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Rodenticides are a key component of rodent management strategies, but birds of prey are susceptible to non-target exposure. New rules on sale and use of rodenticide products were introduced across the UK in 2016 in an industry-led stewardship scheme, with the aim of reducing this risk. To determine if this intervention has achieved its aim, exposure to second generation anticoagulant rodenticides (SGARs) was measured in buzzards. Liver samples from 790 buzzards collected between 2005 and 2022 (excluding 2016 and 2017 samples) were analyzed and the percentage presence and concentrations of SGARs from pre-stewardship and post-stewardship samples were compared. There was no statistically significant decrease in the percentage of buzzards exposed to bromadiolone, difenacoum or combined SGAR residues after the introduction of stewardship. The percentage of buzzards exposed to brodifacoum increased significantly post-stewardship, from 8 % to 27 %. There were no significant decreases in the concentrations of individual SGARs post-stewardship but concentration of combined SGARs increased significantly post-stewardship. Individual buzzards were significantly more likely to be exposed to multiple SGARs post-stewardship. Rodenticide poisoning was recorded as the cause of death for 5 % of pre- and post-stewardship buzzards with detectable levels of SGARs, and 90 % of these had combined SGAR residues >0.1 mg/kg. These findings suggest that the industry-led stewardship scheme has not yet had the intended impact of reducing SGAR exposure in non-target wildlife. The study highlights a substantial increase in exposure of buzzards to brodifacoum and to multiple SGARs post-stewardship, indicating that further changes to the stewardship scheme may be necessary., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

The contamination of the environment by some veterinary medicines and their impact on wild animals is of increasing concern. However, there is a lack of information about their residues in wildlife. The sentinel animals most commonly used for monitoring the level of environmental contamination are birds of prey, and information on other carnivores and scavengers scarce. This study examined the livers from 118 foxes for residues of a range of 18 veterinary medicines (16 anthelmintic agents and 2 metabolites) used on farm livestock. The samples were collected from foxes, primarily in Scotland, shot during legal pest control activities conducted between 2014 and 2019. Closantel residues were detected in 18 samples, and the concentrations found ranged from 6.5 µgkg -1 to 1383 µgkg -1 . No other compounds were found in significant quantities. The results show a surprising frequency and level of closantel contamination, raising concerns about both the route of contamination and the potential impacts on wild animals and the environment, such as the potential for significant wildlife contamination to contribute to the development of closantel-resistant parasites. The results also suggest that red fox (Vulpes vulpes) could be a useful sentinel species for detecting and monitoring some veterinary medicine residues in the environment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2023. Published by Elsevier Inc. All rights reserved.)

