More time in a community setting: A service evaluation of the impact of intrathecal drug delivery systems on place of care of patients with cancer pain.

BACKGROUND: Intrathecal Drug Delivery Systems are underutilised in the management of refractory cancer pain despite evidence of their efficacy. Not all patients who are offered this treatment modality accept it. There is no current evidence that indicates if the use of intrathecal drug delivery systems impacts on place of care for patients with cancer related pain. AIMS: This service evaluation compared place of care, place of death and morphine equivalent daily dose at end of life for patients in whom Intrathecal Drug Delivery was successfully established versus those who chose comprehensive medical management. SETTING/PARTICIPANTS: A retrospective longitudinal cohort study of 45 patients with cancer pain comparing those who had ongoing analgesia successfully delivered via an implanted Intrathecal Drug Delivery System (n = 28) with those who continued to receive comprehensive medical management (n = 17). RESULTS: There was a markedly greater time spent in the community in the intrathecal group than the medical management group (median 126.5vs 25.5 days; p = 0.002) and a lower morphine equivalent daily dose at end of life (median 127.5vs 440.0 p = 0.022). CONCLUSION: In patients with advanced cancer, the successful establishment of intrathecal analgesia is associated with more time in the community and a lower morphine equivalent daily dose at end of life. The study has low numbers, and the sample was retrospectively selected. Nevertheless, these findings suggest the initial investment of time in an inpatient setting may be beneficial. Further research is required, using larger, prospective studies of patient outcomes in this setting.

Do Microscopes Have Politics? Gendering the Electron Microscope in Laboratory Biological Research.

Objects like microscopes are gendered depending on their context. The introduction of the electron microscope at Leeds University in early 1940s Britain was under the control of high-status physicists, most of whom were men, who regulated its access over and against biologists. Moreover, the microscope required physical strength more associated with men than women, combined with a sound knowledge of physics. This article explores the challenges women encountered including access to scientific instruments when entering post-World War II electron microscopy through Irene Manton's career. It combines techno-political and gendered perspectives on the history of women in science. In particular, the study invites gendered understanding of early biological electron microscopy, at a university world-renowned on the subject, through the lens of one capital intensive microscope.

Efficacy of a low-dose candidate malaria vaccine, R21 in adjuvant Matrix-M, with seasonal administration to children in Burkina Faso: a randomised controlled trial.

BACKGROUND: Stalled progress in controlling Plasmodium falciparum malaria highlights the need for an effective and deployable vaccine. RTS,S/AS01, the most effective malaria vaccine candidate to date, demonstrated 56% efficacy over 12 months in African children. We therefore assessed a new candidate vaccine for safety and efficacy. METHODS: In this double-blind, randomised, controlled, phase 2b trial, the low-dose circumsporozoite protein-based vaccine R21, with two different doses of adjuvant Matrix-M (MM), was given to children aged 5-17 months in Nanoro, Burkina Faso-a highly seasonal malaria transmission setting. Three vaccinations were administered at 4-week intervals before the malaria season, with a fourth dose 1 year later. All vaccines were administered intramuscularly into the thigh. Group 1 received 5 µg R21 plus 25 µg MM, group 2 received 5 µg R21 plus 50 µg MM, and group 3, the control group, received rabies vaccinations. Children were randomly assigned (1:1:1) to groups 1-3. An independent statistician generated a random allocation list, using block randomisation with variable block sizes, which was used to assign participants. Participants, their families, and the local study team were all masked to group allocation. Only the pharmacists preparing the vaccine were unmasked to group allocation. Vaccine safety, immunogenicity, and efficacy were evaluated over 1 year. The primary objective assessed protective efficacy of R21 plus MM (R21/MM) from 14 days after the third vaccination to 6 months. Primary analyses of vaccine efficacy were based on a modified intention-to-treat population, which included all participants who received three vaccinations, allowing for inclusion of participants who received the wrong vaccine at any timepoint. This trial is registered with ClinicalTrials.gov, NCT03896724. FINDINGS: From May 7 to June 13, 2019, 498 children aged 5-17 months were screened, and 48 were excluded. 450 children were enrolled and received at least one vaccination. 150 children were allocated to group 1, 150 children were allocated to group 2, and 150 children were allocated to group 3. The final vaccination of the primary series was administered on Aug 7, 2019. R21/MM had a favourable safety profile and was well tolerated. The majority of adverse events were mild, with the most common event being fever. None of the seven serious adverse events were attributed to the vaccine. At the 6-month primary efficacy analysis, 43 (29%) of 146 participants in group 1, 38 (26%) of 146 participants in group 2, and 105 (71%) of 147 participants in group 3 developed clinical malaria. Vaccine efficacy was 74% (95% CI 63-82) in group 1 and 77% (67-84) in group 2 at 6 months. At 1 year, vaccine efficacy remained high, at 77% (67-84) in group 1. Participants vaccinated with R21/MM showed high titres of malaria-specific anti-Asn-Ala-Asn-Pro (NANP) antibodies 28 days after the third vaccination, which were almost doubled with the higher adjuvant dose. Titres waned but were boosted to levels similar to peak titres after the primary series of vaccinations after a fourth dose administered 1 year later. INTERPRETATION: R21/MM appears safe and very immunogenic in African children, and shows promising high-level efficacy. FUNDING: The European & Developing Countries Clinical Trials Partnership, Wellcome Trust, and National Institute for Health Research Oxford Biomedical Research Centre.

