Electronic in-plane symmetry breaking at field-tuned quantum criticality in CeRhIn5.

Electronic nematic materials are characterized by a lowered symmetry of the electronic system compared to the underlying lattice, in analogy to the directional alignment without translational order in nematic liquid crystals. Such nematic phases appear in the copper- and iron-based high-temperature superconductors, and their role in establishing superconductivity remains an open question. Nematicity may take an active part, cooperating or competing with superconductivity, or may appear accidentally in such systems. Here we present experimental evidence for a phase of fluctuating nematic character in a heavy-fermion superconductor, CeRhIn5 (ref. 5). We observe a magnetic-field-induced state in the vicinity of a field-tuned antiferromagnetic quantum critical point at Hc ≈ 50 tesla. This phase appears above an out-of-plane critical field H* ≈ 28 tesla and is characterized by a substantial in-plane resistivity anisotropy in the presence of a small in-plane field component. The in-plane symmetry breaking has little apparent connection to the underlying lattice, as evidenced by the small magnitude of the magnetostriction anomaly at H*. Furthermore, no anomalies appear in the magnetic torque, suggesting the absence of metamagnetism in this field range. The appearance of nematic behaviour in a prototypical heavy-fermion superconductor highlights the interrelation of nematicity and unconventional superconductivity, suggesting nematicity to be common among correlated materials.

The first week following insemination is the period of major pregnancy failure in pasture-grazed dairy cows.

A 60% pregnancy success for inseminations is targeted to optimize production efficiency for dairy cows within a seasonal, pasture-grazed system. Routine measures of pregnancy success are widely available but are limited, in practice, to a gestation stage beyond the first 28 d. Although some historical data exist on embryonic mortality before this stage, productivity of dairy systems and genetics of the cows have advanced significantly in recent decades. Accordingly, the aim was to construct an updated estimate of pregnancy success at key developmental stages during the first 70 d after insemination. Blood samples were collected for progesterone concentrations on d 0 and 7. A temporal series of 4 groups spanning fertilization through d 70 were conducted on 4 seasonal, pasture-grazed dairy farms (n = 1,467 cows) during the first 21 d of the seasonal breeding period. Morphological examination was undertaken on embryos collected on d 7 (group E7) and 15 (group E15), and pregnancy was diagnosed via ultrasonography on approximately d 28 and 35 (group E35) as well as d 70 (group E70). Fertilization, embryo, and fetal evaluation for viability established a pregnancy success pattern. Additionally, cow and on-farm risk factor variables associated with pregnancy success were evaluated. We estimated pregnancy success rates of 70.9%, 59.1%, 63.8%, 62.3%, and 56.7% at d 7, 15, 28, 35, and 70, respectively. Fertilization failure (15.8%) and embryonic arrest before the morula stage (10.3%) were the major developmental events contributing to first-week pregnancy failures. Embryo elongation failure of 7% contributed to pregnancy failure during the second week. The risk factors for pregnancy success that were related to the cows included interval between calving and insemination, and d-7 plasma progesterone concentrations, whereas insemination sire was associated with pregnancy outcome. Most pregnancy failure occurs during the first week among seasonal-calving pasture-grazed dairy cows.

Exploration of diet, physical activity, health knowledge and the cardiometabolic profile of young adults with intellectual disability.

BACKGROUND: Young adults with intellectual disability (ID) are experiencing early mortality, and it is suggested that they are living with undiagnosed cardiovascular and metabolic risk factors (hereafter referred to as cardiometabolic). METHODS: We investigated the association between modifiable risk factors and cardiometabolic health profile in adults with ID aged 18-45 years through clinical evaluation of traditional cardiometabolic parameters, and assessment of physical activity levels, diet and associated health knowledge. RESULTS: We found that young adults with ID have an increased obesity (mean body mass index; ID group: 32.9 ± 8.6 vs. control group: 26.2 ± 5.5, P = 0.001), are engaging in less physical activity than the age-matched general population (total activity minutes per week; ID group: 172.2 ± 148.9 vs. control group: 416.4 ± 277.1, P < 0.001), and overall have unhealthier diets. Additionally, knowledge about nutrition and physical activity appears to be an important predictor of cardiometabolic risk in this population. If young people with ID are to improve their cardiometabolic health to reduce morbidity and early mortality, we need to further explore how to consistently apply health messaging to get lasting behavioural change in this population.