Introduction: There is a stage migration for detection of kidney cancer, thus we aim to evaluate the distribution of metastatic renal cell carcinoma by presenting clinical T stage over time., Materials and Methods: The National Cancer Database was evaluated for patients with metastatic kidney cancer from 2010 to 2016. The primary outcome was the temporal trend of presenting clinical T stage over time. The secondary outcome was overall survival. Kaplan-Meier and Cox regression analyses were performed., Results: The incidence of metastatic kidney cancer has increased, from 3426 new cases in 2010 to 4510 in 2016. While diagnosis of metastasis has increased for all tumor stages over time, there has been a more rapid increase in metastasis of localized renal masses (cT1-T2) as compared to locally advanced disease (cT3-T4). In 2010, 46% of the new metastatic cases diagnosed were cT3-T4, while in 2016 this proportion decreased to 38.2%. Conversely, metastatic cases with cT1-T2 tumors increased from 54% in 2010 to 61.9% in 2016. Cox regression noted an increased risk of death correlating with higher clinical T stage. On Kaplan Meier analysis, the 2-year survival was 29.3%, 30.3%, 28.3%, and 16.0% for cT1, cT2, cT3, and cT4, respectively (logrank P < .001)., Conclusion: Metastatic kidney cancer is increasingly diagnosed at a lower presenting cT stage. Survival outcomes worsen with increasing cT stage in the setting of metastasis., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Manipulation under anaesthesia and arthroscopic capsular release are costly and invasive treatments for frozen shoulder, but their effectiveness remains uncertain. We compared these two surgical interventions with early structured physiotherapy plus steroid injection., Methods: In this multicentre, pragmatic, three-arm, superiority randomised trial, patients referred to secondary care for treatment of primary frozen shoulder were recruited from 35 hospital sites in the UK. Participants were adults (≥18 years) with unilateral frozen shoulder, characterised by restriction of passive external rotation (≥50%) in the affected shoulder. Participants were randomly assigned (2:2:1) to receive manipulation under anaesthesia, arthroscopic capsular release, or early structured physiotherapy. In manipulation under anaesthesia, the surgeon manipulated the affected shoulder to stretch and tear the tight capsule while the participant was under general anaesthesia, supplemented by a steroid injection. Arthroscopic capsular release, also done under general anaesthesia, involved surgically dividing the contracted anterior capsule in the rotator interval, followed by manipulation, with optional steroid injection. Both forms of surgery were followed by postprocedural physiotherapy. Early structured physiotherapy involved mobilisation techniques and a graduated home exercise programme supplemented by a steroid injection. Both early structured physiotherapy and postprocedural physiotherapy involved 12 sessions during up to 12 weeks. The primary outcome was the Oxford Shoulder Score (OSS; 0-48) at 12 months after randomisation, analysed by initial randomisation group. We sought a target difference of 5 OSS points between physiotherapy and either form of surgery, or 4 points between manipulation and capsular release. The trial registration is ISRCTN48804508., Findings: Between April 1, 2015, and Dec 31, 2017, we screened 914 patients, of whom 503 (55%) were randomly assigned. At 12 months, OSS data were available for 189 (94%) of 201 participants assigned to manipulation (mean estimate 38·3 points, 95% CI 36·9 to 39·7), 191 (94%) of 203 participants assigned to capsular release (40·3 points, 38·9 to 41·7), and 93 (94%) of 99 participants assigned to physiotherapy (37·2 points, 35·3 to 39·2). The mean group differences were 2·01 points (0·10 to 3·91) between the capsular release and manipulation groups, 3·06 points (0·71 to 5·41) between capsular release and physiotherapy, and 1·05 points (-1·28 to 3·39) between manipulation and physiotherapy. Eight serious adverse events were reported with capsular release and two with manipulation. At a willingness-to-pay threshold of £20 000 per quality-adjusted life-year, manipulation under anaesthesia had the highest probability of being cost-effective (0·8632, compared with 0·1366 for physiotherapy and 0·0002 for capsular release)., Interpretation: All mean differences on the assessment of shoulder pain and function (OSS) at the primary endpoint of 12 months were less than the target differences. Therefore, none of the three interventions were clinically superior. Arthoscopic capsular release carried higher risks, and manipulation under anaesthesia was the most cost-effective., Funding: The National Institute for Health Research Health Technology Assessment programme., (Copyright © 2020 The Author(s). Publishedx by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Anticoagulant rodenticides (ARs) are highly toxic compounds that are exclusively used for the control of rodent pests. Despite their defined use, they are nonetheless found in a large number of non-target species indicating widespread penetration of wildlife. Attempts to quantify the scale of problem are complicated by non-random sampling of individuals tested for AR contamination. The American mink (Neovison vison) is a wide ranging, non-native, generalist predator that is subject to wide scale control efforts in the UK. Exposure to eight ARs was determined in 99 mink trapped in NE Scotland, most of which were of known age. A high percentage (79%) of the animals had detectable residues of at least one AR, and more than 50% of the positive animals had two or more ARs. The most frequently detected compound was bromadiolone (75% of all animals tested), followed by difenacoum (53% of all mink), coumatetralyl (22%) and brodifacoum (9%). The probability of mink exposure to ARs increased by 4.5% per month of life, and was 1.7 times higher for mink caught in areas with a high, as opposed to a low, density of farms. The number of AR compounds acquired also increased with age and with farm density. No evidence was found for sexual differences in the concentration and number of ARs. The wide niche and dietary overlap of mink with several native carnivore species, and the fact that American mink are culled for conservation throughout Europe, suggest that this species may act as a sentinel species, and the application of these data to other native carnivores is discussed., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

A relatively rapid and specific method for the determination of chloralose in animal tissues by LCMSMS was developed. Isocratic reverse phase HPLC was used to introduce samples for electrospray negative ionisation tandem mass spectrometry. Methanol extracts were diluted to approximate the mobile phase composition, then filtered prior to analysis. Residues were identified by monitoring the multiple reaction monitoring (MRM) transitions of precursor ions mass:charge (m/z) 309 and 307 to a common m/z 161 product ion. Qualitative and quantitative confirmation data were acquired simultaneously by monitoring alternative MRM transitions. Calibration was linear over a working range of 0.025-1.3 microg/ml, and the limit of quantitation (LOQ) was 0.28 mg/kg for liver. The mean recovery was 88.5% from chicken muscle tissue fortified at 198-237 mg/kg, and ranged from 81.3 to 94.3% from liver tissue fortified at 1-52 mg/kg. The method is compared to a gas chromatography (GC) procedure previously employed.

