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In February 2023, a report of morbidity and mortality in waterbirds triggered a collaborative regional wildlife disease outbreak investigation and response, led by Parks Victoria. Triage, rehabilitation and diagnosis of sick and dead birds were undertaken by Zoos Victoria (ZV), Agriculture Victoria, Vets for Compassion, Wildlife Victoria and Melbourne Veterinary School (MVS). The field response focused on collection of sick and dead birds for wildlife welfare, for diagnosis, and to reduce environmental contamination. Botulism was suspected, based on clinical signs and lack of significant gross pathology, and this diagnosis was confirmed by PCR testing. Low pathogenicity avian influenza (LPAI) viruses non H5 or H7 were detected in two birds and ruled out in all in others tested. These incidental, non‐clinical LPAI detections are considered part of the natural wild bird virus community in Australia. A number of elements contributed to the collaborative effort. Regional individuals had the necessary connections for reporting, collecting and transporting birds. There was rapid determination by the Victorian Department of Energy, Environment and Climate Action (DEECA) that Parks Victoria, as the land managers, should lead the response. Zoos Victoria provided capacity and expertise in wildlife triage and rehabilitation, and Agriculture Victoria, ZV and MVS were responsible for veterinary management of the response and diagnosis. Field investigation and response were conducted by Parks Victoria, Agriculture Victoria, MVS and veterinary teams from Vets for Compassion and Wildlife Victoria. Wildlife Health Australia (WHA) provided guidance and information, approved National Significant Disease Investigation Program funding and captured the event in the national wildlife health information database. Communication and media were important for community understanding of the event. [ABSTRACT FROM AUTHOR]

Globally, there were an estimated 9.8 million measles cases and 207 500 measles deaths in 2019. As the effort to eliminate measles around the world continues, modeling remains a valuable tool for public health decision‐makers and program implementers. This study presents a novel approach to the use of a yearly transition function that formulates mathematically the vaccine schedules for different age groups while accounting for the effects of the age of vaccination, the timing of vaccination, and disease seasonality on the yearly number of measles cases in a country. The methodology presented adds to an existing modeling framework and expands its analysis, making its utilization more adjustable for the user and contributing to its conceptual clarity. This article also adjusts for the temporal interaction between vaccination and exposure to disease, applying adjustments to estimated yearly counts of cases and the number of vaccines administered that increase population immunity. These new model features provide the ability to forecast and compare the effects of different vaccination timing scenarios and seasonality of transmission on the expected disease incidence. Although the work presented is applied to the example of measles, it has potential relevance to modeling other vaccine‐preventable diseases. [ABSTRACT FROM AUTHOR]

Free nicotine patches may promote pre-operative smoking cessation. Smokers (≥ 10 cigarettes.day-1 ) awaiting non-urgent surgery were randomly assigned (3:1) to an offer of free nicotine patches or a control group who were not offered free nicotine patches. The suggested regimen lasted 5 weeks, with patch strength decreasing incrementally after 3 and 4 weeks. The primary outcome was smoking abstinence for ≥ 4 weeks, as self-reported by participants on the day of surgery, including, where possible, corroboration using exhaled carbon monoxide testing. Out of 600 included smokers, 447 (74.5%) were randomly assigned to an offer of pre-operative nicotine patches, with 175 (39.1%) of these accepting the offer and 56 (12.5%) using patches for ≥ 3 weeks. Out of 396 participants offered nicotine patches who were included for analysis, 36 (9.1%) quit smoking for ≥ 4 weeks before surgery as compared with 8 (5.9%) controls, OR 1.5 [95%CI 0.7-3.2], p = 0.300. Sixty-three (15.9%) quit smoking for 24 h before surgery as compared with 15 (11.1%) controls, OR 1.4 [95%CI 0.8-2.4], p = 0.200. Participants offered nicotine patches were more likely to engage in a cessation attempt lasting more than 24 h, 46 (11.6%) vs. 5 (3.7%), OR 3.4 [95%CI 1.8-8.8], p = 0.010. Out of 78 participants who quit smoking by the day of surgery and were followed up at 6 months, 46 (59%) had relapsed. Offering free nicotine patches stimulated interest in quitting compared with controls, but our protocol had limited effectiveness. [ABSTRACT FROM AUTHOR]

