Evaluating the accuracy of facial expressions as emotion indicators across contexts in dogs.

Facial expressions potentially serve as indicators of animal emotions if they are consistently present across situations that (likely) elicit the same emotional state. In a previous study, we used the Dog Facial Action Coding System (DogFACS) to identify facial expressions in dogs associated with conditions presumably eliciting positive anticipation (expectation of a food reward) and frustration (prevention of access to the food). Our first aim here was to identify facial expressions of positive anticipation and frustration in dogs that are context-independent (and thus have potential as emotion indicators) and to distinguish them from expressions that are reward-specific (and thus might relate to a motivational state associated with the expected reward). Therefore, we tested a new sample of 28 dogs with a similar set-up designed to induce positive anticipation (positive condition) and frustration (negative condition) in two reward contexts: food and toys. The previous results were replicated: Ears adductor was associated with the positive condition and Ears flattener, Blink, Lips part, Jaw drop, and Nose lick with the negative condition. Four additional facial actions were also more common in the negative condition. All actions except the Upper lip raiser were independent of reward type. Our second aim was to assess basic measures of diagnostic accuracy for the potential emotion indicators. Ears flattener and Ears downward had relatively high sensitivity but low specificity, whereas the opposite was the case for the other negative correlates. Ears adductor had excellent specificity but low sensitivity. If the identified facial expressions were to be used individually as diagnostic indicators, none would allow consistent correct classifications of the associated emotion. Diagnostic accuracy measures are an essential feature for validity assessments of potential indicators of animal emotion.

Alpelisib plus fulvestrant for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: final overall survival results from SOLAR-1.

BACKGROUND: Activation of the phosphatidylinositol-3-kinase (PI3K) pathway via PIK3CA mutations occurs in 28%-46% of hormone receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2-) advanced breast cancers (ABCs) and is associated with poor prognosis. The SOLAR-1 trial showed that the addition of alpelisib to fulvestrant treatment provided statistically significant and clinically meaningful progression-free survival (PFS) benefit in PIK3CA-mutated, HR+, HER2- ABC. PATIENTS AND METHODS: Men and postmenopausal women with HR+, HER2- ABC whose disease progressed on or after aromatase inhibitor (AI) were randomized 1 : 1 to receive alpelisib (300 mg/day) plus fulvestrant (500 mg every 28 days and once on day 15) or placebo plus fulvestrant. Overall survival (OS) in the PIK3CA-mutant cohort was evaluated by Kaplan-Meier methodology and a one-sided stratified log-rank test was carried out with an O'Brien-Fleming efficacy boundary of P ≤ 0.0161. RESULTS: In the PIK3CA-mutated cohort (n = 341), median OS [95% confidence interval (CI)] was 39.3 months (34.1-44.9) for alpelisib-fulvestrant and 31.4 months (26.8-41.3) for placebo-fulvestrant [hazard ratio (HR) = 0.86 (95% CI, 0.64-1.15; P = 0.15)]. OS results did not cross the prespecified efficacy boundary. Median OS (95% CI) in patients with lung and/or liver metastases was 37.2 months (28.7-43.6) and 22.8 months (19.0-26.8) in the alpelisib-fulvestrant and placebo-fulvestrant arms, respectively [HR = 0.68 (0.46-1.00)]. Median times to chemotherapy (95% CI) for the alpelisib-fulvestrant and placebo-fulvestrant arms were 23.3 months (15.2-28.4) and 14.8 months (10.5-22.6), respectively [HR = 0.72 (0.54-0.95)]. No new safety signals were observed with longer follow-up. CONCLUSIONS: Although the analysis did not cross the prespecified boundary for statistical significance, there was a 7.9-month numeric improvement in median OS when alpelisib was added to fulvestrant treatment of patients with PIK3CA-mutated, HR+, HER2- ABC. Overall, these results further support the statistically significant prolongation of PFS observed with alpelisib plus fulvestrant in this population, which has a poor prognosis due to a PIK3CA mutation. CLINICALTRIALS. GOV ID: NCT02437318.

Time course and management of key adverse events during the randomized phase III SOLAR-1 study of PI3K inhibitor alpelisib plus fulvestrant in patients with HR-positive advanced breast cancer.

