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Objectives. The role of noroviruses in both foodborne and person-to-person outbreaks of acute gastroenteritis (AGE) has been difficult to determine in the U.S. because of lack of routine norovirus testing and of national reporting of person-to-person outbreaks. We conducted a prospective study in one state in which enhanced testing for noroviruses was performed to better understand the relative contribution of all gastroenteric pathogens.Methods. During the two-year period, 2000–2001, we took all fecal specimens from AGE outbreaks reported in Georgia that were negative for bacteria and tested these for norovirus.Results. We investigated 78 AGE outbreaks, from which suitable fecal samples were collected from 57 of them. Norovirus was identified in 25 (44%) outbreaks, bacteria in 20 (35%) outbreaks, and parasites in one (2%) outbreak. Forty-three (75%) of the outbreaks tested were foodborne, of which 17 (40%) were attributable to norovirus and 18 (42%) were attributable to bacteria. Adjusting for incomplete testing, we estimated that 53% of all AGE outbreaks were attributable to norovirus. A total of 2,674 people were reported ill in the 57 outbreaks, and norovirus infections accounted for 1,735 (65%) of these cases. Norovirus outbreaks tended to be larger than bacterial outbreaks, with a median number of 30 vs. 16 cases per outbreak, respectively (p=0.057).Conclusions. This study provides further evidence that noroviruses are, overall, the most common cause of AGE outbreaks in the U.S. Improved specimen collection, reporting person-to-person outbreaks, and access to molecular assays are needed to further understand the role of these viruses and methods for their prevention.

We sought to determine the source of a norovirus outbreak among attendees of 46 weddings taking place during a single weekend. Norovirus-compatible illness was experienced by 332 (39%) of wedding guests surveyed; the outbreak affected up to 2700 persons. Illness was associated with eating wedding cake provided by a bakery common to the weddings (adjusted RR 4·5, P<0·001). A cake requiring direct hand contact during its preparation accounted for the majority of illness. At least two bakery employees experienced norovirus-compatible illness during the week preceding the weddings. Identical sequence types of norovirus were detected in stool specimens submitted by two wedding guests, a wedding hall employee, and one of the ill bakery employees. It is likely that one or more food workers at the bakery contaminated the wedding cakes through direct and indirect contact. These findings reinforce the necessity of proper food-handling practices and of policies that discourage food handlers from working while ill.

Follicular fluid steroid content and theca and granulosa cell steroidogenesis in pelvic congestion cystic ovaries were compared with steroidogenic function in both normal and polycystic ovaries. Ovaries were obtained at oophorectomy for benign gynaecological conditions, and classified according to gross morphology at dissection. Individual follicles were dissected out, follicular fluid aspirated, and granulosa and theca cells cultured in vitro. Androstenedione, progesterone and oestradiol content of the follicular fluid and overlying culture medium were measured by radioimmunoassay. There was a significant elevation of both basal and LH-stimulated androstenedione production by theca from both polycystic ovaries (n = 10; P < 0.005) and pelvic congestion cystic ovaries (n = 8; P < 0.05 and < 0.01 respectively) as compared with normal ovaries (n = 5). Granulosa cells from pelvic congestion ovaries (n = 7) had a diminished oestradiol response to FSH as compared with those from normal ovaries (n = 8). Follicular fluid from the majority of follicles in the pelvic congestion cystic ovaries had a high androgen:oestrogen ratio consistent with atresia. For the first time, pelvic congestion ovaries characterized by predominantly atretic follicles scattered throughout the stroma in a normal volume ovary are reported. Follicular atresia was reflected by reduced granulosa cell responsiveness to FSH, theca cell hyperplasia and increased basal and LH-stimulated androgen production. These ovaries are functionally distinct from polycystic ovaries, which do not have a higher proportion of atretic follicles than normal ovaries.

Objective To test the hypothesis that women with pelvic venous congestion have a reduction of reactivity of their peripheral circulation.