Objective: The PARENTS 1 study (Parents' Active Role and ENgagement in The review of their Stillbirth/perinatal death) found that parents would endorse the opportunity to give feedback into the perinatal mortality review (PNMR) process. In subsequent focus groups, healthcare professionals were positive about parental engagement, although they considered that there may be significant challenges. The objective of this study was to develop core principles and recommendations for parental engagement in PNMR in the UK.Methods: A two-round Delphi technique was followed to reach consensus on core principles for parental engagement in the PNMR process; Round 1 included a national consensus workshop and Round 2 an online questionnaire. The consensus meeting was attended by a national panel of stakeholders (clinical and academic experts, parent advocates, managers and commissioners) in stillbirth and neonatal and bereavement care. To develop recommendations for parental engagement, participants discussed four key areas comprising: communication with parents, including receiving feedback; the format of the PNMR meeting; the parental engagement pathway; and challenging aspects of engaging with parents in reviews. Content analysis was conducted to generate recommendations from the meeting for a subsequent anonymous web-based survey. Attendees of the consensus workshop and members of the PARENTS 2 Project Advisory Board were asked to rank recommendations using a 9-point Likert scale from 1 (not important) to 9 (critically important). It had been agreed a priori, in compliance with established Grading of Recommendations, Assessment, Development and Evaluation (GRADE) criteria, that 'consensus' would be achieved if over 70% of participants scored the principle as 'critical' (score of 7-9) and fewer than 15% scored the principle as 'not important' (score of 1-3). Principles for which consensus was achieved were included in the core recommendations.Results: Of the 29 invited stakeholders, 22 participated in the consensus meeting and 25 (86% response rate) in the subsequent online questionnaire in June 2017. Consensus was agreed on 12 core principles. Of the 25 participants, 96% agreed that a face-to-face explanation of the PNMR process was of critical importance, 72% considered that parents should be offered the opportunity to nominate a suitable advocate, 92% believed that responses to parents' comments should be formally documented, 96% indicated that it was vital for action plans to be translated into lessons learnt and that this process should be monitored, and 100% of stakeholders voted that a plain-English summary should be produced for the parents following the meeting. There was good agreement on a further seven principles.Conclusions: Key national stakeholders were unanimously supportive of parental engagement in the PNMR process and agreed on core principles to make this process feasible, meaningful and robust. A 6-month pilot of parental engagement in the PNMR process (PARENTS 2 study) in two UK units took place after the consensus on core principles. In collaboration with the National Perinatal Epidemiology Unit, the findings will inform the national standardized PNMR tool. © 2018 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Background: Stillbirth has a profound impact on women, families, and healthcare workers. The burden is highest in low- and middle-income countries (LMICs). There is need for respectful and supportive care for women, partners, and families after bereavement.Objective: To perform a qualitative meta-summary of parents' and healthcare professionals' experiences of care after stillbirth in LMICs.Search Strategy: Search terms were formulated by identifying all synonyms, thesaurus terms, and variations for stillbirth. Databases searched were AMED, EMBASE, MEDLINE, PsychINFO, BNI, CINAHL.Selection Criteria: Qualitative, quantitative, and mixed method studies that addressed parents' or healthcare professionals' experience of care after stillbirth in LMICs.Data Collection and Analysis: Studies were screened, and data extracted in duplicate. Data were analysed using the Sandelowski meta-summary technique that calculates frequency and intensity effect sizes (FES/IES).Main Results: In all, 118 full texts were screened, and 34 studies from 17 countries were included. FES range was 15-68%. Most studies had IES 1.5-4.5. Women experience a broad range of manifestations of grief following stillbirth, which may not be recognised by healthcare workers or in their communities. Lack of recognition exacerbates negative experiences of stigmatisation, blame, devaluation, and loss of social status. Adequately developed health systems, with trained and supported staff, are best equipped to provide the support and information that women want after stillbirth.Conclusions: Basic interventions could have an immediate impact on the experiences of women and their families after stillbirth. Examples include public education to reduce stigma, promoting the respectful maternity care agenda, and investigating stillbirth appropriately.Tweetable Abstract: Reducing stigma, promoting respectful care and investigating stillbirth have a positive impact after stillbirth for women and families in LMICs. [ABSTRACT FROM AUTHOR]

Solar radio bursts have the potential to affect space and terrestrial navigation, communication, and other technical systems that are sometimes overlooked. However, over the last decade a series of extreme L band solar radio bursts in December 2006 have renewed interest in these effects. In this paper we point out significant deficiencies in the solar radio data archives of the National Centers for Environmental Information (NCEI) that are used by most researchers in analyzing and producing statistics on solar radio burst phenomena. In particular, we examine the records submitted by the United States Air Force (USAF) Radio Solar Telescope Network (RSTN) and its predecessors from the period 1966 to 2010. Besides identifying substantial missing burst records we show that different observatories can have statistically different burst distributions, particularly at 245 MHz. We also point out that different solar cycles may show statistically different distributions and that it is a mistake to assume that the Sun shows similar behavior in different sunspot cycles. Large solar radio bursts are not confined to the period around sunspot maximum, and prediction of such events that utilize historical data will invariably be an underestimate due to archive data deficiencies. It is important that researchers and forecasters use historical occurrence frequency with caution in attempting to predict future cycles. [ABSTRACT FROM AUTHOR]

The vasculature is essential for proper organ function. Many pathologies are directly and indirectly related to vascular dysfunction, which causes significant morbidity and mortality. A common pathophysiological feature of diseased vessels is extracellular matrix (ECM) remodelling. Analysing the protein composition of the ECM by conventional antibody-based techniques is challenging; alternative splicing or post-translational modifications, such as glycosylation, can mask epitopes required for antibody recognition. By contrast, proteomic analysis by mass spectrometry enables the study of proteins without the constraints of antibodies. Recent advances in proteomic techniques make it feasible to characterize the composition of the vascular ECM and its remodelling in disease. These developments may lead to the discovery of novel prognostic and diagnostic markers. Thus, proteomics holds potential for identifying ECM signatures to monitor vascular disease processes. Furthermore, a better understanding of the ECM remodelling processes in the vasculature might make ECM-associated proteins more attractive targets for drug discovery efforts. In this review, we will summarize the role of the ECM in the vasculature. Then, we will describe the challenges associated with studying the intricate network of ECM proteins and the current proteomic strategies to analyse the vascular ECM in metabolic and cardiovascular diseases. [ABSTRACT FROM AUTHOR]