BACKGROUND: Alpelisib (α-selective phosphatidylinositol 3-kinase inhibitor) plus fulvestrant is approved in multiple countries for men and postmenopausal women with PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer following progression on or after endocrine therapy. A detailed understanding of alpelisib's safety profile should inform adverse event (AE) management and enhance patient care. PATIENTS AND METHODS: AEs in the phase III SOLAR-1 trial were assessed in patients with and without PIK3CA mutations. The impact of protocol-specified AE-management recommendations was evaluated, including an amendment to optimize hyperglycemia and rash management. RESULTS: Patients were randomly assigned to receive fulvestrant plus alpelisib (n = 284) or placebo (n = 287). The most common grade 3/4 AEs with alpelisib were hyperglycemia (grade 3, 32.7%; grade 4, 3.9%), rash (grade 3, 9.9%), and diarrhea (grade 3, 6.7%). Median time to onset of grade ≥3 toxicity was 15 days (hyperglycemia, based on fasting plasma glucose), 13 days (rash), and 139 days (diarrhea). Metformin alone or in combination with other antidiabetic agents was used by most patients (87.1%) with hyperglycemia. Preventive anti-rash medication resulted in lower incidence (any grade, 26.7% versus 64.1%) and severity of rash (grade 3, 11.6% versus 22.7%) versus no preventative medication. Discontinuations due to grade ≥3 AEs were lower following more-detailed AE management guidelines (7.9% versus 18.1% previously). Patients with PIK3CA mutations had a median alpelisib dose intensity of 248 mg/day. Median progression-free survival with alpelisib was 12.5 and 9.6 months for alpelisib dose intensities of ≥248 mg/day and <248 mg/day, respectively, compared with 5.8 months with placebo. CONCLUSIONS: Hyperglycemia and rash occurred early during alpelisib treatment, while diarrhea occurred at a later time point. Early identification, prevention, and intervention, including concomitant medications and alpelisib dose modifications, resulted in less severe toxicities. Reductions in treatment discontinuations and improved progression-free survival at higher alpelisib dose intensities support the need for optimal AE management. CLINICALTRIALS. GOV ID: NCT02437318.

Towards a fuller assessment of the economic benefits of reducing air pollution from fossil fuel combustion: Per-case monetary estimates for children's health outcomes.

BACKGROUND: Impacts on children's health are under-represented in benefits assessments of policies related to ambient air quality and climate change. To complement our previous compilation of concentration-response (C-R) functions for a number of children's health outcomes associated with air pollution, we provide per-case monetary estimates of the same health outcomes. OBJECTIVES: Our goal was to establish per-case monetary estimates for a suite of prevalent children's health outcomes (preterm birth, low birth weight, asthma, autism spectrum disorder, attention-deficit/hyperactivity disorder, and IQ reduction) that can be incorporated into benefits assessments of air pollution regulations and climate change mitigation policies. METHODS: We conducted a systematic review of the literature published between January 1, 2000 and June 30, 2018 to identify relevant economic costs for these six adverse health outcomes in children. We restricted our literature search to studies published in the U.S., with a supplemental consideration of studies from the U.K. and prioritized literature reviews with summary cost estimates and papers that provided lifetime cost of illness estimates. RESULTS: Our literature search and evaluation process reviewed 1065 papers and identified 12 most relevant papers on per-case monetary estimates for preterm birth, low birth weight, asthma, autism spectrum disorder, and attention-deficit/hyperactivity disorder. Details are presented in full. We separately identified estimates of the lost lifetime earnings associated with the loss of a single IQ point. The final per-case cost estimates for each outcome were selected based on the most robust evidence. These estimates range from $23,573 for childhood asthma not persisting into adulthood to $3,109,096 for a case of autism with a concurrent intellectual disability. CONCLUSION: To our knowledge, this is the first time that the child-specific health outcomes of preterm birth, low birth weight, asthma, autism spectrum disorder, attention-deficit/hyperactivity disorder, and IQ reduction have been systematically valued and presented in one place. This is an important addition to the body of health-related valuation literature as these outcomes have substantial economic costs that are not considered in most assessments of the benefits of air pollution and climate mitigation policies. In general, however, the available per-case estimates presented here did not incorporate the broad societal and long-term costs and are likely underestimates. Although our context has been air pollution and climate policies, the per-case monetary estimates presented here can be applied to other environmental exposures. Fuller assessments of health benefits to children and their corresponding economic gains will improve decision-making on environmental policy.