Pelvic venous congestion is a common cause of chronic pelvic pain in women of reproductive age. Although this condition represents a functional disturbance of the pelvic circulation which is related to the menstrual cycle, its aetiology remains unknown. Indirect techniques demonstrate that the vasoconstrictive reflex response of the microcirculation of the foot to a rise in venous pressure is attenuated throughout the menstrual cycle. We wished to develop a simple and non-invasive direct measure of pelvic blood flow to aid diagnosis of this condition. Laser doppler blood flux measurements of the skin of the big toe and of the vaginal and rectal mucosa in the follicular and luteal phases of the menstrual cycle in 12 healthy asymptomatic premenopausal women (mean age 30 years) with regular cycles and in four healthy asymptomatic postmenopausal women (mean age 59 years) were carried out both in the supine position and in response to 40° head-up tilt. The coefficient of variation of resting vaginal flux was lower for measurements in postmenopausal women (0.04) and in premenopausal women in the follicular phase (0.07) compared with those in the luteal phase (0.16). At rest, vaginal blood flow was higher than rectal and skin flux in both premenopausal and postmenopausal women. In the follicular phase a decrease in flow was observed in response to head-up tilt in the skin (-32.0%), vagina (-34.3%) and rectum (-9.4%). In the luteal phase this reflex was attenuated at these three sites (-8.6%, +6.7% and +7.4% respectively). There were no significant reflex changes in postmenopausal women. Thus laser doppler fluximetry is a reproducible method for comparing the flux of blood in the microcirculation of the skin and of the vaginal and rectal mucosa. The skin is the least sensitive site for testing vascular reactivity in response to cyclical changes. The vaginal and rectal microcirculations are the most sensitive sites for testing visceral cyclical reactivity, and have the advantage of direct anatomical relevance. The follicular phase of the menstrual cycle is associated with greatest vascular reactivity and is the most appropriate phase during which to test for abnormal vascular responses.

The Global Positioning System (GPS), in addition to providing precise navigation and positioning information, produces precise time and frequency measurements. These measurements result from the atomic clocks in the GPS satellites, which are closely coupled to Universal Coordinated Time as maintained by the U. S. Naval Observatory [UTC(USNO)]. The application of these measurements to timekeeping and other systems requiring precise time and frequency is distinct from the navigation/positioning mission. This article will describe the differences in application of GPS to time and frequency uses. These uses will be described in the major areas of timekeeping; stationary uses, such as communications networking; and mobile use for aircraft and shipboard applications. The major considerations in application and operation with precise and less-capable oscilators will be described. Examples and data will be presented to illustrate the applications. © 1999 John Wiley & Sons, Inc.

To establish an accurate and reliable comparative database of discharge abstracts and to appraise its value for assessments of quality of care.

Separation of liquids from fine particle suspensions plays an important role in many industrial processes. In the past few years a number of technologies have been developed for the separation of slurries with coarse particle suspensions and intermediate particle sizes. However, separation of fine particles from their suspensions can be difficult and prohibitively costly.Battelle has developed a solid/liquid separation technology that utilizes differences in electro-kinetic and acoustic properties to enhance the efficiency of conventional solid/liquid separation techniques such as vacuum filters or presses. This method can dewater colloidal stable suspensions better than conventional techniques. Typical applications of this technology to food processing will be presented. Mechanisms involved during separation will also be discussed.

To investigate the consequences of different levels of caesarean section (CS) rate in terms of fetal and maternal outcomes.

Zusammenfassung Bei sechs Kaninchen wurde kontinuierlich der Gewebe-pH-Wert und diskontinuierlich der zentrale arterielle pH-Wert gemessen, während die Tiere 10 min lang mit 10% CO2 und 90% O2 beatmet wurden.

One hundred and fifty-five women attending antenatal clinics in an inner city area where the rate of AIDS reporting is high were interviewed to examine the acceptability of different modes and purposes of antenatal HIV testing. Eighty-two per cent of women felt the test should be available in antenatal clinics, but only 48% reported that they themselves would take the test. Seventy-four per cent would accept anonymous testing. Potential anxiety levels surrounding the HIV test were significantly higher than for other (currently routine) tests in antenatal clinics. The implications of these findings for policy are discussed.