The author discusses the pregnancy of women who underwent into bariatric surgery. The author mentioned the common bariatric surgery procedures for weight loss which include laparoscopic adjustable gastric banding (LAGB), Roux-en-Y gastric bypass and sleeve gastrectomy. The author also discusses the nutritional deficiencies after malabsorptive surgery, sociodemographic factors on pregnant women such as smoking, parity, and age, and the effectiveness of surgical procedures.

Introduction Distress may affect a patient's ability to cope with and manage disease. Aim To report distress prevalence in adult patients with bleeding disorders and determine whether specific clinical and health characteristics, including disease severity and employment status, are associated with distress. Methods Patients who visited a Haemophilia Treatment Centre ( HTC) between January 1st, 2012 through February 28th, 2014 and who completed a distress screen, pain screen and questionnaire were evaluated cross sectionally. Distress was measured by the National Comprehensive Cancer Network Distress Management Tool, which allowed patients to rate recent distress on a 0-10 point scale. A rating of five or more was categorized as high distress. Pain was measured by the Brief Pain Inventory Short Form, which asked patients to rate pain types on 0-10 point scales. Patients reported employment and other demographic and behavioural information on the questionnaire. Primary diagnosis, age, HIV and HCV status were abstracted from medical records. Adjusted logistic regression was used to identify distress associations. Results High distress prevalence among 152 patients with bleeding disorders was 31.6%. Unemployment, disability, greater depressive symptoms and higher pain were associated with high distress in multivariable models. Bleeding disorder diagnosis, race/ethnicity, HIV/ HCV status and on-demand treatment regimen were not associated with high distress. Conclusion Distress among patients with congenital bleeding disorders followed at a comprehensive HTC was high and similar to that reported among patients with cancer. Future research should determine whether distress impacts clinical outcomes in patients with bleeding disorders as demonstrated in other chronic disorders. [ABSTRACT FROM AUTHOR]

Background A semiautomated hand-held device has been introduced in some phototherapy centres to establish the minimal erythema dose ( MED) before treatment with narrowband ultraviolet ( NBUV) B. Objectives To compare the semiautomated hand-held device with the conventional method of MED testing (a UV-opaque template and a panel of UVB fluorescent tubes), using the same series of incremented doses. Methods Twenty-four patients referred for treatment with NBUVB phototherapy were included. Each patient had MED testing with the conventional method and the semiautomated hand-held device at the same level of the left and right back. The results were read by four investigators each time. Results The semiautomated hand-held device was a significant estimator of the MED using the conventional panel method ( P < 0.001; r = 0.97). The average ratio of the hand-held MED to the conventional MED was 67%. The mean difference between the methods was 165 mJ/cm2. The interobserver test showed very high agreement for both methods of MED testing (Cronbach α coefficient 0.97 for the hand-held MED tester vs. 0.93 for the conventional method). Conclusions The semiautomated hand-held device MED results were lower than that of the conventional panel method and may prolong the treatment course by 2-3 treatments. The hand-held tester is a fast and reproducible method, and may allow more phototherapy units, limited by staff and time, to do MED testing. [ABSTRACT FROM AUTHOR]

Background/Purpose Vascular abnormalities play an acute role in the pathogenesis of psoriasis. In order to characterize vascular involvement in psoriasis and its regular clinical assessment in vivo, non-invasive high speed imaging with high resolution and high sensitivity is needed. Methods The correlation mapping optical coherence tomography (cm OCT) technique was used for in vivo microcirculation imaging of human forearm under normal and psoriatic conditions. The cm OCT technique developed by our group uses dense scanning OCT image acquisition and post-processing software based on correlation statistics. The frequency domain OCT system was used for imaging which acquires a 3D volume of 1024 × 1024 A-scans, each of 512 pixels deep in approximately 70 s. The cm OCT technique processes the resulting OCT volume within 116 s using a 7 × 7 kernel. Results 3D structural and functional (microcirculation) maps of the healthy tissue and the psoriatic plaque were obtained using the cm OCT technique. The presented results indicate that cm OCT allows not only the identification of the microvessels, but also produces more detailed microvascular networks showing how the blood vessels relate to each other in healthy tissue and within the plaque. The microcirculation pattern within the plaque is totally different from the healthy tissue. The distinct changes are also observed in vessel density, tortuosity, and orientation. Conclusion The cm OCT provides high sensitivity and imaging speed for in vivo microcirculation imaging within the human skin under normal and diseased conditions. [ABSTRACT FROM AUTHOR]