A restatement of the natural science evidence base regarding the source, spread and control of Campylobacter species causing human disease.

Food poisoning caused by Campylobacter (campylobacteriosis) is the most prevalent bacterial disease associated with the consumption of poultry, beef, lamb and pork meat and unpasteurized dairy products. A variety of livestock industry, food chain and public health interventions have been implemented or proposed to reduce disease prevalence, some of which entail costs for producers and retailers. This paper describes a project that set out to summarize the natural science evidence base relevant to campylobacteriosis control in as policy-neutral terms as possible. A series of evidence statements are listed and categorized according to the nature of the underlying information. The evidence summary forms the appendix to this paper and an annotated bibliography is provided in the electronic supplementary material.

'Take my kidneys but not my corneas'-Selective preferences as a hidden problem for 'opt-out' organ donation policy.

With aims to both increase organ supply and better reflect individual donation preferences, many nations worldwide have shifted from 'opt-in' to 'opt-out' systems for post-mortem organ donation (PMOD). In such countries, while a prospective donor's willingness to donate their organs/tissues for PMOD was previously ascertained-at least partially-by their having recorded positive donation preferences on an official register prior to death, this willingness is now presumed or inferred-at least partially-from their not having recorded an objection to PMOD-on an official organ donation register. Using evidence regarding the presence and prevalence of selective donation preferences, and via exploration of how appeals to donation preferences are used to both motivate and legitimate shifts to opt-out frameworks, this paper draws attention to a set of previously unexplored problems for opt-out organ donation arising in contexts where: (a) individuals demonstrate selective post-mortem organ/tissue donation preferences, (b) legislation provides prospective donors with the opportunity to selectively permit/refuse the donation of certain organs/tissues in line with these preferences. While selective preferences pose few problems for opt-in systems where a selective occasion is built into the process of signing the donor register, this is not the case for opt-out systems. The loss of this selective occasion can cause significant problems where appeals to preferences motivate/legitimate shifts to opt-out but evidence regarding variable preferences does not feed into determinations regarding organ/tissue exclusions. The nature of these problems depends on how the authorization aspect of 'opt-out' systems is framed (e.g. as presumed consent, deemed consent or, given the role of familial consent in many jurisdictions as consent in name only).

Presumed Dissent? Opt-out Organ Donation and the Exclusion of Organs and Tissues.

It is often claimed that a legitimate approach to organ donation is an opt-out system, also known as 'presumed consent', 'deemed consent', or 'deemed authorisation', whereby individuals are presumed or deemed willing to donate at least some of their organs and tissues after death unless they have explicitly refused permission. While sharing a default in favour of donation, such systems differ in several key respects, such as the role and importance assigned to the family members of prospective donors and their preferences, and exclusions and safeguards which often specify the demographic groups, purposes, or organs and tissues that will remain outside the scope of the opt-out system. Using the recent shift to opt-out in England, Scotland, and Northern Ireland as case studies, and by reference to the key goals motivating this shift across the UK, this article asks whether and, if so, why, and how, opt-out systems for post-mortem organ donation should restrict the types of organs and tissues for which consent is deemed. In other words, ought opt-out systems for PMOD presume dissent regarding the donation of certain organs and tissues?

