts that raise concern for specific PID disorders in light of the challenges reported by the clinical immunologist members of the CIS in a recent membership survey. Finally, we delineate the CIS's recommendations for the use of genetic testing in light of these issues.

Research notes : solar powered markers not up to challenge.

DOT National Transportation Integrated Search

2008-06-01

ODOT performed preliminary tests on eight different models of solar powered raised pavement markers. These included environmental tests (extreme temperatures, immersion), optical performance tests, and observation tests. Federal Highway Administratio...

African American church-based HIV testing and linkage to care: assets, challenges and needs.

PubMed

Stewart, Jennifer M; Thompson, Keitra; Rogers, Christopher

2016-01-01

The US National HIV AIDS strategy promotes the use of faith communities to lessen the burden of HIV in African American communities. One specific strategy presented is the use of these non-traditional venues for HIV testing and co-location of services. African American churches can be at the forefront of this endeavour through the provision of HIV testing and linkage to care. However, there are few interventions to promote the churches' involvement in both HIV testing and linkage to care. We conducted 4 focus groups (n = 39 participants), 4 interviews and 116 surveys in a mixed-methods study to examine the feasibility of a church-based HIV testing and linkage to care intervention in Philadelphia, PA, USA. Our objectives were to examine: (1) available assets, (2) challenges and barriers and (3) needs associated with church-based HIV testing and linkage to care. Analyses revealed several factors of importance, including the role of the church as an access point for testing in low-income neighbourhoods, challenges in openly discussing the relationship between sexuality and HIV, and buy-in among church leadership. These findings can support intervention development and necessitate situating African American church-based HIV testing and linkage to care interventions within a multi-level framework.

Challenging Gait Conditions Predict 1-Year Decline in Gait Speed in Older Adults With Apparently Normal Gait

PubMed Central

Perera, Subashan; VanSwearingen, Jessie M.; Hile, Elizabeth S.; Wert, David M.; Studenski, Stephanie A.

2011-01-01

Background Mobility often is tested under a low challenge condition (ie, over a straight, uncluttered path), which often fails to identify early mobility difficulty. Tests of walking during challenging conditions may uncover mobility difficulty that is not identified with usual gait testing. Objective The purpose of this study was to determine whether gait during challenging conditions predicts decline in gait speed over 1 year in older people with apparently normal gait (ie, gait speed of ≥1.0 m/s). Design This was a prospective cohort study. Methods Seventy-one older adults (mean age=75.9 years) with a usual gait speed of ≥1.0 m/s participated. Gait was tested at baseline under 4 challenging conditions: (1) narrow walk (15 cm wide), (2) stepping over obstacles (15.24 cm [6 in] and 30.48 cm [12 in]), (3) simple walking while talking (WWT), and (4) complex WWT. Usual gait speed was recorded over a 4-m course at baseline and 1 year later. A 1-year change in gait speed was calculated, and participants were classified as declined (decreased ≥0.10 m/s, n=18), stable (changed <0.10 m/s, n=43), or improved (increased ≥0.10 m/s, n=10). Analysis of variance was used to compare challenging condition cost (usual − challenging condition gait speed difference) among the 3 groups. Results Participants who declined in the ensuing year had a greater narrow walk and obstacle walk cost than those who were stable or who improved in gait speed (narrow walk cost=0.43 versus 0.33 versus 0.22 m/s and obstacle walk cost=0.35 versus 0.26 versus 0.13 m/s). Simple and complex WWT cost did not differ among the groups. Limitations The participants who declined in gait speed over time walked the fastest, and those who improved walked the slowest at baseline; thus, the potential contribution of regression to the mean to the findings should not be overlooked. Conclusions In older adults with apparently normal gait, the assessment of gait during challenging conditions appears to uncover mobility difficulty that is not identified by usual gait testing. PMID:22003167

Design of Electrical Systems for Rocket Propulsion Test Facilities at the John C. Stennis Space Center

NASA Technical Reports Server (NTRS)

Hughes, Mark S.; Davis, Dawn M.; Bakker, Henry J.; Jensen, Scott L.

2007-01-01

This viewgraph presentation reviews the design of the electrical systems that are required for the testing of rockets at the Rocket Propulsion Facility at NASA Stennis Space Center (NASA SSC). NASA/SSC s Mission in Rocket Propulsion Testing Is to Acquire Test Performance Data for Verification, Validation and Qualification of Propulsion Systems Hardware. These must be accurate reliable comprehensive and timely. Data acquisition in a rocket propulsion test environment is challenging: severe temporal transient dynamic environments, large thermal gradients, vacuum to 15 ksi pressure regimes SSC has developed and employs DAS, control systems and control systems and robust instrumentation that effectively satisfies these challenges.

Benefit of the basophil activation test in deciding when to reintroduce cow's milk in allergic children.

PubMed

Rubio, A; Vivinus-Nébot, M; Bourrier, T; Saggio, B; Albertini, M; Bernard, A

2011-01-01

Oral challenges are required to establish the persistence or resolution of IgE-mediated cow's milk allergy (CMA). Determining the appropriate timing for challenging is the main difficulty. The benefit of the basophil activation test (BAT) in predicting a child's reaction to the oral challenge was evaluated and compared to the specific IgE and skin prick tests' (SPT) results. One hundred and twelve consecutive children with CMA admitted for an oral challenge to reassess their allergy were included. Allergen-induced basophil activation was detected as a CD63-upregulation by flow cytometry. Thirty-six children (32%) had a positive oral challenge. The percentage of activated basophils in patients with a positive challenge (mean = 20.9; SD = 18.8) was significantly higher than that of patients with a negative challenge (mean = 3.9; SD = 9.8, P < 0.0001), and was well correlated with the eliciting dose of cow's milk (P < 0.0001). The BAT had an efficiency of 90%, a sensitivity of 91%, a specificity of 90%, and positive and negative predictive values of 81% and 96% in detecting persistently allergic patients. The area under the ROC curve was 0.866. These scores were higher than those obtained with SPT and IgE values, whichever positivity cut-point was chosen. Referring to a decisional algorithm combining BAT, specific IgE and SPT allowed the correct identification of 94% of patients as tolerant or persistently allergic to cow's milk proteins (CMP) in our cohort. The BAT could be a valuable tool in the management of paediatric CMA in addition to specific IgE quantification and SPT, by contributing in determining whether an oral challenge can safely be undertaken. © 2010 John Wiley & Sons A/S.

The Impact of Challenging Geometry and Measurement Units on the Achievement of Grade 2 Students

ERIC Educational Resources Information Center

Gavin, M. Katherine; Casa, Tutita M.; Adelson, Jill L.; Firmender, Janine M.

2013-01-01

The primary goal of Project M[superscript 2] was to develop and field-test challenging geometry and measurement units for all K-2 students. This article reports on the achievement results for students in Grade 2 at 12 urban and suburban sites in 4 states using the Iowa Tests of Basic Skills (ITBS) mathematics concepts subtest and an open-response…

Using Project-Based Learning to Design, Build, and Test Student-Made Photometer by Measuring the Unknown Concentration of Colored Substances

ERIC Educational Resources Information Center

Diawati, Chansyanah; Liliasari; Setiabudi, Agus; Buchari

2018-01-01

Students learned the principles and practice of photometry through project-based learning. They addressed the challenge of measuring the unknown concentration of a colored substance using a photometer they were required to design, build, and test. Then, they used that instrument to carry out the experiment and fulfill the challenge. A photometer…

Drug prescribing during pregnancy in a central region of Italy, 2008-2012.

PubMed

Ventura, Martina; Maraschini, Alice; D'Aloja, Paola; Kirchmayer, Ursula; Lega, Ilaria; Davoli, Marina; Donati, Serena

2018-05-15

Drug consumption during pregnancy is a matter of concern, especially regarding drugs known or suspected to be teratogens. Little is known about drug use in pregnant women in Italy. The present study is aimed at examining the prevalence, and to detect potential inappropriateness of drug prescribing among pregnant women in Latium, a region of central Italy. This retrospective study was conducted on a cohort of women aged 18-45 years who delivered between 2008 and 2012 in public hospitals. Women were enrolled through the Regional Birth Register. After linking the regional Health Information Systems and the Regional Drug Claims Register, women's clinical data and prescribed medications were analyzed. Italian Medicine Agency (AIFA) and US Food and Drug Administration (FDA) evidence were used to investigate inappropriate prescribing and teratogenic risk. Excluding vitamins and minerals, 80.6% (n = 153,079) of the women were prescribed at least one drug during pregnancy, with an average of 4.6 medications per pregnancy. Drugs for blood and hematopoietic organs were the most commonly prescribed (53.0%,), followed by anti-infectives for systemic use (50.7%). Among the inappropriate prescriptions, progestogen supplementation was given in 20.1% of pregnancies; teratogen drugs were prescribed in 0.8%, mostly angiotensin co-enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) (0.3%). In Latium, drugs are widely used in pregnancy. Prescriptions of inappropriate drugs are observed in more than a fifth of pregnancies, and teratogens are still used, despite their known risk. Continuous updates of information provided to practitioners and an increased availability of information to women might reduce inappropriate prescribing.

Diet and endometrial cancer: a focus on the role of fruit and vegetable intake, Mediterranean diet and dietary inflammatory index in the endometrial cancer risk.

PubMed

Ricceri, Fulvio; Giraudo, Maria Teresa; Fasanelli, Francesca; Milanese, Dario; Sciannameo, Veronica; Fiorini, Laura; Sacerdote, Carlotta

2017-11-13

Endometrial cancer is the fourth most common cancer in European women. The major risk factors for endometrial cancer are related to the exposure of endometrium to estrogens not opposed to progestogens, that can lead to a chronic endometrial inflammation. Diet may play a role in cancer risk by modulating chronic inflammation. In the framework of a case-control study, we recruited 297 women with newly diagnosed endometrial cancer and 307 controls from Northern Italy. Using logistic regression, we investigated the role of fruit and vegetable intake, adherence to the Mediterranean diet (MD), and the dietary inflammatory index (DII) in endometrial cancer risk. Women in the highest quintile of vegetable intake had a statistically significantly lower endometrial cancer risk (adjusted OR 5th quintile vs 1st quintile: 0.34, 95% CI 0.17-0.68). Women with high adherence to the MD had a risk of endometrial cancer that was about half that of women with low adherence to the MD (adjusted OR: 0.51, 95% CI 0.39-0.86). A protective effect was detected for all the lower quintiles of DII, with the highest protective effect seen for the lowest quintile (adjusted OR 5th quintile vs 1st quintile: 3.28, 95% CI 1.30-8.26). These results suggest that high vegetable intake, adherence to the MD, and a low DII are related to a lower endometrial cancer risk, with several putative connected biological mechanisms that strengthen the biological plausibility of this association.

Developmental programming: Prenatal BPA treatment disrupts timing of LH surge and ovarian follicular wave dynamics in adult sheep

PubMed Central

Veiga-Lopez, A; Beckett, EM; Abi Salloum, B; Ye, W; Padmanabhan, V

2014-01-01

Developmental exposure to BPA adversely affects reproductive function. In sheep, prenatal BPA treatment induces reproductive neuroendocrine defects, manifested as LH excess and dampened LH surge and perturbs early ovarian gene expression. In this study we hypothesized that prenatal BPA treatment will also disrupt ovarian follicular dynamics. Pregnant sheep were treated from days 30 to 90 of gestation with 3 different BPA doses (0.05, 0.5, or 5 mg/kg BW/day). All female offspring were estrus synchronized and transrectal ultrasonography was performed daily for 22 days to monitor ovarian follicular and corpora lutea dynamics. Blood samples were collected to assess hormonal preovulatory changes and luteal progesterone dynamics. Statistical analysis revealed that the time interval between the estradiol rise and the preovulatory LH surge was shortened in the BPA-treated females. None of the three BPA doses had an effect on corpora lutea, progestogenic cycles, and mean or duration of ovulatory and non-ovulatory follicles. However, differences in follicular count trajectories were evident in all three follicular size classes (2–3 mm, 4–5 mm, and ≥ 6 mm) of prenatal BPA-treated animals compared to controls. Number of follicular waves tended also to be more variable in the prenatal BPA-treated groups ranging from 2 to 5 follicular waves per cycle, while this was restricted to 3 to 4 waves in control females. These changes in ovarian follicular dynamics coupled with defects in time interval between estradiol rise and preovulatory LH release are likely to lead to subfertility in prenatal BPA-treated females. PMID:24923655

Cardiovascular disease incidence among females in South Carolina by type of oral contraceptives, 2000-2013: a retrospective cohort study.

PubMed

Samson, Marsha E; Adams, Swann A; Merchant, Anwar T; Maxwell, Whitney D; Zhang, Jiajia; Bennett, Charles L; Hebert, James R

2016-11-01

Certain types of oral contraceptives can produce favorable effects on lipid metabolism and vascular tone, while others have potentially detrimental effects. Endogenous and exogenous hormones exert different effects on high-density lipoprotein (HDL) and low-density lipoprotein (LDL) depending on the type, combination, and dose of the hormone. The estrogenic and progestogenic effects of exogenous hormones on HDL and LDL are inconsistent. Studying surrogate end points (LDL, HDL levels) may provide a misleading picture of OCs. Medicaid data from 2000 to 2013 were used to assess the relationship between the type of OCs and CVD incidence. Multivariable logistic regression was used to model relationships between cardiovascular disease and OC use adjusting for potential confounders. Compared to combined oral contraceptives (COC), progestin-only oral contraceptives (POC) were associated with decreased heart disease and stroke incidence after adjusting for important covariates (OR 0.74; 95 % CI 0.57, 0.97 and OR 0.39; 95 % CI 0.16, 0.95, respectively). However, there was a positive association between POC + COC and both heart disease and stroke incidence (OR 2.28; 95 % CI 1.92, 2.70 and OR 2.12; 95 % CI 1.34, 3.35, respectively). In light of an association between POC use and decreased heart disease and stroke, women's CVD risk factors should be carefully considered when choosing which OC to use. Baseline CVD risk should be a part of the discussion between women and their primary care providers when making choices regarding OCs.

The effect of hormone therapy on plasma homocysteine levels: a randomized clinical trial.

PubMed

Tutuncu, Levent; Ergur, Ali Rustu; Mungen, Ercument; Gun, Ismet; Ertekin, Aktug; Yergok, Yusuf Ziya

2005-03-01

An elevated plasma homocysteine level is a risk factor for cardiovascular diseases. Hormone therapy (HT) may reduce fasting plasma homocysteine levels. We studied 80 postmenopausal women to determine the effect of medroxyprogesterone acetate (MPA) combined with conjugated equine estrogens (CEE) on fasting plasma homocysteine levels. In a randomized, double blind, prospective, placebo-controlled study, we randomly assigned 80 healthy postmenopausal women between CEE 0.625 mg/d combined with MPA 2.5 mg/d (n = 20), CEE 0.625 mg/d combined with MPA 5 mg/d (n = 20), unopposed CEE 0.625 mg/d (n = 20), and placebo (n = 20) all given for a duration of 6 months. Fasting plasma homocysteine levels were measured before and at the end of the treatment. Before treatment, plasma homocysteine concentrations were similar in all groups. After 6 months of unopposed CEE, the mean fasting plasma homocysteine levels decreased by 19.02% when compared with baseline levels (P < 0.05). The mean fasting plasma homocysteine concentrations decreased by 17.63% and 19.56% from baseline in both the CEE plus MPA 2.5 mg/d and CEE plus MPA 5 mg/d groups, respectively (P < 0.05 for each group). In contrast, plasma homocysteine levels increased by 11.66% in the placebo group. The homocysteine lowering effect did not differ significantly among the three groups of women receiving unopposed CEE alone and CEE plus MPA at two different doses. Six months of estrogen therapy (ET) and combined estrogen-progestogen therapy (EPT) significantly lower fasting plasma homocysteine levels in healthy postmenopausal women with equal efficacy.

Efficacy and Safety of an Injectable Combination Hormonal Contraceptive for Men.

PubMed

Behre, Hermann M; Zitzmann, Michael; Anderson, Richard A; Handelsman, David J; Lestari, Silvia W; McLachlan, Robert I; Meriggiola, M Cristina; Misro, Man Mohan; Noe, Gabriela; Wu, Frederick C W; Festin, Mario Philip R; Habib, Ndema A; Vogelsong, Kirsten M; Callahan, Marianne M; Linton, Kim A; Colvard, Doug S

2016-12-01

The development of a safe and effective reversible method of male contraception is still an unmet need. Evaluation of suppression of spermatogenesis and contraceptive protection by coadministered im injections of progestogen and testosterone. Prospective multicentre study. Ten study centers. Healthy men, aged 18-45 years, and their 18- to 38-year-old female partners, both without known fertility problems. Intramuscular injections of 200-mg norethisterone enanthate combined with 1000-mg testosterone undecanoate, administered every 8 weeks. Suppression of spermatogenesis by ejaculate analysis, contraceptive protection by pregnancy rate. Of the 320 participants, 95.9 of 100 continuing users (95% confidence interval [CI], 92.8-97.9) suppressed to a sperm concentration less than or equal to 1 million/mL within 24 weeks (Kaplan-Meier method). During the efficacy phase of up to 56 weeks, 4 pregnancies occurred among the partners of the 266 male participants, with the rate of 1.57 per 100 continuing users (95% CI, 0.59-4.14). The cumulative reversibility of suppression of spermatogenesis after 52 weeks of recovery was 94.8 per 100 continuing users (95% CI, 91.5-97.1). The most common adverse events were acne, injection site pain, increased libido, and mood disorders. Following the recommendation of an external safety review committee the recruitment and hormone injections were terminated early. The study regimen led to near-complete and reversible suppression of spermatogenesis. The contraceptive efficacy was relatively good compared with other reversible methods available for men. The frequencies of mild to moderate mood disorders were relatively high.

Diffusion of progestogens through Silastic rubber implants.

PubMed

Lifchez, A S; Scommegna, A

1970-05-01

Silastic rubber capsules in 2 thicknesses (.42 mm and .80 mm) and 3 lengths (9, 14, and 19 mm) were filled with progesterone, Provera, Norgestrel, or chlormadinone acetate and implanted under the skin of rats, and the amount of steroid released was measured after 1, 2, 4, and 8 weeks. The amount of steroid released was also measured from progesterone-filled capsules .42 mm thick and varying from 19-32 mm long inserted in the uterus of 16 women volunteers for 1-7 days. The rate of release of each steroid in the rats was found to be proportionate to the length of the capsule and related, but not proportional to the thickness of the capsule. The release rate of progesterone was 3-20 times greater than that of the other steroids, while Norgestrel diffused at the lowest rate. The influence of thickness of capsule was greater for the steroids with the highest diffusion rate, progesterone and chlormadinone acetate. The release rates of all except chlormadinone acetate were higher in the 1st week. The release rates of the synthetic progestins, unlike that of progesterone, were relatively constant after the 1st week. The release rate of progesterone tended to be related to the amount remaining in the capsule when the amount became small. The measured amount of progesterone released each day from each intrauterine capsule was also proportional to its length. It appears that Norgestrel, Provera, and chlormadinone acetate are all released slowly enough and have enough biologic activity at low concentrations to have a contraceptive effect for well over 1 year when administered in a 30 mm intrauterine capsule.

Progesterone increases resistance of ophthalmic and central retinal arteries in climacteric women.

PubMed

Souza, M A M De; Souza, B M De; Geber, S

2013-04-01

To evaluate the effect of a synthetic progestin on the vascular resistance of the ophthalmic and central retinal arteries in climacteric women, compared to placebo, using transorbital ultrasound with Doppler velocimetry. We performed a prospective, randomized, double-blinded, placebo-controlled study with 216 climacteric women. Subjects were randomly allocated to one of two groups: either the group receiving placebo (one pill/day for 30 days) (n = 108) or the group receiving progestin (5 mg medroxyprogesterone acetate/day for 30 days) (n = 108). Transorbital Doppler velocimetric ultrasound was performed, before and after treatment; we measured the pulsatility index, resistance index and systole/diastole ratio. The mean ages of the participants in the study group and the control group were 54 ± 6.2 years (range 48-59 years) and 55 ± 6.8 years (range 46-60 years), respectively. When we compared the effect of the progestin on the central retinal artery before and after treatment, we observed a significant increase after the treatment in all Doppler indices. The same was observed when we compared the effect of the progestin on the ophthalmic artery. In the group of women receiving placebo, the Doppler indices were similar before and after treatment. Our results demonstrate the existence of a progestogenic vasoconstrictive effect in the ophthalmic and central retinal arteries. As this study provides new data, the observed effect needs further investigations to better elucidate its extent. Moreover, our findings may be particularly useful to others interested in understanding the vascular dynamics of the cerebral vessels and to researchers running clinical trials related to hormone replacement therapy.

Discovery of a steroid 11α-hydroxylase from Rhizopus oryzae and its biotechnological application.

PubMed

Petrič, S; Hakki, T; Bernhardt, R; Zigon, D; Crešnar, B

2010-11-01

To overcome the chemically laborious stereo- and regioselective hydroxylation steps in the pharmaceutical production of corticosteroids and progestogens, certain fungal species, e.g. Rhizopus spp. and Aspergillus spp., are employed to perform the 11α-hydroxylation of the steroid skeleton, thereby significantly simplifying steroid drug production. Here we report for the first time the identification and expression of a fungal 11α-steroid hydroxylase, CYP509C12. The newly identified cytochrome P450, which is one of the 48 putative CYP genes in Rhizopus oryzae, was induced in the fungus by progesterone. By functionally expressing CYP509C12 in recombinant fission yeast, we were able to determine that its substrate spectrum includes progesterone as well as testosterone, 11-deoxycorticosterone, and 11-deoxycortisol, with the hydroxylations taking place predominantly at 11α and 6β positions of the steroid ring system. To increase the 11α-hydroxylation activity of CYP509C12 in recombinant fission yeast, its natural redox partner, the R. oryzae NAD(P)H-dependent reductase, was coexpressed. The coexpression improved electron transfer to CYP509C12 and thus an increase in productivity from 246 to 300 μM hydroxyPg d(-1) was observed, as well as a 7-fold increase of rate of hydroxyprogesterone formation within the linear phase of transformation. This newly developed strain displayed total bioconversion of progesterone into 11α-hydroxyprogesterone and small amounts of 6β-hydroxyprogesterone within the first 6h of incubation with progesterone as substrate, hence demonstrating its potential for biotechnological application. Copyright © 2010 Elsevier B.V. All rights reserved.

Use of hormone replacement therapy in the Hong Kong public health sector after the Women's Health Initiative trial.