The voluntary phase of an industry-led national Bovine Viral Diarrhoea (BVD) eradication programme began in Ireland on January 1, 2012 with the goal of progressing to a compulsory programme in 2013. The development and implementation of the programme in 2012 was informed by a review of current and prior eradication programmes elsewhere in Europe and extensive stakeholder consultation. The programme was based on tissue tag testing of newborn calves in participating herds, with the status of the mothers of calves with positive or inconclusive results requiring clarification. Participating herd owners were required to comply with a series of guidelines, including not selling cattle suspected of being persistently infected. For herds compliant with the guidelines, the results from 2012 counted as one of three years of tag testing anticipated in the compulsory phase of the programme. Testing was carried out in laboratories designated for this purpose by the crossindustry BVD Implementation Group that oversees the programme. Results were reported to a central database managed by the Irish Cattle Breeding Federation, and the majority of results were reported to farmers' mobile telephones by SMS message. A detailed review of the programme was conducted, encompassing the period between January 1, 2012 and July 15, 2012, based on results from approximately 500,000 calves. This paper describes the establishment and structure of the programme, and the outcomes of the review, including findings at herd and animal level. [ABSTRACT FROM AUTHOR]

A cut plot experiment was undertaken at two sites in Ireland, one a free-draining acid brown earth at Moorepark ( MPK) and the other a fine loam soil with imperfect drainage at Johnstown Castle ( JC). The effect of applying the nitrification inhibitor dicyandiamide ( DCD) at 10 kg ha−1 in July, August and September or not applying DCD to plots receiving synthetic urine or zero urine on spring and annual herbage production was examined. In the experiment, each site received 350 kg nitrogen ( N) fertilizer ha−1 year−1. The application of DCD in August at a rate of 10 kg ha−1 significantly increased spring and annual herbage production by 14 and 15%, respectively, at MPK, when applied following urine application in year 1. There was no effect of DCD applied in year 1 on herbage production at JC. The application of DCD in August resulted in lower soil total oxidized N ( TON) content up to sampling day 56 post-urine application, at MPK in year 1, retaining higher N content in the soil. There was no effect of DCD on any of the parameters measured in year 2 at MPK or at JC. Urine application did not increase spring herbage production at either site. Urine application significantly increased annual herbage production at MPK only in year 1. Urine application increased annual herbage N uptake, herbage crude protein ( CP) content and soil mineral N at both sites in both years. [ABSTRACT FROM AUTHOR]

Monthly, overwinter and annual instantaneous growth rates for round goby Neogobius melanostomus were calculated with maximal growth occurring in July and August and almost no growth observed between ice appearance (October) and melt (March). Annual absolute growth rates averaged 27·3 ± 1·9 mm for males and 19·8 ± 2·4 mm for females. The most parsimonious Cormack-Jolly-Seber model indicated that both the survival and recapture probabilities were dependent on sampling date, but not sex. Survival estimates remained high throughout the 13 month study with a median weekly survival probability of 0·920 (25 and 75% quartiles: 0·767 and 0·991), an overwinter survival probability of 99% and an annual survival rate of 67%. Survival probabilities were lowest for both sexes near the completion of the N. melanostomus reproductive season in July and August which supports existing evidence of higher mortality after reproduction, while challenging the paradigm that male N. melanostomus suffer comparatively higher mortality as a result of reproduction than females. Evidence indicating that growth and mortality rates are highest at the end of the reproductive season not only highlights seasonal variability in N. melanostomus natural history, but may also guide the control of this invasive species to periods when they are most vulnerable. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Frajzyngier V, Ruminjo J, Asiimwe F, Barry T, Bello A, Danladi D, Ganda S, Idris S, Inoussa M, Lynch M, Mussell F, Podder D, Barone M. Factors influencing choice of surgical route of repair of genitourinary fistula, and the influence of route of repair on surgical outcomes: findings from a prospective cohort study. BJOG 2012;119:1344-1353. Objective The abdominal route of genitourinary fistula repair may be associated with longer term hospitalisation, hospital-associated infection and increased resource requirements. We examined: (1) the factors influencing the route of repair; (2) the influence of the route of repair on fistula closure 3 months following surgery; and (3) whether the influence of the route of repair on repair outcome varied by whether or not women met the published indications for abdominal repair. Design Prospective cohort study. Setting Eleven health facilities in sub-Saharan Africa and Asia. Population The 1274 women with genitourinary fistula presenting for surgical repair services. Methods Risk ratios (RRs) and 95% confidence intervals (95% CIs) were generated using log-binomial and Poisson (log-link) regression. Multivariable regression and propensity score matching were employed to adjust for confounding. Main outcome measures Abdominal route of repair and fistula closure at 3 months following fistula repair surgery. Results Published indications for abdominal route of repair (extensive scarring or tissue loss, genital infibulation, ureteric involvement, trigonal, supratrigonal, vesico-uterine or intracervical location or other abdominal pathology) predicted the abdominal route [adjusted risk ratio (ARR), 15.56; 95% CI, 2.12-114.00]. A vaginal route of repair was associated with increased risk of failed closure (ARR, 1.41; 95% CI, 1.05-1.88); stratified analyses suggested elevated risk among women meeting indications for the abdominal route. Conclusions Additional studies powered to test effect modification hypotheses are warranted to confirm whether the abdominal route of repair is beneficial for certain women. [ABSTRACT FROM AUTHOR]