Investigating surface binding effects: antibacterial efficacy of bound 8-hydroxyquinoline against Staphylococcus aureus and Escherichia coli.

AIMS: To investigate the binding of the antimicrobial compound 8-hydroxyquinoline (8HQ) to a material interface and to determine whether immobilization affects the antibacterial efficacy. METHODS AND RESULTS: The 8HQ derivative 5-carboxy-8-hydroxyquinoline (5C8HQ) was attached to silica beads through amide bond coupling at the carboxyl moiety of 5C8HQ. Attachment of 5C8HQ was confirmed using a combination of mass spectrometry, thermogravimetric analysis, colorimetric testing and Soxhlet extraction. Computational modelling results indicated that this substitution did not compromise the active sites on the molecule, whereas other positions on the ring system could potentially inhibit antimicrobial activity. The antibacterial effect of 8HQ and the 5C8HQ-modified silica complex against Escherichia coli 15597 (ATCC® 25922) and Staphylococcus aureus (ATCC 25923) was evaluated. CONCLUSIONS: The test results show that the immobilized 8HQ continues to exhibit antibacterial activity, however, quantifying the efficacy compared to free 8HQ bears further investigation. The expected antibacterial mechanism requires that the metal chelation site of 8HQ be retained and available after attachment to a surface. The retention of antibacterial activity after surface bonding represents a novel mechanism of action not previously reported. SIGNIFICANCE AND IMPACT OF THE STUDY: Recent changes in regulations due to environmental concerns prompted many companies and organizations to explore antimicrobial treatments that are chemically bound to the product. Chemically bonding biocidal compounds to a surface limits environmental release; however, molecular mechanisms that drive antibacterial activity when compounds are immobilized are limited. The results reported here demonstrate that the 8HQ reactive site retains antibacterial efficacy even after covalent attachment to a surface. This approach supersedes other antimicrobial treatments where the active component is gradually released from the material surface in order to elicit antimicrobial effects. This specific antibacterial activity of bound 8HQ represents a novel mechanism of action not previously reported, and a potential conduit to a new class of bound antimicrobial materials.

Evidence of Incoherent Carriers Associated with Resonant Impurity Levels and Their Influence on Superconductivity in the Anomalous Superconductor Pb_{1-x}Tl_{x}Te.

We present a combined experimental and theoretical study of the evolution of the Fermi surface of the anomalous superconductor Pb_{1-x}Tl_{x}Te as a function of thallium concentration, drawing on a combination of magnetotransport measurements (Shubnikov-de Haas oscillations and the Hall coefficient), angle resolved photoemission spectroscopy, and density functional theory calculations of the electronic structure. Our results indicate that for Tl concentrations beyond a critical value, the Fermi energy coincides with resonant impurity states in Pb_{1-x}Tl_{x}Te, and we rule out the presence of an additional valence band maximum at the Fermi energy. A comparison to nonsuperconducting Pb_{1-x}Na_{x}Te implies that the presence of these impurity states at the Fermi energy provides the enhanced pairing interaction and thus also the anomalously high temperature superconductivity in this material.

A mathematical model of in vivo bovine blastocyst developmental to gestational Day 15.

Bovine embryo growth involves a complex interaction between the developing embryo and the growth-promoting potential of the uterine environment. We have previously established links between embryonic factors (embryo stage, embryo gene expression), maternal factors (progesterone, body condition score), and embryonic growth to 8 d after bulk transfer of Day 7 in vitro-produced blastocysts. In this study we recovered blastocysts on Days 7 and 15 after artificial insemination to test the hypothesis that in vivo and in vitro embryos follow a similar growth program. We conducted our study using 4 commercial farms and repeated our study over 2 yr (2014, 2015), with data available from 2 of the 4 farms in the second year. Morphological and gene expression measurements (196 candidate genes) of the Day 7 embryos were measured and the progesterone concentration of the cows were measured throughout the reproductive cycle as a reflection of the state of the uterine environment. These data were also used to assess the interaction between the uterine environment and the developing embryo and to examine how well Day 7 embryo stage can be predicted from the Day 7 gene expression profile. Progesterone was not a strong predictor of in vivo embryo growth to Day 15. This contrasts with a range of Day 7 embryo transfer studies which demonstrated that progesterone is a very good predictor of embryo growth to Day 15. Our analysis demonstrates that in vivo embryos are 3 times less sensitive to progesterone than in vitro-transferred embryos (up to Day 15). This highlights that caution must be applied when extrapolating the results of in vitro embryo transfer studies to the in vivo situation. The similar variance in measured and predicted (based on Day 15 length) Day 7 embryo stage indicate low stochastic perturbations for in vivo embryo growth (large stochastic growth effects would generate a significantly larger standard deviation in measured embryo length on Day 15). We also identified that Day 7 embryo stage could be predicted based on the Day 7 gene expression profile (58% overall success rate for classification of 5 embryo stages). Our analysis also associated genes with each developmental stage and demonstrates the high level of temporal regulation of genes that occurs during early embryonic development.