Safety, pharmacokinetics and pharmacodynamics of a topical SYK inhibitor in cutaneous lupus erythematosus: A double-blind Phase Ib study.

The immunoregulator spleen tyrosine kinase (SYK) is upregulated in cutaneous lupus erythematosus (CLE). This double-blind, multicentre, Phase Ib study evaluated the safety, tolerability, pharmacokinetics, pharmacodynamics and clinical efficacy of the selective SYK inhibitor GSK2646264 in active CLE lesions. Two lesions from each participant (n = 11) were each randomized to topical application of 1% (w/w) GSK2646264 or placebo for 28 days; all participants received GSK2646264 and placebo. The primary endpoint was safety and tolerability of GSK2646264, assessed by adverse event incidence and a skin tolerability test. Secondary endpoints included change from baseline in clinical activity and mRNA expression of interferon-related genes in skin biopsies. Levels of several immune cell markers were evaluated over time. Eight (73%) participants experienced ≥ 1 adverse event (all mild in intensity), and maximal dermal response was similar for GSK2646264 and placebo. The expression of several interferon-related genes, including CXCL10 and OAS1, showed modest decreases from baseline after 28 days of treatment with GSK2646264 compared with placebo. Similar findings were observed for CD3 + T cell and CD11c + dendritic cell levels; however, overall clinical activity remained unchanged with GSK2646264 vs. placebo. Further studies are warranted to assess SYK inhibitors as potential treatment for CLE.

Effects of a topical treatment with spleen tyrosine kinase inhibitor in healthy subjects and patients with cold urticaria or chronic spontaneous urticaria: Results of a phase 1a/b randomised double-blind placebo-controlled study.

AIMS: To explore the safety, tolerability, pharmacokinetics and pharmacodynamics (PD) of GSK2646264 using skin challenge models. METHODS: Healthy volunteers (HV) with a positive allergen skin prick test received GSK2646264 (0.5% or 1% ww) and placebo creams on up to 10% body surface area (BSA). Cold (ColdU) or chronic spontaneous (CSU) urticaria patients received 1% GSK2646264 or placebo on up to 10% BSA. PD assessments included weal characteristics after skin allergen challenge, critical temperature threshold (CTT) in ColdU patients and defined area urticaria activity score in CSU patients. RESULTS: Thirty-four patients were randomised (17 HV, 12 ColdU, 5 CSU). Topical application of GSK2646264 and placebo was well tolerated. Systemic pharmacokinetics (AUC [0-24] h*ng/mL) was similar between HVs (Geomean 97.9 [%CV 37]) and ColdU patients (Geomean 68.2 [%CV 14; 3.5% BSA] or 167 [%CV 120; 10% BSA]). Whilst in HVs a similar reduction in skin allergen challenge weal area was observed following 3 applications of GSK2646264 and placebo, a trend towards a greater reduction was seen in ColdU with GSK2646264 compared to placebo. A clinically meaningful reduction in CTT, in ColdU patients treated with GSK2646264, was observed in 4 of 9 patients, who demonstrated either a complete inhibition of ColdU to ≤4°C (n = 2) or partial response (reduction by >4°C, n = 2). Due to the small number of CSU patients recruited, no meaningful conclusions could be drawn from the defined area urticaria activity score PD endpoint. CONCLUSION: This Phase 1/1b study confirms that GSK2646264 cream applied topically penetrates the skin and some reduction in CTT was observed. (NCT02424799).

Factors Associated with Prescription of Antimicrobial Drugs for Dogs and Cats, United Kingdom, 2014-2016.

Antimicrobial stewardship is a cornerstone of efforts to curtail antimicrobial resistance. To determine factors potentially influencing likelihood of prescribing antimicrobials for animals, we analyzed electronic health records for unwell dogs (n = 155,732 unique dogs, 281,543 consultations) and cats (n = 69,236 unique cats, 111,139 consultations) voluntarily contributed by 173 UK veterinary practices. Using multivariable mixed effects logistic regression, we found that factors associated with decreased odds of systemic antimicrobial prescription were client decisions focused on preventive health: vaccination (dogs, odds ratio [OR] 0.93, 95% CI, 0.90-0.95; cats, OR 0.92, 95% CI 0.89-0.95), insurance (dogs, OR 0.87, 95% CI 0.84-0.90; cats, OR 0.82, 95% CI 0.79-0.86), neutering of dogs (OR 0.90, 95% CI 0.88-0.92), and practices accredited by the Royal College of Veterinary Surgeons (OR 0.79, 95% 95% CI 0.68-0.92). This large multicenter companion animal study demonstrates the potential of preventive healthcare and client engagement to encourage responsible antimicrobial drug use.