Verocytotoxigenic Escherichia coli (VTEC) are highly significant zoonotic threats to public health, and have been the causative agent implicated in numerous high-profile outbreaks affecting large numbers of people. Serovar O157 is most frequently linked with human illness; however, other serovars, such as O26, O103, O111 and O145, have also been implicated. This study aimed to characterize the prevalence and virulence determinants of these five serovars in Irish dairy farm herds, and their milk. Using real-time PCR (RTi-PCR), bovine rectal faecal swabs and raw milk samples, along with milk filters, were screened for the presence of vt genes. Positive samples were then screened for the five serovars using sero-specific PCR. Serovar-positive samples were subjected to immunomagnetic separation, to isolate viable VTEC strains. These isolates were subsequently screened for four virulence factors: vt1, vt2, eaeA and hlyA. Three hundred and eighty six of the 600 rectal faecal swabs, 85 of the 117 milk-filters and 43 of the 120 bulk-tank milk samples, were positive for vt genes. From these 514 total vt-positive samples, 58 O26, 162 O103, 1 O111, 324 O145 and 26 O157 positives were detected by sero-specific RTi-PCR. Immunomagnetic separation yielded 12 O26, 26 O103, 0 O111, 19 O145 and 10 O157 isolates. Ten of these isolates contained at least one of the four virulence determinants screened for (i.e. vt1, vt2, eaeA and hlyA). Of these 10 isolates, pulsed-field gel electrophoresis showed that two of the O26 isolates from different farms were indistinguishable. Two O157 isolates were also indistinguishable. This study found serovars O103 and O145 to be the most prevalent in samples tested. Apart from the occurrence of VTEC in dairy herds, this study shows a high occurrence of vt genes in the environment, creating the possibility of horizontal gene transfer and emergence of new VTEC strains. [ABSTRACT FROM AUTHOR]

Salix spp. genotypes were grown in random intimate mixtures comprising 5, 10, 15 and 20 components at 3 planting densities (10 000, 15 000 and 20 000 cuttings ha−1). Planted in 1994/95, plots were harvested every 3 years in 1998/99 (previously reported), 2001/02, 2004/05 and 2007/08. Each individual stool in both mono- and mixture plots was weighed. The total yield from mixture plots was consistently higher than the mean of the components in mono-plots and with only limited exceptions higher than the yield of any of the individual components grown in mono-plots. This occurred despite the loss of a number of disease-susceptible genotypes. When a stool died the remaining plants were able to colonise the vacant space and compensate for the loss. There was no clear benefit in increasing the number of components from 10 to 15 or 20 although host diversity is considered to be an important contributor to the effectiveness of a mixture both in disease reduction and yield enhancement. It is argued that the use of Salix spp. mixtures is highly advantageous, even in the absence of any disease pressure, and that mixtures increase the sustainability of a willow plantation. [ABSTRACT FROM AUTHOR]

Background and Purpose: Increases in intracellular cyclic AMP (cAMP) augment the release/secretion of glucagon-like peptide-1 (GLP-1). As cAMP is hydrolysed by cAMP phosphodiesterases (PDEs), we determined the role of PDEs and particularly PDE4 in regulating GLP-1 release.Experimental Approach: GLP-1 release, PDE expression and activity were investigated using rats and GLUTag cells, a GLP-1-releasing cell line. The effects of rolipram, a selective PDE4 inhibitor both in vivo and in vitro and stably overexpressed catalytically inactive PDE4D5 (D556A-PDE4D5) mutant in vitro on GLP-1 release were investigated.Key Results: Rolipram (1.5 mg x kg(-1) i.v.) increased plasma GLP-1 concentrations approximately twofold above controls in anaesthetized rats and enhanced glucose-induced GLP-1 release in GLUTag cells (EC(50) approximately 1.2 nmol x L(-1)). PDE4D mRNA transcript and protein were detected in GLUTag cells using RT-PCR with gene-specific primers and Western blotting with a specific PDE4D antibody respectively. Moreover, significant PDE activity was inhibited by rolipram in GLUTag cells. A GLUTag cell clone (C1) stably overexpressing the D556A-PDE4D5 mutant, exhibited elevated intracellular cAMP levels and increased basal and glucose-induced GLP-1 release compared with vector-transfected control cells. A role for intracellular cAMP/PKA in enhancing GLP-1 release in response to overexpression of D556A-PDE4D5 mutant was demonstrated by the finding that the PKA inhibitor H89 reduced both basal and glucose-induced GLP-1 release by 37% and 39%, respectively, from C1 GLUTag cells.Conclusions and Implications: PDE4D may play an important role in regulating intracellular cAMP linked to the regulation of GLP-1 release. [ABSTRACT FROM AUTHOR]