Towards a fuller assessment of benefits to children's health of reducing air pollution and mitigating climate change due to fossil fuel combustion.

BACKGROUND: Fossil fuel combustion by-products, including particulate matter (PM2.5), polycyclic aromatic hydrocarbons (PAH), nitrogen dioxide (NO2) and carbon dioxide (CO2), are a significant threat to children's health and equality. Various policies to reduce emissions have been implemented to reduce air pollution and mitigate climate change, with sizeable estimated health and economic benefits. However, only a few adverse outcomes in children have been considered, resulting in an undercounting of the benefits to this vulnerable population. OBJECTIVES: Our goal was to expand the suite of child health outcomes addressed by programs to assess health and economic benefits, such as the Environmental Protection Agency (EPA) Benefits Mapping and Analysis Program (BenMAP), by identifying concentration-response (C-R) functions for six outcomes related to PM2.5, NO2, PAH, and/or PM10: preterm birth (PTB), low birthweight (LBW), autism, attention deficit hyperactivity disorder, IQ reduction, and the development of childhood asthma. METHODS: We conducted a systematic review of the literature published between January 1, 2000 and April 30, 2018 to identify relevant peer-reviewed case-control and cohort studies and meta-analyses. In some cases meta-analyses were available that provided reliable C-R functions and we assessed their consistency with subsequent studies. Otherwise, we reviewed all eligible studies published between our search dates. RESULTS: For each pollutant and health outcome, we present the characteristics of each selected study. We distinguish between C-R functions for endpoints having a causal or likely relationship (PTB, LBW, autism, asthma development) with the pollutants for incorporation into primary analyses and endpoints having a suggestive causal relationship with the pollutants (IQ reduction, ADHD) for secondary analyses. CONCLUSION: We have identified C-R functions for a number of adverse health outcomes in children associated with air pollutants largely from fossil fuel combustion. Their incorporation into expanded assessments of health benefits of clean air and climate mitigation policies will provide an important incentive for preventive action.

Approaches to 3D printing teeth from X-ray microtomography.

Artificial teeth have several advantages in preclinical training. The aim of this study is to three-dimensionally (3D) print accurate artificial teeth using scans from X-ray microtomography (XMT). Extracted and artificial teeth were imaged at 90 kV and 40 kV, respectively, to create detailed high contrast scans. The dataset was visualised to produce internal and external meshes subsequently exported to 3D modelling software for modification before finally sending to a slicing program for printing. After appropriate parameter setting, the printer deposited material in specific locations layer by layer, to create a 3D physical model. Scans were manipulated to ensure a clean model was imported into the slicing software, where layer height replicated the high spatial resolution that was observed in the XMT scans. The model was then printed in two different materials (polylactic acid and thermoplastic elastomer). A multimaterial print was created to show the different physical characteristics between enamel and dentine. LAY DESCRIPTION: Objectives Trainee dentists practice procedures using artificial teeth that are far from real teeth. Using x-rays and 3D printing technology the project will recreate a real tooth, artificially. Methods X-rays produce a 3D image that can be printed out as a physical replica, after several conversions of files. Different settings can be used to allow the printed model, to be as accurate as possible. Data were collected on the forces from a dental drill on a tooth's surface, to measure hardness and resistance. Results Multiple teeth replicas were printed with a high accuracy. The materials printed did not mimic actual tooth properties, but using the data from real teeth, materials can be tested in future.

Can SLE classification rules be effectively applied to diagnose unclear SLE cases?