Rationale and design of the Medical Research Council's Precision Medicine with Zibotentan in Microvascular Angina (PRIZE) trial.

Microvascular angina is caused by cardiac small vessel disease, and dysregulation of the endothelin system is implicated. The minor G allele of the non-coding single nucleotide polymorphism (SNP) rs9349379 enhances expression of the endothelin 1 gene in human vascular cells, increasing circulating concentrations of ET-1. The prevalence of this allele is higher in patients with ischemic heart disease. Zibotentan is a potent, selective inhibitor of the ETA receptor. We have identified zibotentan as a potential disease-modifying therapy for patients with microvascular angina. METHODS: We will assess the efficacy and safety of adjunctive treatment with oral zibotentan (10 mg daily) in patients with microvascular angina and assess whether rs9349379 (minor G allele; population prevalence ~36%) acts as a theragnostic biomarker of the response to treatment with zibotentan. The PRIZE trial is a prospective, randomized, double-blind, placebo-controlled, sequential cross-over trial. The study population will be enriched to ensure a G-allele frequency of 50% for the rs9349379 SNP. The participants will receive a single-blind placebo run-in followed by treatment with either 10 mg of zibotentan daily for 12 weeks then placebo for 12 weeks, or vice versa, in random order. The primary outcome is treadmill exercise duration using the Bruce protocol. The primary analysis will assess the within-subject difference in exercise duration following treatment with zibotentan versus placebo. CONCLUSION: PRIZE invokes precision medicine in microvascular angina. Should our hypotheses be confirmed, this developmental trial will inform the rationale and design for undertaking a larger multicenter trial.

Developing an International Registry for Uterus Transplantation (IRUTx): Promises and Challenges.

Uterus Transplantation (UTx) is an experimental vascular composite allograft designed to provide women with absolute uterine factor infertility with the opportunity to gestate and give birth to their future offspring. The number of UTx procedures performed worldwide now stands at ≥70 and as the number of cases performed increases so too does the volume of potential data that may be gathered to inform the development, practice and regulation of UTx. Given the value of this data, and the challenges associated with keeping track of cases and outcomes where data remains unpublished and/or scattered, scientists and academics conducting research into UTx have increasingly called for the swift creation, implementation and management of an international registry for Uterus Transplantation (IRUTx). This article explores and provides practical guidance regarding the potential benefits the IRUTx may provide to stakeholders, as well as the legal and ethical challenges that its creation may pose in terms of dataset design, consent, privacy, researcher compliance and governance.

Climate, human behaviour or environment: individual-based modelling of Campylobacter seasonality and strategies to reduce disease burden.

BACKGROUND: With over 800 million cases globally, campylobacteriosis is a major cause of food borne disease. In temperate climates incidence is highly seasonal but the underlying mechanisms are poorly understood, making human disease control difficult. We hypothesised that observed disease patterns reflect complex interactions between weather, patterns of human risk behaviour, immune status and level of food contamination. Only by understanding these can we find effective interventions. METHODS: We analysed trends in human Campylobacter cases in NE England from 2004 to 2009, investigating the associations between different risk factors and disease using time-series models. We then developed an individual-based (IB) model of risk behaviour, human immunological responses to infection and environmental contamination driven by weather and land use. We parameterised the IB model for NE England and compared outputs to observed numbers of reported cases each month in the population in 2004-2009. Finally, we used it to investigate different community level disease reduction strategies. RESULTS: Risk behaviours like countryside visits (t = 3.665, P < 0.001 and t = - 2.187, P = 0.029 for temperature and rainfall respectively), and consumption of barbecued food were strongly associated with weather, (t = 3.219, P = 0.002 and t = 2.015, P = 0.045 for weekly average temperature and average maximum temperature respectively) and also rain (t = 2.254, P = 0.02527). This suggests that the effect of weather was indirect, acting through changes in risk behaviour. The seasonal pattern of cases predicted by the IB model was significantly related to observed patterns (r = 0.72, P < 0.001) indicating that simulating risk behaviour could produce the observed seasonal patterns of cases. A vaccination strategy providing short-term immunity was more effective than educational interventions to modify human risk behaviour. Extending immunity to 1 year from 20 days reduced disease burden by an order of magnitude (from 2412-2414 to 203-309 cases per 50,000 person-years). CONCLUSIONS: This is the first interdisciplinary study to integrate environment, risk behaviour, socio-demographics and immunology to model Campylobacter infection, including pathways to mitigation. We conclude that vaccination is likely to be the best route for intervening against campylobacteriosis despite the technical problems associated with understanding both the underlying human immunology and genetic variation in the pathogen, and the likely cost of vaccine development.