Objective: To describe our experience in recognizing an unusual presentation of severe dyskaryosis at two large cytology centres using ThinPrep liquid-based cytology (LBC). LBC has been introduced in England following successful pilot studies. It is clear that LBC improves visualization and preservation of cells, and that sensitivity for high-grade dyskaryosis is at least as good as for conventional cytology, and may be better. Several variants of high-grade dyskaryosis have been described on conventional cytology, including small and pale cell dyskaryosis. These are also seen on LBC. We are reporting a new variant of dyskaryosis which in our experience is seen only in LBC specimens prepared by the Thinprep® method, which we have named bland dyskaryosis. This has not to our knowledge been previously described. Bland dyskaryosis is characterized by cells with a high nuclear/cytoplasmic ratio, nuclear hyperchromasia and is present in groups with a chaotic architecture. The chromatin pattern appears bland at low power screening examination. On high power examination, however, the chromatin pattern can be seen to be subtly abnormal. Nuclear membranes are smooth. These changes mimic endocervical cells or immature squamous metaplasia at low power. Method: Identification and description of cytological appearances observed in routine practice and correlation with histological diagnosis. Conclusion: The features of bland dyskaryosis should be disseminated through teaching activities. Recognition of this previously undescribed variant will prevent false negative reporting of LBC samples. [ABSTRACT FROM AUTHOR]

An overview of the pharmacokinetics of dirlotapide in beagle dogs is presented. The following mean parameters were observed after a 0.3-mg/kg i.v. dose of dirlotapide: plasma clearance of 7.8 mL/min/kg and volume of distribution of 1.3 L/kg. Following single oral doses of 0.05, 0.3, and 1.0 mg/kg to fed dogs and 0.3 mg/kg to fasted dogs using the commercial formulation, mean Cmax of 7.5, 46, 97, and 31 ng/mL, respectively, were observed at mean tmax of 0.8–2.0 h. AUC and Cmax increased with increasing dose, but not proportionally. Oral bioavailability was 22–41%. Exposure, as reflected by AUC, was 54% higher in the fed than fasted state. In a 14-day repeated-dose study (0.3 mg/kg dose), the mean accumulation ratio was 3.7. In a 3-month study at doses of 0.4–2.5 mg/kg, accumulation ratios ranged from 2.0 to 6.7 at day 29 and from 1.3 to 4.1 at day 87. In summary, dirlotapide exhibited low clearance, low first-pass metabolism, moderate volume of distribution, low-to-moderate oral bioavailability, a modest food effect, and variable accumulation. Large interanimal variability in systemic exposure was noted for all routes and doses, but there were no consistent sex differences. [ABSTRACT FROM AUTHOR]

Three once-daily oral doses of 0.2 mg/kg [14C]dirlotapide were administered to beagle dogs to study the absorption, distribution, metabolism, and excretion of dirlotapide. Mean 14C recovered at 2.5 and 4.5 h after the last dose was 90%. Mean 14C in urine, bile, and feces was <1%, 1.7%, and 56% of the dose, respectively. In tissues, 26% of the 14C dose was present in the gastrointestinal tract, 6.0% in liver, and <1% each in kidney, gall bladder, heart, and brain. To further characterize drug disposition, a single 2.5-mg/kg oral dose of [14C]dirlotapide was administered to beagle dogs. More than 84% of the dose had been eliminated by 72 h in feces, with 21% of the dose present in feces as parent dirlotapide. Less than 1% of the dose was excreted in urine. In bile collected during the first 24-h postdose from three dogs, 32% and 11% of the 14C dose was present in samples from male and female dogs, respectively. Based upon metabolite profiling of plasma, excreta, and bile samples, dirlotapide was extensively metabolized to more than 20 metabolites. Biliary/fecal excretion and the potential for enterohepatic recycling of metabolites are suggested. [ABSTRACT FROM AUTHOR]

Malaria vector control targeting the larval stages of mosquitoes was applied successfully against many species of Anopheles (Diptera: Culicidae) in malarious countries until the mid-20th Century. Since the introduction of DDT in the 1940s and the associated development of indoor residual spraying (IRS), which usually has a more powerful impact than larval control on vectorial capacity, the focus of malaria prevention programmes has shifted to the control of adult vectors. In the Afrotropical Region, where malaria is transmitted mainly by Anopheles funestus Giles and members of the Anopheles gambiae Giles complex, gaps in information on larval ecology and the ability of An. gambiae sensu lato to exploit a wide variety of larval habitats have discouraged efforts to develop and implement larval control strategies. Opportunities to complement adulticiding with other components of integrated vector management, along with concerns about insecticide resistance, environmental impacts, rising costs of IRS and logistical constraints, have stimulated renewed interest in larval control of malaria vectors. Techniques include environmental management, involving the temporary or permanent removal of anopheline larval habitats, as well as larviciding with chemical or biological agents. This present review covers large-scale trials of anopheline larval control methods, focusing on field studies in Africa conducted within the past 15 years. Although such studies are limited in number and scope, their results suggest that targeting larvae, particularly in human-made habitats, can significantly reduce malaria transmission in appropriate settings. These approaches are especially suitable for urban areas, where larval habitats are limited, particularly when applied in conjunction with IRS and other adulticidal measures, such as the use of insecticide treated bednets. [ABSTRACT FROM AUTHOR]