Objective The objective of this paper is to develop novel classification criteria to distinguish between unclear systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD) cases. Methods A total of 205 variables from 111 SLE and 55 MCTD patients were evaluated to uncover unique molecular and clinical markers for each disease. Binomial logistic regressions (BLRs) were performed on currently used SLE and MCTD classification criteria sets to obtain six reduced models with power to discriminate between unclear SLE and MCTD patients that were confirmed by receiving operating characteristic (ROC) curve. Decision trees were employed to delineate novel classification rules to discriminate between unclear SLE and MCTD patients. Results SLE and MCTD patients exhibited contrasting molecular markers and clinical manifestations. Furthermore, reduced models highlighted SLE patients exhibiting prevalence of skin rashes and renal disease while MCTD cases show dominance of myositis and muscle weakness. Additionally decision tree analyses revealed a novel classification rule tailored to differentiate unclear SLE and MCTD patients (Lu-vs-M) with an overall accuracy of 88%. Conclusions Validation of our novel proposed classification rule (Lu-vs-M) includes novel contrasting characteristics (calcinosis, CPK elevated and anti-IgM reactivity for U1-70K, U1A and U1C) between SLE and MCTD patients and showed a 33% improvement in distinguishing these disorders when compared to currently used classification criteria sets. Pending additional validation, our novel classification rule is a promising method to distinguish between patients with unclear SLE and MCTD diagnosis.

Characterization of porcine milk oligosaccharides during early lactation and their relation to the fecal microbiome.

The composition of porcine milk oligosaccharides (PMO) was analyzed during early lactation and their relation to piglet gut microbiome was investigated. Pigs are considered ideal intestinal models to simulate humans because of the striking similarity in intestinal physiopathology to humans. The evolution of PMO was investigated in the milk from 3 healthy sows at prefarrowing, farrowing, and d 7 and 14 postpartum by Nano-LC Chip Quadrupole-Time-of-Flight mass spectrometer (Agilent Technologies, Santa Clara, CA). Previously sequenced metagenome libraries were reanalyzed to examine changes with specific gut bacterial populations. Over 30 oligosaccharides (OS) were identified in the milk, with 3'-sialyllactose, lacto-N-tetraose, α1-3,ß1-4-d-galactotriose, 2'-fucosyllactose, and 6'-sialyllactose being the most abundant species (accounting for ~70% of the total OS). Porcine milk had lower OS diversity (number of unique structures) than human milk, and appeared closer to bovine and caprine milk. In agreement with previous studies, only 3 fucosylated OS were identified. Surprisingly, their contribution to total OS abundance was greater than in bovine milk (9 vs. 1%). Indeed, fucosylated PMO increased during lactation, mirroring a similar trend observed for neutral and type I OS content during early lactation. Taken together, these results suggest that, in terms of abundance, PMO are closer to human milk than other domestic species, such as bovine and caprine milks. Metagenomic sequencing revealed that fucose-consuming bacterial taxa in the gut microbiota of piglets were qualitatively but not quantitatively different between nursing and weaning stages, suggesting that both the composition and structure of dietary glycans may play a critical role in shaping the distal gut microbiome. The similarity of both intestinal physiopathology and milk OS composition in human and porcine species suggests similar effects on gastrointestinal development of early nutrition, reinforcing the use of the pig intestinal model to simulate human intestinal models in the clinical setting.

Potential of Lactobacillus curvatus LFC1 to produce slits in Cheddar cheese.

Defects in Cheddar cheese resulting from undesired gas production are a sporadic problem that results in significant financial losses in the cheese industry. In this study, we evaluate the potential of a facultatively heterofermentative lactobacilli, Lactobacillus curvatus LFC1, to produce slits, a gas related defect in Cheddar cheese. The addition of Lb. curvatus LFC1 to cheese milk at log 3 CFU/ml resulted in the development of small slits during the first month of ripening. Chemical analyses indicated that the LFC1 containing cheeses had less galactose and higher levels of lactate and acetate than the control cheeses. The composition the cheese microbiota was examined through a combination of two culture independent approaches, 16S rRNA marker gene sequencing and automated ribosomal intergenic spacer analysis; the results indicated that no known gas producers were present and that high levels of LFC1 was the only significant difference between the cheese microbiotas. A ripening cheese model system was utilized to examine the metabolism of LFC1 under conditions similar to those present in cheeses that exhibited the slit defect. The combined cheese and model system results indicate that when Lb. curvatus LFC1 was added to the cheese milk at log 3 CFU/ml it metabolized galactose to lactate, acetate, and CO2. For production of sufficient CO2 to result in the formation of slits there needs to be sufficient galactose and Lb. curvatus LFC1 present in the cheese matrix. To our knowledge, facultatively heterofermentative lactobacilli have not previously been demonstrated to result in gas-related cheese defects.

On fragmenting, densely mineralised acellular protrusions into articular cartilage and their possible role in osteoarthritis.