Productive efficiency and its determinants in the Community Dental Service in the north-west of England.

OBJECTIVES: To assess the efficiency of service provision in the Community Dental Services and its determinants in the North-West of England. SETTING AND SAMPLE: 40 Community Dental Services sites operating across the North-West of England. BASIC RESEARCH DESIGN: A data envelopment analysis was undertaken of inputs (number of surgeries, hours worked by dental officers, therapists, hygienists and others) and outputs (treatments delivered, number of courses of treatment and patients seen) of the Community Dental Services to produce relative efficiency ratings by health authority. These were further analyzed in order to identify which inputs (determined within the Community Dental Services) or external factors outside the control of the Community Dental Services are associated with efficiency. MAIN OUTCOME MEASURE: Relative efficiency rankings in Community Dental Services production of dental healthcare. RESULTS: Using the quantity of treatments delivered as the measure of output, on average the Community Dental Services in England is operating at a relative efficiency of 85% (95% confidence interval 77%- 99%) compared to the best performing services. Average efficiency is lower when courses of treatment and unique patients seen are used as output measures, 82% and 68% respectively. Neither the input mix nor the patient case mix explained variations in the efficiency across Community Dental Services. CONCLUSIONS: Although large variations in performance exist across Community Dental Services, the data available was not able to explain these variations. A useful next step would be to undertake detailed case studies of several best and under-performing services to explore the factors that influence relative performance levels.

Cell survival signaling in the bovine mammary gland during the transition from lactation to involution.

In dairy cows, mammary gland involution, and thus a decline in milk production, occurs following peak lactation. To examine the cell signaling pathways regulating involution of the mammary gland, signal transducer and activator of transcription factors (STAT5 and 3), suppressors of cytokine signaling (SOCS1-3 and CIS), insulin-like growth factors (IGF1 and 2), and protein kinase B (Akt) were examined. Mammary involution was induced by termination of milking, and alveolar tissue was collected from 52 nonpregnant, primiparous, mid-lactation Holstein-Friesian cows killed at 0, 6, 12, 18, 24, 36, 72, and 192h postmilking. Qualitative immunohistochemistry showed that activated (phosphorylated) STAT5-P was localized in nuclei of mammary epithelial cells at the early time points, with detection levels decreasing by 24h postmilking. In contrast, STAT3-P was barely detectable at the early time points, with detection levels increasing following longer postmilking periods. This was supported by Western analysis, which showed a decline in STAT5 and STAT5-P protein levels by 24h postmilking, no change in STAT3 levels, and an increase in STAT3-P protein (barely detectable at the early time points) by 72h postmilking. Quantitative real-time reverse transcription PCR analysis showed SOCS1 and SOCS3 mRNA increased by 72h postmilking compared with 6h postmilking. The SOCS2 mRNA remained unchanged across the time series, whereas CIS decreased by 18h postmilking and remained lower compared with that at 6h postmilking until 72h postmilking. The IGF1 mRNA increased by 192h postmilking, whereas IGF2 mRNA decreased by 18h postmilking compared with 6h postmilking. The IGFBP5 mRNA and protein levels of Akt and Akt-P remained unchanged over the time series. These results show that reciprocal activation of STAT5 and STAT3 occurs at the onset of mammary gland involution in the bovine, albeit at a slower rate than in rodents. Mathematical modeling of the pathways indicated that activated STAT3 could block the STAT5 pathway by upregulating SOCS3. The regulation of IGF1-Akt signaling suggests that by 192h postmilking in dairy cows, the involution process is still in the reversible phase, with quiescent mammary epithelial cells not yet in the senescent phase.