PubMed

Leung, K Y; Ling, Matina; Tang, G W K

2005-01-01

To determine the impact of Women Health Initiative (WHI) trial on the use of hormone replacement therapy (HRT) in the Hong Kong public health sector. The central prescription database of the Hospital Authority was used to describe the half-yearly trend in the use of HRT between July 2000 and December 2003. The data of hysterectomy was retrieved from another clinical database. Before the publication of the WHI trial in July 2002, conjugated equine estrogens (CEE) and its related products dominated HRT prescribing. Relative to the first half of 2002, there was an immediate and substantial decline by 43.5% in the prescriptions of combined CEE/progestogen products and a modest decline by 22.4% in the prescriptions of CEE-alone therapy in the second half of 2002. In the first half of 2003, a decline in the prescriptions of all HRT preparations except raloxifene was observed. However, in the second half of 2003, there were no more declines in overall HRT users. Relative to the first half of 2002, the decline in the overall HRT users in the first half of 2003 was more than 46% in women aged 50-69. The decline was greater in women with a history of hysterectomy (60.3%) than women without (38.6%), but was similar between gynaecology specialty (41.7%) and non-gynaecology specialty (43.9%). Similar to the U.S., an immediate and substantial decline in the use of CEE and its related products was observed in Hong Kong after the publication of the WHI trial.

Thermal Protection for Mars Sample Return Earth Entry Vehicle: A Grand Challenge for Design Methodology and Reliability Verification

NASA Technical Reports Server (NTRS)

Venkatapathy, Ethiraj; Gage, Peter; Wright, Michael J.

2017-01-01

Mars Sample Return is our Grand Challenge for the coming decade. TPS (Thermal Protection System) nominal performance is not the key challenge. The main difficulty for designers is the need to verify unprecedented reliability for the entry system: current guidelines for prevention of backward contamination require that the probability of spores larger than 1 micron diameter escaping into the Earth environment be lower than 1 million for the entire system, and the allocation to TPS would be more stringent than that. For reference, the reliability allocation for Orion TPS is closer to 11000, and the demonstrated reliability for previous human Earth return systems was closer to 1100. Improving reliability by more than 3 orders of magnitude is a grand challenge indeed. The TPS community must embrace the possibility of new architectures that are focused on reliability above thermal performance and mass efficiency. MSR (Mars Sample Return) EEV (Earth Entry Vehicle) will be hit with MMOD (Micrometeoroid and Orbital Debris) prior to reentry. A chute-less aero-shell design which allows for self-righting shape was baselined in prior MSR studies, with the assumption that a passive system will maximize EEV robustness. Hence the aero-shell along with the TPS has to take ground impact and not break apart. System verification will require testing to establish ablative performance and thermal failure but also testing of damage from MMOD, and structural performance at ground impact. Mission requirements will demand analysis, testing and verification that are focused on establishing reliability of the design. In this proposed talk, we will focus on the grand challenge of MSR EEV TPS and the need for innovative approaches to address challenges in modeling, testing, manufacturing and verification.

Skin test sensitivity to mouse predicts allergic symptoms to nasal challenge in urban adults.

PubMed

Chong, Laura K; Ong, Mary Jane; Curtin-Brosnan, Jean; Matsui, Elizabeth C

2010-01-01

Epidemiologic studies have shown an association between mouse allergen exposure and asthma morbidity among urban populations, but confirmatory challenge studies in community populations have not been performed. This study was designed to examine the clinical relevance of mouse sensitization using a nasal challenge model. Forty-nine urban adults with asthma underwent skin-prick testing (SPT) and intradermal testing (IDT) with mouse epithelia extract. A positive SPT was defined as a net wheal size ≥3 mm and a positive IDT was defined as a net wheal size ≥6 mm using a 1:100 dilution of extract (1:10 w/v was obtained from Greer Laboratories (Lenoir, NC) as a single lot [Mus m 1 concentration = 2130 ng/mL]). Mouse-specific IgE (m-IgE) was measured by ImmunoCAP (Phadia, Uppsala, Sweden). Nasal challenge was performed with increasing concentrations of mouse epithelia extract and symptoms were assessed by visual analog scale. A positive challenge was defined as a 20-mm increase in the scale. The age range of the 49 participants was 18-50 years; 41% were men and 86% were black. Fourteen participants were SPT(+) to mouse, 15 participants were SPT(-) but (IDT(+)), and 20 participants were negative on both SPT(-) and IDT(-) (SPT(-)/IDT(-)). Sixty-four percent of the SPT(+) group, 40% of the IDT(+) group, and 20% of the SPT(-)/IDT(-) group had a positive nasal challenge. Sixty-seven percent (10/15) of those who were either SPT(+) or m-IgE(+) had a positive nasal challenge. SPT or the combination of SPT plus m-IgE performed best in diagnosing mouse allergy. The great majority of mouse-sensitized urban adults with asthma appear to have clinically relevant sensitization. Urban adults with asthma should be evaluated for mouse sensitization using SPT or SPT plus m-IgE testing.

Diagnostic challenges of childhood asthma.

PubMed

Bakirtas, Arzu

2017-01-01

Diagnosis of asthma in childhood is challenging. Both underdiagnosis and overdiagnosis of asthma are important issues. The present review gives information about challenging factors for an accurate diagnosis of childhood asthma. Although underdiagnosis of asthma in childhood has always been the most important diagnostic problem, overdiagnosis of asthma has also been increasingly recognized. This is probably due to diagnosis of asthma based on symptoms and signs alone. Demonstration of variable airflow obstruction by lung function tests is the most common asthma diagnostic tests used in practice and is therefore strongly recommended in children who can cooperate. Recently, an asthma guideline combining the clinical and economic evidences with sensitivity and specificity of diagnostic procedures was developed to improve accuracy of diagnosis and to avoid overdiagnosis. This guideline provided an algorithmic clinical and cost-effective approach and included fractional exhaled nitric oxide measurement as one of the diagnostic tests in addition to lung function. Diagnosis of asthma in children should be made by combining relevant history with at least two confirmatory diagnostic tests whenever possible. Diagnosis based on short-period treatment trials should be limited to young children who are unable to cooperate with these tests.

Status of Cognitive Testing of Adults in India

PubMed Central

Porrselvi, A. P.; Shankar, V.

2017-01-01

The assessment of cognitive function is a challenging yet an integral component of psychological, psychiatric, and neurological evaluation. Cognitive assessment tools either can be administered quickly for screening for neurocognitive disorders or can be comprehensive and detailed to identify cognitive deficits for the purpose of localization, diagnosis, and rehabilitation. This article is a comprehensive review of published research that discusses the current challenges for cognitive testing in India, available tools used for the assessment of cognitive function in India, and future directions for cognitive testing in India. PMID:29184333

Genetic testing in congenital heart disease: ethical considerations.

PubMed

Lin, Kimberly Y; D'Alessandro, Lisa C A; Goldmuntz, Elizabeth

2013-01-01

On March 16, 2012, the Ethics of the Heart 2012: Ethical and Policy Challenges in Pediatric and Adult Congenital Heart Disease Conference took place in Philadelphia, Pennsylvania. The first session focused on the ethics surrounding genetic testing in patients with congenital heart disease. Summarized here is the introductory presentation given by Dr Elizabeth Goldmuntz entitled "The Role of Genetic Testing in Congenital Heart Disease," followed by a case presentation given by Dr Lisa D'Alessandro. The case and the panel discussion that ensued highlight several ethical principles and challenges in this unique patient population.

Performances on the CogState and Standard Neuropsychological Batteries Among HIV Patients Without Dementia

PubMed Central

Overton, Edgar Turner; Kauwe, John S.K.; Paul, Rob; Tashima, Karen; Tate, David F.; Patel, Pragna; Carpenter, Chuck; Patty, David; Brooks, John T.; Clifford, David B

2013-01-01

HIV-associated neurocognitive disorders (HAND) remain prevalent but challenging to diagnose particularly among non-demented individuals. To determine whether a brief computerized battery correlates with formal neurocognitive testing, we identified 46 HIV-infected persons who had undergone both formal neurocognitive testing and a brief computerized battery. Simple detection tests correlated best with formal neuropsychological testing. By multivariable regression model, 53% of the variance in the composite Global Deficit Score was accounted for by elements from the brief computerized tool (p<0.01). These data confirm previous correlation data with the computerized battery, yet illustrate remaining challenges for neurocognitive screening. PMID:21877204

Managing the Mars Science Laboratory Thermal Vacuum Test for Safety and Success

NASA Technical Reports Server (NTRS)

Evans, Jordan P.

2010-01-01

The Mars Science Laboratory is a NASA/JPL mission to send the next generation of rover to Mars. Originally slated for launch in 2009, development problems led to a delay in the project until the next launch opportunity in 2011. Amidst the delay process, the Launch/Cruise Solar Thermal Vacuum Test was undertaken as risk reduction for the project. With varying maturity and capabilities of the flight and ground systems, undertaking the test in a safe manner presented many challenges. This paper describes the technical and management challenges and the actions undertaken that led to the ultimate safe and successful execution of the test.

Failure of introduction of food allergens after negative oral food challenge tests in children.

PubMed

van der Valk, J P M; Gerth van Wijk, R; Vergouwe, Y; de Jong, N W

2015-08-01

One of the purposes to perform an oral food challenge (FC) test is to avoid unnecessary elimination of food allergens. In case of a negative FC test result, the food can be introduced. It is, however, unknown if patients act according to the outcome of the test. This study evaluates the rate of introduction of peanut, hazelnut, cow's milk or hen's egg allergens after a negative FC test. We investigated the introduction rate of children (0-18 years) with a negative FC test visiting the Department of Allergology, Erasmus Medical Centre Rotterdam from 2008 till 2013 and the factors that influence the rate of introduction. Patients were asked to complete a comprehensive questionnaire about their FC test. In total, 157 (38% girls, mean age during challenge 6.9 years) participated in the study. Of these FC tests, 104 (56%) were followed by a successful introduction, 30 (16%) by a partly introduction (traces or processed foods) and 52 (28%) by a failed introduction. Peanut and hazelnut showed a statistically significant lower successful introduction rate. Age, gender, symptoms during FC test, dietary advice and time period to introduction significantly influenced the rate of introduction. One fourth of the children with failure of introducing foods experienced symptoms during the introduction. More than one quarter of all children with a negative FC test result did not introduce the food. The FC test in its current form does not achieve its objective for this group of children.

Sensory-Challenge Balance Exercises Improve Multisensory Reweighting in Fall-Prone Older Adults.

PubMed

Allison, Leslie K; Kiemel, Tim; Jeka, John J

2018-04-01

Multisensory reweighting (MSR) deficits in older adults contribute to fall risk. Sensory-challenge balance exercises may have value for addressing the MSR deficits in fall-prone older adults. The purpose of this study was to examine the effect of sensory-challenge balance exercises on MSR and clinical balance measures in fall-prone older adults. We used a quasi-experimental, repeated-measures, within-subjects design. Older adults with a history of falls underwent an 8-week baseline (control) period. This was followed by an 8-week intervention period that included 16 sensory-challenge balance exercise sessions performed with computerized balance training equipment. Measurements, taken twice before and once after intervention, included laboratory measures of MSR (center of mass gain and phase, position, and velocity variability) and clinical tests (Activities-specific Balance Confidence Scale, Berg Balance Scale, Sensory Organization Test, Limits of Stability test, and lower extremity strength and range of motion). Twenty adults 70 years of age and older with a history of falls completed all 16 sessions. Significant improvements were observed in laboratory-based MSR measures of touch gain (P = 0.006) and phase (P = 0.05), Berg Balance Scale (P = 0.002), Sensory Organization Test (P = 0.002), Limits of Stability Test (P = 0.001), and lower extremity strength scores (P = 0.005). Mean values of vision gain increased more than those for touch gain, but did not reach significance. A balance exercise program specifically targeting multisensory integration mechanisms improved MSR, balance, and lower extremity strength in this mechanistic study. These valuable findings provide the scientific rationale for sensory-challenge balance exercise to improve perception of body position and motion in space and potential reduction in fall risk.

Halothane and halothane/succinylcholine induced malignant hyperthermia (porcine stress syndrome) in a population of Ontario boars.

PubMed

Seeler, D C; McDonell, W N; Basrur, P K

1983-07-01

This paper recounts a study of the prevalence of malignant hyperthermia in a population of boars entering the Record of Performance Test Station at New Hamburg, Ontario over a period of ten months. The literature is briefly reviewed and an account of the present status of malignant hyperthermia (porcine stress syndrome) in Ontario boars using the halothane or halothane/succinylcholine screening tests is presented. It was determined in this population of boars that there was a 1.5% prevalence rate of malignant hyperthermia susceptible boars. This was based on a five minute halothane challenge carried out on 786 boars from 107 herds. The halothane reactors came from a total of eight herds or 7.5% of the total number of herds. A majority of 58.3% of the animals reacted after the three minute mark of the halothane challenge. In contrast, an 18.0% prevalence rate was determined using halothane/succinylcholine challenge on 123 boars. This further identified an additional eight herds with the problem, bringing the total to 16 or 15% of the total number of herds. It is suggested that the prevalence of malignant hyperthermia in Ontario breeding herds is much higher than was originally thought and that the halothane challenge is an inadequate screening test for this trait if the intention is to remove the genetic trait from the breeding herd. At the same time halothane challenge testing will identify those animals which have a strong susceptibility to the trait and if used on key breeding stock will help to maintain some control on the condition until a more definitive test is readily available.(ABSTRACT TRUNCATED AT 250 WORDS)

College Access Improves for Black Students but for Which Ones?

ERIC Educational Resources Information Center

Cokley, Kevin; Obaseki, Victor; Moran-Jackson, Karen; Jones, Leonie; Vohra-Gupta, Shetal

2016-01-01

The challenges for increasing opportunities and college access for black students typically focus on the traditional barriers related to academic preparation, the racial gap in standardized test scores, and dropping out of high school. While these challenges remain, new and emerging challenges to college access are also important to discuss. They…

Will learning to solve one-step equations pose a challenge to 8th grade students?

NASA Astrophysics Data System (ADS)

Ngu, Bing Hiong; Phan, Huy P.

2017-08-01

Assimilating multiple interactive elements simultaneously in working memory to allow understanding to occur, while solving an equation, would impose a high cognitive load. Element interactivity arises from the interaction between elements within and across operational and relational lines. Moreover, operating with special features (e.g. negative pronumeral) poses additional challenge to master equation solving skills. In an experiment, 41 8th grade students (girls = 16, boys = 25) sat for a pre-test, attended a session about equation solving, completed an acquisition phase which constituted the main intervention and were tested again in a post-test. The results showed that at post-test, students performed better on one-step equations tapping low rather than high element interactivity knowledge. In addition, students performed better on those one-step equations that contained no special features. Thus, both the degree of element interactivity and the operation with special features affect the challenge posed to 8th grade students on learning how to solve one-step equations.

Comparison of Drospirenone- with Cyproterone Acetate-Containing Oral Contraceptives, Combined with Metformin and Lifestyle Modifications in Women with Polycystic Ovary Syndrome and Metabolic Disorders: A Prospective Randomized Control Trial.

PubMed

Wang, Qiu-Yi; Song, Yong; Huang, Wei; Xiao, Li; Wang, Qiu-Shi; Feng, Gui-Mei

2016-04-20

While combined oral contraceptives (COCs) are commonly used to treat polycystic ovary syndrome (PCOS), comparative data regarding metabolic effects of different progestogens on this patient population are missing. This study aimed to compare the different effects of drospirenone (DRP)-containing COCs with cyproterone acetate (CPA)-containing COCs, combined with metformin and lifestyle modifications in women with PCOS and metabolic disorders. Ninety-nine women with PCOS and a metabolic disorder between January 2011 and January 2013 were enrolled into this prospective randomized clinical trial. Participants were randomized into two groups such as DRP-containing COCs, and CPA-containing COCs. Participants took COCs cyclically for 6 months, combined with metformin administration (1.5 g/d) and lifestyle modifications (diet and exercise). Clinical measures and biochemical and hormone profiles were compared. Comparisons for continuous variables were evaluated with paired and unpaired Student's t-tests. The Wilcoxon signed rank test was used when the data were not normally distributed. Analysis of covariance was used to control for age, body mass index (BMI), and baseline data of each analyzed parameter when compared between the two groups. A total of 68 patients have completed the study. The combination regimen of COCs, metformin, and lifestyle modifications in these patients resulted in a significant decrease in BMI, acne, and hirsutism scores when compared to baseline levels in both groups (P < 0.05). Blood pressure (BP) was significantly different in the CPA group when compared to baseline (75.14 ± 6.77 mmHg vs. 80.70 ± 5.60 mmHg, P < 0.01), and after 6 months of treatment, only the change in systolic BP was significantly different between the two groups (4.00 [-6.00, 13.00] mmHg vs. -3.50 [-13.00, 9.00] mmHg, P = 0.009). Fasting glucose, fasting insulin, and homeostasis model assessment-insulin resistance decreased significantly in the DRP group (5.40 ± 0.41 mmol/L vs. 5.21 ± 0.32 mmol/L, P = 0.041; 13.90 [10.50, 18.40] μU/ml vs. 10.75 [8.60, 13.50] μU/ml, P = 0.020; 3.74 [2.85, 4.23] vs. 2.55 [1.92, 3.40], P = 0.008) but did not differ between the two groups. While individual lipid profiles increased in both groups, no statistically significant difference was observed. DRP-containing COCs combined with metformin and lifestyle modifications could better control BP and correct carbohydrate metabolism in women with PCOS and metabolic disorders compared with CPA-containing COCs. Chinese Clinical Trial Registry, ChiCTR-TRC-11001143; http://www.chictr.org.cn/showproj.aspx?proj=8395.

Hormones in international meat production: biological, sociological and consumer issues.

PubMed

Galbraith, Hugh

2002-12-01

Beef and its products are an important source of nutrition in many human societies. Methods of production vary and include the use of hormonal compounds ('hormones') to increase growth and lean tissue with reduced fat deposition in cattle. The hormonal compounds are naturally occurring in animals or are synthetically produced xenobiotics and have oestrogenic (oestradiol-17beta and its esters; zeranol), androgenic (testosterone and esters; trenbolone acetate) or progestogenic (progesterone; melengestrol acetate) activity. The use of hormones as production aids is permitted in North American countries but is no longer allowed in the European Union (EU), which also prohibits the importation of beef and its products derived from hormone-treated cattle. These actions have resulted in a trade dispute between the two trading blocs. The major concern for EU authorities is the possibility of adverse effects on human consumers of residues of hormones and metabolites. Methods used to assess possible adverse effects are typical of those used by international agencies to assess acceptability of chemicals in human food. These include analysis of quantities present in the context of known biological activity and digestive, absorptive, post-absorptive and excretory processes. Particular considerations include the low quantities of hormonal compounds consumed in meat products and their relationships to endogenous production particularly in prepubertal children, enterohepatic inactivation, cellular receptor- and non-receptor-mediated effects and potential for interference with growth, development and physiological function in consumers. There is particular concern about the role of oestradiol-17beta as a carcinogen in certain tissues. Now subject to a 'permanent' EU ban, current evidence suggests that certain catechol metabolites may induce free-radical damage of DNA in cell and laboratory animal test systems. Classical oestrogen-receptor mediation is considered to stimulate proliferation in cells maintaining receptivity. Mathematical models describing quantitative relationships between consumption of small amounts of oestrogens in meat in addition to greater concentrations from endogenous production, chemical stoichiometry at cellular level and human pathology have not been developed. Such an approach will be necessary to establish 'molecular materiality' of the additional hormone intake as a component of relative risk assessment. The other hormones, although generally less well researched, are similarly subject to a range of tests to determine potentially adverse effects. The resulting limited international consensus relates to the application of the 'precautionary principle' and non-acceptance by the European Commission of the recommendations of the Codex Alimentarius Commission, which determined that meat from cattle, hormone-treated according to good practice, was safe for human consumers. The present review considers the hormone issue in the context of current international social methodology and regulation, recent advances in knowledge of biological activity of hormones and current status of science-based evaluation of food safety and risk for human consumers.

Hair loss in women.

PubMed

Camacho-Martínez, Francisco M

2009-03-01

Female pattern hair loss (FPHL) is a clinical problem that is becoming more common in women. Female alopecia with androgen increase is called female androgenetic alopecia (FAGA) and without androgen increase is called female pattern hair loss. The clinical picture of typical FAGA begins with a specific "diffuse loss of hair from the parietal or frontovertical areas with an intact frontal hairline." Ludwig called this process "rarefaction." In Ludwig's classification of hair loss in women, progressive type of FAGA, 3 patterns were described: grade I or minimal, grade II or moderate, and grade III or severe. Ludwig also described female androgenetic alopecia with male pattern (FAGA.M) that should be subclassified according to Ebling's or Hamilton-Norwood's classification. FAGA.M may be present in 4 conditions: persistent adrenarche syndrome, alopecia caused by an adrenal or an ovarian tumor, posthysterectomy, and as an involutive alopecia. A more recent classification (Olsen's classification of FPHL) proposes 2 types: early- and late-onset with or without excess of androgens in each. The diagnosis of FPHL is made by clinical history, clinical examination, wash test, dermoscopy, trichoscan, trichograms and laboratory test, especially androgenic determinations. Topical treatment of FPHL is with minoxidil, 2-5% twice daily. When FPHL is associated with high levels of androgens, systemic antiandrogenic therapy is needed. Persistent adrenarche syndrome (adrenal SAHA) and alopecia of adrenal hyperandrogenism is treated with adrenal suppression and antiandrogens. Adrenal suppression is achieved with glucocorticosteroids. Antiandrogens therapy includes cyproterone acetate, drospirenone, spironolactone, flutamide, and finasteride. Excess release of ovarian androgens (ovarian SAHA) and alopecia of ovarian hyperandrogenism is treated with ovarian suppression and antiandrogens. Ovarian suppression includes the use of contraceptives containing an estrogen, ethinylestradiol, and a progestogen. Antiandrogens such as cyproterone acetate, always accompanied by tricyclic contraceptives, are the best choice of antiandrogens to use in patients with FPHL. Gonadotropin-releasing hormone agonists such as leuprolide acetate suppress pituitary and gonadal function through a reduction in luteinizing hormone and follicle-stimulating hormone levels. Subsequently, ovarian steroid levels also will be reduced, especially in patients with polycystic ovary syndrome. When polycystic ovary syndrome is associated with insulin resistance, metformin must be considered as treatment. Hyperprolactinemic SAHA and alopecia of pituitary hyperandrogenism should be treated with bromocriptine or cabergoline. Postmenopausal alopecia, with previous high levels of androgens or with prostatic-specific antigen greater than 0.04 ng/mL, improves with finasteride or dutasteride. Although we do not know the reason, postmenopausal alopecia in normoandrogenic women also improves with finasteride or dutasteride at a dose of 2.5 mg per day. Dermatocosmetic concealment with a hairpiece, hair prosthesis as extensions, or partial hairpieces can be useful. Lastly, weight loss undoubtedly improves hair loss in hyperandrogenic women.

CD-sens can be a reliable and easy-to-use complement in the diagnosis of allergic rhinitis.