High density mineralised protrusions (HDMP) from the tidemark mineralising front into hyaline articular cartilage (HAC) were first described in Thoroughbred racehorse fetlock joints and later in Icelandic horse hock joints. We now report them in human material. Whole femoral heads removed at operation for joint replacement or from dissection room cadavers were imaged using magnetic resonance imaging (MRI) dual echo steady state at 0.23 mm resolution, then 26-µm resolution high contrast X-ray microtomography, sectioned and embedded in polymethylmethacrylate, blocks cut and polished and re-imaged with 6-µm resolution X-ray microtomography. Tissue mineralisation density was imaged using backscattered electron SEM (BSE SEM) at 20 kV with uncoated samples. HAC histology was studied by BSE SEM after staining block faces with ammonium triiodide solution. HDMP arise via the extrusion of an unknown mineralisable matrix into clefts in HAC, a process of acellular dystrophic calcification. Their formation may be an extension of a crack self-healing mechanism found in bone and articular calcified cartilage. Mineral concentration exceeds that of articular calcified cartilage and is not uniform. It is probable that they have not been reported previously because they are removed by decalcification with standard protocols. Mineral phase morphology frequently shows the agglomeration of many fine particles into larger concretions. HDMP are surrounded by HAC, are brittle, and show fault lines within them. Dense fragments found within damaged HAC could make a significant contribution to joint destruction. At least larger HDMP can be detected with the best MRI imaging ex vivo.

Inspiratory muscle warm-up does not improve cycling time-trial performance.

PURPOSE: This study examined the effects of an active cycling warm-up, with and without the addition of an inspiratory muscle warm-up (IMW), on 10-km cycling time-trial performance. METHODS: Ten cyclists (VO2 = 65 ± 9 mL kg(-1) min(-1)) performed a habituation 10-km cycling time-trial and three further time-trials preceded by either no warm-up (CONT), a cycling-specific warm-up (CYC) comprising three consecutive 5-min bouts at powers corresponding to 70, 80, and 90% of the gas exchange threshold, or a cycling-specific warm-up preceded by an IMW (CYC + IMW) comprising two sets of 30 inspiratory efforts against a pressure-threshold load of 40% maximal inspiratory pressure (MIP). The cycling warm-up was followed by 2-min rest before the start of the time-trial. RESULTS: Time-trial performance times during CYC (14.75 ± 0.79 min) and CYC + IMW (14.70 ± 0.75 min) were not different, although both were faster than CONT (14.99 ± 0.90 min) (P < 0.05). Throughout the time-trial, physiological (minute ventilation, breathing pattern, pulmonary gas exchange, heart rate, blood lactate concentration and pH) and perceptual (limb discomfort and dyspnoea) responses were not different between CYC and CYC + IMW. Baseline MIP during CONT and CYC was 151 ± 31 and 156 ± 39 cmH2O, respectively, and was unchanged following the time-trial. MIP increased by 8% after IMW (152 ± 27 vs. 164 ± 27 cmH2O, P < 0.05) and returned to baseline after the time-trial. CONCLUSIONS: Improvements in 10-km cycling time-trial performance following an active cycling warm-up were not magnified by the addition of an IMW. Therefore, an appropriately designed active whole-body warm-up does adequately prepare the inspiratory muscles for cycling time-trials lasting approximately 15 min.

Volumetric Response and Survival of Patients With Bulky IDH-Mutated Grade 3 Glioma Managed With FET-FDG-Guided Integrated Boost IMRT.