Ethical and policy issues raised by uterus transplants.

INTRODUCTION: In 2014, Brännström and colleagues reported the first human live birth following uterine transplantation (UTx). Research into this treatment for absolute uterine factor infertility has since grown with clinical trials currently taking place across centers in at least thirteen countries worldwide. SOURCES OF DATA: This review summarizes and critiques the academic literature on ethical and policy issues raised by UTx. AREAS OF AGREEMENT: There is general agreement on the importance of risk reduction and, in principle, to the sharing and maintenance of patient data on an international registry. AREAS OF CONTROVERSY: There are numerous areas of controversy ranging from whether it is ethically justified to carry out uterus transplants at all (considering the associated health risks) to how deceased donor organs for transplant should be allocated. This review focuses on three key issues: the choice between deceased and living donors, ensuring valid consent to the procedure and access to treatment. GROWING POINTS: UTx is presently a novel and rare procedure but is likely to become more commonplace in the foreseeable future, given the large number of surgical teams working on it worldwide. AREAS TIMELY FOR DEVELOPING RESEARCH: Uterus transplantation requires us to re-examine fundamental questions about the ethical and social value of gestation. If eventually extended to transgender women or even to men, it may also require us to reconceptualize what it is to be a 'father' or to be a 'mother', and the definition of these terms in law.

Acute changes in the colonic microbiota are associated with large intestinal forms of surgical colic.

BACKGROUND: Horses that undergo surgery for treatment of primary large colon disease have been reported to be at increased risk of developing recurrent colic episodes postoperatively. The reasons for this are currently unknown. The aim of the current study was to characterise the faecal microbiota of horses with colic signs associated with primary large colon lesions treated surgically and to compare the composition of their faecal microbiota to that of a control group of horses undergoing emergency orthopaedic treatment. Faecal samples were collected from horses in both groups on admission to hospital, during hospitalisation and following discharge from hospital for a total duration of 12 weeks. Additionally, colonic content samples were collected from surgical colic patients if pelvic flexure enterotomy was performed during laparotomy. A total of 12 samples were collected per horse. DNA was extracted from samples using a commercial kit. Amplicon mixtures were created by PCR amplification of the V1 - V2 regions of the bacterial 16S rRNA genes and submitted for sequencing using the Ion Torrent PGM next-generation sequencing system. Multivariate data analysis was used to characterise the faecal microbiota and to investigate differences between groups. RESULTS: Reduced species richness was evident in the colonic samples of the colic group compared to concurrent sampling of the faeces. Alpha and beta diversity differed significantly between the faecal and colonic microbiota with 304 significantly differentially abundant OTUs identified. Only 46 OTUs varied significantly between the colic and control group. There were no significant differences in alpha and beta diversity of faecal microbiota between colic and control horses at admission. However, this lack of significant differences between groups should be interpreted with caution due to a small sample size. CONCLUSIONS: The results of the current study suggest that faecal samples collected at hospital admission in colic cases may not accurately represent changes in upper gut microbiota in horses with colic due to large colon disease.

Context-Specific Economic Evaluation for Molecular Pathology Tests: An Application in Colorectal Cancer in the West of Scotland.