An invasive non-native mammal population conserves genetic diversity lost from its native range.

Invasive, non-native species are one of the major causes of global biodiversity loss. Although they are, by definition, successful in their non-native range, their populations generally show major reductions in their genetic diversity during the demographic bottleneck they experience during colonization. By investigating the mitochondrial genetic diversity of an invasive non-native species, the stoat Mustela erminea, in New Zealand and comparing it to diversity in the species' native range in Great Britain, we reveal the opposite effect. We demonstrate that the New Zealand stoat population contains four mitochondrial haplotypes that have not been found in the native range. Stoats in Britain rely heavily on introduced rabbits Oryctolagus cuniculus as their primary prey and were introduced to New Zealand in a misguided attempt at biological control of rabbits, which had also been introduced there. While invasive stoats have since decimated the New Zealand avifauna, native stoat populations were themselves decimated by the introduction to Britain of Myxoma virus as a control measure for rabbits. We highlight the irony that while introduced species (rabbits) and subsequent biocontrol (myxomatosis) have caused population crashes of native stoats, invasive stoats in New Zealand, which were also introduced for biological control, now contain more genetic haplotypes than their most likely native source.

Co-morbid beta-amyloid toxicity and stroke produce impairments in an ambiguous context task in rats without any impairment in spatial working memory.

Sporadic Alzheimer's disease (AD) accounts for a high proportion of AD cases. Therefore, it is of importance to investigate other factors that contribute to the etiology and progression of AD. AD is characterized by decreased cholinergic tone, tau hyperphosphorylation and beta-amyloid (Aß) accumulation. In addition to the hallmark pathology, other factors have been identified that increase the risk of AD, including stroke. This study examined the combined effects of beta-amyloid administration and unilateral stroke in an animal model of AD. Adult rats were given a sham surgery, bilateral intraventricular infusion of 10 µL of 50n mol Aß(25-35), a unilateral injection of endothelin-1 into the right striatum, or Aß and endothelin-1 administration in combination. Following a recovery period, rats were tested in the 1-trial place learning variant of the Morris water task followed by an ambiguous discriminative fear-conditioning to context task. After behavioural assessment, rats were euthanized, and representative sections of the medial septum were analyzed for differences in choline-acetyltransferase (ChAT) immunohistochemistry. No differences were observed in spatial working memory, but the combined effect of Aß and stroke resulted in deficits in the discriminative fear-conditioning to context task. A trend towards decreased ChAT-positive staining in the medial septum was observed. This study indicates that Aß and stroke in combination produce worse functional consequences than when experienced alone, furthering the concept of AD as a disease with multiple and complex etiologies.

Ondansetron rapidly dissolving film for the prophylactic treatment of radiation-induced nausea and vomiting-a pilot study.

INTRODUCTION: The purpose of the present study was to investigate the efficacy of an ondansetron rapidly dissolving film (rdf) in the prophylaxis of radiation-induced nausea and vomiting (rinv). Rapidly dissolving film formulations facilitate drug delivery in circumstances in which swallowing the medication might be difficult for the patient. METHODS: Patients undergoing palliative radiotherapy at risk for rinv were prescribed ondansetron rdf 8 mg twice daily while on treatment and were asked to complete a nausea and vomiting-specific daily diary, the Functional Living Index-Emesis (flie), and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C15 Palliative (qlq-C15-pal). Patients were categorized as receiving primary or secondary prophylaxis based on whether they had already experienced emetic episodes. "Overall control" was defined as a maximum increase of 2 episodes of nausea or vomiting from baseline. "Acute phase" was defined as the days during radiation until the first day after radiation; "delayed phase" was defined as days 2-10 after radiation. RESULTS: The study accrued 30 patients. Rates of overall control for nausea and for vomiting during the acute phase in the primary prophylaxis group were 88% and 93% respectively; during the delayed phase, they were 73% and 75%. Rates of overall control for nausea and for vomiting during the acute phase in the secondary prophylaxis group were both 100%; during the delayed phase, they were 50%. The number of nausea and vomiting episodes was found to be significantly correlated with the flie and qlq-C15-pal questionnaires. CONCLUSIONS: Ondansetron rdf is effective for the prophylaxis of rinv.

