Characteristics of women presenting with hepatitis B at antenatal care services in London, 2008-2018.

BACKGROUND: To support interventions to prevent mother-to-child transmission of hepatitis B and fill gaps in surveillance, the Enhanced Surveillance of Antenatal Hepatitis B (ESAHB) programme was implemented in London from 2008 to 2018 to collect demographic information on women who tested positive for hepatitis B during antenatal screening. We describe the epidemiology of hepatitis B in pregnancy, as reported to ESAHB. METHODS: The characteristics of pregnant women living with hepatitis B were described and rates were calculated by year, local authority and residence deprivation decile (1 being most deprived). Poisson regression tested the association between pregnant women living with hepatitis B and deprivation decile. RESULTS: Between 2008 and 2018, 8879 women living with hepatitis B in London (0.35 per 1000 women) reported 11 193 pregnancies. Annual hepatitis B rates remained stable, but there was strong evidence for an inverse association between rate and deprivation decile (P < 0.001). The majority of women in the cohort presented late to antenatal care, were born outside the UK in a hepatitis B endemic area or required an interpreter for consultations. CONCLUSIONS: ESAHB provided important data to inform service quality improvements for women living with hepatitis B. This analysis highlights the link between deprivation and hepatitis B.

Learning about COVID-19 across borders: public health information and adherence among international travellers to the UK.

OBJECTIVE: Public health control measures at borders have long been central to national strategies for the prevention and containment of infectious diseases. Travel was inevitably associated with the rapid global transmission of COVID-19. In the UK, public health authorities tried to reduce the risks of travel-associated spread by providing public health information at ports of entry. This study investigates risk assessment processes, decision-making and adherence to official advice among international travellers, to provide evidence for future policy on the provision of public health information to facilitate safer international travel. STUDY DESIGN: This study is a qualitative study evaluation. METHOD: International air passengers arriving at the London Heathrow Airport on scheduled flights from China and Singapore were approached for interview after consenting to contact in completed surveys. Semi-structured interviews were conducted by telephone, using two topic guides to explore views of official public health information and self-isolation. Interview transcripts were coded and analysed thematically. RESULTS: Participants regarded official advice from Public Health England as adequate at the time, despite observing differences with intervention measures implemented in their countries of departure. Most participants also described adopting precautionary measures, including self-isolation and the use of face coverings that went beyond official advice, but reported adherence to guidance on contacting health authorities was more variable. Adherence to the official guidance was informed by the perceived salience of specific transmission possibilities and containment measures assessed in relation to participants' local social and institutional environments. CONCLUSION: Analysis of study findings demonstrates that international air travellers' responses to public health advice constitute a proactive process of risk assessment and rationalised decision-making to guide preventive action. This process incorporates consideration of the current living situation, trust in information sources, correspondence with cultural logics and willingness to accept potential risk to self and significant others. Our findings concerning international passengers' understanding of, and compliance with, official advice and mitigation measures provide valuable evidence to inform future policy and generate recommendations on the presentation of public health information to facilitate safer international travel. Access to a central source of regularly updated official information would help minimise confusion between different national guidelines. Greater attention to the differentiated information needs of diverse groups in creating future public-facing guidance would help to minimise the uncertainties generated by the receipt of generic information.

Epidemiological investigation of recurrent outbreaks of haemolytic uraemic syndrome caused by Shiga toxin-producing Escherichia coli serotype O55:H7 in England, 2014-2018.

Recurrent outbreaks of haemolytic uraemic syndrome (HUS) caused by Shiga toxin-producing Escherichia coli (STEC) serotype O55:H7 occurred in England between 2014 and 2018. We reviewed the epidemiological evidence to identify potential source(s) and transmission routes of the pathogen, and to assess the on-going risk to public health. Over the 5-year period, there were 43 confirmed and three probable cases of STEC O55:H7. The median age of cases was 4 years old (range 6 months to 69 years old) and over half of all cases were female (28/46, 61%). There were 36/46 (78.3%) symptomatic cases, and over half of all cases developed HUS (25/46, 54%), including two fatal cases. No common food or environmental exposures were identified, although the majority of cases lived in rural or semi-rural environments and reported contact with both wild and domestic animals. This investigation informed policy on the clinical and public health management of HUS caused by STEC other than serotype O157:H7 (non-O157 STEC) in England, including comprehensive testing of all household contacts and household pets and more widespread use of polymerase chain reaction assays for the rapid diagnosis of STEC-HUS.