PubMed

Nopp, A; Cardell, L O; Johansson, S G O

2013-01-01

A reproducible standard for a graded allergen response in allergic rhinitis is lacking. The aim was to evaluate basophil allergen threshold sensitivity, CD-sens, as a diagnostic complement to nasal allergen challenge. Twenty-six patients with a history of allergic rhinitis due to grass pollen were intranasally challenged and nasal symptom score and peak nasal inspiratory flow (PNIF) changes were determined after 15 min. A 20% decrease in PNIF or a symptom score ≥2 were considered a positive test. A blood sample for CD-sens was drawn before each challenge. Eighteen patients were tested twice. CD-sens agreed with the positive or negative nasal symptom score in 22/26 and PNIF in 24/26 patients. After the second challenge, 14/18 patients had the same symptom, 17/18 the same PNIF, while all had identical CD-sens classification. CD-sens appears to be a reproducible test for diagnosis of allergic rhinitis with great advantages also for follow-up of disease development and treatment effects. Copyright © 2012 S. Karger AG, Basel.

Mitigating Interconnection Challenges of the High Penetration Utility-Interconnected Photovoltaic (PV) in the Electrical Distribution Systems: Cooperative Research and Development Final Report, CRADA Number CRD-14-563

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chakraborty, Sudipta

Various interconnection challenges exist when connecting distributed PV into the electrical distribution grid in terms of safety, reliability, and stability of the electric power systems. Some of the urgent areas for research, as identified by inverter manufacturers, installers and utilities, are potential for transient overvoltage from PV inverters, multi-inverter anti-islanding, impact of smart inverters on volt-VAR support, impact of bidirectional power flow, and potential for distributed generation curtailment solutions to mitigate grid stability challenges. Under this project, NREL worked with SolarCity to address these challenges through research, testing and analysis at the Energy System Integration Facility (ESIF). Inverters from differentmore » manufacturers were tested at ESIF and NREL's unique power hardware-in-the-loop (PHIL) capability was utilized to evaluate various system-level impacts. Through the modeling, simulation, and testing, this project eliminated critical barriers on high PV penetration and directly supported the Department of Energy's SunShot goal of increasing the solar PV on the electrical grid.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

In this project, three production home builders—K. Hovnanian Homes, David Weekley Homes, and Transformations, Inc.—partnered with Building America team Building Science Corporation to evaluate the certification of five test homes to the new DOE Challenge Home program performance standard (now DOE Zero Energy Ready Home program). The builders identified key benefits and barriers that impacted the certification of the test homes, and the likelihood of whether DOE Challenge Home certification would be pursued in future homes

Methodical Challenges Concerning the Draw-A-Scientist Test: A Critical View about the Assessment and Evaluation of Learners' Conceptions of Scientists

ERIC Educational Resources Information Center

Reinisch, Bianca; Krell, Moritz; Hergert, Susann; Gogolin, Sarah; Krüger, Dirk

2017-01-01

Students' and pre-service teachers' conceptions of scientists have been assessed in a variety of studies. One of the most commonly used instruments is the Draw-A-Scientist Test (DAST) which offers the advantage that no verbal skills are needed by the participants. In some studies, methodical challenges related to the DAST have been discussed; for…

Computational fragment-based screening using RosettaLigand: the SAMPL3 challenge

NASA Astrophysics Data System (ADS)

Kumar, Ashutosh; Zhang, Kam Y. J.

2012-05-01

SAMPL3 fragment based virtual screening challenge provides a valuable opportunity for researchers to test their programs, methods and screening protocols in a blind testing environment. We participated in SAMPL3 challenge and evaluated our virtual fragment screening protocol, which involves RosettaLigand as the core component by screening a 500 fragments Maybridge library against bovine pancreatic trypsin. Our study reaffirmed that the real test for any virtual screening approach would be in a blind testing environment. The analyses presented in this paper also showed that virtual screening performance can be improved, if a set of known active compounds is available and parameters and methods that yield better enrichment are selected. Our study also highlighted that to achieve accurate orientation and conformation of ligands within a binding site, selecting an appropriate method to calculate partial charges is important. Another finding is that using multiple receptor ensembles in docking does not always yield better enrichment than individual receptors. On the basis of our results and retrospective analyses from SAMPL3 fragment screening challenge we anticipate that chances of success in a fragment screening process could be increased significantly with careful selection of receptor structures, protein flexibility, sufficient conformational sampling within binding pocket and accurate assignment of ligand and protein partial charges.

[Induced abortion: Guidelines for clinical practice - Text of the Guidelines (short text)].

PubMed

Vayssière, C; Gaudineau, A; Attali, L; Bettahar, K; Eyraud, S; Faucher, P; Fournet, P; Hassoun, D; Hatchuel, M; Jamin, C; Letombe, B; Linet, T; Msika Razon, M; Ohanessian, A; Segain, H; Vigoureux, S; Winer, N; Wylomanski, S; Agostini, A

2016-12-01

Develop recommendations for the practice of induced abortion. The Pubmed database, the Cochrane Library and the recommendations from the French and foreign Gyn-Obs societies or colleges have been consulted. The number of induced abortions (IA) has been stable for several decades. There are a lot of factors explaining the choice of abortion when there is an unplanned pregnancy (UPP). Early initiation and choice of contraception in connection to the woman's life are associated with lower NSP. Reversible contraceptives of long duration of action should be positioned fist in line for the teenager because of its efficiency (grade C). Ultrasound before induced abortion must be encouraged but should not be obligatory before performing IA (Professional consensus). As soon as the sonographic apparition of the embryo, the estimated date of pregnancy is done by measuring the crown-rump length (CRL) or by measuring the biparietal diameter (BIP) from 11 weeks on (grade B). Reliability of these parameters being±5 days, IA could be done if measurements are respectively less than 90mm for CRL and less than 30mm for BIP (Professional consensus). A medical IA performed with a dose of 200mg mifepristone combined with misoprostol is effective at any gestational age (EL1). Before 7 weeks, mifepristone followed between 24 and 48hours by taking misoprostol orally, buccally sublingually or eventually vaginally at a dose of 400 ug possibly renewed after 3hours (EL1, grade A). Beyond 7 weeks, misoprostol given vaginally, sublingually or buccally are better tolerated with fewer side effects than oral route (EL1). It is recommended to always use a cervical preparation during an instrumental abortion (Professional consensus). Misoprostol is a first-line agent for cervical preparation at a dose of 400 mcg (grade A). Aspiration evacuation is preferable to curettage (grade B). A perforated uterus during an instrumental suction should not be considered as a scarred uterus (Professional consensus). IA is not associated with increased subsequent risk of infertility or ectopic pregnancy (EL2). The pre-abortion medical consultations does not affect, most of the time, the decision to request an IA. Indeed, a majority of women is quite sure of her choice during these consultations. Acceptability of the method of IA and satisfaction appears to be larger when they are able to choose the abortion method (grade B). There is no relationship between an increase in psychiatric disorders and IA (EL2). Women with psychiatric histories are at increased risk of mental disorders after the occurrence of an UPP (EL2). In case of instrumental abortion, oral estrogen-progestogen contraceptives and the patch should be started from the day of the abortion, the vaginal ring inserted within 5 days of IA (grade B). In case of medical abortion, the vaginal ring should be inserted within a week of taking mifepristone, oral estrogen-progestogen contraceptives and the patch should be initiated on the same day or the day after taking prostaglandins (grade C). In case of instrumental abortion, the contraceptive implant may be inserted on the day of the abortion (grade B). In case of medical abortion, the implant can be inserted on the day of mifepristone (grade C). The copper Intrauterine Device (IUD) and levonorgestrel should be inserted preferably on the day of instrumental abortion (grade A). In case of medical abortion, an IUD can be inserted within 10 days following mifepristone after ensuring by ultrasound of the absence of intrauterine pregnancy (grade C). The implementation of these guidelines may promote a better and more homogenous care for women requesting IA in our country. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Crowdsourcing the creation of image segmentation algorithms for connectomics.

PubMed

Arganda-Carreras, Ignacio; Turaga, Srinivas C; Berger, Daniel R; Cireşan, Dan; Giusti, Alessandro; Gambardella, Luca M; Schmidhuber, Jürgen; Laptev, Dmitry; Dwivedi, Sarvesh; Buhmann, Joachim M; Liu, Ting; Seyedhosseini, Mojtaba; Tasdizen, Tolga; Kamentsky, Lee; Burget, Radim; Uher, Vaclav; Tan, Xiao; Sun, Changming; Pham, Tuan D; Bas, Erhan; Uzunbas, Mustafa G; Cardona, Albert; Schindelin, Johannes; Seung, H Sebastian

2015-01-01

To stimulate progress in automating the reconstruction of neural circuits, we organized the first international challenge on 2D segmentation of electron microscopic (EM) images of the brain. Participants submitted boundary maps predicted for a test set of images, and were scored based on their agreement with a consensus of human expert annotations. The winning team had no prior experience with EM images, and employed a convolutional network. This "deep learning" approach has since become accepted as a standard for segmentation of EM images. The challenge has continued to accept submissions, and the best so far has resulted from cooperation between two teams. The challenge has probably saturated, as algorithms cannot progress beyond limits set by ambiguities inherent in 2D scoring and the size of the test dataset. Retrospective evaluation of the challenge scoring system reveals that it was not sufficiently robust to variations in the widths of neurite borders. We propose a solution to this problem, which should be useful for a future 3D segmentation challenge.

Addressing challenges to MMPI-2-RF-based testimony: questions and answers.

PubMed

Ben-Porath, Yossef S

2012-11-01

Introduction of a new version of a psychological test brings with it challenges that can be accentuated by the adversarial nature of the legal process. In the case of the Minnesota Multiphasic Personality Inventory-2 Restructured Form (MMPI-2-RF), these challenges can be addressed by becoming familiar with the rationale for and the methods used in revising the inventory, the information contained in the test manuals, and the growing peer-reviewed literature on the test. Potential challenges to MMPI-2-RF-based testimony are identified in this article and discussed in question and answer format. The questions guiding this discussion are based on the Daubert factors, established in 1993 by the US Supreme Court as criteria for gauging the scientific validity of proffered expert testimony. The answers to these questions apply more broadly to testimony in depositions, pre-trial hearings, and at trial. Consideration of the MMPI-2-RF in light of the Daubert factors indicates that the instrument has been subjected to extensive empirical testing and that a substantial peer-reviewed literature is available to guide and support its use. Information about the known and potential rate of error associated with MMPI-2-RF scores is available, and standard procedures for administration, scoring, and interpretation of the inventory are detailed in the test administration manual. Indicators of MMPI-2-RF acceptance can be cited, and criticisms of the MMPI-2-RF can be addressed with information available in the test documents and an extensive, modern, and actively growing peer-reviewed literature.

Effect of Paneer and Cheese Consumption on Salivary Acidogenicity and Calcium Concentration: A Comparative Study.

PubMed

Somaraj, Vinej; Shenoy, Rekha P; Panchmal, Ganesh Shenoy; Jodalli, Praveen S; Sonde, Laxminarayan; Nagaraj, Kundapur

2018-01-01

To assess and compare the salivary pH reversal phenomenon and calcium concentration in subjects consuming paneer and cheese after an acidogenic challenge and also to compare the salivary pH measurements using pH strips and a portable pen-type pH meter. Sixty caries free undergraduate students were randomly selected and divided into two group: 1. paneer; 2. cheese. After determining the resting salivary pH using pH strips and a pen-type pH meter, participants were subjected to an acidogenic challenge (10% sucrose). Following consumption of test foods (10-gram cubes), salivary pH was measured at intervals of 5, 10, 15, 30 and 60 min to record the time taken for the salivary pH to return to baseline. Colorimetric salivary calcium concentration was estimated (Biochemical Analyzer) at baseline and after 60 min of test food consumption. The statistical tests used were Shapiro-Wilk's test for normality, repeated measures ANOVA, and the independent t-test. Test meals reversed the fall in pH after acidogenic challenge starting at 5 min and returning to baseline values after 30 min in both groups (p = 1.000). Colorimetric estimates showed higher salivary calcium concentrations with paneer (p < 0.001). The pen-type pH meter showed superior efficiency in terms of time (p < 0.001) compared to pH strips. The salivary pH reversal phenomenon was evident after consumption of both paneer and cheese following the acidogenic challenge. Consumption of paneer significantly increased salivary calcium concentration. The pen-type pH meter proved to be more efficient.

Caffeine challenge test in panic disorder and depression with panic attacks.

PubMed

Nardi, Antonio E; Lopes, Fabiana L; Valença, Alexandre M; Freire, Rafael C; Veras, André B; de-Melo-Neto, Valfrido L; Nascimento, Isabella; King, Anna Lucia; Mezzasalma, Marco A; Soares-Filho, Gastão L; Zin, Walter A

2007-01-01

Our aim was to observe if patients with panic disorder (PD) and patients with major depression with panic attacks (MDP) (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria) respond in a similar way to the induction of panic attacks by an oral caffeine challenge test. We randomly selected 29 patients with PD, 27 with MDP, 25 with major depression without panic attacks (MD), and 28 healthy volunteers. The patients had no psychotropic drug for at least a 4-week period. In a randomized double-blind experiment performed in 2 occasions 7 days apart, 480 mg caffeine and a caffeine-free (placebo) solution were administered in a coffee form and anxiety scales were applied before and after each test. A total of 58.6% (n = 17) of patients with PD, 44.4% (n = 12) of patients with MDP, 12.0% (n = 3) of patients with MD, and 7.1% (n= 2) of control subjects had a panic attack after the 480-mg caffeine challenge test (chi(2)(3) = 16.22, P = .001). The patients with PD and MDP were more sensitive to caffeine than were patients with MD and healthy volunteers. No panic attack was observed after the caffeine-free solution intake. The patients with MD had a lower heart rate response to the test than all the other groups (2-way analysis of variance, group by time interaction with Greenhouse-Geisser correction: F(3,762) = 2.85, P = .026). Our data suggest that there is an association between panic attacks, no matter if associated with PD or MDP, and hyperreactivity to an oral caffeine challenge test.

2016 ROVER CHALLENGE EVENTS

NASA Image and Video Library

2015-01-08

2016 ROVER CHALLENGE EVENTS AT THE U.S. SPACE AND ROCKET CENTER IN HUNTSVILLE, ALABAMA. NATIONAL AND INTERNATIONAL COLLEGE AND HIGH SCHOOL STUDENTS COME TOGETHER TO TEST THEIR ENGINEERING SKILLS OVER A SIMULATED OUTER PLANET OBSTACLE COURSE.

Direct-field acoustic testing of a flight system : logistics, challenges, and results.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stasiunas, Eric Carl; Gurule, David Joseph; Babuska, Vit

2010-10-01

Before a spacecraft can be considered for launch, it must first survive environmental testing that simulates the launch environment. Typically, these simulations include vibration testing performed using an electro-dynamic shaker. For some spacecraft however, acoustic excitation may provide a more severe loading environment than base shaker excitation. Because this was the case for a Sandia Flight System, it was necessary to perform an acoustic test prior to launch in order to verify survival due to an acoustic environment. Typically, acoustic tests are performed in acoustic chambers, but because of scheduling, transportation, and cleanliness concerns, this was not possible. Instead, themore » test was performed as a direct field acoustic test (DFAT). This type of test consists of surrounding a test article with a wall of speakers and controlling the acoustic input using control microphones placed around the test item, with a closed-loop control system. Obtaining the desired acoustic input environment - proto-flight random noise input with an overall sound pressure level (OASPL) of 146.7 dB-with this technique presented a challenge due to several factors. An acoustic profile with this high OASPL had not knowingly been obtained using the DFAT technique prior to this test. In addition, the test was performed in a high-bay, where floor space and existing equipment constrained the speaker circle diameter. And finally, the Flight System had to be tested without contamination of the unit, which required a contamination bag enclosure of the test unit. This paper describes in detail the logistics, challenges, and results encountered while performing a high-OASPL, direct-field acoustic test on a contamination-sensitive Flight System in a high-bay environment.« less

Rapid Automated Antimicrobial Susceptibility Testing of Streptococcus pneumoniae by Use of the bioMerieux VITEK 2

PubMed Central

Jorgensen, James H.; Barry, Arthur L.; Traczewski, M. M.; Sahm, Daniel F.; McElmeel, M. Leticia; Crawford, Sharon A.

2000-01-01

The VITEK 2 is a new automated instrument for rapid organism identification and susceptibility testing. It has the capability of performing rapid susceptibility testing of Streptococcus pneumoniae with specially configured cards that contain enriched growth medium and antimicrobial agents relevant for this organism. The present study compared the results of testing of a group of 53 challenge strains of pneumococci with known resistance properties and a collection of clinical isolates examined in two study phases with a total of 402 and 416 isolates, respectively, with a prototype of the VITEK 2. Testing was conducted in three geographically separate laboratories; the challenge collection was tested by all three laboratories, and the unique clinical isolates were tested separately by the individual laboratories. The VITEK 2 results of tests with 10 antimicrobial agents were compared to the results generated by the National Committee for Clinical Laboratory Standards reference broth microdilution MIC test method. Excellent interlaboratory agreement was observed with the challenge strains. The overall agreement within a single twofold dilution of MICs defined by the VITEK 2 and reference method with the clinical isolates was 96.3%, although there were a number of off-scale MICs that could not be compared. The best agreement with the clinical isolates was achieved with ofloxacin and chloramphenicol (100%), and the lowest level of agreement among those drugs with sufficient on-scale MICs occurred with trimethoprim-sulfamethoxazole (89.7%). Overall there were 1.3% very major, 6.6% minor, and no major interpretive category errors encountered with the clinical isolates, although >80% of the minor interpretive errors involved only a single log2 dilution difference. The mean time for generation of susceptibility results with the clinical isolates was 8.1 h. The VITEK 2 provided rapid, reliable susceptibility category determinations with both the challenge and clinical isolates examined in this study. PMID:10921932

Removal of Viruses in Drinking Water- Ultrafiltration Module with a Cut Fiber, Dow Chemical Company - Dow Water & Process Solutions, SFD-2880 - Ultrafiltration Module

EPA Science Inventory

The purpose of this verification was a cut fiber challenge study for the Dow Chemical Company SFD-2880 UF membrane module. MS2 coliphage virus was the surrogate challenge organism. The challenge tests followed the requirements of the Department of Health Victoria (Australia) Dr...

Genetic Testing Integration Panels (GTIPs): A novel approach for considering integration of direct-to-consumer and other new genetic tests into patient care

PubMed Central

Uhlmann, Wendy R.; Sharp, Richard R.

2014-01-01

There has been a dramatic increase in the number of genetic tests available but few tests have practice guidelines. In addition, many tests have become available outside of genetics clinics through direct-to-consumer (DTC) companies and several offer tests not considered standard of care. To address several practical challenges associated with the rapid introduction of clinical and DTC genetic tests, we propose that genetic counselors and geneticists organize expert panels in their institutions to discuss the integration of new tests into patient care. We propose the establishment of Genetic Testing Integration Panels (GTIPs) to bring together local experts in medical genetics, genetic counseling, bioethics and law, health communication and clinical laboratory genetics. We describe key features of this approach and consider some of the potential advantages and limitations of using a GTIP to address the many clinical challenges raised by rapidly emerging clinical and DTC genetic tests. PMID:22246561

Challenges of CPAS Flight Testing

NASA Technical Reports Server (NTRS)

Ray, Eric S.; Morris, Aaron L.

2011-01-01

The Crew Exploration Vehicle Parachute Assembly System (CPAS) is being designed to land the Orion Crew Module (CM) at a safe rate of descent at splashdown via a series of Drogue, Pilot, and Main parachutes. Because Orion is considerably larger and heavier than Apollo, many of the flight test techniques developed during the Apollo program must be modified. The Apollo program had a dedicated C-133 aircraft, which was modified to allow a simple airdrop of "boilerplate" flight test vehicles. However, the CPAS program must use either commercial or military assets with minimal modifications to airframes or procedures. Conceptual envelopes from 2-Degree Of Freedom trajectories are presented for several existing and novel architectures. Ideally, the technique would deliver a representative capsule shape to the desired altitude and dynamic pressure at test initiation. However, compromises must be made on the characteristics of trajectories or the fidelity of test articles to production hardware. Most of the tests to date have used traditional pallet and weight tub or missile-shaped test vehicles. New test vehicles are being designed to better incorporate Orion structural components and deploy parachutes in a more representative fashion. The first attempt to test a capsule-shaped vehicle failed due to unexpected events while setting up the test condition through a series of complex procedures. In order to avoid the loss of another expensive test article which will delay the program, simpler deployment methods are being examined and more positive control of the vehicle will be maintained. Existing challenges include interfacing with parent aircraft, separating test vehicles, achieving test conditions, and landing within limited test ranges. All these challenges must be met within cost and schedule limits.

Selection of a discriminant and biorelevant in vitro dissolution test for the development of fenofibrate self-emulsifying lipid-based formulations.

PubMed

Pestieau, Aude; Krier, Fabrice; Brouwers, Adeline; Streel, Bruno; Evrard, Brigitte

2016-09-20

Fenofibrate, a BCS class II compound, has a low bioavailability especially when taken orally on an empty stomach. The challenge to find a new formulation for providing bioavailability, independent of food, is still ongoing. If the development of a suitable oral delivery formulation of BCS class II compounds is a frequent and great challenge to formulation scientists, the in vitro evaluation of these new formulations is also a great challenge. The purpose of this study was therefore to select an in vitro dissolution test that would be useful and as biorelevant as possible for the development of fenofibrate self-emulsifying lipid-based formulations. In this context, three different fenofibrate formulations, for which in vivo data are available in the literature, were tested using different dissolution tests until we found the one that was the most suitable. As part of this approach, we started with the simplest in vitro dissolution tests and progressed to tests that were increasingly more complex. The first tests were different single phase dissolution tests: a test under sink conditions based on the USP monograph, and different tests under non-sink conditions in non-biorelevant and biorelevant media. Given the inconclusive results obtained with these tests, biphasic dissolution systems were then tested: one with USP apparatus type II alone and another which combined USP apparatus types II and IV. This last combined test seemed the most suitable in vitro dissolution test for the development of the future fenofibrate lipid-based formulations we intend to develop in our own laboratory. Copyright © 2016 Elsevier B.V. All rights reserved.