The contributing role of real-life hand skill performance in self-care function of children with and without disabilities.

BACKGROUND: Children's hand skills when performing in real-life contexts have been commonly thought as a possible determinant of their self-care function; however, there is a paucity of research investigating this potential predictive relationship. The purpose of this study was to provide evidence regarding whether children's real-life hand skill performance is contributive to or predictive of their self-care function by considering other child and cultural factors. METHODS: A total of 139 typically developing children and 114 with disabilities, ages 2-12 years from Australia and Taiwan, participated in the study. The outcome measures used were the Assessment of Children's Hand Skills (a measure of real-life hand skill performance) and the Personal Living Skills subscale of the Vineland Adaptive Behavior Scales - Classroom Edition (a measure of self-care function). RESULTS: Hierarchical regression analysis revealed that the children's demographic variables (age, gender, disability status, handedness and cultural context) accounted for 43% of the variance of the self-care function in the combined group of children with and without disabilities. Age, presence of disability and cultural context were the statistically significant independent factors. However, after the entry of the real-life hand skill performance factor, the contributing values of age and disability status decreased and the age factor became non-significant. The hand skill performance factor was found to be the strongest, and its addition led to significant increments of 24.6% of the explained variance for children's self-care function. Similar results were also found in the regression analyses based on separate groups of typically developing children or those with disabilities. CONCLUSIONS: The findings provide evidence that children's real-life hand skill performance is a contributing factor of their self-care function. The assessment of children's hand skill performance in real-life contexts is therefore needed.

High prevalence of ceftriaxone-resistant and XDR Neisseria gonorrhoeae in several cities of Cambodia, 2022-23: WHO Enhanced Gonococcal Antimicrobial Surveillance Programme (EGASP).

Objectives: Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a global public health concern. Ceftriaxone is the last effective and recommended option for empirical gonorrhoea therapy worldwide, but several ceftriaxone-resistant cases linked to Asia have been reported internationally. During January 2022-June 2023, the WHO Enhanced Gonococcal Antimicrobial Surveillance Programme (EGASP) investigated N. gonorrhoeae AMR and epidemiological factors in patients from 10 clinical sentinel sites in Cambodia. Methods: Urethral swabs from males with urethral discharge were cultured. ETEST determined the MIC of five antimicrobials, and EGASP MIC alert values and EUCAST breakpoints were used. EGASP demographic, behavioural and clinical variables were collected using a standardized questionnaire. Results: From 437 male patients, 306 had positive N. gonorrhoeae cultures, AMR testing and complete epidemiological data. Resistance to ceftriaxone, cefixime, azithromycin and ciprofloxacin was 15.4%, 43.1%, 14.4% and 97.1%, respectively. Nineteen (6.2%) isolates were resistant to all four antimicrobials and, accordingly, categorized as XDR N. gonorrhoeae. These XDR isolates were collected from 7 of the 10 sentinel sites. No EGASP MIC alert values for gentamicin were reported. The nationally recommended cefixime 400 mg plus azithromycin 1 g (65.4%) or ceftriaxone 1 g plus azithromycin 1 g (34.6%) was used for treatment. Conclusions: A high prevalence of ceftriaxone-resistant, MDR and XDR N. gonorrhoeae in several cities of Cambodia were found during 2022-23 in WHO EGASP. This necessitates expanded N. gonorrhoeae AMR surveillance, revision of the nationally recommended gonorrhoea treatment, mandatory test of cure, enhanced sexual contact notification, and ultimately novel antimicrobials for the treatment of gonorrhoea.

Partial complementation of Sinorhizobium meliloti bacA mutant phenotypes by the Mycobacterium tuberculosis BacA protein.