Public health information on COVID-19 for international travellers: lessons learned from a mixed-method evaluation.

OBJECTIVES: In the containment phase of the response to the COVID-19 outbreak, Public Health England (PHE) delivered advice to travellers arriving at major UK ports. We aimed to rapidly evaluate the impact and effectiveness of these communication materials for passengers in the early stages of the pandemic. STUDY DESIGN: The study design used is the mixed-methods evaluation. METHODS: A questionnaire survey and follow-up interviews with passengers arriving at London Heathrow Airport on scheduled flights from China and Singapore. The survey assessed passengers' knowledge of symptoms, actions to take, and attitudes towards PHE COVID-19 public health information; interviews explored their views of official public health information and self-isolation. RESULTS: One hundred and twenty-one passengers participated in the survey and 15 in follow-up interviews. Eighty three percentage of surveyed passengers correctly identified all three COVID-19 associated symptoms listed in PHE information at that time. Most could identify the recommended actions and found the advice understandable and trustworthy. Interviews revealed that passengers shared concerns about the lack of wider official action, and that passengers' knowledge had been acquired elsewhere as much from PHE. Respondents also noted their own agency in choosing to self-isolate, partially as a self-protective measure. CONCLUSION: PHE COVID-19 public health information was perceived as clear and acceptable, but we found that passengers acquired knowledge from various sources and they saw the provision of information alone on arrival as an insufficient official response. Our study provides fresh insights into the importance of taking greater account of diverse information sources and of the need for public assurance in creating public health information materials to address global health threats.

Metabolomic Profiles in Starved Light Breed Horses during the Refeeding Process.

The large population of emaciated horses continues to be an issue troubling the equine industry. However, little is known regarding the collection of equine metabolites (metabolome) during a malnourished state and the changes that occur throughout nutritional rehabilitation. In this study, ten emaciated horses underwent a refeeding process, during which blood samples were collected for a blood chemistry panel and metabolomics analysis via ultrahigh performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS). Significant differences among blood chemistry analytes and metabolite abundance during the critical care period (CCP; Days 1-10 of rehabilitation) and the recovery period (RP; the remainder of the rehabilitation process) were observed. Potentially toxic compounds, analytes related to liver, kidney, and muscle function, as well as energy-related metabolites were altered during the refeeding process. The combination of blood chemistry and metabolomics analyses on starved equine during rehabilitation provide vital biological insight and evidence that the refeeding process has a significant impact on the equine metabolome.

Nicotine blocks the suckling-induced rise in circulating prolactin in lactating rats.

In lactating rats the rapid suckling-induced release of pituitary prolactin into circulating blood is inhibited by a subcutaneous injection of nicotine. This treatment does not block the lesser "stress-induced" rise in prolactin in response to either. Although nicotine may impair milk production by its effect on prolactin release, it does not appear to block milk ejection from the lactating mammary gland.

Electrical activity of the hypothalamus effects of intraventricular catecholamines.

The injection of epinephrine into the third ventricle of the rat brain causes a biphasic elevation and depression in the integrated multiple-unit electrical activity of the median eminence. Activity in the arcuate nucleus decreases after the injection of the catecholamines. These changes in the integrated multiple-unit electrical activity may be related to the secretion of hormones by the anterior pituitary gland.

Voyager 2 radio observations of uranus.

Within distances to Uranus of about 6 x 10(6) kilometers (inbound) and 35 x 10(6) kilometers (outbound), the planetary radio astronomy experiment aboard Voyager 2 detected a wide variety of radio emissions. The emission was modulated in a period of 17.24 +/- 0.01 hours, which is identified as the rotation period of Uranus' magnetic field. Of the two poles where the axis of the off-center magnetic dipole (measured by the magnetometer experiment aboard Voyager 2) meets the planetary surface, the one closer to dipole center is now located on the nightside of the planet. The radio emission generally had maximum power and bandwidth when this pole was tipped toward the spacecraft. When the spacecraft entered the nightside hemisphere, which contains the stronger surface magnetic pole, the bandwidth increased dramatically and thereafter remained large. Dynamically evolving radio events of various kinds embedded in these emissions suggest a Uranian magnetosphere rich in magnetohydrodynamic phenomena.