In this paper, we develop a new method to approximate the solution to the Hamilton–Jacobi–Bellman (HJB) equation which arises in optimal control when the plant is modeled by nonlinear dynamics. The approximation is comprised of two steps. First, successive approximation is used to reduce the HJB equation to a sequence of linear partial differential equations. These equations are then approximated via the Galerkin spectral method. The resulting algorithm has several important advantages over previously reported methods. Namely, the resulting control is in feedback form and its associated region of attraction is well defined. In addition, all computations are performed off-line and the control can be made arbitrarily close to optimal. Accordingly, this paper presents a new tool for designing nonlinear control systems that adhere to a prescribed integral performance criterion.

Women who attended a gynaecological outpatient clinic complaining of pelvic pain of at least 6 months' duration were thoroughly investigated by examination, pathological tests and a laparoscopy to determine the cause of the pain. Those in whom no pathology could be demonstrated (32 women) were referred to a psychologist who attended the gynaecological clinic and who randomly assigned each woman to one of three treatment groups or to a control group. The object was to determine which of a number of simple therapeutic approaches proved most effective in the treatment of the pain. Results indicated that, although there was improvement (in terms of number of painfree days in the month) in all the treatment groups at three months, it was most marked in the non-directive counselling group. The results of a follow-up one year later are presented. During the study it became clear that the close association between the psychologist and the gynaecologist was an important factor in the acceptance by the patients of a psychological approach to their problem.

In reference [1] Dr. G. C. Taylor has described a useful advance in the techniques available for verification of outstanding claims estimates when the data provided is the cohort development of numbers and amounts of claims. In this note it is assumed that the numbers relate to settled claims and that the amounts relate to claim payments, so there is an implicit assumption that the pattern of partial payments is constant. If the amounts of settled claims were to be used, there would be a one/one relationship between the numbers and amounts, but the effect of the exogeneous factor would be blurred because the settlements in a year other than the first include partial payments made some time previously, and, by hypothesis, based on different factors. If information relating to partial payments is available the data can be examined for any major fluctuation in the pattern and allowance made accordingly.In paragraph (2) of reference [1] a brief description is given of a standard routine calculation in which the average distribution function of claim payments in time is estimated from the triangle of payments by a chain ladder technique. This distribution function is then used to estimate the expected development of the incomplete cohorts, the implicit assumption being made that the function was stable in time. With a constant rate of inflation the results obtained by this technique were found to be satisfactory but with a rapid increase in the rate of inflation the distribution function changed so that projection led to underestimates of the future claims payments. Various methods of adjusting the projections to allow for the change in the rate of inflation have been investigated, but they all involve an important element of subjective judgment and so far no generally suitable basis for “automatic” verification by this particular technique has been discovered. See however reference [2].

Astin is formally twenty years old, or should I say young, and the occasion of the 13th Colloquium being held in the country where it was constituted seems a very suitable opportunity for making a record of the ten years prior to its formal constitution. This is a personal account and sets out facts and impressions which are now becoming coloured by the vagaries of memory; others will have their own impressions of some of the events and I hope will be stimulated to correct any biasses or to supplement the historical record.Inevitably this record will not be complete and I apologise in advance for any significant omissions. Over the years I have accumulated a large mass of correspondence and had hoped to codify this in anticipation of this article but unfortunately a series of complications arising from my move to a part of rural England as a further stage in my retirement programme have delayed sorting through the mass of paper.My interest in non-life insurance was first stimulated when I was involved in the early 1930's in an analysis of the results of Fire and Auto Property business written in the US. This brought me face to face with the differences between the UK and US approach to profit measurement, in particular the real meaning of unearned premiums. The conventional UK method of basing the provision for unexpired risks on 40% of the premiums written during the year led to significant distortion in the emergence of profits (or losses) with an increasing volume of business, a large proportion of which was for periods of three years. Equally the US method of basing a statutory result without any allowance for the equity in the unearned premiums led to further distortions of the true profit, quite apart from the practice, then permitted, of substantial portfolio reinsurance transactions at the close of accounting periods.