Until recently, an enormous effort was needed to apply genomic tools to ecological investigations, especially when striving to uncover the functional mechanisms of phenotypic plasticity and the genetic basis of evolutionary adaptation within natural populations. This present study aimed to develop a genomic resource for an organism ideally suited for functional ecology and evolutionary research. Over 760 unique DNA fragments containing microsatellite loci were isolated and characterized from Daphnia to provide more than 500 molecular markers for constructing a genetic map and for localizing chromosomal regions containing genes of ecological importance via quantitative trait locus analyses. Although primarily developed to genotype members of the Daphnia pulex species complex, a significant fraction of these markers is potentially valuable for population genetics and recombination mapping of distantly related species. Over 60% of markers tested in cross-specific amplifications are possibly conserved within the subgenus Daphnia, whereas 48 and 18% of tested primers are found to amplify subgenus Hyalodaphnia and subgenus Ctenodaphnia DNA, which represents ∼140 and 200 million years of evolutionary preservation. [ABSTRACT FROM AUTHOR]

It has long been suspected that cellular senescence is an anticancer mechanism; however, it has been difficult to understand the advantage for the organism of retaining mutant cells in a postmitotic state rather than simply deleting them by apoptosis. It is proposed that in certain circumstances apoptosis promotes neoplasia by causing cells adjacent to the deleted cell to divide and that the role of cellular senescence is to prevent this. This may be particularly important in mammalian stem cell niches. After loss of a stem cell from a niche, another stem cell within the same niche divides symmetrically to restore the original number. The most important human malignancies arise from tissues maintained by stem cells, and there is increasing evidence that stem cells are the targets for at least the initial genetic changes that occur during carcinogenesis. If a subset of stem cells within a niche arises containing an oncogenic mutation, then tumor suppressor mechanisms promote apoptosis of these cells, and the niche restores the original number of stem cells by replication of both normal and mutated stem cells. Thus, paradoxically apoptosis increases turnover of mutant cells with associated risk of further genetic changes. However, if in addition mutant cells can become senescent, then the niche is progressively filled by senescent cells until either the mutant cells are eliminated or the niche is completely occupied by postmitotic cells, thereby preventing further evolution of the neoplastic clone. The consequences of this hypothesis are explored by computer modeling. [ABSTRACT FROM AUTHOR]

Overall, about one-third of women operated upon because of suspected ovarian cancer turn out to have benign disease. This proportion will be even higher when the tumours are small. A more accurate method of determining which are malignant would reduce the number of unnecessary referrals to the cancer centre and increase the scope for conservative management. This pilot study of ultrasound and intravenous microbubble contrast in 20 women with small ovarian tumours enabled the identification of all four malignant lesions with good inter-observer agreement. These preliminary findings suggest that intravenous contrast improves the ultrasound identification of small ovarian malignancies and may provide an accurate way of selecting women who require to be referred urgently for surgery under the auspices of a gynaecological oncologist. The remainder might be considered for laparoscopic surgery or even for observation in some cases. [ABSTRACT FROM AUTHOR]

Aldehyde lipid oxidation products and protein:aldehyde adducts were detected in vitro and in stored ground beef. Propional, pentenal, hexanal and 4-hydroxynonenal (4-HNE) were the primary aldehydes formed during lipid oxidation. The 4-HNE concentration was higher in 1,2-dilinoleoyl-phosphatidylcholine liposomes (PCL) exposed to Mb than to AAPH (P < 0.05). Elevated concentrations of α-tocopherol (α-Toc) in PCL or microsomes reduced the production of aldehyde lipid oxidation products compared to controls (P < 0.05). Proteins adducted by 4-HNE, malondialdehyde, and hexenal, heptenal, octenal and nonenal (C6-C9enal) were detected in PCL, microsomes and beef by indirect ELISA. These results demonstrate that aldehydes produced during lipid oxidation can form adducts with proteins and that this may have implications for protein stability and functionality. [ABSTRACT FROM AUTHOR]

Objective To assess the role of mitozantrone, active in relapsed prostate cancer, as an adjuvant to hormonal treatment in patients with advanced prostate cancer. Patients and methods Between October 1990 and May 1995, 96 patients were entered into a stratified, randomized, single-institution study of hormonal therapy with a luteinizing hormone-releasing hormone agonist and flutamide, with or without four cycles of adjuvant mitozantrone. Of these, 93 patients were evaluable and the results were analysed in June 1999. Results Patients with localized prostate cancer receiving adjuvant chemotherapy had a higher initial objective response rate (95% vs 53%, P = 0.008) and median survival (80 vs 36 months, P = 0.04) than patients who were treated with hormonal therapy alone. There was no advantage to adjuvant chemotherapy in patients with metastatic prostate cancer. There were insignificant advantages to chemotherapy in overall response rates (55% vs 39%, P = 0.3) and PSA responses (82% vs 64%, P = 0.11). There was no difference between the patient groups in time to treatment failure. Conclusion There was a survival advantage in using adjuvant mitozantrone in patients with locally advanced prostate cancer. Although the study comprised relative few patients, the follow-up period was long and the advantage significant. We recommend that the study be extended to include more patients. [ABSTRACT FROM AUTHOR]