Voyager planetary radio astronomy at neptune.

Detection of very intense short radio bursts from Neptune was possible as early as 30 days before closest approach and at least 22 days after closest approach. The bursts lay at frequencies in the range 100 to 1300 kilohertz, were narrowband and strongly polarized, and presumably originated in southern polar regions ofthe planet. Episodes of smooth emissions in the frequency range from 20 to 865 kilohertz were detected during an interval of at least 10 days around closest approach. The bursts and the smooth emissions can be described in terms of rotation in a period of 16.11 +/- 0.05 hours. The bursts came at regular intervals throughout the encounter, including episodes both before and after closest approach. The smooth emissions showed a half-cycle phase shift between the five episodes before and after closest approach. This experiment detected the foreshock of Neptune's magnetosphere and the impacts of dust at the times of ring-plane crossings and also near the time of closest approach. Finally, there is no evidence for Neptunian electrostatic discharges.

Two erbB-4 transcripts are expressed in normal breast and in most breast cancers.

ErbB-4 is a recently described member of the epidermal growth factor receptor (EGFR) family which together with erbB-3 acts as a receptor for a group of ligands known as the neuregulins (NRGs) or heregulins (HRGs). Unlike the EGFR and erbB-2 relatively little is known about the expression of erbB-4 in human tumours. Using RT-PCR and Southern blotting analysis we have investigated the expression of erbB-4 mRNA in a range of human tumour cell lines and in normal and malignant breast tissue. Using primers which amplified a 658 base pair (bp) region corresponding to part of the cytoplasmic domain of c-erbB-4 we found the receptor was expressed in some but not all breast and ovarian tumour cell lines and also in a glioma cell line. The highest level of erbB-4 expression was found in the ovarian carcinoma OVCAR-3 and the breast carcinoma T-47D. In all cell lines where the 'full-length' erbB-4 was detected, a second previously undescribed c-erbB-4 sequence was also found as a 610 bp PCR product. The alternative PCR product was identical in sequence to c-erbB-4 except for a deletion of 48 bp which encodes a consensus phosphatidylinositol 3-kinase (PI3K) binding site. This suggested that the two forms of erbB-4 might interact with different intracellular signalling pathways and therefore influence a wider variety of cellular responses to heregulin than previously thought. Expression of both erbB-4 variants was found in 7/7 normal breast tissues but only in 9/12 breast tumours analysed. In line with the terminology of Elenius et al. (1997b) we have designated the two isoforms of the C-terminal transcripts as CT-a (full-length) and CT-b which lacks the P13K binding motif. These results identify suitable cell lines for the further investigation of erbB-4 expression and function and suggest that the role of erbB-4 in breast cancer warrants further investigation with larger numbers of normal and malignant breast tissues.

Positive and negative feedback effects of ovarian steroids on luteinizing hormone release in ovariectomized rats following chronic depletion of hypothalamic norepinephrine.

The involvement of central noradrenergic mechanisms in the feedback control of LH secretion was studied in ovariectomized rats. Permanent depletion of hypothalamic norepinephrine (NE) was accomplished by transecting the ascending noradrenergic pathway (ANP) in the midbrain. A postcastration elevation in serum LH was observed in rats with complete transections of the ANP, and although the rise was somewhat slower than that seen in sham-cut animals, there was no significant difference between the two groups 5 weeks or more after ovariectomy. Both the positive and negative feedback actions of ovarian steroids remained intact after chronic depletion of NE, and animals with transections of the ANP actually had greater responses than sham-cut controls. In addition, phenoxybenzamine, an alpha-adrenergic receptor blocker which effectively blocked the steroid-induced LH surge in six of eight sham-cut ahimals, was ineffective in NE-depleted rats. These results support the concept that NE acts as a modulator of LH secretion but is not indispensable for feedback control mechanisms.

Effects of intraventricular catecholamines on luteinizing hormone release in ovariectomized-steroid-primed rats.