This paper was inspired by comments by H. L. Seal in a series of lectures given to the Actuaries Club in New York and by a paper of his recently published in the Swiss Actuarial Journal (Seal, 1972 [6]). In his lectures he showed that the probability U(w, t)that a risk reserve at every epoch t, where o < t= twill be non negative when the initial risk reserve is wis related to , the probability that the aggregate claim outgo through epoch tdoes not exceed by the relationshipwhere ?is the security loading and f(x, t)= (?/?x) F(x, t).It is assumed that the d.f. F(x, t)is differentiable eith regard to xwith a possible exception at the point x= o.Using an extension of the “ballot theorem” in Chapter III of Feller (1968 [4]) he showed that and observed that if numerical values of F(x, t)were available values of U(w, t)could be computed.

Retinoids exert their biological effects by binding to and activating nuclear receptors that interact with responsive elements on DNA to promote gene transcription. There are two families of retinoid receptors, the retinoic acid receptor (RAR) family and the retinoid X receptor (RXR) family, which are each further divided into three subclasses:  RARα,β,γ and RXRα,β,γ. Herein we describe the synthesis and structure−activity relationships of a new series of diaryl sulfide retinoid analogs that specifically bind and transactivate the RXRs. Furthermore, the sulfoxide and sulfone derivatives of these analogs are partial agonists which activate the RXRs only at high concentrations. Thus, these compounds possess a potential site of metabolic deactivation and may have less prolonged systemic effects than other compounds with arotinoid-like structures. We show also that these compounds have activity in nontransfected cells as demonstrated by their ability to induce TGase activity in HL-60 cells. Finally, we corroborate our earlier report that RXR-specific agonists may possess reduced teratogenic toxicity compared to RAR-specific agonists since these compounds are much less potent inhibitors of chondrogenesis than RAR-specific agonists such as TTNPB.

In-vitro studies in both rodents and man suggest that GH can stimulate ovarian steroidogenesis, but it is not clear whether this effect is mediated by changes in circulating concentrations of insulin-like growth factor-1 (IGF-1) or whether it is a direct action on the ovary (or, indeed, both). In this study the effects of biosynthetic human GH (hGH) on the production of oestradiol and IGF-1 by human granulosa cells in culture were examined using ovarian tissue (from both normal and polycystic ovaries) which had not previously been exposed to exogenous gonadotrophin therapy. Addition of hGH (1 or 10ng/ml) to the incubation medium resulted in a significant (1.7 to 3.6 fold) increase in oestradiol accumulation after 48h in culture. Human GH also had a significant additive effect on the dose-related responsiveness of granulosa cell oestradiol production to hFSH. Concentrations of IGF-1 in the medium were undetectable in each of these experiments. These studies demonstrate that hGH has a potent, direct stimulatory effect on production of oestradiol by the human ovary which is independent of the effect of FSH. These findings have important implications for understanding the physiological role of hGH in human ovarian function as well as for therapeutic use of biosynthetic hGH for induction of ovulation.

SummaryInterim findings are reported from a planned 3-year study of the psychological, hormonal and plasma tryptophan changes occurring in women following hysterectomy and who have been treated with either piperazine oestrone sulphate (1.5 mg b.d.) or placebo for 6 months or longer. In patients treated with piperazine oestrone sulphate, there was a highly significant reduction in depressive symptoms, and a significant increase in total plasma tryptophan. In contrast to the hormone-treated patients, the placebo-treated group showed no such changes, but a significant increase in plasma luteinizing hormone.