Experimental PVC Material Challenge in Subjects with Occupational PVC Exposure

PubMed Central

Tuomainen, Anneli; Stark, Harri; Seuri, Markku; Hirvonen, Maija-Riitta; Linnainmaa, Markku; Sieppi, Anne; Tukiainen, Hannu

2006-01-01

Background Polyvinyl chloride (PVC) materials have been linked to asthma in several epidemiologic studies, but the possible causal factors remain unknown. Participants We challenged 10 subjects experimentally to degraded PVC products under controlled conditions. All of the subjects had previously experienced respiratory symptoms suspected to be caused by this kind of exposure in their work place. Five subjects had doctor-diagnosed asthma. Methods The subjects were exposed to degraded PVC material in an exposure chamber; a challenge with ceramic tile was used as the control test. We followed exhaled nitric oxide, nasal NO, lung functions, cytokines [tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), IL-6, and IL-12] and NO in nasal lavage fluid (NAL) during and after the exposures. We also measured 2-ethylhexanol in exhaled breath samples and NAL. Results On the morning after the PVC exposure, subjects reported respiratory tract symptoms significantly more often than they did after the control test (50% vs. 0%, respectively; p = 0.029; n = 10). We did not detect any changes in lung functions or levels of exhaled NO, nasal NO, or NO in NAL after PVC challenge compared with the control test. Cytokine levels increased after both exposures, with no statistically significant difference between situations. All of the exhaled breath samples collected during the PVC exposure contained 2-ethylhexanol. Conclusions PVC flooring challenge can evoke respiratory tract symptoms in exposed subjects. Our results do not support the hypothesis that PVC materials themselves evoke immediate asthmatic reactions. The chamber test used is well suited to this type of exposure study. PMID:16966097

Cognitive and Noncognitive Improvements Among ChalleNGe Cadets: A Survey of Seven Sites

DTIC Science & Technology

2016-06-01

Distribution unlimited Cognitive and Noncognitive Improvements Among ChalleNGe Cadets: A Survey of Seven Sites Lauren D. Malone and Jennifer R...completion and test score improvement. Using data on cadets’ scores on the Test of Adult Basic Education (TABE) and cadets’ responses to survey questions...total score. The sites also provided information on which cadets completed the program and cadets’ ages. In addition, we use data from a survey that

Education in Anti-Doping: The Art of Self-Imposed Constraints.

PubMed

Loland, Sigmund

2017-01-01

The pillars of anti-doping are detection, deterrence, and prevention. Detection takes the form of testing for banned substances. Deterrence builds on testing and gathering evidence. Athletes who test positive are exposed to penalties. The main tool of prevention is education. Education takes many forms and can be implemented in many ways. This chapter addresses the nature and challenges of current anti-doping education. Firstly, general goals of education and their connection to sport are discussed. Secondly, three normative interpretations of sport are presented, and their implications for anti-doping education are examined. Instrumentalist interpretations and interpretations with emphasis on performance and enhancement challenge the anti-doping campaign. A human excellence interpretation is advocated in which anti-doping is considered a consistent and integral part of sport. Thirdly, future challenges for anti-doping education are reflected upon. © 2017 S. Karger AG, Basel.

Barriers and Strategies Related to Qualitative Research on Genetic Ancestry Testing in Indigenous Communities.

PubMed

Blanchard, Jessica W; Tallbull, Gloria; Wolpert, Chantelle; Powell, Jill; Foster, Morris W; Royal, Charmaine

2017-07-01

Conducting genetics-related research with populations that have historically experienced considerable harm and little benefit from genetics research poses unique challenges for understanding community-based perceptions of new genetic technologies. This article identifies challenges and strategies for collecting qualitative data on the perceptions of direct-to-consumer (DTC) Genetic Ancestry tests (GAT) among diverse Indigenous communities. Based on a 3-year project related to perceptions, attitudes, and values associated with genetic ancestry testing among diverse Indigenous communities in Oklahoma, the engagement process revealed specific opportunities to improve the process of qualitative data collection related to GAT, and more broadly, to conduct genetics-related research with Indigenous communities in culturally and methodologically appropriate ways. Priority areas include issues related to participant recruitment and tribal advisory boards, challenges of self-identification as a recruitment mechanism, and the necessity of including Indigenous researchers in all aspects of the research process.

Space Environmental Effects Testing and Characterization of the Candidate Solar Sail Material Aluminized Mylar

NASA Technical Reports Server (NTRS)

Edwards, D. L.; Hubbs, W. S.; Wertz, G. E.; Alstatt, R.; Munafo, Paul (Technical Monitor)

2001-01-01

The usage of solar sails as a propellantless propulsion system has been proposed for many years. The technical challenges associated with solar sails are fabrication of ultralightweight films, deploying the sails and controlling the spacecraft. Integral to all these challenges is the mechanical property integrity of the sail while exposed to the harsh environment of space. This paper describes testing and characterization of a candidate solar sail material, Aluminized Mylar. This material was exposed to a simulated Geosynchronous Transfer Orbit (GTO) and evaluated by measuring thermooptical and mechanical property changes. Testing procedures and results are presented.

Radiation Testing, Characterization and Qualification Challenges for Modern Microelectronics and Photonics Devices and Technologies

NASA Technical Reports Server (NTRS)

LaBel, Kenneth A.; Cohn, Lewis M.

2008-01-01

At GOMAC 2007, we discussed a selection of the challenges for radiation testing of modern semiconductor devices focusing on state-of-the-art memory technologies. This included FLASH non-volatile memories (NVMs) and synchronous dynamic random access memories (SDRAMs). In this presentation, we extend this discussion in device packaging and complexity as well as single event upset (SEU) mechanisms using several technology areas as examples including: system-on-a-chip (SOC) devices and photonic or fiber optic systems. The underlying goal is intended to provoke thought for understanding the limitations and interpretation of radiation testing results.

Methotrexate Hypersensitivity Reactions in Pediatrics: Evaluation and Management

PubMed Central

Dilley, Meredith A.; Lee, Joyce P.; Broyles, Ana Dioun

2017-01-01

Reports of hypersensitivity reactions (HSRs) to MTX are limited to single case studies. We retrospectively reviewed HSRs to MTX during a 12-year period in our tertiary care pediatric center. Seven patients were evaluated for HSRs to MTX. Skin testing was positive in one of the 4 patients tested. One patient underwent successful graded challenge to MTX. Seventeen desensitizations to MTX were successfully performed in the other 6 patients. Skin testing, graded challenge, and desensitization were safe and effective procedures in the evaluation and management of patients with HSRs to MTX in our pediatric population. PMID:27786403

NASA Langley Distributed Propulsion VTOL Tilt-Wing Aircraft Testing, Modeling, Simulation, Control, and Flight Test Development

NASA Technical Reports Server (NTRS)

Rothhaar, Paul M.; Murphy, Patrick C.; Bacon, Barton J.; Gregory, Irene M.; Grauer, Jared A.; Busan, Ronald C.; Croom, Mark A.

2014-01-01

Control of complex Vertical Take-Off and Landing (VTOL) aircraft traversing from hovering to wing born flight mode and back poses notoriously difficult modeling, simulation, control, and flight-testing challenges. This paper provides an overview of the techniques and advances required to develop the GL-10 tilt-wing, tilt-tail, long endurance, VTOL aircraft control system. The GL-10 prototype's unusual and complex configuration requires application of state-of-the-art techniques and some significant advances in wind tunnel infrastructure automation, efficient Design Of Experiments (DOE) tunnel test techniques, modeling, multi-body equations of motion, multi-body actuator models, simulation, control algorithm design, and flight test avionics, testing, and analysis. The following compendium surveys key disciplines required to develop an effective control system for this challenging vehicle in this on-going effort.

Economic analysis of model validation for a challenge problem

DOE PAGES

Paez, Paul J.; Paez, Thomas L.; Hasselman, Timothy K.

2016-02-19

It is now commonplace for engineers to build mathematical models of the systems they are designing, building, or testing. And, it is nearly universally accepted that phenomenological models of physical systems must be validated prior to use for prediction in consequential scenarios. Yet, there are certain situations in which testing only or no testing and no modeling may be economically viable alternatives to modeling and its associated testing. This paper develops an economic framework within which benefit–cost can be evaluated for modeling and model validation relative to other options. The development is presented in terms of a challenge problem. Asmore » a result, we provide a numerical example that quantifies when modeling, calibration, and validation yield higher benefit–cost than a testing only or no modeling and no testing option.« less

Assemby, test, and launch operations for the Mars Exploration Rovers

NASA Technical Reports Server (NTRS)

Wallace, Matthew T.; Hardy, Paul V.; Romero, Raul A.; Salvo, Christopher G.; Shain, Thomas W.; Thompson, Arthur D.; Wirth, John W.

2005-01-01

In January of 2004, NASA's twin Mars rovers, Spirit and Opportunity, successfully landed on opposite sides of the Red Planet after a seven month Earth to Mars cruise period. Both vehicles have operated well beyond their 90 day primary mission design life requirements. The Assembly, Test, and Launch Operations (ATLO) program for these missions presented unique technical and schedule challenges to the team at the Jet Propulsion Laboratory (JPL). Among these challenges were a highly compressed schedule and late deliveries leading to extended double shift staffing, dual spacecraft operations requiring test program diversification and resource arbitration, multiple atypical test configurations for airbag/rocket landings and surface mobility testing, and verification of an exceptionally large number of separations, deployments, and mechanisms. This paper discusses the flight system test philosophies and approach, and presents lessons learned.

KSC-2009-6464

NASA Image and Video Library

2009-11-19

CAPE CANAVERAL, Fla. – This newly designed glove is one of the entries in the 2009 Astronaut Glove Challenge, part of NASA’s Centennial Challenges Program, at the Astronaut Hall of Fame near NASA’s Kennedy Space Center in Florida. The nationwide competition focused on developing improved pressure suit gloves for astronauts to use while working in space. During the challenge, inventors tested the gloves to measure dexterity and strength during operation in a glove box which simulates the vacuum of space. Centennial Challenges is NASA’s program of technology prizes for the citizen-inventor. The winning prize for the Glove Challenge is $250,000 provided by the Centennial Challenges Program. Photo credit: NASA/Kim Shiflett

Reusable Launch Vehicle Technology Program

NASA Technical Reports Server (NTRS)

Freeman, Delma C., Jr.; Talay, Theodore A.; Austin, R. Eugene

1996-01-01

Industry/NASA Reusable Launch Vehicle (RLV) Technology Program efforts are underway to design, test, and develop technologies and concepts for viable commercial launch systems that also satisfy national needs at acceptable recurring costs. Significant progress has been made in understanding the technical challenges of fully reusable launch systems and the accompanying management and operational approaches for achieving a low-cost program. This paper reviews the current status of the Reusable Launch Vehicle Technology Program including the DC-XA, X-33 and X-34 flight systems and associated technology programs. It addresses the specific technologies being tested that address the technical and operability challenges of reusable launch systems including reusable cryogenic propellant tanks, composite structures, thermal protection systems, improved propulsion, and subsystem operability enhancements. The recently concluded DC-XA test program demonstrated some of these technologies in ground and flight tests. Contracts were awarded recently for both the X-33 and X-34 flight demonstrator systems. The Orbital Sciences Corporation X-34 flight test vehicle will demonstrate an air-launched reusable vehicle capable of flight to speeds of Mach 8. The Lockheed-Martin X-33 flight test vehicle will expand the test envelope for critical technologies to flight speeds of Mach 15. A propulsion program to test the X-33 linear aerospike rocket engine using a NASA SR-71 high speed aircraft as a test bed is also discussed. The paper also describes the management and operational approaches that address the challenge of new cost-effective, reusable launch vehicle systems.

A new model for low-dose food challenge in children with allergy to milk or egg.

PubMed

Devenney, Irene; Norrman, Gunilla; Oldaeus, Göran; Strömberg, Leif; Fälth-Magnusson, Karin

2006-09-01

Atopic eczema and food allergy are common in early childhood. Children seem to gradually develop tolerance to milk and egg, and it is a relief for families when their child can tolerate small amounts of these basic foods, even if larger doses may still cause symptoms. To develop a model for low-dose oral food challenge, facilitating re-/introduction of milk or egg. In 39 children sensitized to milk and/or egg, we performed 52 challenges using a new standardized model for low-dose oral food challenge. The recipes were validated for blinding with sensorial tests. Four children challenged to milk had a positive challenge outcome. There were no significant differences with respect to family history, associated atopic manifestations, nutritional supply, eczema severity, or skin-prick test compared with the non-reacting children, but total and specific IgE values were significantly higher. All but two of the non-reacting children were able to introduce milk and egg into their diet without problems. We report recipes and a protocol to be used for standardized open and double-blind placebo-controlled low-dose food challenge in young children, enabling the introduction of small amounts of egg and milk into the diet during tolerance development.

Stability Testing of Herbal Drugs: Challenges, Regulatory Compliance and Perspectives.

PubMed

Bansal, Gulshan; Suthar, Nancy; Kaur, Jasmeen; Jain, Astha

2016-07-01

Stability testing is an important component of herbal drugs and products (HDPs) development process. Drugs regulatory agencies across the globe have recommended guidelines for the conduct of stability studies on HDPs, which require that stability data should be included in the product registration dossier. From the scientific viewpoint, numerous chemical constituents in an herbal drug are liable to varied chemical reactions under the influence of different conditions during its shelf life. These reactions can lead to altered chemical composition of HDP and consequently altered therapeutic profile. Many reports on stability testing of HDPs have appeared in literature since the last 10 years. A review of these reports reveals that there is wide variability in temperature (-80 to 100 °C), humidity (0-100%) and duration (a few hours-36 months) for stability assessment of HDPs. Of these, only 1% studies are conducted in compliance with the regulatory guidelines for stability testing. The present review is aimed at compiling all stability testing reports, understanding key challenges in stability testing of HDPs and suggesting possible solutions for these. The key challenges are classified as chemical complexity and biochemical composition variability in raw material, selection of marker(s) and influences of enzymes. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

A computerized test battery for the assessment of cardiovascular reactivity.

PubMed

Debski, T T; Kamarck, T W; Jennings, J R; Young, L W; Eddy, M J; Zhang, Y X

1991-01-01

Recent evidence has suggested a possible relationship between the tendency to exhibit excessive cardiovascular reactions during psychological challenge and the risk of cardiovascular disease. Valid techniques for reliably assessing such reactions are, however, minimally available. A test battery for the assessment of cardiovascular reactivity to experimental challenge is currently being developed at the University of Pittsburgh in conjunction with the University of Miami and Duke University. An IBM-AT compatible microcomputer is being used for the concurrent collection of physiological data and presentation of the laboratory stressors. Digitized cardiovascular data being collected include EKG, Impedance Cardiogram (ICG), phonocardiogram, and a peripheral pulse wave measure. Blood pressure readings are also being collected and stored on disk. The computer presents three challenging video games, each designed to elicit cardiovascular reactions. Processing programs are being used and developed for the standardized scoring of the digitized signals. To assist in epidemiological research a mobile testing unit has been assembled for the easy administration of the test battery in varying geographical locations. The test battery being developed will increase the feasibility of epidemiological and clinical assessment of stress-induced cardiovascular responses which may substantiate a link between reactivity and cardiovascular disease.

Laboratory considerations of United States Pharmacopeia Chapter <71> sterility tests and its application to pharmaceutical compounding.

PubMed

Hyde, Tiffany D

2014-01-01

The purpose of this article is to describe United States Pharmacopeia Chapter <71> Sterility Tests from the perspective of Current Good Manufacturing Practices in order to aid compounding pharmacists in understanding the details and complexities that are required. Compounding pharmacists face a unique challenge in the industry today, with their compounding practice and the U.S. Food and Drug Administration trying to impose Current Good Manufacturing Practices guidelines. Naturally, this becomes a challenge to contract testing laboratories as well, as they are caught between the testing for non-Current Good Manufacturing Practices compounding standards and Current Good Manufacturing Practices manufacturing. It is important that the compounding pharmacist and their partner testing laboratory work closely together to ensure appropriate requirements are being met.

Staff in Services for People with Intellectual Disabilities: The Impact of Stress on Attributions of Challenging Behaviour

ERIC Educational Resources Information Center

Rose, D.; Rose, J.

2005-01-01

Background: There is a lack of a conceptual framework as to how stress and attribution variables interact and influence staff behaviour in response to challenging behaviour. To address this, a model is tested examining the impact of stress on attributions of challenging behaviour within Weiner's model of helping. Method: A total of 107 staff…

Oral glutamine challenge and magnetic resonance spectroscopy in three patients with congenital portosystemic shunts.

PubMed

Ortiz, María; Córdoba, Juan; Alonso, Juli; Rovira, Alex; Quiroga, Sergi; Jacas, Carlos; Esteban, Rafael; Guardia, Jaume

2004-03-01

Congenital portosystemic shunts are rare abnormalities of liver vasculature that can cause neurological symptoms, probably secondarily to the effects of the metabolism of ammonia in the brain. Our aim was to investigate the relationship between capillary blood ammonia after oral glutamine challenge and magnetic resonance spectroscopy in three patients with congenital portosystemic shunts. Neuropsychological tests, oral glutamine challenge and magnetic resonance spectroscopy were performed at baseline and after 6 months of follow-up in three patients with congenital portosystemic shunts. The results were compared to those obtained in a group of six cirrhotic patients with prior episodes of hepatic encephalopathy and healthy controls. Patients with congenital portosystemic shunts exhibited abnormalities of neuropsychological tests, magnetic resonance spectroscopy and a response to the oral glutamine challenge similar to those observed in patients with cirrhosis. The intensity of the rise of brain glutamine was correlated to the area under the curve of ammonia after the oral glutamine challenge (R=0.72). Neurological manifestations of patients with congenital portosystemic shunts are mediated through similar mechanisms that are involved in the pathogenesis of hepatic encephalopathy. The area under the curve appears to be the better parameter that defines the response to the oral glutamine challenge.

Effectiveness of touch and feel (TAF) technique on first aid measures for visually challenged.

PubMed

Mary, Helen; Sasikalaz, D; Venkatesan, Latha

2013-01-01

There is a common perception that a blind person cannot even help his own self. In order to challenge that view, a workshop for visually-impaired people to develop the skills to be independent and productive members of society was conceived. An experimental study was conducted at National Institute of Visually Handicapped, Chennai with the objective to assess the effectiveness of Touch and Feel (TAF) technique on first aid measures for the visually challenged. Total 25 visually challenged people were selected by non-probability purposive sampling technique and data was collected using demographic variable and structured knowledge questionnaire. The score obtained was categorised into three levels: inadequate (0-8), moderately adequate (8 - 17), adequate (17 -25). The study revealed that most of the visually challenged (40%) had inadequate knowledge, and 56 percent had moderately adequate and only few (4%) had adequate knowledge in the pre-test, whereas most (68%) of them had adequate knowledge in the post-test which is statistically significant at p < 0.000 with t-value 6.779. This proves that TAF technique was effective for the visually challenged. There was no association between the demographic variables and their level of knowledge regarding first aid.

Limited accessibility to HIV services for persons with disabilities living with HIV in Ghana, Uganda and Zambia.

PubMed

Tun, Waimar; Okal, Jerry; Schenk, Katie; Esantsi, Selina; Mutale, Felix; Kyeremaa, Rita Kusi; Ngirabakunzi, Edson; Asiah, Hilary; McClain-Nhlapo, Charlotte; Moono, Grimond

2016-01-01

Knowledge about experiences in accessing HIV services among persons with disabilities who are living with HIV in sub-Saharan Africa is limited. Although HIV transmission among persons with disabilities in Africa is increasingly acknowledged, there is a need to bring to life the experiences and voices from persons with disabilities living with HIV to raise awareness of programme implementers and policy makers about their barriers in accessing HIV services. This paper explores how the barriers faced by persons with disabilities living with HIV impede their ability to access HIV-related services and manage their disease. We conducted focus group discussions with 76 persons (41 females; 35 males) with physical, visual and/or hearing impairments who were living with HIV in Ghana, Uganda and Zambia (2012-2013). We explored challenges and facilitators at different levels (individual, psychosocial and structural) of access to HIV services. Transcripts were analyzed using a framework analysis approach. Persons with disabilities living with HIV encountered a wide variety of challenges in accessing HIV services. Delays in testing for HIV were common, with most waiting until they were sick to be tested. Reasons for delayed testing included challenges in getting to the health facilities, lack of information about HIV and testing, and HIV- and disability-related stigma. Barriers to HIV-related services, including care and treatment, at health facilities included lack of disability-friendly educational materials and sign interpreters, stigmatizing treatment by providers and other patients, lack of skills to provide tailored services to persons with disabilities living with HIV and physically inaccessible infrastructure, all of which make it extremely difficult for persons with disabilities to initiate and adhere to HIV treatment. Accessibility challenges were greater for women than men due to gender-related roles. Challenges were similar across the three countries. Favourable experiences in accessing HIV services were reported in Uganda and Zambia, where disability-tailored services were offered by non-governmental organizations and government facilities (Uganda only). Persons with disabilities living with HIV encounter many challenges in accessing HIV testing and continued care and treatment services. Changes are needed at every level to ensure accessibility of HIV services for persons with disabilities.

The diagnostic value of component-resolved diagnostics in peanut allergy in children attending a Regional Paediatric Allergology Clinic.

PubMed

van Veen, Leonieke N; Heron, Michiel; Batstra, Manou; van Haard, Paul M M; de Groot, Hans

2016-06-02

To date, diagnosing food allergies in children still presents a diagnostic dilemma, leading to uncertainty concerning the definite diagnosis of peanut allergy, as well as to the need for strict diets and the potential need for adrenalin auto-injectors. This uncertainty in particular is thought to contribute to a lower quality of life. In the diagnostic process double-blind food challenges are considered the gold standard, but they are time-consuming as well as potentially hazardous. Other diagnostic tests have been extensively studied and among these component-resolved diagnostics appeared to present a promising alternative: Ara h2, a peanut storage protein in previous studies showed to have a significant predictive value. Sixty-two out of 72 children, with suspected peanut allergy were analyzed using serum specific IgE and/or skin prick tests and specific IgE to several components of peanut (Ara h 1, 2, 3, 6, 8, 9). Subsequently, double-blind food challenges were performed. The correlation between the various diagnostic tests and the overall outcome of the double-blind food challenges were studied, in particular the severity of the reaction and the eliciting dose. The double-blind provocation with peanut was positive in 33 children (53 %). There was no relationship between the eliciting dose and the severity of the reaction. A statistically significant relationship was found between the skin prick test, specific IgE directed to peanut, Ara h 1, Ara h 2 or Ara h 6, and the outcome of the food challenge test, in terms of positive or negative (P < .001). However, we did not find any relationship between sensitisation to peanut extract or the different allergen components and the severity of the reaction or the eliciting dose. There was no correlation between IgE directed to Ara h 3, Ara h 8, Ara h 9 and the clinical outcome of the food challenge. This study shows that component-resolved diagnostics is not superior to specific IgE to peanut extract or to skin prick testing. At present, it cannot replace double-blind placebo-controlled food challenges for determination of the eliciting dose or the severity of the peanut allergy in our patient group.

Challenges for achieving safe and effective radical cure of Plasmodium vivax: a round table discussion of the APMEN Vivax Working Group.