The effects of intraventricular norepinephrine (NE) and dopamine (DA) were studied in the awake, freely behaving rat. In long-term ovariectomized, estrogen-progesterone-primed (OVE E2-P) animals, blood samples were taken via indwelling intra-atrial catheters before and after intraventricular infusion of either pH-adjusted saline, NE )5 mug, 15 mug, 20 mug), or DA (4 mug, 15 mug), and plasma LH was measured by radioimmunoassay. Under urethane anesthesia, records were made of the effects of intraventricular saline and NE on the electrical activity of the arcuate nucleus in the form of multi-unit spike activity. In unanesthetized animals, intraventricular NE caused marked changes in behavior. The typical response consisted of three phases: generalized activation (5-7 min), feeding (5-15 min), and sleep 1-2 h). DA exerted similar behavioral effects but without the marked sleep phase characteristic of the NE response. The effects of the catecholamines on LH output were significant increases in plasma LH levels for all NE doses tested (5 mug, p less than .025; 15 mug, p less than .05; 20 mug, p less than .005), while DA had no effect. The dynamics of the LH response to NEwere similar at all dosage levels, and the increase caused by 20 mug NE was found to be essentially equal to that induced by a quick intravenous infusion of 1.25 ng LHRH. Arcuate nucleus multi-unit spike activity (MUSA) showed a clear response to intraventricular NE at a dosage capable of stimulating the release of LH. In every case, the initial effect was a decrease in spike activity. These results, considered in relation to previous findings, suggest that NE may be stimulatory to neurons secreting LH-releasing hormone (LHRH). The decrease in arcuate nucleus MUSA in response to NE implies that certain elements of this nucleus are inhibited during LH release, perhaps the dopaminergic tuberoinfundibular neurons.

Episodic patterns of luteinizing hormone and follicle-stimulating hormone release: differential secretory dynamics and adrenergic control in ovariectomized rats.

Long term (4 weeks) ovariectomized rats were bled sequentially at 5-min intervals for 5 h via indwelling intraatrial cannulas. Plasma LH and FSH secretory patterns were determined from the same plasma samples by RIA. Hormonal profiles were subjected to power spectral analysis to determine periodicities of plasma LH and FSH. Distinct and regular release patterns were observed for LH, with significant periodicities between 20-40 min. In contrast to LH, FSH oscillations were neither as distinct nor as regular. However, significant periodicities in FSH (50-60 min) were often detected. At times, plasma LH and FSH appeared to be synchronized, but there were numerous instances of differential secretion. The effects of intracerebroventricular infusion of norepinephine (NE) and clonidine (an alpha 2-agonist) were tested in another group of animals. After a 2- to 3-h control bleeding period each animal bearing a chronic third ventricle cannula received an intracerebroventricular infusion of 0.3 mumol NE, clonidine, or vehicle. Blood sampling was continued for 2-3 h after infusion. Intracerebroventricular infusion of NE caused rapid and potent inhibition of LH secretion with FSH affected to a lesser extent. NE infusion decreased mean plasma LH levels and LH pulse amplitude while causing a marked increase in pulse period. Although mean FSH levels declined after NE infusion, secretory episodes of FSH were detectable even in the absence of pulsatile LH secretion. Infusion of an equimolar dose of clonidine produced a biphasic response in LH, a transient elevation followed by a decrease in overall plasma levels. In contrast to LH, plasma FSH levels showed only a delayed decrease after clonidine infusion. No significant changes in pulse amplitude or pulse period for either gonadotropin were observed. These data show that plasma FSH, like LH, oscillates in a periodic manner, but when compared with episodic LH secretion there are both quantitative and qualitative differences. Although the neural mechanisms involved in periodic LH release are also involved to a lesser extent in FSH secretion, it appears that independent regulatory mechanisms exist for LH and FSH as well.

Limbic system involvement in the increase in plasma prolactin following cortical spreading depression in gonadotropin-treated female rats.