In a prospective study, 127 patients attending a Menopause Clinic had uterine curettage performed prior to oestrogen therapy and at intervals during treatment with three different natural oestrogen regimes. At pre-treatment curettage three patients (2%) were found to have carcinoma of the endometrium and nine patients (7%) were found to have endometrial hyperplasia. Thirty seven patients with normal endometrium at pre-treatment curettage received cyclical natural oestrogen regimes or sequential oestrogen/progestogen regimes. Eleven (44%) of the 25 patients given cyclical high dose oestrogen regimes developed endometrial hyperplasia but only one (13%) of eight patients given cyclical low dose oestrogen regimes developed this condition. All four patients given sequential oestrogen/progestogen regimes continued to have normal endometrium during therapy. Four patients (33%) developed endometrial hyperplasia within seven months of the commencement of therapy but de novo development of hyperplasia could be delayed for as long as 24 months. Pre-treatment hyperplasia was associated with elevated urinary total oestrogen excretion. During cyclical oestrogen therapy the urinary total oestrogen levels were high, in and above the range known to be associated with pre-treatment hyperplasia. Eleven patients with endometrial hyperplasia, either pre-treatment or oestrogen induced, were subsequently treated with sequential oestrogen/progestogen regimes; and in all cases there was a reversal from endometrial hyperplasia to normal endometrium. In one patient a reduction in exogenous oestrogens from a cyclical high dose to a cyclical low dose regime was not followed by a reversal in endometrial hyperplasia. Two patients with pre-treatment endometrial hyperplasia developed adenocarcinoma of the endometrium during cyclical high dose oestrogen therapy. Five of the nine patients with endometrial hyperplasia at pre-treatment curettage had experienced no abnormal vaginal bleeding. Of the patients with normal endometrium, both pre-treatment and during cyclical oestrogen therapy, regular withdrawal bleeding was experienced by ten patients (53%) during therapy; withdrawal or breakthrough bleeding by 17 patients (90%) and two patients (10%) had no vaginal bleeding. Of the patients with normal endometrium at pre-treatment curettage who developed endometrial hyperplasia during cyclical oestrogen therapy regular withdrawal bleeding was experienced by three patients (25%) during therapy; withdrawal or breakthrough bleeding by eight patients (67%) and four patients (33%) had no vaginal bleeding. In total, 15 patients received sequential oestrogen/progestogen regimes; 14 patients (93%) had regular withdrawal bleeding while one patient had breakthrough bleeding during sequential therapy.

Gynaecological pain of apparently unknown aetiology is an extremely common problem in gynaecological practice. It is ill understood and wreaks havoc with women's lives. The economic cost of gynaecological pain is discussed elsewhere in this supplement. The human cost must not be overlooked. Postcoital ache and dyspareunia are common symptoms in the pelvic pain syndrome and are associated with a high incidence of apareunia (Beard et al., 1977). Naturally this causes a great deal of unhappiness and irretrievable breakdown of relationships are common in our experience (Gangar et al., unpublished studies).

Retinoid induction of epidermal hyperplasia was investigated in hairless mice with synthetic ligands for the retinoic acid (RAR) and retinoid X (RXR) nuclear receptors. Induction of hyperplasia by all-trans retinoic acid and the RAR-specific retinoids TTNPB, tazarotene and AGN 190121 varied over a wide range (ED50 = 0.2-100 nmol/animal in three daily applications). Potency of induction was not directly correlated to receptor-binding affinity, but specificity of action could be demonstrated by inhibition with the high-affinity antagonist of the RARs, AGN 193109. Although RAR is functionally complexed with RXR in vivo, RXR-selective compounds have only weak potency in induction of hyperplasia. The ED50 value of the RXR-selective AGN 191701 was 600 nmol/animal compared with an ED50 value of 0.2 nmol for the structurally similar RAR-selective TTNPB. SR11237 and SR11217, also RXR-selective, each have an ED50 value of >1000 nmol. Unlike RAR-specific retinoids, RXR-selective retinoids cause only very mild skin flaking at high doses. Relative potencies for cumulative topical irritation (flaking and abrasion) of both RAR and RXR ligands were well correlated with epidermal hyperplasia. These data are consistent with RXR as a silent partner in the RAR-RXR heterodimer in skin.