PubMed

Thriemer, Kamala; Ley, Benedikt; Bobogare, Albino; Dysoley, Lek; Alam, Mohammad Shafiul; Pasaribu, Ayodhia P; Sattabongkot, Jetsumon; Jambert, Elodie; Domingo, Gonzalo J; Commons, Robert; Auburn, Sarah; Marfurt, Jutta; Devine, Angela; Aktaruzzaman, Mohammad M; Sohel, Nayeem; Namgay, Rinzin; Drukpa, Tobgyel; Sharma, Surender Nath; Sarawati, Elvieda; Samad, Iriani; Theodora, Minerva; Nambanya, Simone; Ounekham, Sonesay; Mudin, Rose Nanti Binti; Da Thakur, Garib; Makita, Leo Sora; Deray, Raffy; Lee, Sang-Eun; Boaz, Leonard; Danansuriya, Manjula N; Mudiyanselage, Santha D; Chinanonwait, Nipon; Kitchakarn, Suravadee; Nausien, Johnny; Naket, Esau; Duc, Thang Ngo; Do Manh, Ha; Hong, Young S; Cheng, Qin; Richards, Jack S; Kusriastuti, Rita; Satyagraha, Ari; Noviyanti, Rintis; Ding, Xavier C; Khan, Wasif Ali; Swe Phru, Ching; Guoding, Zhu; Qi, Gao; Kaneko, Akira; Miotto, Olivo; Nguitragool, Wang; Roobsoong, Wanlapa; Battle, Katherine; Howes, Rosalind E; Roca-Feltrer, Arantxa; Duparc, Stephan; Bhowmick, Ipsita Pal; Kenangalem, Enny; Bibit, Jo-Anne; Barry, Alyssa; Sintasath, David; Abeyasinghe, Rabindra; Sibley, Carol H; McCarthy, James; von Seidlein, Lorenz; Baird, J Kevin; Price, Ric N

2017-04-05

The delivery of safe and effective radical cure for Plasmodium vivax is one of the greatest challenges for achieving malaria elimination from the Asia-Pacific by 2030. During the annual meeting of the Asia Pacific Malaria Elimination Network Vivax Working Group in October 2016, a round table discussion was held to discuss the programmatic issues hindering the widespread use of primaquine (PQ) radical cure. Participants included 73 representatives from 16 partner countries and 33 institutional partners and other research institutes. In this meeting report, the key discussion points are presented and grouped into five themes: (i) current barriers for glucose-6-phosphate deficiency (G6PD) testing prior to PQ radical cure, (ii) necessary properties of G6PD tests for wide scale deployment, (iii) the promotion of G6PD testing, (iv) improving adherence to PQ regimens and (v) the challenges for future tafenoquine (TQ) roll out. Robust point of care (PoC) G6PD tests are needed, which are suitable and cost-effective for clinical settings with limited infrastructure. An affordable and competitive test price is needed, accompanied by sustainable funding for the product with appropriate training of healthcare staff, and robust quality control and assurance processes. In the absence of quantitative PoC G6PD tests, G6PD status can be gauged with qualitative diagnostics, however none of the available tests is currently sensitive enough to guide TQ treatment. TQ introduction will require overcoming additional challenges including the management of severely and intermediately G6PD deficient individuals. Robust strategies are needed to ensure that effective treatment practices can be deployed widely, and these should ensure that the caveats are outweighed by  the benefits of radical cure for both the patients and the community. Widespread access to quality controlled G6PD testing will be critical.

Top ten challenges when interfacing a laboratory information system to an electronic health record: Experience at a large academic medical center.

PubMed

Petrides, Athena K; Tanasijevic, Milenko J; Goonan, Ellen M; Landman, Adam B; Kantartjis, Michalis; Bates, David W; Melanson, Stacy E F

2017-10-01

Recent U.S. government regulations incentivize implementation of an electronic health record (EHR) with computerized order entry and structured results display. Many institutions have also chosen to interface their EHR to their laboratory information system (LIS). Reported long-term benefits include increased efficiency and improved quality and safety. In order to successfully implement an interfaced EHR-LIS, institutions must plan years in advance and anticipate the impact of an integrated system. It can be challenging to fully understand the technical, workflow and resource aspects and adequately prepare for a potentially protracted system implementation and the subsequent stabilization. We describe the top ten challenges that we encountered in our clinical laboratories following the implementation of an interfaced EHR-LIS and offer suggestions on how to overcome these challenges. This study was performed at a 777-bed, tertiary care center which recently implemented an interfaced EHR-LIS. Challenges were recorded during EHR-LIS implementation and stabilization and the authors describe the top ten. Our top ten challenges were selection and harmonization of test codes, detailed training for providers on test ordering, communication with EHR provider champions during the build process, fluid orders and collections, supporting specialized workflows, sufficient reports and metrics, increased volume of inpatient venipunctures, adequate resources during stabilization, unanticipated changes to laboratory workflow and ordering specimens for anatomic pathology. A few suggestions to overcome these challenges include regular meetings with clinical champions, advanced considerations of reports and metrics that will be needed, adequate training of laboratory staff on new workflows in the EHR and defining all tests including anatomic pathology in the LIS. EHR-LIS implementations have many challenges requiring institutions to adapt and develop new infrastructures. This article should be helpful to other institutions facing or undergoing a similar endeavor. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparison of contamination rates between preserved and preservative-free fluoroquinolone eyedrops.

PubMed

Kim, Mo Sae; Kim, Hong Kyun; Kim, Joon Mo; Choi, Chul Young

2013-03-01

To evaluate the antimicrobial effectiveness of preservative-free fluoroquinolone products compared with benzalkonium chloride containing fluoroquinolones using the challenge test provided by the United States Pharmacopeia (USP) and the in-use test. 1. Challenge test: to compare the growth of microorganisms between different fluoroquinolone preparations, four test organisms, including Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans, and Aspergillus niger were chosen among five microorganisms listed by USP 2004. The inoculated products were sampled for microbial survivors at days 7, 14, and 28 following initial inoculation at room temperature. The number of surviving organisms were calculated as a Log10 reduction from the original inocula. 2. In-use test: a total of 100 bottles were collected after instillation of preservative-free fluoroquinolone eyedrops in volunteer patients after 1 week of use. The remaining fluid and tips of the bottles were cultured. Colonies on the plates were counted at the end of the incubation period. All microorganisms were identified by Gram staining and biochemical assays. 1. Challenge test: preservative-free gatifloxacin and levofloxacin demonstrated a lower log reduction against A. niger than preserved fluoroquinolones and preservative-free moxifloxacin at all time points. 2. In-use test: There was no contamination identified on plates inoculated by preservative-free quinolone bottles after 1 week of use in this study. Physicians should be aware of the lower antifungal preservative effectiveness of some preservative-free fluoroquinolone preparations than preserved ones.

Jensen's Last Stand.

ERIC Educational Resources Information Center

Gould, Stephen Jay

1980-01-01

Challenges Jensen's arguments (set forth in the book "Bias in Mental Testing") that intelligence tests are scientifically unbiased and that IQ and other mental tests measure something called "intelligence" by refuting Jensen's reading of the psychometric research literature. (EF)

The Tests and the "Brightest." How Fair Are the College Boards?

ERIC Educational Resources Information Center

Fallows, James

1980-01-01

The role of standardized tests in American education is being challenged as many feel that they are unfair and actually reinforce and legitimize existing inequalities. The Educational Testing Service, the SAT, meritocracy, test coaching, and economic bias are discussed. (MLW)

40 CFR 141.719 - Additional filtration toolbox components.

Code of Federal Regulations, 2013 CFR

2013-07-01

... establish a quality control release value (QCRV) for a non-destructive performance test that demonstrates... test; and Cp = the filtrate concentration measured during the challenge test. Equivalent units must be... or the applicability of the non-destructive performance test and associated QCRV, additional...

40 CFR 141.719 - Additional filtration toolbox components.

Code of Federal Regulations, 2014 CFR

2014-07-01

... establish a quality control release value (QCRV) for a non-destructive performance test that demonstrates... test; and Cp = the filtrate concentration measured during the challenge test. Equivalent units must be... or the applicability of the non-destructive performance test and associated QCRV, additional...

40 CFR 141.719 - Additional filtration toolbox components.

Code of Federal Regulations, 2012 CFR

2012-07-01

... establish a quality control release value (QCRV) for a non-destructive performance test that demonstrates... test; and Cp = the filtrate concentration measured during the challenge test. Equivalent units must be... or the applicability of the non-destructive performance test and associated QCRV, additional...

Truth in Testing: Arguments Examined.

ERIC Educational Resources Information Center

Burns, Daniel J.

1981-01-01

Costs and benefits of New York's Truth-in-Testing law are reviewed and related to constitutional issues and fairness to test-makers as well as test-takers. Besides matters of cost and test question availability, challenges to the legislation also involve issues of due process, equal protection, and infringement of existing copyright laws. (MSE)

Word Families and Frequency Bands in Vocabulary Tests: Challenging Conventions

ERIC Educational Resources Information Center

Kremmel, Benjamin

2016-01-01

Vocabulary test development often appears to be based on the design principles of previous tests, without questioning or empirically examining the assumptions underlying those principles. Given the current proliferation of vocabulary tests, it seems timely for the field of vocabulary testing to problematize some of those traditionalised…

The Drug Testing of College Athletes.

ERIC Educational Resources Information Center

Leeson, Todd A.

1989-01-01

The paper examines the state of drug testing of college athletes and the challenges faced by the National Collegiate Athletic Association and university testing programs. State and federal litigation on drug testing is reviewed along with other issues in the drug-testing debate. Practical recommendations are offered to educational institutions.…

Preventive effect of a high fluoride toothpaste and arginine-carbonate toothpaste on dentinal tubules exposure followed by acid challenge: a dentine permeability evaluation

PubMed Central

2014-01-01

Background Considering the current high use of high fluoride toothpastes, the aim of the study was to quantify alterations in the root dentine permeability submitted to treatment with a high fluoride toothpaste and 8% arginine, calcium carbonate, sodium monofluorophosphate toothpaste as a preventive treatment for dentinal tubules exposure followed by acid challenge. Methods Thirty-third molars were sectioned below the cementoenamel. The root segments were connected to a hydraulic pressure apparatus to measure dentine permeability after the following sequential steps (n = 10 per group): I) Baseline; II) treatment with phosphoric acid for 30 s (maximum permeability); III) Toothbrushing (1 min) according to the experimental groups (G1- control; G2- 5000 ppm fluoride toothpaste; G3- 8% arginine-calcium carbonate toothpaste); IV) acid challenge for 5 min (orange juice). The data were converted into percentage, considering stage II as 100%. Results The results have shown a statistically significant decreasing on dentine permeability after treatment with toothpaste (Friedman test and Dunn’s post hoc test). Comparison among groups demonstrated a high increasing on dentine permeability when acid challenge was performed after toothbrushing with distilled water (control group) (Kruskal-Wallis and Dunn’s post hoc test). Conclusion The toothpaste treatment may provide sufficient resistance on dentine surface, preventing dentinal tubules exposure after acid challenge. PMID:24958423

D3R Grand Challenge 2: blind prediction of protein-ligand poses, affinity rankings, and relative binding free energies

NASA Astrophysics Data System (ADS)

Gaieb, Zied; Liu, Shuai; Gathiaka, Symon; Chiu, Michael; Yang, Huanwang; Shao, Chenghua; Feher, Victoria A.; Walters, W. Patrick; Kuhn, Bernd; Rudolph, Markus G.; Burley, Stephen K.; Gilson, Michael K.; Amaro, Rommie E.

2018-01-01

The Drug Design Data Resource (D3R) ran Grand Challenge 2 (GC2) from September 2016 through February 2017. This challenge was based on a dataset of structures and affinities for the nuclear receptor farnesoid X receptor (FXR), contributed by F. Hoffmann-La Roche. The dataset contained 102 IC50 values, spanning six orders of magnitude, and 36 high-resolution co-crystal structures with representatives of four major ligand classes. Strong global participation was evident, with 49 participants submitting 262 prediction submission packages in total. Procedurally, GC2 mimicked Grand Challenge 2015 (GC2015), with a Stage 1 subchallenge testing ligand pose prediction methods and ranking and scoring methods, and a Stage 2 subchallenge testing only ligand ranking and scoring methods after the release of all blinded co-crystal structures. Two smaller curated sets of 18 and 15 ligands were developed to test alchemical free energy methods. This overview summarizes all aspects of GC2, including the dataset details, challenge procedures, and participant results. We also consider implications for progress in the field, while highlighting methodological areas that merit continued development. Similar to GC2015, the outcome of GC2 underscores the pressing need for methods development in pose prediction, particularly for ligand scaffolds not currently represented in the Protein Data Bank (http://www.pdb.org), and in affinity ranking and scoring of bound ligands.

In vitro testing to diagnose venom allergy and monitor immunotherapy: a placebo-controlled, crossover trial.

PubMed

Brown, S G A; Haas, M A; Black, J A; Parameswaran, A; Woods, G M; Heddle, R J

2004-05-01

In people with a history of sting allergy, only prior reaction severity and older age are known to predict subsequent reaction risk. Furthermore, no diagnostic test other than a deliberate sting challenge has been found to identify people in whom venom immunotherapy (VIT) has been unsuccessful. We aimed to assess the utility of a number of in vitro tests to diagnose venom allergy and to monitor immunotherapy. During a double-blind randomized placebo-controlled crossover trial of Myrmecia pilosula ant VIT the following venom-specific tests were performed at enrolment, and at completion of treatment prior to a diagnostic sting challenge; leucocyte stimulation index (SI), IL-4 production, IgE RAST, histamine release test (HRT), leukotriene release test (LRT) and basophil activation test (BAT). Intradermal venom skin testing (VST) was also performed at trial entry. Only VST and HRT identified those at risk of sting anaphylaxis in the placebo group. Although IgE RAST, leucocyte SI and IL-4 production, LRT and BAT all correlated well with intradermal VSTs, they did not predict sting challenge outcome. After successful VIT, venom-induced leucocyte IL-4 production tended to fall, whereas IgE RAST increased and a natural decline in HRT reactivity was reversed. A confounding seasonal affect on laboratory results was suspected. The HRT warrants further assessment for diagnosis of venom allergy. Uninformative performance of the commercially available LRT and BAT tests may be due to pre-incubation with IL-3. None of the tests evaluated appear to be reliable markers of successful VIT.

Direct to consumer genetic testing-law and policy concerns in Ireland.

PubMed

de Paor, Aisling

2017-11-25

With rapid scientific and technological advances, the past few years has witnessed the emergence of a new genetic era and a growing understanding of the genetic make-up of human beings. These advances have propelled the introduction of companies offering direct to consumer (DTC) genetic testing, which facilitates the direct provision of such tests to consumers, (for example, via the internet). Although DTC genetic testing offers benefits by enhancing consumer accessibility to such technology, promoting proactive healthcare and increasing genetic awareness, it presents a myriad of challenges, from an ethical, legal and regulatory perspective. As DTC genetic testing usually eliminates the need for a medical professional in accessing genetic tests, this lack of professional guidance and counselling may result in misinterpretation and confusion regarding results. In addition, an evident concern relates to the scientific validity and quality of these tests. A further problem arising is the lack or inadequacy of regulation in this field. Despite the increasing accessibility of DTC genetic testing, this legislative vacuum is apparent in Ireland, where there is no concrete legislation. This article explores the main ethical, legal and regulatory issues arising with the advent of rapid advances in DTC genetic testing in Ireland. Further, with inevitable future advances in genetic science, as well as increasing internet accessibility, the challenges presented are likely to become more amplified. In consideration of the ethical and legal challenges, this paper highlights the regulation of DTC genetic testing as a growing concern in Ireland, recognising its importance to both the scientific community as well as in respect of enhancing consumer confidence in such technologies.

Quantitative genetics of taura syndrome resistance in pacific white shrimp (penaeus vannamei): a cure model approach

PubMed Central

2011-01-01

Background In aquaculture breeding, resistance against infectious diseases is commonly assessed as time until death under exposure to a pathogen. For some diseases, a fraction of the individuals may appear as "cured" (non-susceptible), and the resulting survival time may thus be a result of two confounded underlying traits, i.e., endurance (individual hazard) and susceptibility (whether at risk or not), which may be accounted for by fitting a cure survival model. We applied a cure model to survival data of Pacific white shrimp (Penaeus vannamei) challenged with the Taura syndrome virus, which is one of the major pathogens of Panaeid shrimp species. Methods In total, 15,261 individuals of 513 full-sib families from three generations were challenge-tested in 21 separate tests (tanks). All challenge-tests were run until mortality naturally ceased. Time-until-event data were analyzed with a mixed cure survival model using Gibbs sampling, treating susceptibility and endurance as separate genetic traits. Results Overall mortality at the end of test was 28%, while 38% of the population was considered susceptible to the disease. The estimated underlying heritability was high for susceptibility (0.41 ± 0.07), but low for endurance (0.07 ± 0.03). Furthermore, endurance and susceptibility were distinct genetic traits (rg = 0.22 ± 0.25). Estimated breeding values for endurance and susceptibility were only moderately correlated (0.50), while estimated breeding values from classical models for analysis of challenge-test survival (ignoring the cured fraction) were closely correlated with estimated breeding values for susceptibility, but less correlated with estimated breeding values for endurance. Conclusions For Taura syndrome resistance, endurance and susceptibility are apparently distinct genetic traits. However, genetic evaluation of susceptibility based on the cure model showed clear associations with standard genetic evaluations that ignore the cure fraction for these data. Using the current testing design, genetic variation in observed survival time and absolute survival at the end of test were most likely dominated by genetic variation in susceptibility. If the aim is to reduce susceptibility, earlier termination of the challenge-test or back-truncation of the follow-up period should be avoided, as this may shift focus of selection towards endurance rather than susceptibility. PMID:21418636

Passive Thermal Control Challenges for Future Exploration Missions

NASA Technical Reports Server (NTRS)

Rickman, Steven L.

2004-01-01

This slide presentation reviews the importance of developing passive thermal control for the future exploration missions envisioned in President Bush's call for human exploration of the Moon and Mars. Included in the presentation is a review of the conditions that make the thermal control very challenging on the Moon and Mars. With the future miniaturization of electronics components, power density and the associated challenges of electronics heat dissipation will provide new challenges. There is a challenge for improvement in modeling and analysis of thermal control systems, and for improved facilities to support testing of thermal-vacuum systems.

Testing Methods for Challenging the National Wetland Plant List: Using Tsuga canadensis (L.) Carr. (Eastern Hemlock) as a Case Study

DTIC Science & Technology

2017-07-01

ESRI (Nature Conservancy and Environmental Systems Research Institute). 1994. Field Methods . In Field Methods for Vegetation Mapping: United States...ER D C/ CR RE L TR -1 7- 9 Wetlands Regulatory Assistance Program (WRAP) Testing Methods for Challenging the National Wetland Plant List...Robert W. Lichvar and Jennifer J. Goulet July 2017 Approved for public release; distribution is unlimited. The U.S. Army Engineer Research

[Occupational allergic "march". Rapid evolution of contact dermatitis to ammonium persulfate into airborne contact dermatitis with rhinitis and asthma in a hairdresser].

PubMed

Poltronieri, Anna; Patrini, L; Pigatto, P; Riboldi, L; Marsili, Chiara; Previdi, M; Margonari, M; Marraccini, P

2010-01-01

Hairdressers are exposed to irritants and allergenic compounds that may cause contact dermatitis, rhinitis and asthma. In this paper we describe the case of a female, age 33 years, who developed contact dermatitis after 10 years of exposure to ammonium persulfate. After 7 months of progressively extensive and persistent skin lesions, respiratory symptoms appeared that were related to the occupational exposure (on-off test). SIDAPA and specific occupational patch test for hairdressers and occupational challenge with ammonium persulfate were performed. Clinical parameters of inflammation, ECP (eosinophil cationic protein) and exhaled nitric oxide (FeNO) were detected before and after the specific bronchial challenge. The patch test was positive to ammonium persulfate (++), and bronchial challenge for ammonium persulfate showed a significant late response (FEV1 decrease--33%). Both FeNO and ECP showed a significant increase after 24 hours. Dermatitis, urticaria and angioedema occurred on the uncovered skin due to airborne contact. Topic steroids and anti-histaminic drugs resolved the clinical symptoms. Bronchial challenge is, in fact, considered to be the gold standard for the diagnosis of occupational asthma, although new inflammatory parameters can contribute to the diagnosis and can be useful for monitoring after a specific inhalation test with occupational agents. The described case summarizes the evolution from contact dermatitis to inhalation allergy, suggesting the occurrence of an allergic "march" for occupational allergy.

Secretory IgA as an indicator of oro-pharyngeal foot-and-mouth disease virus replication and as a tool for post vaccination surveillance.

PubMed

Parida, Satya; Anderson, John; Cox, Sarah J; Barnett, Paul V; Paton, David J

2006-02-20

A serotype-specific ELISA was developed to detect foot-and-mouth disease virus (FMDV) specific IgA antibody in the saliva of cattle, and the method was evaluated for its feasibility in detecting serotype O FMDV carrier animals, particularly amongst vaccinated cattle that had subsequently become sub-clinically infected. For this purpose, saliva samples were collected from naïve cattle (n = 173), FMDV challenged cattle (n = 10), FMDV vaccinated cattle (n = 40) and FMDV vaccinated-and-challenged cattle (n = 40). A subset of 29 cattle was sampled for 105-168 days after challenge. The FMDV infection status of each of the cattle was determined by virus isolation and RT-PCR tests on oesophago-pharyngeal fluids and the ability of the IgA test to detect viral infection and persistence was compared to an ELISA for the detection of serum antibodies against the 3ABC non-structural proteins of FMDV. Eleven out of twelve vaccinated cattle that were shown to be persistently infected with FMDV up to or beyond 28 days post challenge, were also detected by the IgA test on saliva. With some modification and further validation, this test could be useful in post-vaccination surveillance to help confirm the absence of sub-clinical infection in order to regain the FMD-free status of a region or country.

The 'think test': a further technique to elicit hyperventilation.

PubMed Central

Nixon, P G; Freeman, L J

1988-01-01

Hyperventilation can undermine cardiovascular homeostasis by generating autonomic imbalance, sympathetic dominance, hypokalaemia, and intracellular alkalosis with calcium ion shifts. The role of hyperventilation in episodic disorders such as arrhythmia and coronary vasospasm can be difficult to identify if the patient does not present in an attack and so a provocation challenge is required. Today, the standard challenge is the forced hyperventilation provocation test (FHPT). A capnograph enables the resting end-tidal PCO2 to be compared with the level 3 min after the period of overbreathing. We report the use of a patient-specific challenge. After the FHPT, the subject is invited to close his eyes and think about the circumstances of an attack, feelings and sensations experienced (breathing is not mentioned) or topics that were seen to disturb the rhythm of breathing when the medical history was taken. A fall of end-tidal PCO2 of 10 mmHg or more lasting at least one minute was taken as a positive response. Out of 57 patients with cardiovascular symptoms suggesting a hypocapnic influence, resting hypocapnia (end-tidal PCO2 = 30 mmHg) was present in 3 (5%). Of the remaining 54, the FHPT was positive in 16 (30%) and the 'think test' in 33 (61%). This suggests that patient-specific stimulation has advantages over an unspecific challenge in testing for episodic hypocapnia. PMID:3133476

Methodological strategies in using home sleep apnea testing in research and practice.