Cortical spreading depression (SD) was induced by applying 25% KCl to the frontal cerebral cortex in female rats under continuous ether anesthesia. Three weeks previously the animals had been subjected to sham operation, bilateral surgical "deefferentation" of the amygdala or transection of the dorsal columns of the fornix. During the week prior to experiment the rats were made "pseudopregnant" by treatment with PMS and hCG. Plasma prolactin was measured by radioimmunoassay in blood samples obtained from the peripheral circulation at 20 min intervals. After two control samples had been taken, KCl was applied to the cortex and sampling continued for another 100 min; In the sham-operated group prolactin levels increased with time following the application of KCl. Fornix-cut animals showed a similar, although briefer, increase with values significantly lower than those found in sham-operated animals at 80 min. The increase in plasma prolactin observed in sham-operated and fornix groups was completely abolished in amygdala-cut animals. These results indicate that limbic structures play a significant role in the mechanisms by which cortical SD elevates plasma prolactin levels under the present experimental conditions.

Electrical stimulation of mesencephalic noradrenergic pathway: effects on luteinizing hormone levels in blood of ovariectomized and ovariectomized, steroid-primed rats.

This study examined the effect of electrical stimulation of the dorsal mesencephalic tegmentum (DMT) region on blood LH levels in long term ovariectomized (OVX), pentobarbital-anesthetized rats, with the aim of activating the principal ascending noradrenergic (NE) bundle. In OVX unprimed rats, electrical stimulation (with parameters of 100 Hz, 0.5-msec effective biphasic pulses, 150-200 microA, and 15 sec on/off for up to 1.5 h) of the DMT region inside the ascending NE bundle either completely or partially inhibited the pulsatile pattern of blood LH levels characteristic of OVX animals; stimulation outside the NE bundle was ineffective. Pretreatment of OVX rats with a serotonin synthesis inhibitor, p-chlorophenylalanine (320 mg/kg, ip) 71 h before electrical stimulation of the DMT did not affect the stimulation-induced inhibition of pulsatile LH release. On the other hand, pretreatment of OVX rats with a tyrosine hydroxylase inhibitor, alpha-methyl-p-tyrosine (250 mg/kg, ip) 4.5 h before electrical stimulation of the DMT was effective in preventing the stimulation-induced inhibition of pulsatile LH release, thereby supporting a NE-mediated mechanism. In OVX rats primed with estradiol benzoate alone (5 micrograms/100 g BW for 2 days) or with 50 micrograms estradiol benzoate and 25 mg progesterone, electrical stimulation in the DMT was ineffective in altering the low, nonpulsatile blood levels of LH. The results in OVX unprimed rats suggest that activation of the ascending NE system can inhibit pulsatile LH release, thus indicating a possible functional importance of inhibitory (in addition to well-documented stimulatory) NE synapses in the modulation of LH release.

Blockade of LH release and ovulation in the rabbit with inhibitory analogues of luteinizing hormone releasing hormone.

Plasma LH levels and ovulation were studied in female rabbits following administration of several inhibitory analogues of luteinizing hormone-releasing hormone (LHRH) before and after mating with experienced males. Administration of (D-Phe2, D-Leu6)-LHRH (1.5 mg/kg sc) to does 30 min before mating did not prevent either LH release or ovulation. However, a single sc injection of (D-Phe2, L-Phe3, D-Phe6y-LHRH (6 mg/kg) given 30 min before mating in 4 rabbits resulted in a 30-60 min delay in the coitus-induced release of LH when compared with post-coital changes in the same animals injected with vehicle; however, all of the does ovulated. When multiple dosages of 4 mg/kg (D-Phe2, L-Phe3, D-Phe6)-LHRH were administered 3-5 times at half-hourly intervals beginning 30 min prior to mating there was a considerable reduction in plasma LH elevations at 0.5, 1.0, 2.0 and 4.0 h after mating and 3/5 treated rabbits showed partial or complete blockade of ovulation. Quite similar results were obtained with the same dosage of (D-Phe2, D-Trp3, D-Phe6)-LHRH. An early sharp peak in LH release and full ovulation were stimulated in 6 out of 6 does by a single iv injection of synthetic LHRH (500 ng/kg). However, in another experiment, three half-hourly sc injections (4 mg/kg) of (D-Phe2, L-Phe3, D-Phe6)-LHRH beginning 30 min before administering LHRH markedly reduced the rise in plasma LH (P less than 0.01) and completely blocked ovulation in all of the same 6 animals. An unsuccessful attempt was made to provide a test animal for LHRH analogue investigations by implanting 4 cm of silastic tubing filled with crystalline estradiol (E2) sc in ovariectomized (OVX) AND INTACT DOES. In OVX does the silastic E2 implants resulted in a progressive decline in the ability to release LH in response to mating at 6 and at 20 days after implantation. With ovaries present, the E2 implant permitted post-coital LH release and ovulation at 4 d but not at 30 d post-implantation. At 30 d after removal of the E2 implant three out of four does had fully recovered the ability to release LH and ovulate post-coitally. Collectively, these results indicate that inhibitory analogues of LHRH can effectively block the ovulatory response to exogenous LHRH in rabbits, but that coitally-induced LH release and ovulation are less susceptible to blockade by the analogues. Silastic E2 implants, however, progressively and reversibly reduce the capacity of does to release LH after mating.