Objective: To determine whether pulsatile perfusion is clinically beneficial for adult cardiac operations., Methods: Data concerning consecutive patients undergoing isolated coronary bypass surgery (n=1820) from January 1, 1997 to July 31, 1999 were reviewed., Results: Nine hundred fifteen patients received pulsatile perfusion (PP) while perfusion in the remaining 905 patients was nonpulsatile (NP). Patients in the PP group were older (64.0 +/- 9.2 years versus 63.1 +/- 9.9 years) and experienced more of the following: urgent operations (42.4% versus 38.0%), preoperative intra-aortic balloon pump (4.8% versus 1.8%), preoperative cerebrovascular accidents (CVA; 3.1% versus 1.3%) and renal insufficiency (10.5% versus 7.0%). The PP group had higher incidence of early postoperative mortality (2.6% versus 1.5%), CVA (3.1% versus 1.3%), need for dialysis (3.2% versus 2.2%) and longer hospital stay (9.2 +/- 8.3 days versus 8.5 +/- 5.8 days). The incidence of postoperative myocardial infarction and renal dysfunction was similar in both groups (2.0% versus 2.2% and 3.3% versus 3.9% respectively; not significant). Because of the significant difference in preoperative parameters for the PP and NP groups, the following three statistical techniques were used to isolate the effect of perfusion characteristics on operative outcome: multiple regression, propensity score and risk stratification. Multivariate analysis did not find PP to be protective against mortality, morbidity and mortality, and CVA or for the development of postoperative renal dysfunction. When propensity score analysis was applied, the incidence of cardiac morbidity and mortality was strongly associated with the quintile (first quintile 6.7%, fifth quintile 27.0%, P<0.001). Multivariate analysis including quintiles did not find PP to be an independent predictor for mortality or for morbidity and mortality. Risk stratification was performed for age and for preoperative creatinine clearance levels. In all groups, PP did not seem to reduce the incidence of morbidity, morbidity and mortality, or the development of postoperative renal dysfunction. In patients with preoperative renal dysfunction, mean postoperative creatinine levels and the need for dialysis following surgery were similar in the PP and NP groups., Conclusion: Pulsatile flow does not appear to offer any clinical benefit over nonpulsatile flow for cardiac surgery patients.

Knowledge and technologic advancements have created a myriad of new screening, diagnostic, and treatment options for women of reproductive age. These new options often raise ethical issues as the women, their health care professionals, and society adapt to the benefits while coping with the pressures and burdens these options create. Threats to accomplishing the good that midwifery strives to contribute to health care for the benefit of women are identified from the perspective of the midwife's instrumental and expressive roles. Suggestions are presented for resolving ethical dilemmas that may occur in the selection and implementation of health care options. A distinction is made between midwifery practice at the microlevel, which achieves the good through direct interaction with the woman, and the institutional macrolevel that promotes accomplishing the good in reproductive health care through policy developmental and management decisions.

Three dominant second-chromosome rearrangement mutations in Drosophila melanogaster, Aristapedioid1 (Arp), vestigial-Depilate (vgD), and vestigial62 (vg62), result in developmental abnormalities of the bristle sense organs on the notum, abdomen, legs, and wing margin. The bristle abnormalities are associated with overexpression of Suppressor 2 of zeste (Su(z)2). We constructed and transformed into flies Hsp70:cDNA constructs for Su(z)2 and the related and neighboring Polycomb group (Pc-G) gene Posterior Sex Combs (Psc). Heat shock-induced overexpression of these two genes (hs-Su(z)2 and hs-Psc) resulted in similar bristle abnormalities that in a developmental stage-specific manner mimicked those seen with the three rearrangement mutations. In addition, hs-Psc overexpression at white prepupae was lethal. The bristle abnormalities are reminiscent of those seen with reduced function of Notch, a neurogenic gene. We found that hs-Su(z)2 overexpression reduced the expression of a lac z enhancer trap in the neurogenic gene neuralized. Previous experiments found that loss of function mutations in Su(z)2 resulted in no bristle abnormalities. Analysis of Psc mitotic clones revealed no essential function of Psc in bristle development. Antibody staining of salivary gland polytene chromosomes showed that after heat shock induction of hs-Psc, Psc protein binds ectopically to hundreds of polytene chromosome loci. These data suggest that the bristle abnormalities seen with overexpression of Su(z)2 and Psc may result from altered expression of genes involved in bristle sense organ development that are not normal regulatory targets of these genes.