OBJECTIVES: The cost-effectiveness of molecular pathology testing is highly context dependent. The field is fast-moving, and national health technology assessment may not be relevant or timely for local decision makers. This study illustrates a method of context-specific economic evaluation that can be carried out in a limited timescale without extensive resources. METHODS: We established a multi-disciplinary group including an oncologist, pathologists and a health economist. We set out diagnostic and treatment pathways and costs using registry data, health technology assessments, guidelines, audit data, and estimates from the group. Sensitivity analysis varied input parameters across plausible ranges. The evaluation setting was the West of Scotland and UK NHS perspective was adopted. The evaluation was assessed against the AdHopHTA checklist for hospital-based health technology assessment. RESULTS: A context-specific economic evaluation could be carried out on a timely basis using limited resources. The evaluation met all relevant criteria in the AdHopHTA checklist. Health outcomes were expected to be at least equal to the current strategy. Annual cost savings of £637,000 were estimated resulting primarily from a reduction in the proportion of patients receiving intravenous infusional chemotherapy regimens. The result was not sensitive to any parameter. The data driving the main cost saving came from a small clinical audit. We recommended this finding was confirmed in a larger population. CONCLUSIONS: The method could be used to evaluate testing changes elsewhere. The results of the case study may be transferable to other jurisdictions where the organization of cancer services is fragmented.

Lanosterol Synthase Regulates Human Rhinovirus Replication in Human Bronchial Epithelial Cells.

Human rhinovirus (RV) infections are a significant risk factor for exacerbations of asthma and chronic obstructive pulmonary disease. Thus, approaches to prevent RV infection in such patients would give significant benefit. Through RNA interference library screening, we identified lanosterol synthase (LSS), a component of the cholesterol biosynthetic pathway, as a novel regulator of RV replication in primary normal human bronchial epithelial cells. Selective knock down of LSS mRNA with short interfering RNA inhibited RV2 replication in normal human bronchial epithelial cells. Small molecule inhibitors of LSS mimicked the effect of LSS mRNA knockdown in a concentration-dependent manner. We further demonstrated that the antiviral effect is not dependent on a reduction in total cellular cholesterol but requires a 24-hour preincubation with the LSS inhibitor. The rank order of antiviral potency of the LSS inhibitors used was consistent with LSS inhibition potency; however, all compounds showed remarkably higher potency against RV compared with the LSS enzyme potency. We showed that LSS inhibition led to an induction of 24(S),25 epoxycholesterol, an important regulator of the sterol pathway. We also demonstrated that LSS inhibition led to a profound increase in expression of the innate antiviral defense protein, IFN-ß. We found LSS to be a novel regulator of RV replication and innate antiviral immunity and identified a potential molecular mechanism for this effect, via induction of 24(S),25 epoxycholesterol. Inhibition of LSS could therefore be a novel therapeutic target for prevention of RV-induced exacerbations.

Routine antibiotic therapy in dogs increases the detection of antimicrobial-resistant faecal Escherichia coli.

Background: Antimicrobial resistance (AMR) is a critical health problem, with systemic antimicrobial therapy driving development of AMR across the host spectrum. Objectives: This study compares longitudinal carriage, at multiple timepoints, of AMR faecal Escherichia coli in dogs undergoing routine antimicrobial treatment. Methods: Faecal samples (n = 457) from dogs (n = 127) were examined pretreatment, immediately after treatment and 1 month and 3 months post-treatment with one of five antimicrobials. Isolates were tested for susceptibility to a range of antimicrobials using disc diffusion for each treatment group at different timepoints; the presence/absence of corresponding resistance genes was investigated using PCR assays. The impact of treatment group/timepoint and other risk factors on the presence of resistance [MDR, fluoroquinolone resistance, third-generation cephalosporin resistance (3GCR) and ESBL and AmpC production] was investigated using multilevel modelling. Samples with at least one AMR E. coli from selective/non-selective agar were classed as positive. Resistance was also assessed at the isolate level, determining the abundance of AMR from non-selective culture. Results: Treatment with ß-lactams or fluoroquinolones was significantly associated with the detection of 3GCR, AmpC-producing, MDR and/or fluoroquinolone-resistant E. coli, but not ESBL-producing E. coli, immediately after treatment. However, 1 month post-treatment, only amoxicillin/clavulanate was significantly associated with the detection of 3GCR; there was no significant difference at 3 months post-treatment for any antimicrobial compared with pretreatment samples. Conclusions: Our findings demonstrated that ß-lactam and fluoroquinolone antibiotic usage is associated with increased detection of important phenotypic and genotypic AMR faecal E. coli following routine therapy in vet-visiting dogs. This has important implications for veterinary and public health in terms of antimicrobial prescribing and biosecurity protocols, and dog waste disposal.

Positioning uterus transplantation as a 'more ethical' alternative to surrogacy: Exploring symmetries between uterus transplantation and surrogacy through analysis of a Swedish government white paper.