The Sinorhizobium meliloti BacA ABC transporter protein plays an important role in its nodulating symbiosis with the legume alfalfa (Medicago sativa). The Mycobacterium tuberculosis BacA homolog was found to be important for the maintenance of chronic murine infections, yet its in vivo function is unknown. In the legume plant as well as in the mammalian host, bacteria encounter host antimicrobial peptides (AMPs). We found that the M. tuberculosis BacA protein was able to partially complement the symbiotic defect of an S. meliloti BacA-deficient mutant on alfalfa plants and to protect this mutant in vitro from the antimicrobial activity of a synthetic legume peptide, NCR247, and a recombinant human ß-defensin 2 (HBD2). This finding was also confirmed using an M. tuberculosis insertion mutant. Furthermore, M. tuberculosis BacA-mediated protection of the legume symbiont S. meliloti against legume defensins as well as HBD2 is dependent on its attached ATPase domain. In addition, we show that M. tuberculosis BacA mediates peptide uptake of the truncated bovine AMP, Bac7(1-16). This process required a functional ATPase domain. We therefore suggest that M. tuberculosis BacA is important for the transport of peptides across the cytoplasmic membrane and is part of a complete ABC transporter. Hence, BacA-mediated protection against host AMPs might be important for the maintenance of latent infections.

405 nm Light exposure of osteoblasts and inactivation of bacterial isolates from arthroplasty patients: potential for new disinfection applications?

Infection rates after arthroplasty surgery are between 1-4 %, rising significantly after revision procedures. To reduce the associated costs of treating these infections, and the patients' post-operative discomfort and trauma, a new preventative method is required. High intensity narrow spectrum (HINS) 405 nm light has bactericidal effects on a wide range of medically important bacteria, and it reduced bacterial bioburden when used as an environmental disinfection method in a Medical Burns Unit. To prove its safety for use for environmental disinfection in orthopaedic theatres during surgery, cultured osteoblasts were exposed to HINS-light of intensities up to 15 mW/cm2 for 1 h (54 J/cm2). Intensities of up to 5 mW/cm2 for 1 h had no effect on cell morphology, activity of alkaline phosphatase, synthesis of collagen or osteocalcin expression, demonstrating that under these conditions this dose is the maximum safe exposure for osteoblasts; after exposure to 15 mW/cm2 all parameters of osteoblast function were significantly decreased. Viability (measured by protein content and Crystal Violet staining) of the osteoblasts was not influenced by exposure to 5 mW/cm2 for at least 2 h. At 5 mW/cm2 HINS-light is an effective bactericide. It killed 98.1 % of Staphylococcus aureus and 83.2 % Staphylococcus epidermis populations seeded on agar surfaces, and is active against both laboratory strains and clinical isolates from infected hip and knee arthroplasties. HINS-light could have potential for development as a method of disinfection to reduce transmission of bacteria during arthroplasty, with wider applications in diverse surgical procedures involving implantation of a medical device.

Patterns of direct and indirect contact between cattle and badgers naturally infected with tuberculosis.

Tuberculosis (TB) due to infection with Mycobacterium bovis is transmitted between cattle and badgers (Meles meles) in the UK and Ireland but it is unclear where or when transmission occurs. We investigated direct and indirect interactions between badgers and cattle using automated proximity loggers on animals and at badger latrines located on pasture, in an area of south-west England with a high-density badger population. Direct contacts (interactions within 1.4 m) between badgers and cattle at pasture were very rare (four out of >500000 recorded animal-to-animal contacts) despite ample opportunity for interactions to occur. Indirect interactions (visits to badger latrines by badgers and cattle) were two orders of magnitude more frequent than direct contacts: 400 visits by badgers and 1700 visits by cattle were recorded. This suggests that indirect contacts might be more important than direct contacts in terms of disease transmission at pasture. The TB infection status of individual badgers (ascribed with 93% accuracy using three diagnostic tests) did not affect the frequency or duration of their visits to latrines located on pasture grazed by cattle. Nevertheless, there was wide variation in contact behaviour between individuals, which highlights the importance of understanding heterogeneity in contact patterns when developing strategies to control disease spread in wildlife and livestock.

Multi-state modelling reveals sex-dependent transmission, progression and severity of tuberculosis in wild badgers.

Statistical models of epidemiology in wildlife populations usually consider diseased individuals as a single class, despite knowledge that infections progress through states of severity. Bovine tuberculosis (bTB) is a serious zoonotic disease threatening the UK livestock industry, but we have limited understanding of key epidemiological processes in its wildlife reservoirs. We estimated differential survival, force of infection and progression in disease states in a population of Eurasian badgers (Meles meles), naturally infected with bTB. Our state-dependent models overturn prevailing categorizations of badger disease states, and find novel evidence for early onset of disease-induced mortality in male but not female badgers. Males also have higher risk of infection and more rapid disease progression which, coupled with state-dependent increases in mortality, could promote sex biases in the risk of transmission to cattle. Our results reveal hidden complexities in wildlife disease epidemiology, with implications for the management of TB and other zoonotic diseases.