To identify causes and risk factors for pregnancy-related mortality in New York City, we analyzed 224 pregnancy-related deaths that occurred from 1980 to 1984. The leading causes of death were ectopic pregnancy complications, embolism, intrapartum cardiac arrest, and hypertension. Mortality ratios were determined by comparing the characteristics of the women whose death was pregnancy-related with those of women who had survived delivery of a live infant in New York City during the same period. Black and Hispanic women had mortality ratios that were respectively 4.2 and 2.0 times higher than those for white, non-Hispanic women. In comparison with women aged 20 to 24, those older than 30 were more than twice as likely to die from pregnancy-related causes, and those older than 40 were five times as likely to do so. Other factors that were associated with an increased risk of pregnancy-related mortality included 9 to 11 years of education, lack of private medical insurance, more than five previous pregnancies, and fewer than five prenatal visits. This study suggests that changes in current maternal-health and family-planning services will be required to achieve further reductions in preventable pregnancy-related mortality.

In an effort to explore the use of polypeptide growth factors as potential markers for cancer detection, we have identified the presence of transforming growth factor-alpha (TGF-alpha) in pooled urine of patients with metastatic breast cancer by a commercial radioimmunoassay (RIA) based on a rabbit antiserum raised to the C-terminal 17aa synthetic fragment of rat TGF-alpha. This TGF-alpha RIA detected both high molecular weight (HMW) and low molecular weight (LMW) forms of TGF-alpha in the conditioned media of a breast cancer cell line (MDA-MB-231) and in the urine of healthy women and those with breast cancer. The ratio of HMW to LMW species of TGF-alpha by RIA after Bio-Gel P-100 chromatography was approximately equal in pooled urine samples from both healthy women and those with breast cancer, and in the conditioned media from the cell line MDA-MB-231. Using established procedures for concentrating urinary proteins from 24-h urine samples by adsorption onto methyl-bonded microparticulate silica and selective elution by acetonitrile, TGF-alpha RIA results from women with disseminated breast carcinoma were compared with those of healthy pre- and post-menopausal control women. Analysis indicated a median TGF-alpha value of 981 ng/g urinary creatinine for urine samples from cancer patients (range 608 to 1737) and 642 ng/g creatinine (range 417 to 941) for control urine samples. Although the difference was statistically significant (p less than 0.05), urinary TGF-alpha detection with this assay method appears to have limited usefulness as a diagnostic marker for metastatic human adenocarcinoma of the breast.(ABSTRACT TRUNCATED AT 250 WORDS)

In an effort to make interleukin-2/lymphokine-activated killer cell (IL-2/LAK) therapy safer for cancer patients, we examined the efficacy of using Fenwal PL732 bags as tissue culture flasks. These bags can be sterilly connected using tubing kits thus reducing the risk of contamination to the cells. Peripheral blood mononuclear cells were obtained from normal donors or cancer patients undergoing IL-2/LAK cell therapy. Following Ficoll-Hypaque purification, these cells were incubated in the presence of IL-2 in either PL732 plastic bags or standard tissue culture flasks. Our results showed that LAK cells could be generated from either normal donors or cancer patients in the bags as well as in the flasks. Comparisons were made of the LAK cell populations obtained from the two sources and showed that each was similar in terms of morphology as determined by Wright stain differentials. The populations of cells were also similar in regard to cell surface phenotype as determined by flow cytometric analysis. In addition, recoveries from either tissue culture vessel as well as cell viability of the LAK cells were comparable. Finally, the LAK cells obtained from both sources were assessed for cytolytic activity against the tumor cell lines K562 and Daudi. These results showed that the cytolytic activity of the LAK cells against these target cells was the same whether the cells were obtained from the flasks or the bags.

Two components isolated by semi-preparative normal phase high-performance liquid chromatography (HPLC) of bromadiolone reference material were tentatively identified as diastereoisomeric forms. Examination by mass spectroscopy confirmed this identification and supporting evidence was provided by identical UV fluorescence characteristics. The separated isomers were used to examine the chromatographic properties of bromadiolone in ion-pair, ion-suppression and weak ion-exchange HPLC modes. Conditions suitable for the analytical determination of the individual diastereoisomers were established for each mode. The influence of mobile phase pH on the resolution of coumarin-based rodenticides by weak ion-exchange HPLC on an aminopropyl-bonded phase was studied. Clean-up techniques for the determination of residues of bromadiolone in animal tissue extracts were compared. A combined gel permeation and adsorption chromatographic procedure was preferred for sensitive assay; it permitted the use of either fluorescence or UV detection. The lower practical limit of determination of each isomer in animal tissues was 0.005 mg kg-1 using UV detection and 0.0005 mg kg-1 using fluorescence detection.