PubMed

Miller, Jennifer N; Schulz, Paula; Pozehl, Bunny; Fiedler, Douglas; Fial, Alissa; Berger, Ann M

2017-11-14

Home sleep apnea testing (HSAT) has increased due to improvements in technology, accessibility, and changes in third party reimbursement requirements. Research studies using HSAT have not consistently reported procedures and methodological challenges. This paper had two objectives: (1) summarize the literature on use of HSAT in research of adults and (2) identify methodological strategies to use in research and practice to standardize HSAT procedures and information. Search strategy included studies of participants undergoing sleep testing for OSA using HSAT. MEDLINE via PubMed, CINAHL, and Embase with the following search terms: "polysomnography," "home," "level III," "obstructive sleep apnea," and "out of center testing." Research articles that met inclusion criteria (n = 34) inconsistently reported methods and methodological challenges in terms of: (a) participant sampling; (b) instrumentation issues; (c) clinical variables; (d) data processing; and (e) patient acceptability. Ten methodological strategies were identified for adoption when using HSAT in research and practice. Future studies need to address the methodological challenges summarized in this paper as well as identify and report consistent HSAT procedures and information.

Allergenicity and safety of recombinant human C1 esterase inhibitor in patients with allergy to rabbit or cow's milk.

PubMed

van den Elzen, Mignon T; van Os-Medendorp, Harmieke; Röckmann-Helmbach, Heike; van Hoffen, Els; Lebens, Ans F M; van Doorn, Helma; Klemans, Rob J B; Bruijnzeel-Koomen, Carla A F M; Hack, C Erik; Kaufman, Leonard; Relan, Anurag; Knulst, André C

2016-08-01

Recombinant human C1 inhibitor (rhC1INH) for on-demand treatment of hereditary angioedema is purified from milk of transgenic rabbits. It contains low amounts (<0.002%) of host-related impurities, which could trigger hypersensitivity reactions in patients with rabbit allergy (RA) and/or cow's milk allergy (CMA). This study is an assessment of allergenicity and safety of rhC1INH in patients with RA and/or CMA. Patients with CMA and/or RA underwent skin prick test (SPT), intracutaneous test (ICT), and, when results for both were negative, subcutaneous (SC) challenge with up to 2100U (14 mL) rhC1INH. The negative predictive value of the skin test protocol was calculated, defined as the ratio of patients without systemic symptoms of hypersensitivity following SC challenge, over the number of patients having tested negative for both the SPT and the ICT. Adverse events after exposure to rhC1INH were recorded. Twenty-six patients with RA and/or CMA were enrolled. Twenty-four had negative SPT and ICT results for rhC1INH, whereas 2 had negative SPT result but positive ICT result to rhC1INH (only the highest concentration). Twenty-two patients with negative SPT and ICT results underwent SC challenge. None developed allergic symptoms. Local treatment-emergent adverse events occurred in 7 patients (32%) after SC challenge. In 5 these were considered drug related. All were mild. None of the patients with negative SPT and ICT results for rhC1INH had allergic symptoms during rhC1INH challenge. The negative predictive value of the combination of SPT and ICT for the outcome of the SC challenge was 100% (95% CI, 84.6%-100%). SC administration of rhC1INH was well tolerated. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Development and validation of a real-time TaqMan assay for the detection and enumeration of Pseudomonas fluorescens ATCC 13525 used as a challenge organism in testing of food equipments.

PubMed

Saha, Ratul; Bestervelt, Lorelle L; Donofrio, Robert S

2012-02-01

Pseudomonas fluorescens ATCC 13525 is used as the challenge organism to evaluate the efficacy of the clean-in-place (CIP) process of food equipment (automatic ice-maker) as per NSF/ANSI Standard 12. Traditional culturing methodology is presently used to determine the concentration of the challenge organism, which takes 48 h to confirm the cell density. Storage of the challenge preparation in the refrigerator might alter the cell density as P. fluorescens is capable of growing at 4 °C. Also, background organism can grow on the Pseudomonas F agar (PFA) used for the recovery of P. fluorescens thus affecting the results of the test. Real-time TaqMan assay targeting the cpn60 gene was developed for the enumeration and the identification of P. fluorescens because of its specificity, accuracy, and shorter turnaround time. The TaqMan primer-probe pair developed using the Allele ID® 7.0 probe design software was highly specific and sensitive for the target organism. The sensitivity of the assay was 10 colony forming units (CFU)/mL. The assay was also successful in determining the concentration of the challenge preparation within 2 h. Based on these observations, TaqMan assay targeting the cpn60 gene can be efficiently used for strain level identification and enumeration of bacteria. Pseudomonas fluorescens ATCC 13525 is used as a challenge organism in the efficacy testing of clean-in-place process of food equipments. Currently, culturing technique is used for its identification and estimation, which is not only time-consuming but also prone to error. Real-time TaqMan assay is more specific, sensitive, and accurate along with a shorter turnaround time compared to culturing techniques, thereby increasing the overall quality of the testing methodology to evaluate the clean-in-place process critical for the food industry to protect public health and safety. © 2012 Institute of Food Technologists®

Workshop proceedings: challenges and opportunities in evaluating protein allergenicity across biotechnology industries.

PubMed

Stagg, Nicola J; Ghantous, Hanan N; Ladics, Gregory S; House, Robert V; Gendel, Steven M; Hastings, Kenneth L

2013-01-01

A workshop entitled "Challenges and Opportunities in Evaluating Protein Allergenicity across Biotechnology Industries" was held at the 51st Annual Meeting of the Society of Toxicology (SOT) in San Francisco, California. The workshop was sponsored by the Biotechnology Specialty Section of SOT and was designed to present the science-based approaches used in biotechnology industries to evaluate and regulate protein allergenicity. A panel of experts from industry and government highlighted the allergenicity testing requirements and research in the agricultural, pharmaceutical/biopharma, and vaccine biotechnology industries and addressed challenges and opportunities for advancing the science of protein allergenicity. The main learning from the workshop was that immunoglobulin E-mediated allergenicity of biotechnology-derived products is difficult to assess without human data. The approaches currently being used to evaluate potential for allergenicity across biotechnology industries are very different and range from bioinformatics, in vitro serology, in vivo animal testing, in vitro and in vivo functional assays, and "biosimilar" assessments (ie, biotherapeutic equivalents to innovator products). The challenge remains with regard to the different or lack of regulatory requirements for allergenicity testing across industries, but the novel approaches being used with bioinformatics and biosimilars may lead to opportunities in the future to collaborate across biotechnology industries.

Individual and Collective Protection Program

DTIC Science & Technology

2007-11-30

98 8.2.1 PREPARATION OF STOCK SUSPENSION OF MS2 COLIPHAGE ...103 8.3.1 PROCEDURE FOR ASSAYING MS2 COLIPHAGE ...CHALLENGE NUMBER OF TEST MICROORGANISMS..................106 8.4.1 METHOD FOR DETERMINATION OF CHALLENGE NUMBER OF MS2 COLIPHAGE

42 CFR 493.959 - Immunohematology.

Code of Federal Regulations, 2014 CFR

2014-10-01

... challenges per testing event a program must provide for each analyte or test procedure is five. Analyte or... Compatibility testing Antibody identification (d) Evaluation of a laboratory's analyte or test performance. HHS... program must compare the laboratory's response for each analyte with the response that reflects agreement...

42 CFR 493.959 - Immunohematology.

Code of Federal Regulations, 2013 CFR

2013-10-01

... challenges per testing event a program must provide for each analyte or test procedure is five. Analyte or... Compatibility testing Antibody identification (d) Evaluation of a laboratory's analyte or test performance. HHS... program must compare the laboratory's response for each analyte with the response that reflects agreement...

42 CFR 493.959 - Immunohematology.

Code of Federal Regulations, 2012 CFR

2012-10-01

... challenges per testing event a program must provide for each analyte or test procedure is five. Analyte or... Compatibility testing Antibody identification (d) Evaluation of a laboratory's analyte or test performance. HHS... program must compare the laboratory's response for each analyte with the response that reflects agreement...

42 CFR 493.959 - Immunohematology.

Code of Federal Regulations, 2011 CFR

2011-10-01

... challenges per testing event a program must provide for each analyte or test procedure is five. Analyte or... Compatibility testing Antibody identification (d) Evaluation of a laboratory's analyte or test performance. HHS... program must compare the laboratory's response for each analyte with the response that reflects agreement...

Overview of Propellant Delivery Systems at the NASA John C. Stennis Space Center

NASA Technical Reports Server (NTRS)

Haselmaier, L. Haynes; Field, Robert E.; Ryan, Harry M.; Dickey, Jonathan C.

2006-01-01

A wide range of rocket propulsion test work occurs at he NASA John C. Stennis Space Center (SSC) including full-scale engine test activities at test facilities A-1, A-2, B-1 and B-2 as well as combustion device research and development activities at the E-Complex (E-1, E-2. E-3 and E-4) test facilities. One of the greatest challenges associated with operating a test facility is maintaining the health of the primary propellant system and test-critical support systems. The challenge emerges due to the fact that the operating conditions of the various system components are extreme (e.g., low temperatures, high pressures) and due to the fact that many of the components and systems are unique. The purpose of this paper is to briefly describe the experience and modeling techniques that are used to operate the unique test facilities at NASA SSC that continue to support successful propulsion testing.

Truth in Testing Legislation and Private Property Concepts.

ERIC Educational Resources Information Center

Burns, Daniel J.

1981-01-01

Truth in testing laws are subject to challenge on the grounds that they invade federally protected rights and interests of the test-makers through the due process clauses of the Constitution and federal copyright protections. (Author/MLF)

Test Driven Development of Scientific Models

NASA Technical Reports Server (NTRS)

Clune, Thomas L.

2014-01-01

Test-Driven Development (TDD), a software development process that promises many advantages for developer productivity and software reliability, has become widely accepted among professional software engineers. As the name suggests, TDD practitioners alternate between writing short automated tests and producing code that passes those tests. Although this overly simplified description will undoubtedly sound prohibitively burdensome to many uninitiated developers, the advent of powerful unit-testing frameworks greatly reduces the effort required to produce and routinely execute suites of tests. By testimony, many developers find TDD to be addicting after only a few days of exposure, and find it unthinkable to return to previous practices.After a brief overview of the TDD process and my experience in applying the methodology for development activities at Goddard, I will delve more deeply into some of the challenges that are posed by numerical and scientific software as well as tools and implementation approaches that should address those challenges.

Side effects induced by the acute levodopa challenge in Parkinson's Disease and atypical parkinsonisms.

PubMed

Vasta, Rosario; Nicoletti, Alessandra; Mostile, Giovanni; Dibilio, Valeria; Sciacca, Giorgia; Contrafatto, Donatella; Cicero, Calogero Edoardo; Raciti, Loredana; Luca, Antonina; Zappia, Mario

2017-01-01

Acute levodopa challenge may be performed to predict levodopa chronic responsiveness. The aim of the study was to investigate frequency of side effects during the acute levodopa challenge in PD and atypical parkinsonisms. We enrolled 34 de novo PD patients and 29 patients affected by atypical parkinsonisms (Multiple System Atrophy, MSA, n = 10; Progressive Supranuclear Palsy, PSP, n = 12 and Corticobasal Degeneration, CBD, n = 7) who underwent an acute levodopa challenge. Side effects occurring during test were recorded. Side effects were more frequent among atypical parkinsonisms as unique group when compared to PD patients (64.3% versus 23.5%; p-value 0.002) with an adjusted OR of 4.36 (95%CI 1.40-13.5). Each atypical parkinsonisms showed almost double occurrence of side effects (MSA 90%, PSP 41.7% and CBD 57%). Side effects during acute levodopa challenge may be frequent in atypical parkinsonisms. This information could be useful in order to better prepare the patient for the test. Furthermore, it could represent a useful cue in differential diagnosis with PD.

Challenges of using Hospital Information Systems by nurses: comparing academic and non-academic hospitals.

PubMed

Ahmadian, Leila; Dorosti, Nafise; Khajouei, Reza; Gohari, Sadrieh Hajesmaeel

2017-06-01

Hospital Information Systems (HIS) are used for easy access to information, improvement of documentation and reducing errors. Nonetheless, using these systems is faced with some barriers and obstacles. This study identifies the challenges and the obstacles of using these systems in the academic and non-academic hospitals in Kerman. This is a cross-sectional study which was carried out in 2015. The statistical population in this study consisted of the nurses who had been working in the academic and non-academic hospitals in Kerman. A questionnaire consisting of two sections was used. The first section consisted of the demographic information of the participants and the second section comprised 34 questions about the challenges of HIS use. Data were analyzed by the descriptive and statistical analysis (t-test, and ANOVA) using SPSS 19 software. The most common and important challenges in the academic hospitals were about human environment factors, particularly "negative attitude of society toward using HIS". In the non-academic hospitals, the most common and important challenges were related to human factors, and among them, "no incentive to use system" was the main factor. The results of the t-test method revealed that there was a significant relationship between gender and the mean score of challenges related to the organizational environment category in the academic hospitals and between familiarity with HIS and mean score of human environment factors (p<0.05). The results of the ANOVA test also revealed that the educational degree and work experience in the healthcare environment (years) in the academic hospitals have a significant relationship with the mean score related to the hardware challenges, as well, experience with HIS has a significant relationship, with the mean score related to the human challenges (p<0.05). The most important challenges in using the information systems are the factors related to the human environment and the human factors. The results of this study can bring a good perspective to the policy makers and the managers regarding obstacles of using HISs from the nurses' perspective, so that they can solve their problems and can successfully implement these systems.

Challenges in the delivery of public HIV testing and counselling (HTC) in Douala, Cameroon: providers perspectives and implications on quality of HTC services.

PubMed

Ngangue, Patrice; Gagnon, Marie-Pierre; Bedard, Emmanuelle

2017-04-08

The Cameroon government has made HIV testing and counselling (HTC) a priority in its HIV/AIDS strategic plan. However, there is a dearth of literature on the perspectives of providers on the quality of HTC services. The aim of this study was to explore challenges in the provision of HTC services and their implications on quality of HTC services in Douala's district hospitals. Two primary data collection methods supported by the Donabedian's model of healthcare were used to explain the challenges in the provision of HTC services and their implications on quality of HTC services. This consisted of semi-structured individual interviews with 6 nurses and 16 lay counsellors and a non-participant observation of the physical environment for HTC by site. The study sites were the prevention and voluntary testing and counselling centre (PVTCC) of the six district hospitals of the city of Douala. The study reveals concerns about confidentiality and privacy during the counselling sessions due to inadequate and limited space. An absence of consent, even verbal, was reported in one PVTCC. There is no specific accredited training curriculum that leads to a formal registration as a PVTCC staff, and some lay counsellors work without training. Lay counsellors carry the burden of HIV counselling, but the majority of them work for many years without remuneration and recognition. Another quality challenge is the high workload in the district hospitals' lab, which leads to long waiting times for HIV test results, thus contributing to failure to return for results. The findings of this study highlighted some issues such as lack of adequate space and equipment for HIV testing and counselling that hinder the quality of HTC services and should challenge the health authorities of Cameroon on the need to reorganize HTC services and create a national HIV quality assurance program.

Measurement of allergen-specific IgG in serum is of limited value for the management of dogs diagnosed with cutaneous adverse food reactions.

PubMed

Hagen-Plantinga, E A; Leistra, M H G; Sinke, J D; Vroom, M W; Savelkoul, H F J; Hendriks, W H

2017-02-01

Conflicting results have been reported in the literature in terms of the usefulness of serological testing for IgG against food allergens in dogs with cutaneous adverse food reaction (CAFR). The aim of the present study was to evaluate the suitability of a commercially available IgG ELISA for identifying food allergens in dogs, by challenging dogs with specific food ingredients, selected on the basis of IgG reactivity in serum samples. A total of 24 adult dogs with CAFR were enrolled into the study and 16 healthy dogs were included as a control group. Blood samples were obtained for measurement of specific IgG antibodies against 39 commonly used pet food ingredients by ELISA. Participating owners were surveyed to obtain information on their pet's dietary history. Eleven healthy control dogs and 12 dogs with CAFR were subsequently challenged in a blinded cross-over design experiment with both positive and negative food ingredients, selected on the basis of the ELISA test results. There was substantial individual variation in ELISA test results to the various food allergens, but no significant difference in IgG reactivity comparing the CAFR and control groups. None of the control dogs developed any clinical signs of an allergic reaction during the dietary challenge study. In the CAFR group, six of 12 dogs developed clinical signs after the negative challenge, and two of nine dogs developed clinical signs after the positive challenge. It was concluded that the ELISA test for dietary allergen-specific IgG is of limited value in the management of dogs with CAFR. Copyright © 2017 Elsevier Ltd. All rights reserved.

Syphilis testing practices in the Americas.

PubMed

Trinh, Thuy T; Kamb, Mary L; Luu, Minh; Ham, D Cal; Perez, Freddy

2017-09-01

To present the findings of the Pan American Health Organization's 2014 survey on syphilis testing policies and practices in the Americas. Representatives of national/regional reference and large, lower-level laboratories from 35 member states were invited to participate. A semi-structured, electronically administered questionnaire collected data on syphilis tests, algorithms, equipment/commodities, challenges faced and basic quality assurance (QA) strategies employed (i.e. daily controls, standard operating procedures, technician training, participating in external QA programmes, on-site evaluations). The 69 participating laboratories from 30 (86%) member states included 41 (59%) national/regional reference and 28 (41%) lower-level laboratories. Common syphilis tests conducted were the rapid plasma reagin (RPR) (62% of surveyed laboratories), venereal disease research laboratory (VDRL) (54%), fluorescent treponemal antibody absorption (FTA-ABS) (41%) and Treponema pallidum haemagglutination assay (TPHA) (32%). Only three facilities reported using direct detection methods, and 28 (41% overall, 32% of lower-level facilities) used rapid tests. Most laboratories (62%) used only traditional testing algorithms (non-treponemal screening and treponemal confirmatory testing); however, 12% used only a reverse sequence algorithm (treponemal test first), and 14% employed both algorithms. Another nine (12%) laboratories conducted only one type of serologic test. Although most reference (97%) and lower-level (89%) laboratories used at least one QA strategy, only 16% reported using all five basic strategies. Commonly reported challenges were stock-outs of essential reagents or commodities (46%), limited staff training (73%) and insufficient equipment (39%). Many reference and clinical laboratories in the Americas face challenges in conducting appropriate syphilis testing and in ensuring quality of testing. © 2017 John Wiley & Sons Ltd The Pan-American Health Organization retains copyright and all other rights in the manuscript of this article as submitted for publication.

Role of specific IgE and skin-prick testing in predicting food challenge results to baked egg.

PubMed

Cortot, Catherine F; Sheehan, William J; Permaul, Perdita; Friedlander, James L; Baxi, Sachin N; Gaffin, Jonathan M; Dioun, Anahita F; Hoffman, Elaine B; Schneider, Lynda C; Phipatanakul, Wanda

2012-01-01

Previous studies suggest that children with egg allergy may be able to tolerate baked egg. Reliable predictors of a successful baked egg challenge are not well established. We examined egg white-specific IgE levels, skin-prick test (SPT) results, and age as predictors of baked egg oral food challenge (OFC) outcomes. We conducted a retrospective chart review of children, aged 2-18 years, receiving an egg white-specific IgE level, SPT, and OFC to baked egg from 2008 to 2010. Fifty-two oral baked egg challenges were conducted. Of the 52 challenges, 83% (n = 43) passed and 17% (n = 9) failed, including 2 having anaphylaxis. Median SPT wheal size was 12 mm (range, 0-35 mm) for passed challenges and 17 mm (range, 10-30 mm) for failed challenges (p = 0.091). The negative predictive value for passing the OFC was 100% (9 of 9) if SPT wheal size was <10 mm. Median egg white-specific IgE was 2.02 kU/L (range, <0.35-13.00 kU/L) for passed challenges and 1.52 kU/L (range, 0.51-6.10 kU/L) for failed challenges (p = 0.660). Receiver operating characteristic (ROC) curve analysis for SPT revealed an area under the curve (AUC) of 0.64. ROC curve analysis for egg white-specific IgE revealed an AUC of 0.63. There was no significant difference in age between patients who failed and those who passed (median = 8.8 years versus 7.0 years; p = 0.721). Based on our sample, SPT, egg white-specific IgE and age are not good predictors of passing a baked egg challenge. However, there was a trend for more predictability with SPT wheal size.

Skin prick testing and peanut-specific IgE can predict peanut challenge outcomes in preschoolchildren with peanut sensitization.

PubMed

Johannsen, H; Nolan, R; Pascoe, E M; Cuthbert, P; Noble, V; Corderoy, T; Franzmann, A; Loh, R; Prescott, S L

2011-07-01

The rise in peanut allergy is a source of considerable burden in the community. A growing number of preschoolchildren have been identified as peanut sensitized in the course of investigation of other allergic conditions. Although many have never knowingly ingested peanuts and their clinical reactivity is not known, it has been common practice to place these children on avoidance diets for many years. To determine the utility of skin prick tests (SPT) and fluorescent-enzyme immunoassays (FEIA) for identifying either peanut allergy or tolerance in preschoolchildren with peanut sensitization. Forty-nine preschoolchildren (<5 years of age) with peanut sensitization (SPT ≥ 2 mm or peanut-specific IgE ≥ 0.35 kU/L) but unknown clinical reactivity had graded open peanut challenges reaching a total of 11 g. A positive challenge was defined as an objective IgE-mediated reaction during challenge or the 2-h observation. Forty-nine percent (24/49) of children had positive challenges. An SPT of >7 mm on the day of challenge predicted a positive challenge with a sensitivity of 83% and a negative predictive value (NPV) of 84%. An FEIA of >2.0 kU/L showed a sensitivity of 79% and an NPV of 80%. Predicting challenge outcome from a combination of SPT and FEIA (SPT >7 and/or FEIA >2 is positive) increased sensitivity to 96% and NPV to 95%. At least half of preschoolchildren with peanut sensitization and no antecedent history of peanut ingestion can tolerate peanuts. A SPT<7 mm and FEIA<2 kU/L identify children most likely to tolerate peanut, with only a 5% likelihood of failing an oral challenge. This study assists clinicians considering challenges in very young peanut-sensitized children. © 2011 Blackwell Publishing Ltd.

Enhancement of a small bowel obstruction model using the gastrografin® challenge test.