Methodology for selection of human antibodies to membrane proteins from a phage-display library.

We describe a simple antigen capture technique for the selection of a specific human antibody to p185erbB-2, a transmembrane glycoprotein, from a library of human Fab genes expressed on the surface of bacteriophage. Magnetic beads coated with the rat antibody ICR55 have been used to capture erbB-2 antigen from Triton X-100 extracts of SKOV3 cells. The antigen-coated beads have then been used to select bacteriophage displaying human Fab with affinity for p185erbB-2. After 4 rounds of selection, 65 phage clones were isolated which bound specifically to p185erbB-2 in a capture assay. Nine of the clones which gave the strongest reaction in an ELISA were selected for further development and the Fab genes were subcloned into the expression vector pUC119his6mycXba and electroporated into E. coli TG1. Colonies were grown, induced and the supernatants tested for the presence of secreted human Fab. Supernatants from two of the 9 clones contained human Fab and one of these bound specifically to erbB-2 in a capture assay, stained the membranes of the erbB-2 overexpressing cell lines BT474 and SKBR3 and immunoprecipitated a protein of molecular weight 185 000 kDa from SKOV3 cells. We conclude that a membrane antigen captured by specific monoclonal antibody can be used successfully to select phage displaying human antibodies specific for the antigen.

A carcinogenic potency database of the standardized results of animal bioassays.

The preceding paper described our numerical index of carcinogenic potency, the TD50 and the statistical procedures adopted for estimating it from experimental data. This paper presents the Carcinogenic Potency Database, which includes results of about 3000 long-term, chronic experiments of 770 test compounds. Part II is a discussion of the sources of our data, the rationale for the inclusion of particular experiments and particular target sites, and the conventions adopted in summarizing the literature. Part III is a guide to the plot of results presented in Part IV. A number of appendices are provided to facilitate use of the database. The plot includes information about chronic cancer tests in mammals, such as dose and other aspects of experimental protocol, histopathology and tumor incidence, TD50 and its statistical significance, dose response, author's opinion and literature reference. The plot readily permits comparisons of carcinogenic potency and many other aspects of cancer tests; it also provides quantitative information about negative tests. The range of carcinogenic potency is over 10 million-fold.

Droperidol elimination after cardiopulmonary bypass surgery.

A high-dose (0.75 to 2.8 mg/kg) pharmacokinetic study of droperidol was undertaken in patients during the recovery phase after cardiac surgery involving hypothermic cardiopulmonary bypass (CPB). The elimination half-life of droperidol in these patients, determined from concentration-time data obtained after CPB, was significantly prolonged relative to previously reported mean values in younger surgical patients not undergoing CPB and receiving lower doses of the drug (0.05-0.20 mg/kg). On stratification of the patients by droperidol dose, there was an inverse correlation between the size of the dose and the elimination half-life of droperidol: mean half-life decreased as mean dose increased. This difference in elimination half-life was not related to the duration of the CPB procedure, or the total anesthetic time, both of which were not significantly different between the patient groups receiving the three different doses of droperidol. The magnitude or duration of hypothermia after CPB did not differ between the three patient groups. The differences in half-lives are more likely due to the clinical condition of the patients, such that the patients who received the higher doses of droperidol were also judged clinically to be less ill and thus eliminated droperidol more efficiently. This hypothesis, however, could not be supported due to the small number of patients studied. The results obtained in this study indicate that droperidol elimination is significantly prolonged after high-dose administration to elderly patients undergoing hypothermic CPB procedures during cardiac surgery.