To investigate the Possible role of substance P as an endothelial factor in the local regulation of vascular tone in the human ovarian vein.

Gestational diabetes is a clinical entity associated with a significant incidence in diabetes in the later life of the mother and increase in fetal and neonatal morbidity. Lack of agreement on diagnostic criteria and the methodology of glucose tolerance testing has led to inconsistency in the results of published studies. It is recommended that all women should be screened for carbohydrate intolerance in pregnancy.

Abstract: The choice of biocompatible stimulating electrodes for various biomedical applications varies with the type of electrode-tissue interface, biomolecules present, electrolyte background, preparation of electrode, interfacial potential, current density, electrode material, porosity, geometry, and inflammatory response. Illustrative examples are given to demonstrate the importance of these parameters. Topics discussed are: A) DC electrodes applied to partially keratinized epithelial membranes; B) Variation of the electrical impedance and biocompatibility of stimulating electrodes with electrode potential and surrounding pH; C) Influence of electrode geometry, porosity and pore size on biocompatibility; D) Body defense mechanisms at the sites of implantable stimulating electrodes; E) Thrombus formation at stimulating electrode interfaces and F) Sterilization of electrodes to ensure biocompatibility.

Abstract. A prospective, national survey of the UK which examined the management and outcome of pregnancy complicated by maternal diabetes is described. The perinatal mortality rate was 3.7 and 1.5 times greater than the overall UK rate and the malformation rate 6.4% and 1.9% in pregnancies where the mother had insulin-dependent and gestational diabetes respectively. In 57% of cases no blood glucose measurement was recorded in the first trimester of pregnancy. Significantly fewer malformed infants resulted from prenancies where a first trimester blood glucose was recorded, irrespective of the value. Second and third trimester blood glucose values did not predict malformation but correlated inversely with gestational age at delivery and this was the major factor predicting the outcome of pregnancy.

Abstract. A randomised prospective study of treatment with dietary restriction alone or insulin therapy with dietary advice was performed in 15 women with glucose intolerance diagnosed early in the third trimester of pregnancy. Twentyfour hour profiles of plasma glucose and 3-hydroxybutyrate were performed before and four weeks after commencing treatment. The effect on neonatal outcome was assessed.The case history of one of the patients in the study was sent to British physicians with a special interest in diabetes to obtain their opinion about the appropriate initial treatment of women with gestational diabetes.

1. A method is described for studying pelvic blood flow in women by the indirect method of measuring vaginal temperature changes in response to a posture change. Ten women with chronic pelvic pain and venous congestion and 10 normal subjects were observed during posture changes over a 2 h period. 2. Vaginal temperature minus axillary temperature rose after subjects changed from the supine to the seated position, indicating a fall in the rate of pelvic blood flow. 3. A significantly greater variance in the rate of change in vaginal temperature minus axillary temperature was found in patients with pelvic venous congestion compared with control subjects (P> 0.005). 4. The findings are consistent with a disorder of blood flow regulation in women with pelvic pain owing to congestion.

In preparing the notes on the subjects for discussion at the 4th ASTIN Colloquium at Trieste [1] I used some of the material which formed the basis of a talk given to the Scandinavian Actuarial Societies in September 1962. The papers presented in Trieste have established on a firm mathematical footing the formula for the excess loss premium derived in my note but the discussions also showed that some of the other 1962 material would be of interest.It will be appreciated that the question originally proposed, i.e. to calculate an excess of loss reinsurance premium when the only information available is the largest claim experienced in each of a succession of periods, was deliberately phrased in this form as being the most troublesome case likely to arise in practice. Clearly if other information is available it would not be rejected in arriving at a premium, but this immediately extends the problem to one of finding the best methods of combining information of different kinds. For example if, say, the largest 5 claims in each period are known, what technique will make the maximum use of the data? Such extensions of the problem are not discussed in this note. Furthermore, I am not unmindful of the valuable comment by Jung, “that there is a natural law which states that you can never get more out of a mincing machine than what you have put into it” [2].