PubMed

Goussous, Naeem; Eiken, Patrick W; Bannon, Michael P; Zielinski, Martin D

2013-01-01

Based on a previous published data on small bowel obstruction (SBO), a management model for predicting the need for exploration has been adopted in our institution. In our model, patients presenting with three criteria-the history of obstipation, the presence of mesenteric edema, and the lack of small bowel fecalization on computed tomography (CT)-undergo exploration. Patients with two or less features were managed nonoperatively. An alternative tool for predicting need for operative intervention is Gastrografin (GG) challenge test. We hypothesized that the GG challenge test, when used in combination with our prior model, will decrease the rate of explorations in patients not meeting the criteria for immediate operation. An approval from IRB was obtained to review patients admitted with a diagnosis of SBO from November 2010 to September 2011. All patients presenting with signs of ischemia, patients with all three model criteria defined previously, and those who had an abdominal operation within 6 weeks of diagnosis were excluded. All patients had an abdominal/pelvic CT and GG challenge at the time of diagnosis. Patients were compared to historic controls managed without the GG challenge (from July to December 2009). Successful GG challenge was defined as the presence of contrast in the colon after a follow-up film or a bowel movement. Data were presented as medians or percentages; significance was considered at p < 0.05. One hundred and twenty-five patients with a diagnosis of small bowel obstruction were identified wherein 47 % were males. Fifty-three received a GG challenge (study), and 72 did not have a GG challenge (historic). There was no difference in age (70 vs 65 years), history of prior SBO (51 vs 49 %), history of diabetes mellitus (21 vs 18 %), history of malignancy (32 vs 39 %), or cardiac disease (30 vs 39 %). Both groups had similar number of previous abdominal operations (two vs two). The presence of mesenteric edema (68 vs 75 %), the lack of small bowel fecalization (47 vs 46 %), and a history of obstipation (25 vs 24 %) were similar in both groups. Patients in the study group had a lesser rate of abdominal exploration (25 vs 42 %, p = 0.05) and fewer complications (13 vs 31 %, p = 0.02) compared to the historic control group. There was equivalent incidence of ischemic bowel (4 vs 7 %), duration of hospital stay (4 vs 7 days), duration from admission to operation (2 vs 3 days), and mortality (8 vs 6 %); 44 patients had a successful GG challenge with nine failures. There was a greater rate of exploration in patients with a failed challenge compared to those with a successful challenge (89 vs 11 %, p < 0.01). The use of the GG challenge enhanced the SBO prediction model by decreasing the need for exploration in patients not meeting the criteria for immediate operation. Patients who failed the GG challenge test were much more likely to undergo an exploration.

Radiation Challenges for Electronics in the Vision for Space Exploration

NASA Technical Reports Server (NTRS)

LaBel, Kenneth A.

2006-01-01

The slides present a brief snapshot discussing electronics and exploration-related challenges. Radiation effects have been the prime target, however, electronic parts reliability issues must also be considered. Modern electronics are designed with a 3-5 year lifetime. Upscreening does not improve reliability, merely determines inherent levels. Testing costs are driven by device complexity; they increase tester complexity, beam requirements, and facility choices. Commercial devices may improve performance, but are not cost panaceas. There is need for a more cost-effective access to high energy heavy ion facilities such as NSCL and NSRL. Costs for capable test equipment can run more than $1M for full testing.

Neonatal endocrine emergencies: a primer for the emergency physician.

PubMed

Park, Elizabeth; Pearson, Nadia M; Pillow, M Tyson; Toledo, Alexander

2014-05-01

The resuscitation principles of securing the airway and stabilizing hemodynamics remain the same in any neonatal emergency. However, stabilizing endocrine disorders may prove especially challenging. Several organ systems are affected simultaneously and the clinical presentation can be subtle. Although not all-inclusive, the implementation of newborn screening tests has significantly reduced morbidity and mortality in neonates. Implementing routine screening tests worldwide and improving the accuracy of present tests remains the challenge for healthcare providers. With further study of these disorders and best treatment practices we can provide neonates presenting to the emergency department with the best possible outcomes. Copyright © 2014 Elsevier Inc. All rights reserved.

Exploring Equity Properties in Equating Using AP® Examinations. Research Report No. 2012-4

ERIC Educational Resources Information Center

Lee, Eunjung; Lee, Won-Chan; Brennan, Robert L.

2012-01-01

In almost all high-stakes testing programs, test equating is necessary to ensure that test scores across multiple test administrations are equivalent and can be used interchangeably. Test equating becomes even more challenging in mixed-format tests, such as Advanced Placement Program® (AP®) Exams, that contain both multiple-choice and constructed…

Regulatory toxicology in the twenty-first century: challenges, perspectives and possible solutions.

PubMed

Tralau, Tewes; Oelgeschläger, Michael; Gürtler, Rainer; Heinemeyer, Gerhard; Herzler, Matthias; Höfer, Thomas; Itter, Heike; Kuhl, Thomas; Lange, Nikola; Lorenz, Nicole; Müller-Graf, Christine; Pabel, Ulrike; Pirow, Ralph; Ritz, Vera; Schafft, Helmut; Schneider, Heiko; Schulz, Thomas; Schumacher, David; Zellmer, Sebastian; Fleur-Böl, Gaby; Greiner, Matthias; Lahrssen-Wiederholt, Monika; Lampen, Alfonso; Luch, Andreas; Schönfelder, Gilbert; Solecki, Roland; Wittkowski, Reiner; Hensel, Andreas

2015-06-01

The advent of new testing systems and "omics"-technologies has left regulatory toxicology facing one of the biggest challenges for decades. That is the question whether and how these methods can be used for regulatory purposes. The new methods undoubtedly enable regulators to address important open questions of toxicology such as species-specific toxicity, mixture toxicity, low-dose effects, endocrine effects or nanotoxicology, while promising faster and more efficient toxicity testing with the use of less animals. Consequently, the respective assays, methods and testing strategies are subject of several research programs worldwide. On the other hand, the practical application of such tests for regulatory purposes is a matter of ongoing debate. This document summarizes key aspects of this debate in the light of the European "regulatory status quo", while elucidating new perspectives for regulatory toxicity testing.

The Internationalization of Testing and New Models of Test Delivery on the Internet

ERIC Educational Resources Information Center

Bartram, Dave

2006-01-01

The Internet has opened up a whole new set of opportunities for advancing the science of psychometrics and the technology of testing. It has also created some new challenges for those of us involved in test design and testing. In particular, we are seeing impacts from internationalization of testing and new models for test delivery. These are…

Design Challenges Encountered in a Propulsion-Controlled Aircraft Flight Test Program

NASA Technical Reports Server (NTRS)

Maine, Trindel; Burken, John; Burcham, Frank; Schaefer, Peter

1994-01-01

The NASA Dryden Flight Research Center conducted flight tests of a propulsion-controlled aircraft system on an F-15 airplane. This system was designed to explore the feasibility of providing safe emergency landing capability using only the engines to provide flight control in the event of a catastrophic loss of conventional flight controls. Control laws were designed to control the flightpath and bank angle using only commands to the throttles. Although the program was highly successful, this paper highlights some of the challenges associated with using engine thrust as a control effector. These challenges include slow engine response time, poorly modeled nonlinear engine dynamics, unmodeled inlet-airframe interactions, and difficulties with ground effect and gust rejection. Flight and simulation data illustrate these difficulties.

Challenges in Rotorcraft Acoustic Flight Prediction and Validation

NASA Technical Reports Server (NTRS)

Boyd, D. Douglas, Jr.

2003-01-01

Challenges associated with rotorcraft acoustic flight prediction and validation are examined. First, an outline of a state-of-the-art rotorcraft aeroacoustic prediction methodology is presented. Components including rotorcraft aeromechanics, high resolution reconstruction, and rotorcraft acoustic prediction arc discussed. Next, to illustrate challenges and issues involved, a case study is presented in which an analysis of flight data from a specific XV-15 tiltrotor acoustic flight test is discussed in detail. Issues related to validation of methodologies using flight test data are discussed. Primary flight parameters such as velocity, altitude, and attitude are discussed and compared for repeated flight conditions. Other measured steady state flight conditions are examined for consistency and steadiness. A representative example prediction is presented and suggestions are made for future research.

Structural Analysis of a Tablet PC Based Language Test

ERIC Educational Resources Information Center

Magal Royo, Teresa; Garcia Laborda, Jesus; Gimenez Lopez, Jose Luis; Otero de Juan, Nuria

2015-01-01

Ubiquitous language learning and testing has become a new challenging trend. Budget constraints in Europe and the rest of the world have made this way of delivery very attractive for materials designers as well as language testing organizations. Ubiquitous testing has a very especial interest in low and medium stakes language testing in which…

The Current Often Implemented Fitness Tests in Physical Education Programs: Problems and Future Directions

ERIC Educational Resources Information Center

Keating, Xiaofen Deng

2003-01-01

This paper aims to examine current nationwide youth fitness test programs, address problems embedded in the programs, and possible solutions. The current Fitnessgram, President's Challenge, and YMCA youth fitness test programs were selected to represent nationwide youth fitness test programs. Sponsors of the nationwide youth fitness test programs…

Can interpreting sediment toxicity tests a mega sites benefit from novel approaches to normalization to address batching of tests?

EPA Science Inventory

Sediment toxicity tests are a key tool used in Ecological Risk Assessments for contaminated sediment sites. Interpreting test results and defining toxicity is often a challenge. This is particularly true at mega sites where the testing regime is large, and by necessity performed ...

Aerothermodynamics of Blunt Body Entry Vehicles. Chapter 3

NASA Technical Reports Server (NTRS)

Hollis, Brian R.; Borrelli, Salvatore

2011-01-01

In this chapter, the aerothermodynamic phenomena of blunt body entry vehicles are discussed. Four topics will be considered that present challenges to current computational modeling techniques for blunt body environments: turbulent flow, non-equilibrium flow, rarefied flow, and radiation transport. Examples of comparisons between computational tools to ground and flight-test data will be presented in order to illustrate the challenges existing in the numerical modeling of each of these phenomena and to provide test cases for evaluation of Computational Fluid Dynamics (CFD) code predictions.

Aerothermodynamics of blunt body entry vehicles

NASA Astrophysics Data System (ADS)

Hollis, Brian R.; Borrelli, Salvatore

2012-01-01

In this chapter, the aerothermodynamic phenomena of blunt body entry vehicles are discussed. Four topics will be considered that present challenges to current computational modeling techniques for blunt body environments: turbulent flow, non-equilibrium flow, rarefied flow, and radiation transport. Examples of comparisons between computational tools to ground and flight-test data will be presented in order to illustrate the challenges existing in the numerical modeling of each of these phenomena and to provide test cases for evaluation of computational fluid dynamics (CFD) code predictions.

Multimodal Advertisement of Pregnancy in Free-Ranging Female Japanese Macaques (Macaca fuscata)

PubMed Central

Rigaill, Lucie; MacIntosh, Andrew J. J.; Higham, James P.; Winters, Sandra; Shimizu, Keiko; Mouri, Keiko; Furuichi, Takeshi; Garcia, Cécile

2015-01-01

The role of multiple sexual signals in indicating the timing of female ovulation, and discrimination of this timing by males, has been particularly well studied among primates. However the exhibition of pregnancy signals, and how such signals might modulate male post-conception mating decisions, is still poorly understood. Here we aimed to determine if Japanese macaque males use changes in female sexual signals (behavioral, visual and auditory) to discriminate pregnancy and adjust their socio-sexual behaviors. We combined behavioral observations, digital photography and endocrinological (progestogen and estrogen) data, collected systematically during three one-month periods: the pre-conceptive period, the 1st month of pregnancy and the 2nd month of pregnancy. We analyzed variation in the probability of detecting male and female socio-sexual behaviors and estrus calls, as well as changes in female face color parameters, in relation to female reproductive state. Based on our focal observations, we found that males did not copulate during the pregnancy period, and that female socio-sexual behaviors generally decreased from the pre-conceptive to post-conceptive periods. Female face luminance decreased from the pre-conceptive month to the pregnancy period whereas face color only varied between the 1st and 2nd month of gestation. Our results suggest that Japanese macaque females display sexual cues of pregnancy that males might use to reduce energy wasted on non-reproductive copulations with pregnant females. We hypothesize that females advertize their pregnancy through changes in behavioral, visual and potential auditory signals that males can use to adjust their mating behaviors. We finish by discussing implications for male and female post-conception strategies. PMID:26308441

Multimodal Advertisement of Pregnancy in Free-Ranging Female Japanese Macaques (Macaca fuscata).

PubMed

Rigaill, Lucie; MacIntosh, Andrew J J; Higham, James P; Winters, Sandra; Shimizu, Keiko; Mouri, Keiko; Furuichi, Takeshi; Garcia, Cécile

2015-01-01

The role of multiple sexual signals in indicating the timing of female ovulation, and discrimination of this timing by males, has been particularly well studied among primates. However the exhibition of pregnancy signals, and how such signals might modulate male post-conception mating decisions, is still poorly understood. Here we aimed to determine if Japanese macaque males use changes in female sexual signals (behavioral, visual and auditory) to discriminate pregnancy and adjust their socio-sexual behaviors. We combined behavioral observations, digital photography and endocrinological (progestogen and estrogen) data, collected systematically during three one-month periods: the pre-conceptive period, the 1st month of pregnancy and the 2nd month of pregnancy. We analyzed variation in the probability of detecting male and female socio-sexual behaviors and estrus calls, as well as changes in female face color parameters, in relation to female reproductive state. Based on our focal observations, we found that males did not copulate during the pregnancy period, and that female socio-sexual behaviors generally decreased from the pre-conceptive to post-conceptive periods. Female face luminance decreased from the pre-conceptive month to the pregnancy period whereas face color only varied between the 1st and 2nd month of gestation. Our results suggest that Japanese macaque females display sexual cues of pregnancy that males might use to reduce energy wasted on non-reproductive copulations with pregnant females. We hypothesize that females advertize their pregnancy through changes in behavioral, visual and potential auditory signals that males can use to adjust their mating behaviors. We finish by discussing implications for male and female post-conception strategies.

Hot flushes, coronary heart disease, and hormone therapy in postmenopausal women

PubMed Central

Huang, Alison J.; Sawaya, George F.; Vittinghoff, Eric; Lin, Feng; Grady, Deborah

2010-01-01

Objective The aim of this study was to examine interactions between hot flushes, estrogen plus progestogen therapy (EPT), and coronary heart disease (CHD) events in postmenopausal women with CHD. Methods We analyzed data from the Heart and Estrogen/Progestin Replacement Study, a randomized, placebo-controlled trial of 0.625 mg conjugated equine estrogens plus 2.5 mg medroxyprogesterone acetate in 2,763 postmenopausal women with CHD. Hot flushes were assessed at baseline using self-administered questionnaires; women reporting bothersome hot flushes “some” to ”all” of the time were considered to have clinically significant flushing. Cox regression models were used to examine the effect of EPT on risk of CHD events among women with and without significant flushing at baseline. Results The mean age of participants was 66.7 ± 6.8 years, and 89% (n = 2,448) were white. Sixteen percent (n = 434) of participants reported clinically significant hot flushes at baseline. Among women with baseline flushing, EPT increased risk of CHD events nine-fold in the first year compared with placebo (hazard ratio = 9.01; 95% CI, 1.15-70.35); among women without baseline flushing, treatment did not significantly affect CHD event risk in the first year (hazard ratio = 1.32; 95% CI, 0.86-2.03; P = 0.07 for interaction of hot flushes with treatment). The trend toward differential effects of EPT on risk for CHD among women with and without baseline flushing did not persist after the first year of treatment. Conclusions Among older postmenopausal women with CHD, EPT may increase risk of CHD events substantially in the first year of treatment among women with clinically significant hot flushes but not among those without hot flushes. PMID:19325499

Provision of contraception after emergency contraception from the pharmacy: evaluating the acceptability of pharmacy for providing sexual and reproductive health services.

PubMed

Michie, L; Cameron, S T; Glasier, A; Chen, Z E; Milne, D; Wilson, S

2016-06-01

Community pharmacies in the United Kingdom (UK) provide sexual and reproductive health (SRH) services such as emergency contraception (EC), although there is scope for provision of additional services. We conducted a pilot study of pharmacy based interventions for initiating effective contraception after EC. By determining the views of participating women and pharmacists we aimed to identify barriers and facilitators to providing interventions from pharmacies routinely. In the pilot study, women presenting for levonorgestrel EC to community pharmacies, were provided with either standard care or one of two interventions: one packet of progestogen-only pills (POPs); or an invitation to present the empty EC packet to a local family planning clinic for contraception. A sample of women participating were asked to undergo a further interview. Operational difficulties with research in the community pharmacy were also documented by the research team. Semi-structured interviews were conducted with 12 women, four from each arm of the pilot study, using a standardised topic guide. Pre- and post-study interviews were conducted with the pharmacists involved. All women welcomed the interventions indicating the benefit of having different options available. They also identified possible advantages and disadvantages of each intervention. All pharmacists were positive about their involvement in the study. Methodological problems included difficulty in retention of participating pharmacists, slow recruitment and failure to accurately complete study paperwork. Women welcomed the interventions offered. Pharmacists viewed their participation in the study positively. The problems encountered provide valuable feedback to inform the development larger scale studies of such interventions. Copyright © 2015 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

Metabolism of the Synthetic Progestogen Norethynodrel by Human Ketosteroid Reductases of the Aldo-Keto Reductase Superfamily

PubMed Central

Jin, Yi; Duan, Ling; Chen, Mo; Penning, Trevor M; Kloosterboer, Helenius J.

2012-01-01

Human ketosteroid reductases of the aldo-keto reductase (AKR) superfamily, i.e. AKR1C1-4, are implicated in the biotransformation of synthetic steroid hormones. Norethynodrel (NOR, 17α-ethynyl-17β-hydroxy-estra-5(10)-en-3-one), the progestin component of the first marketed oral contraceptive, is known to undergo rapid and extensive metabolism to 3α- and 3β-hydroxy metabolites. The ability of the four human AKR1C enzymes to catalyze the metabolism of NOR has now been characterized. AKR1C1 and AKR1C2 almost exclusively converted NOR to 3β-hydroxy NOR, while AKR1C3 gave 3β-hydroxy NOR as the main product and AKR1C4 predominantly formed 3α-hydroxy NOR. Individual AKR1C enzymes also displayed distinct kinetic properties in the reaction of NOR. In contrast, norethindrone (NET), the Δ4-isomer of NOR and the most commonly used synthetic progestin, was not a substrate for the AKR1C enzymes. NOR is also structurally identical to the hormone replacement therapeutic tibolone (TIB), except TIB has a methyl group at the 7α-position. Product profiles and kinetic parameters for the reduction of NOR catalyzed by each individual AKR1C isoform were identical to those for the reduction of TIB catalyzed by the respective isoform. These data suggest that the presence of the 7α-methyl group has a minimal effect on the stereochemical outcome of the reaction and kinetic behavior of each enzyme. Results indicate a role of AKR1C in the hepatic and peripheral metabolism of NOR to 3α- and 3β-hydroxy NOR and provide insights into the differential pharmacological properties of NOR, NET and TIB. PMID:22210085

Study on the removal of hormones from domestic wastewaters with lab-scale constructed wetlands with different substrates and flow directions.

PubMed

Herrera-Melián, José Alberto; Guedes-Alonso, Rayco; Borreguero-Fabelo, Alejandro; Santana-Rodríguez, José Juan; Sosa-Ferrera, Zoraida

2017-05-31

Eight wastewater samples from a university campus were analysed between May and July of 2014 to determine the concentration of 14 natural and synthetic steroid hormones. An on-line solid-phase extraction combined with ultra-high performance liquid chromatography coupled with mass spectrometry (on-line SPE-UHPLC-MS/MS) was used as extraction, pre-concentration and detection method. In the samples studied, three oestrogens (17β-estradiol, estrone and estriol), two androgens (boldenone and testosterone), three progestogens (norgestrel, progesterone and norethisterone) and one glucocorticoid (prednisone) were detected. The removal of hormones was studied in primary and secondary constructed wetland mesocosms. The porous media of the primary constructed wetlands were palm tree mulch. These reactors were used to study the effect of water flow, i.e. horizontal (HF1) vs vertical (VF1). The latter was more efficient in the removal of 17β-estradiol (HF1: 30%, VF1: 50%), estrone (HF1: 63%, VF1: 85%), estriol (100% both), testosterone (HF1: 45%, VF1: 73%), boldenone (HF1:-77%, VF1: 100%) and progesterone (HF1: 84%, VF1: 99%). The effluent of HF1 was used as influent of three secondary constructed wetland mesocosms: two double-stage vertical flow constructed wetlands, one with gravel (VF2gravel) and one with palm mulch (VF2mulch), and a mineral-based, horizontal flow constructed wetland (HFmineral). VF2mulch was the most efficient of the secondary reactors, since it achieved the complete removal of the hormones studied with the exception of 17ß-estradiol. The significantly better removal of BOD and ammonia attained by VF2mulch suggests that the better aeration of mulch favoured the more efficient removal of hormones.

Do Women's Voices Provide Cues of the Likelihood of Ovulation? The Importance of Sampling Regime

PubMed Central

Fischer, Julia; Semple, Stuart; Fickenscher, Gisela; Jürgens, Rebecca; Kruse, Eberhard; Heistermann, Michael; Amir, Ofer

2011-01-01

The human voice provides a rich source of information about individual attributes such as body size, developmental stability and emotional state. Moreover, there is evidence that female voice characteristics change across the menstrual cycle. A previous study reported that women speak with higher fundamental frequency (F0) in the high-fertility compared to the low-fertility phase. To gain further insights into the mechanisms underlying this variation in perceived attractiveness and the relationship between vocal quality and the timing of ovulation, we combined hormone measurements and acoustic analyses, to characterize voice changes on a day-to-day basis throughout the menstrual cycle. Voice characteristics were measured from free speech as well as sustained vowels. In addition, we asked men to rate vocal attractiveness from selected samples. The free speech samples revealed marginally significant variation in F0 with an increase prior to and a distinct drop during ovulation. Overall variation throughout the cycle, however, precluded unequivocal identification of the period with the highest conception risk. The analysis of vowel samples revealed a significant increase in degree of unvoiceness and noise-to-harmonic ratio during menstruation, possibly related to an increase in tissue water content. Neither estrogen nor progestogen levels predicted the observed changes in acoustic characteristics. The perceptual experiments revealed a preference by males for voice samples recorded during the pre-ovulatory period compared to other periods in the cycle. While overall we confirm earlier findings in that women speak with a higher and more variable fundamental frequency just prior to ovulation, the present study highlights the importance of taking the full range of variation into account before drawing conclusions about the value of these cues for the detection of ovulation. PMID:21957453

Acute Effects of Lysergic Acid Diethylamide on Circulating Steroid Levels in Healthy Subjects.