Within the ethics and science literature surrounding uterus transplantation (UTx), emphasis is often placed on the extent to which UTx might improve upon, or offer additional benefits when compared to, existing 'treatment options' for women with absolute uterine factor infertility, such as adoption and gestational surrogacy. Within this literature UTx is often positioned as superior to surrogacy because it can deliver things that surrogacy cannot (such as the experience of gestation). Yet, in addition to claims that UTx is superior in the aforementioned sense it is also often assumed (either implicitly or explicitly) that UTx is less fraught with ethical difficulties and thus should be considered a less morally problematic option. This article seeks to examine this assumption. Given that much UTx research has been performed in Sweden, a country where surrogacy is effectively although not currently explicitly forbidden, we do this through an analysis of the arguments underpinning a 2016 Swedish white paper which considered amending existing policy such that altruistic surrogacy arrangements would be permitted. By applying the white paper's arguments for a restrictive position on altruistic surrogacy to the case of UTx using living altruistic donors we find that such arguments, if they hold in the case of surrogacy, apply similarly to UTx. We thus suggest that, for reasons of consistency, a similar stance should be taken towards the moral and legal permissibility of these two practices.

Impact of systemic antimicrobial therapy on mucosal staphylococci in a population of dogs in Northwest England.

BACKGROUND: Antimicrobial-resistant bacteria are increasingly isolated from veterinary patients. OBJECTIVES: To determine risk factors for antimicrobial resistance (AMR) among canine mucosal staphylococci following routine antimicrobial treatment with cefalexin (CFX), clavulanate-amoxicillin (AC), cefovecin (CVN), clindamycin (CD) or a fluoroquinolone (FQ). ANIMALS: Mucosal swab samples (n = 463) were collected from 127 dogs pre-treatment, immediately, and at one- and three-months post-treatment. METHODS: Staphylococci were identified phenotypically and biochemically as coagulase negative (CoNS) or coagulase positive (CoPS); CoPS were speciated by nuc gene PCR. Antimicrobial susceptibility was determined using disc diffusion and mecA gene carriage by PCR. Multilevel, multivariable models examined associations between risk factors and presence/absence of CoPS, meticillin resistance (MR), multidrug-resistance (MDR) and fluoroquinolone resistance (FQR). RESULTS: The percentage of samples with CoNS increased and with CoPS (including S. pseudintermedius) decreased immediately post-treatment with CFX, CVN and CD (P ≤ 0.001) and one month post-treatment with CD (P = 0.003). By three months post-treatment, there was no significant difference compared to pre-treatment samples. Immediately post-treatment with FQs there was significantly increased risk of isolating MRS (P = 0.002), MDR (P = 0.002) or FQR (P = 0.013) staphylococci and of MDR following CFX treatment (P = 0.019). The percentage of samples with AMR staphylococci declined from immediately to three months post-treatment and there was no significant difference between resistance prevalence at one or three months post-treatment for most AMR traits and treatment groups. Exceptions include increased MDR following FQ (P = 0.048) or CFX (P = 0.021), at one and three months post-treatment, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Systemic antimicrobials impact on mucosal staphylococci. Immediately after therapy, the mucosa may be a reservoir for AMR staphylococci that are a source of mobile genetic elements carrying AMR genes.

On harm thresholds and living organ donation: must the living donor benefit, on balance, from his donation?

For the majority of scholars concerned with the ethics of living organ donation, inflicting moderate harms on competent volunteers in order to save the lives or increase the life chances of others is held to be justifiable provided certain conditions are met. These conditions tend to include one, or more commonly, some combination of the following: (1) The living donor provides valid consent to donation. (2) Living donation produces an overall positive balance of harm-benefit for donors and recipients which cannot be obtained in a less harmful manner. (3) Donation is not liable to cause significant and long-term morbidity to, or the death of, the donor. This paper critically examines the suggestion that these criteria are not sufficient to offer a general account of justified living organ donation in the context of competent volunteers and that key to justified living organ donation is that donors receive sufficient benefits from their donation that these outweigh the harms they suffer. However, although this view-termed here 'The Donor Benefit Standard'-directs welcome attention to the many and complex motives which may underlie living organ donation, this paper ultimately concludes that given the threats this position poses to individual autonomy and the lives of those in need of organ transplants 'The Donor Benefit Standard' should ultimately be rejected.