Heterogeneity in the risk of Mycobacterium bovis infection in European badger (Meles meles) cubs.

The behaviour of certain infected individuals within socially structured populations can have a disproportionately large effect on the spatio-temporal distribution of infection. Endemic infection with Mycobacterium bovis in European badgers (Meles meles) in Great Britain and Ireland is an important source of bovine tuberculosis in cattle. Here we quantify the risk of infection in badger cubs in a high-density wild badger population, in relation to the infection status of resident adults. Over a 24-year period, we observed variation in the risk of cub infection, with those born into groups with resident infectious breeding females being over four times as likely to be detected excreting M. bovis than cubs from groups where there was no evidence of infection in adults. We discuss how our findings relate to the persistence of infection at both social group and population level, and the potential implications for disease control strategies.

Completion surgery following transanal endoscopic microsurgery: assessment of quality and short- and long-term outcome.

AIM: Patients with unfavourable pathology after transanal endoscopic microsurgery (TEM) should be offered completion surgery (CS) if appropriate. The aim of this retrospective cohort study was to assess the short-term outcome and long-term oncological results of CS and identify factors compromising the quality of resection specimens. METHOD: Data were retrieved and analysed on patients who underwent CS from a comprehensive national TEM database (1992-2008) and the institutional prospective database from the Oxford University Hospitals (2008-2011). RESULTS: There were 36 patients eligible for analysis. Postoperative complications occurred in 19 and were minor (grade I-II) in 13 and major (grade III-V) in six patients. The quality of the resected specimen was graded as good in 23 (64%), moderate in six (16.6%) and poor in seven (19.4%). Full-thickness excision by TEM (P = 0.03), an interval to CS greater than 7 weeks (P = 0.05) and distally located lesions (P = 0.04) were associated with increased risk for an inferior surgical specimen. Overall survival after CS was 91% at 1 year and 83% at 5 years. Patients with a 'good' TME specimen had significantly improved disease-free survival compared with patients with an 'inferior' specimen (100 vs 51%, P = 0.001). CONCLUSION: Patients having full-thickness TEM excision, distally placed lesions and a long interval (> 7 weeks) to CS were likely to have an inferior TME specimen. The results confirm that CS after TEM does not negatively influence local recurrence and survival, but the reduced disease-free survival in patients with an inferior specimen is of concern.

Evaluating expansion strategies for startup European Union dairy farm businesses.

A stochastic whole-farm simulation model was used to examine alternative strategies for new entrant dairy farmers to grow and develop dairy farm businesses in the context of European Union (EU) milk quota abolition in 2015. Six alternative strategies were compared: remain static, natural growth expansion, waiting until after EU milk quota abolition to expand, a full-scale expansion strategy without milk quotas and not incurring super levy penalties, a full-scale expansion strategy with milk quotas and incurring super levy penalties, and once-a-day milking until EU milk quota abolition, followed by full-scale expansion. Each discrete whole farm investment strategy was evaluated over a 15-yr period (2013-2027) using multiple financial stability and risk indicators, including overall discounted farm business profitability, net worth change, return on investment, and financial risk. The results of this study indicate that, although associated with increased risk, dairy farm expansion will ensure the future profitability of the farm business. Within the context of EU milk quotas until 2015, the most attractive expansion strategy is to increase cow numbers while avoiding super levy fines using once-a-day milking techniques, increasing to the full capacity of the dairy farm once milk quotas are removed. In contrast, the results also indicate that dairy farms that remain static will experience a significant reduction in farm profitability in the coming year due to production cost inflation. Cash flow deficits were observed during the initial year of expansion and, therefore, rapidly expanding dairy farm businesses require a significant cash reserve to alleviate business risk during the initial year of expansion. The results of this analysis also indicate that dairy farm businesses that expand using lower cost capital investments and avoid milk quota super levy fines significantly reduce the financial risks associated with expansion.