PubMed

Strajhar, P; Schmid, Y; Liakoni, E; Dolder, P C; Rentsch, K M; Kratschmar, D V; Odermatt, A; Liechti, M E

2016-03-01

Lysergic acid diethylamide (LSD) is a serotonin 5-hydroxytryptamine-2A (5-HT2A ) receptor agonist that is used recreationally worldwide. Interest in LSD research in humans waned after the 1970s, although the use of LSD in psychiatric research and practice has recently gained increasing attention. LSD produces pronounced acute psychedelic effects, although its influence on plasma steroid levels over time has not yet been characterised in humans. The effects of LSD (200 μg) or placebo on plasma steroid levels were investigated in 16 healthy subjects using a randomised, double-blind, placebo-controlled, cross-over study design. Plasma concentration-time profiles were determined for 15 steroids using liquid-chromatography tandem mass-spectrometry. LSD increased plasma concentrations of the glucocorticoids cortisol, cortisone, corticosterone and 11-dehydrocorticosterone compared to placebo. The mean maximum concentration of LSD was reached at 1.7 h. Mean peak psychedelic effects were reached at 2.4 h, with significant alterations in mental state from 0.5 h to > 10 h. Mean maximal concentrations of cortisol and corticosterone were reached at 2.5 h and 1.9 h, and significant elevations were observed 1.5-6 h and 1-3 h after drug administration, respectively. LSD also significantly increased plasma concentrations of the androgen dehydroepiandrosterone but not other androgens, progestogens or mineralocorticoids compared to placebo. A close relationship was found between plasma LSD concentrations and changes in plasma cortisol and corticosterone and the psychotropic response to LSD, and no clockwise hysteresis was observed. In conclusion, LSD produces significant acute effects on circulating steroids, especially glucocorticoids. LSD-induced changes in circulating glucocorticoids were associated with plasma LSD concentrations over time and showed no acute pharmacological tolerance. © 2016 British Society for Neuroendocrinology.

Menopause and postmenopausal hormone therapy and risk of hearing loss.

PubMed

Curhan, Sharon G; Eliassen, A Heather; Eavey, Roland D; Wang, Molin; Lin, Brian M; Curhan, Gary C

2017-09-01

Menopause may be a risk factor for hearing loss, and postmenopausal hormone therapy (HT) has been proposed to slow hearing decline; however, there are no large prospective studies. We prospectively examined the independent relations between menopause and postmenopausal HT and risk of self-reported hearing loss. Prospective cohort study among 80,972 women in the Nurses' Health Study II, baseline age 27 to 44 years, followed from 1991 to 2013. Baseline and updated information was obtained from detailed validated biennial questionnaires. Cox proportional-hazards regression models were used to examine independent associations between menopausal status and postmenopausal HT and risk of hearing loss. After 1,410,928 person-years of follow-up, 18,558 cases of hearing loss were reported. There was no significant overall association between menopausal status, natural or surgical, and risk of hearing loss. Older age at natural menopause was associated with higher risk. The multivariable-adjusted relative risk of hearing loss among women who underwent natural menopause at age 50+ years compared with those aged less than 50 years was 1.10 (95% confidence interval [CI] 1.03, 1.17). Among postmenopausal women, oral HT (estrogen therapy or estrogen plus progestogen therapy) was associated with higher risk of hearing loss, and longer duration of use was associated with higher risk (P trend < 0.001). Compared with women who never used HT, the multivariable-adjusted relative risk of hearing loss among women who used oral HT for 5 to 9.9 years was 1.15 (95% CI 1.06, 1.24) and for 10+ years was 1.21 (95% CI 1.07, 1.37). Older age at menopause and longer duration of postmenopausal HT are associated with higher risk of hearing loss.

Trace analysis of 61 natural and synthetic progestins in river water and sewage effluents by ultra-high performance liquid chromatography-tandem mass spectrometry.

PubMed

Shen, Xiaoyan; Chang, Hong; Sun, Dezhi; Wang, Linxia; Wu, Fengchang

2018-04-15

A broad number of natural and synthetic progestins are widely used in human and veterinary therapies. Although progestins exhibit adverse effects in aquatic organisms, information about environmental occurrence and fate have been limited to several compounds, hampering the accuracy of risk assessments of the compounds. In this study, a selective and sensitive analytical method was established to simultaneously determine 19 natural and 42 synthetic progestins in environmental waters, and the synthetic progestins included 19-nortestosterone, 17α-hydroxyprogesterone and progesterone derivatives. All of the target compounds were effectively separated using an HSS T3 column, and the recoveries for effluent and river samples were 80-115% and 75-105%, respectively. The detection limits for the 61 analytes were in the range of 0.05-0.60 ng/L and 0.03-0.40 ng/L for the effluent and river samples, respectively. The developed method is applied to analyze the target progestogens in sewage effluent and river water samples from Beijing. The detected concentrations of natural progesterone metabolites (3α-hydroxy-5β-tetrahydroprogesterone) were up to 63 times higher than those of the parent compound. Of the three groups of synthetic progestins, the progesterone derivatives were detected for the first time and had the highest concentrations followed by the 19-nortestosterone and 17α-hydroxyprogesterone derivatives. In contrast to previous studies, the predominant derivative compounds of 19-nortestosterone were found to be 19-nortestosterone, gestodene and mifepristone, and those of 17α-hydroxyprogesterone were 6-epi-medroxy progesterone 17-acetate and melengestrol acetate. The toxicities and environmental risk of these emerging progestins deserves more attention in the future. Copyright © 2018 Elsevier Ltd. All rights reserved.

Estrogen and progestogen use in postmenopausal women: July 2008 position statement of The North American Menopause Society

PubMed Central

2009-01-01

Objective To update for both clinicians and the lay public the evidence-based position statement published by The North American Menopause Society (NAMS) in March 2007 regarding its recommendations for menopausal hormone therapy (HT) for postmenopausal women, with consideration for the therapeutic benefit-risk ratio at various times through menopause and beyond. Design An Advisory Panel of clinicians and researchers expert in the field of women’s health was enlisted to review the March 2007 NAMS position statement, evaluate new evidence through an evidence-based analysis, and reach consensus on recommendations. The Panel’s recommendations were reviewed and approved by the NAMS Board of Trustees as an official NAMS position statement. The document was provided to other interested organizations to seek their endorsement. Results Current evidence supports a consensus regarding the role of HT in postmenopausal women, when potential therapeutic benefits and risks around the time of menopause are considered. This paper lists all these areas along with explanatory comments. Conclusions that vary from the 2007 position statement are highlighted. Addenda include a discussion of risk concepts, a new component not included in the 2007 paper, and a recommended list of areas for future HT research. A suggested reading list of key references is also provided. Conclusions Recent data support the initiation of HT around the time of menopause to treat menopause-related symptoms; to treat or reduce the risk of certain disorders, such as osteoporosis or fractures in select postmenopausal women; or both. The benefit-risk ratio for menopausal HT is favorable close to menopause but decreases with aging and with time since menopause in previously untreated women. PMID:18580541

Effects of creep feeding and monensin on reproductive performance and lactation of beef heifers.

PubMed

Hixon, D L; Fahey, G C; Kesler, D J; Neumann, A L

1982-09-01

A 23 factorial arrangement of treatments was utilized to determine the effect of breed, creep feeding and monensin on subsequent reproductive performance and lactation of 32 primiparous heifers. One-half of each breed (Angus and Hereford) group had access to creep feed (2.67 Mcal metabolizable energy/kg) while nursing their dams. Approximately 40 d before breeding through 120 d of lactation, all heifers were fed a suboptimal energy diet and 50% of each breed and creep group received 200 mg monensin/head daily. Estrus was synchronized with a progestogen. Volatile fatty acids (VFA) were determined periodically throughout the monensin-feeding portion of the experiment. Twenty-four hour milk production, percentage butterfat and percentage solids-not-fat were determined at 60 and 120 d postpartum. Weaning weights (adjusted to 205 d and for age of dam) of the original heifers were heavier (P less than .05) for those that were creep fed compared with those not creep fed (219 vs 202 kg). Monensin-supplemented females gained significantly more weight from the initiation of treatment to immediately postcalving and gave birth to heavier calves (P less than .05) even though they received comparable amounts of dietary energy as those that did not receive monensin. The energy stressed, monensin-supplemented first-calf heifers exhibited a shorter postpartum interval (P less than .05) to first estrus than did those that did not receive monensin (55.7 vs 69.1 d, respectively). First-calf heifers that had been creep fed while nursing their dams had a lower (P less than .05) daily milk yield at 120 d post-partum than those that did not have access to creep feed. No detrimental effects were observed due to long-term monensin supplementation.

Usual medical treatments or levonorgestrel-IUS for women with heavy menstrual bleeding: long-term randomised pragmatic trial in primary care.

PubMed

Kai, Joe; Middleton, Lee; Daniels, Jane; Pattison, Helen; Tryposkiadis, Konstantinos; Gupta, Janesh

2016-12-01

Heavy menstrual bleeding (HMB) is a common, chronic problem affecting women and health services. However, long-term evidence on treatment in primary care is lacking. To assess the effectiveness of commencing the levonorgestrel-releasing intrauterine system (LNG-IUS) or usual medical treatments for women presenting with HMB in general practice. A pragmatic, multicentre, parallel, open-label, long term, randomised controlled trial in 63 primary care practices across the English Midlands. In total, 571 women aged 25-50 years, with HMB were randomised to LNG-IUS or usual medical treatment (tranexamic/mefenamic acid, combined oestrogen-progestogen, or progesterone alone). The primary outcome was the patient reported Menorrhagia Multi-Attribute Scale (MMAS, measuring effect of HMB on practical difficulties, social life, psychological and physical health, and work and family life; scores from 0 to 100). Secondary outcomes included surgical intervention (endometrial ablation/hysterectomy), general quality of life, sexual activity, and safety. At 5 years post-randomisation, 424 (74%) women provided data. While the difference between LNG-IUS and usual treatment groups was not significant (3.9 points; 95% confidence interval = -0.6 to 8.3; P = 0.09), MMAS scores improved significantly in both groups from baseline (mean increase, 44.9 and 43.4 points, respectively; P<0.001 for both comparisons). Rates of surgical intervention were low in both groups (surgery-free survival was 80% and 77%; hazard ratio 0.90; 95% CI = 0.62 to 1.31; P = 0.6). There was no difference in generic quality of life, sexual activity scores, or serious adverse events. Large improvements in symptom relief across both groups show treatment for HMB can be successfully initiated with long-term benefit and with only modest need for surgery. © British Journal of General Practice 2016.

Contraceptive use among women presenting to pharmacies for emergency contraception: an opportunity for intervention.

PubMed

Michie, Lucy; Cameron, Sharon T; Glasier, Anna; Greed, Elizabeth

2014-07-01

Most women who use emergency contraception (EC) do so because of unprotected sexual intercourse or condom failure and so remain at risk of pregnancy unless they commence an effective method of contraception. In Great Britain, increasingly women now choose to obtain EC from a pharmacy; however, pharmacists do not currently provide effective ongoing contraception. We sought to determine the views of women obtaining EC from pharmacies and clinicians working in sexual and reproductive health care (SRH) about the possibility of pharmacists providing a temporary supply of a progestogen-only pill (POP) together with EC. Self-administered, anonymous questionnaires of (1) women requesting EC from pharmacies in Edinburgh, Scotland and (2) SRH clinicians attending a major UK scientific meeting. A total of 211/232 women completed questionnaires in pharmacies (a 91% response rate). Of those women not using a hormonal method of contraception at the time of EC (n=166; 79%), almost half (44%) wished to use an effective method. Most women (64%) agreed that the option of a pharmacist being able to supply a POP would have been helpful. Among the SRH clinicians, 110 completed questionnaires out of 150 distributed (a 73% response rate). The majority of respondents (92%) were positive about a pharmacist supplying a POP at the time of EC. A reasonable proportion of women requesting EC would like to start using an effective contraceptive method. Both the women and the SRH clinicians we surveyed are positive about the option of a short supply of a POP being provided by the pharmacy in the UK together with EC. Published by the BMJ Publishing Group Limited.

Involvement of G-463A MPO gene polymorphism in the response of postmenopausal women to hormone therapy.

PubMed

del Agua, Ainhoa Ruiz; Aurrekoetxea, Igor; Elorriaga, Miguel Angel; Rodriguez, Fernando; Guéraud, Françoise; Ruiz-Larrea, M Begoña; Ruiz-Sanz, José Ignacio

2011-05-01

The aims of this work were to determine (1) the effects of estrogen plus progestogen therapy (EPT) and raloxifene on oxidative stress and cardiovascular risk biomarkers in postmenopausal women and (2) the involvement of the functional G-463A polymorphism of the myeloperoxidase (MPO) gene in the therapy responses. Postmenopausal women (45-55 y old) were assigned to three groups receiving (1) EPT (continuous 50 μg transdermal estradiol daily and 200 mg/d micronized progesterone orally the first 14 d of each month; n = 21), (2) raloxifene (60 mg daily; n = 17), and (3) no treatment (control; n = 21). Blood and urine samples were taken before and after 6 months of therapy. Measurements were serum lipid profile, C-reactive intercellular adhesion molecule 1 (ICAM-1), α-tocopherol, γ-tocopherol, uric acid, total antioxidant activity (TAA), malondialdehyde, and urinary 1,4-dihydroxynonane-mercapturic acid (the major urinary 4-hydroxynonenal metabolite). The G-463A MPO polymorphism was analyzed by polymerase chain reaction and restriction fragment length polymorphism. EPT significantly decreased TAA and the levels of ICAM-1, not modifying other cardiovascular risk or oxidative stress markers. The raloxifene and control groups experienced no modifications in oxidative stress or endothelial dysfunction markers. The MPO genotype specifically influenced the outcomes in the EPT group. Thus, TAA decreased significantly in GG (high-expression genotype) homozygotes, whereas ICAM-1 levels were reduced in A allele carriers. EPT exerted a negative action on the serum oxidant/antioxidant balance in the MPO GG homozygotes and a positive effect on the ICAM-1 endothelial dysfunction marker in carriers of the low-expression A allele. This observation provides evidence of the importance of this polymorphism in the response to EPT.

In-house monitoring of steroid hormone metabolites in urine informs breeding management of a giant anteater (Myrmechophaga tridactyla).

PubMed

Amendolagine, Laura; Schoffner, Tad; Koscielny, Lynn; Schook, Mandi; Copeland, Debra; Casteel, James; Duff, Brianna; Koester, Diana

2018-01-01

Although numbers of giant anteaters within North American facilities have been steadily increasing for the last 15 years, the population now exhibits an unstable age distribution with genetically valuable individuals nearing reproductive senescence. Contributing to this issue is the Association of Zoos and Aquariums (AZA) described lack of standardization of breeding introduction practices and high risk of female injury occurring during such pairings. This report describes the development of a successful breeding protocol at Cleveland Metroparks Zoo based on hormone monitoring and efficient communication between science and animal management teams that minimizes risk of female injury. By training a female giant anteater for urine sample and body weight data collection, staff members accurately predicted estrus, and timed breeding introductions to facilitate positive interactions between the male and female. Such training also allowed for careful monitoring of two pregnancies through parturition (169-184 days from breeding) and post-partum return to estrus (114-129 days from parturition). Urinary hormone monitoring revealed a sharp progestogen increase averaging >five-fold over basal levels (0.52 ± 0.05 ng/mg creatinine) which was sustained throughout the second half of pregnancy. Mean regular estrous cycle length (n = 14 cycles), was calculated as 46.17 ± 1.39 days, measured as days between estrogen peaks of mean concentration 2.27 ± 0.19 ng/mg creatinine. This report summarizes impressive collaborative efforts among multiple zoological departments to achieve extensive hormonal and body weight monitoring from a female giant anteater, adding valuable information on reproductive parameters, and specifics for novel hormone assay techniques. © 2018 Wiley Periodicals, Inc.

Long-term tolerability of ethinylestradiol 20 μg/drospirenone 3 mg in a flexible extended regimen: results from a randomised, controlled, multicentre study.

PubMed

Klipping, Christine; Duijkers, Ingrid; Fortier, Michel P; Marr, Joachim; Trummer, Dietmar; Elliesen, Jörg

2012-04-01

This study was designed to assess the long-term safety and tolerability of a new flexible extended regimen of ethinylestradiol (EE) 20 μg/drospirenone (DRSP) 3 mg, which allows management of intracyclic (breakthrough) bleeding [flexible management of intracyclic (breakthrough) bleeding (MIB)], in comparison to conventional 28-day and fixed extended regimens. In this Phase III, multicentre, open-label study, women (aged 18-35 years) were randomised to EE/DRSP in the following regimens: flexible(MIB) (24-120 days' active hormonal intake followed by a 4-day tablet-free interval), conventional 28-day (24 days' active hormonal intake followed by a 4-day hormone-free interval) or fixed extended (120 days' uninterrupted active hormonal intake followed by a 4-day tablet-free interval) during a 1-year comparative phase. Thereafter, women entered a 1-year safety extension phase in which the majority received the flexible(MIB) regimen. Safety/tolerability outcomes were measured over 2 years. A separate analysis of certain safety parameters (endometrial, hormonal, lipid, haemostatic and metabolic variables) was conducted at two of the study centres. Results were analysed in 1067 and 783 women in the comparative and safety extension phases. Overall, 56.3% of women experienced ≥1 adverse event (AE) in the safety extension phase. Serious AEs occurred in 3.0%, 1.4% and 3.3% of women receiving the flexible(MIB), conventional and fixed extended regimens, respectively. No unexpected endometrial, hormonal, lipid, haemostatic or metabolic findings occurred with any of the three regimens. EE/DRSP in a flexible extended regimen with management of intracyclic (breakthrough) bleeding is well-tolerated and, when administered for up to 2 years, has a good safety profile comparable to other estrogen/progestogen oral contraceptives.

[Oral contraception and the vascular risk].

PubMed

Garnier, L F; Gruel, Y

1989-01-01

Vascular risk, mainly thromboembolitic risk, attributed to oral contraceptives (OCs) since 1962, has been primarily linked to ethinyl estradiol (EE). OCs which combine estrogen and have been associated with cerebral vascular accidents. A 1977 study showed a 40% increase of mortality due to cardiovascular complications in women taking OCs. There were of both an arterial and a venous character. The risk of myocardial infarction was 3 times more frequent among OC users. Deep venous thrombosis and pulmonary embolism were more numerous. Some other risk factors include smoking, hypertension, diabetes, and age 35. The risk of heart attack vanishes a few years after stopping OC use. The reduction of EE (and similarly progesterone) dosage from 100-50 mcg also lower the risk of hypertension, cerebral vascular accidents, and venous thrombosis. Prolonged use of OCs causes disorders of hemostasis affecting the walls of blood vessels, modifying the viscosity of blood flow (increase of hematocrits, reduction of venous tonus), modifying plasmatic coagulation (increase of platelets, increase of factors VII and X and plasma fibrinogen, and decrease of antithrombin III activity), and increased fibrinolysis. These anomalies are exclusively associated with high doses of estrogens. 5% of women using OCs develop moderate hypertension of 5-10 mm Hg of systolic pressure 5 years later, but after cessation it is reversed. OCs stimulate the renin-angiotensin-aldosterone system causing accelerated production of angiotensin II with the resultant forceful vasotension. 3 months after quitting OC use, high blood pressure returns to normal. EE can provoke diabetes; it increases very low density lipoprotein (VLDL) and high density lipoprotein (HDL) production, but total cholesterol is hardly affected. The androgenic property of progestogens reduces HDL. Combined OCs are contraindicated for women with hypertension, hyperlipidemia, diabetes, and a family history of vascular accidents.

Skin prick testing predicts peanut challenge outcome in previously allergic or sensitized children with low serum peanut-specific IgE antibody concentration.

PubMed

Nolan, Richard C; Richmond, Peter; Prescott, Susan L; Mallon, Dominic F; Gong, Grace; Franzmann, Annkathrin M; Naidoo, Rama; Loh, Richard K S

2007-05-01

Peanut allergy is transient in some children but it is not clear whether quantitating peanut-specific IgE by Skin Prick Test (SPT) adds additional information to fluorescent-enzyme immunoassay (FEIA) in discriminating between allergic and tolerant children. To investigate whether SPT with a commercial extract or fresh foods adds additional predictive information for peanut challenge in children with a low FEIA (<10 k UA/L) who were previously sensitized, or allergic to peanuts. Children from a hospital-based allergy service who were previously sensitized or allergic to peanuts were invited to undergo a peanut challenge unless they had a serum peanut-specific IgE>10 k UA/L, a previous severe reaction, or a recent reaction to peanuts (within two years). SPT with a commercial extract, raw and roasted saline soaked peanuts was performed immediately prior to open challenge in hospital with increasing quantity of peanuts until total of 26.7 g of peanut was consumed. A positive challenge consisted of an objective IgE mediated reaction occurring during the observation period. 54 children (median age of 6.3 years) were admitted for a challenge. Nineteen challenges were positive, 27 negative, five were indeterminate and three did not proceed after SPT. Commercial and fresh food extracts provided similar diagnostic information. A wheal diameter of >or=7 mm of the commercial extract predicted an allergic outcome with specificity 97%, positive predictive value 93% and sensitivity 83%. There was a tendency for an increase in SPT wheal since initial diagnosis in children who remained allergic to peanuts while it decreased in those with a negative challenge. The outcome of a peanut challenge in peanut sensitized or previously allergic children with a low FEIA can be predicted by SPT. In this cohort, not challenging children with a SPT wheal of >or=7 mm would have avoided 15 of 18 positive challenges and denied a challenge to one out of 27 tolerant children.

Technical Challenges for a Comprehensive Test Ban: A historical perspective to frame the future (Invited)

NASA Astrophysics Data System (ADS)

Wallace, T. C.

2013-12-01

In the summer of 1958 scientists from the Soviet block and the US allies met in Geneva to discuss what it would take to monitor a forerunner to a Comprehensive Test Ban Treaty at the 'Conference of Experts to Study the Possibility of Detecting Violations of a Possible Agreement on Suspension of Nuclear Tests'. Although armed with a limited resume of observations, the conference recommended a multi-phenomenology approach (air sampling, acoustics, seismic and electromagnetic) deployed it a network of 170 sites scattered across the Northern Hemisphere, and hypothesized a detection threshold of 1kt for atmospheric tests and 5kt for underground explosions. The conference recommendations spurred vigorous debate, with strong disagreement with the stated detection hypothesis. Nevertheless, the technical challenges posed lead to a very focused effort to improve facilities, methodologies and, most importantly, research and development on event detection, location and identification. In the ensuing 50 years the various challenges arose and were eventually 'solved'; these included quantifying yield determination to enter a Limited Threshold Test Ban, monitoring broad areas of emerging nuclear nations, and after the mid-1990s lowering the global detection threshold to sub-kiloton levels for underground tests. Today there is both an international monitoring regime (ie, the International Monitoring System, or IMS) and a group of countries that have their own national technical means (NTM). The challenges for the international regime are evolving; the IMS has established itself as a very credible monitoring system, but the demand of a CTBT to detect and identify a 'nuclear test' of diminished size (zero yield) poses new technical hurdles. These include signal processing and understanding limits of resolution, location accuracy, integration of heterogeneous data, and accurately characterizing anomalous events. It is possible to extrapolate past technical advances to predict what should be available by 2020; detection of coupled explosions to 100s of tons for all continental areas, as well as a probabilistic assessment of event identification.