We discuss the construct of doubt about one's competence and suggest that doubt can have myriad consequences (e.g., self-handicapping, defensive pessimism). We focus on the effect of self-doubt when it is combined with a concern with performance and assert that this combination leads to the phenomenon of subjective overachievement. In two studies, we present a new 17-item Subjective Overachievement Scale (SOS), which includes two independent subscales measuring individual differences in self-doubt and concern with performance. The first study, consisting of two large samples (Ns = 2,311 and 1,703), provides evidence that the scale has high internal consistency and a clear two-factor structure. Additionally, the subscales have adequate test-retest reliability (Ns = 67 and 115). A second study reveals that the SOS has good convergent and discriminant validity. Both subscales are unrelated to social desirability but exhibit the predicted patterns of associations with other related constructs. The Concern with Performance Subscale is correlated with achievement motivation, whereas the Self-Doubt Subscale is correlated with scales assessing negative affectivity (e.g., self-esteem, social anxiety) and other self-related strategies associated with concerns about one's competence (e.g., self-handicapping, defensive pessimism, impostor phenomenon). The SOS, which combines the two subscales, appears to tap a unique strategy that individuals may use to deal with doubts about their own competence. [ABSTRACT FROM AUTHOR]

Abstract The age-related impairment in long-term potentiation in the rat dentate gyrus is coupled with an increase in the proinflammatory cytokine, interleukin-1β (IL-1β). It is possible that this increase in IL-1β might be a consequence of the age-related increase in reactive oxygen species production in hippocampal tissue. In this study we set out to identify the underlying cause of the age-related increase in reactive oxygen species production and to establish whether any consequences of such a change might impact on the ability of aged rats to sustain long-term potentiation (LTP). We report that there was an age-related increase in the activity of superoxide dismutase but no parallel increases in activities of glutathione peroxidase or catalase, while age-related decreases in the concentration of the scavengers, vitamins E and C and glutathione were also observed. We propose that these compromises in antioxidative strategies may result in an increase in reactive oxygen species production. The data described indicate that IL-1β and H2O2 increase the activity of two stress-activated mitogen-activated protein kinases, c-Jun NH2-terminal kinase (JNK) and p38 in vitro, while age-related increases in both kinases were observed. We propose that the endogenous increase in these parameters which occurs with age induces the increase in activity of the stress-activated kinases, which in turn impacts on the ability of the aged rat to sustain LTP. [ABSTRACT FROM AUTHOR]

Objective To assess the factors associated with loss of implant following penile prosthetic surgery and to make alterations in the management of patients to prevent this from occurring. Patients and methods A retrospective analysis was carried out of the factors associated with post-operative infection and erosion in 188 patients who underwent implantation of penile prostheses. A prospective study was then established in which 62 patients were managed by a set protocol designed to counteract the factors identified as being contributory to loss of implants in the retrospective review. Results In the retrospective study nine (4.8%) patients lost a prosthesis due to erosion. Erosion was noted to be more common with one type of implant which has since been modified. Infection was the cause of prosthesis loss in 12.2% of patients in the retrospective review. The new protocol resulted in a signi6cantly reduced infection rate in penile prostheses to 1.6% (P<0.05). Conclusion With attention to simple antiseptic prophylaxis, antibiotic penetration and continuing audit, a significant improvement in the loss of penile prostheses can be achieved along with a reduction in the amount of antibiotics prescribed. [ABSTRACT FROM AUTHOR]

Since their arrival in Britain most Vietnamese mothers have abandoned traditional infant feeding practices for 'modern' methods which are unsatisfactory and expensive. Health staff are not perceived as a source of information or support. This paper emphasizes the need for culturally sensitive initiatives to reverse this trend. [ABSTRACT FROM AUTHOR]

Phenylbutazone in doses of 200, 300 and 400 mg/day was administered chronically to six rheumatoid arthritic patients. At each steady-state the plasma levels of phenylbutazone, oxyphenbutazone and gamma- hydroxyphenylbutazone as well as the extents of binding of phenylbutazone and oxyphenbutazone to plasma proteins were measured. 2 Plasma concentrations of phenylbutazone did not increase proportionally with dose but when corrected for protein binding unbound concentrations of phenylbutazone did show a proportional increase with dose. 3 Plasma concentrations of oxyphenbutazone decreased with an increase in phenylbutazone dose suggesting either that the elimination of oxyphenbutazone is stimulated or its formation inhibited after chronic administration of phenylbutazone. 4 Binding studies with human serum albumin demonstrated the ability of phenylbutazone and oxyphenbutazone to mutually displace one another. Neither saturation of the protein binding sites nor displacement interactions could account for the changes in binding shown by phenylbutazone with increased dose. 5 gamma- hydroxyphenylbutazone concentrations increased proportionally with phenylbutazone dose reaching 68% of the phenylbutazone concentration in one patient. There was a large inter-subject variation in the gamma- hydroxyphenylbutazone concentrations. [ABSTRACT FROM AUTHOR]