AIMS: Despite relatively favourable outcomes associated with IDH-mutant grade 3 gliomas, many patients present with diffuse non-enhancing disease involving multiple brain regions, prompting concern over both durable disease control and the morbidity associated with large volume radiation therapy. This study audits volumetric response, survival and functional outcomes in this 'large volume' subgroup that undergoes intensity modulated radiation therapy (IMRT). MATERIALS AND METHODS: From a prospective database of 187 patients with IDH-mutant grade 3 gliomas managed with IMRT between 2008 and 2020, recorded PTV was divided into quartiles. The top quartile, termed the 'large volume cohort' (LVC), was identified. IMRT involved FET-FDG guided integrated boost (59.4/54Gy in 33 fractions). Manual volumetric segmentation of baseline, four months and 13 months post-IMRT tumour were performed for T1, T2 and T1gd MRI sequences. The primary endpoint was volumetric reduction on the T1 and T2 sequences at 13 months and analysed with relapse-free survival (RFS) and overall survival (OS). Morbidity endpoints were assessed at year four post-IMRT and included performance status (ECOG PS) and employment outcomes. RESULTS: The fourth quartile (LVC) identified 44 patients for whom volumetric analysis was available. The LVC had median PTV of 320cm3 compared to 186.2cm3 for the total group. Anaplastic astrocytoma and oligodendroglioma were equally distributed and tumour sites were frontal (54%), temporal (18%) and parietal lobes (16%). Median follow-up for survivors was 71.5 months. Projected 10-year RFS and OS in LVC was 40% and 62%, compared to 53% and 62% respectively in the overall cohort. The RFS (p = 0.06) and OS (p = 0.65) of the LVC was not significantly different to other PTV quartiles; however the impact of PTV volume reached significance when analysed as a continuous variable (RFS p < 0.01; OS p = 0.02). Median T1 volumes were 26.1cm3, 8.0cm3 and 5.3cm3 at months +0, +3 and +12, respectively. The corresponding T2 volumes were 120.8cm3, 29.1cm3 and 26.3cm3. The median T1 and T2 volume reductions were 77% (q1-3: 57-92%) and 78% (q1-3: 60-85%) at 13 months post-IMRT. Initial T2 volume was associated with worse RFS (p = 0.04) but not OS (p = 0.96). There was no association between median T2 volume reduction and RFS (p = 0.77). For patients assessable at year 4 post-IMRT, no late CTCAE Grade 3/4 toxicity events were recognised. 92% of patients were ECOG PS 0-1, 45% were employed at prior capacity and 28% were working with impairment. CONCLUSION: Patients with large volume IDH-mutant Grade 3 glioma demonstrated significant tumour reduction post-IMRT, and good long-term outcomes with respect to survival and functional status. Although larger IMRT volumes were associated with poorer RFS, this was also associated with the initial volume of non-enhancing tumour.

The sexuality of women with cervical cancer undergoing definitive radiotherapy in Ghana.

INTRODUCTION: The purpose of this study was to assess the sexuality of cervical cancer patients undergoing radiotherapy at a major cancer treatment center in Ghana. This is an area of interest as globally; cervical cancer kills approximately 342,000 people per annum with an estimated number of 604,000 new cases in 2020. Acknowledging the World Health Organization's definition of sexual health as a state of physical, mental and social well-being in relation to sexuality, this paper sheds light on how these dimensions affect the quality of life of cervical cancer patients. METHODS: This was a longitudinal study, which assessed the impact of radiotherapy on the sexuality of both premenopausal and postmenopausal cervical cancer patients presenting for primary treatment with chemoradiation from April to July, 2021 at a major cancer treatment centre in Ghana. The Female Sexual Function Index and Body Image Scale questionnaires were respectively used to evaluate the sexual functions scores among the cervical cancer patients, and to assess the impact of the treatment on their body image. MATLAB software was used for data analysis. RESULTS: Most of the cervical cancer patients sampled were postmenopausal (57 %). About 79 % premenopausal and 96 % postmenopausal cervical cancer patients were sexually inactive during radiotherapy (day 15). Also, 48 % premenopausal and 24 % postmenopausal patients were very dissatisfied with their bodies at the onset of treatment. The frequency of orgasm in cervical cancer patients declined after treatment causing a deterioration in their sexual function. The patients' sexuality was influenced by age and menopausal status. The decreased sexual desire of the patients resulted in emotional distancing from their partners, which invariably induced changes in their partners' level of sexual interest. This study established significant differences between premenopausal and postmenopausal cervical cancer patients who were generally very dissatisfied with their sexual relationships with their partners on day 1 (p = 0.02) and on day 15 (p = 0.00) of treatment. CONCLUSION: The majority of patients who presented for treatment for cervical cancer in this study were postmenopausal. Their interest in sexual activity was more influenced by their menopausal status than their antineoplastic treatment. This study indicates that cervical cancer patients are more likely to develop sexual health problems which could substantially worsen over the course of their treatment and beyond. IMPLICATION FOR PRACTICE: The study will contribute within the oncology team by assisting personnel in putting in place measures that will guide the treatment of cervical cancer patients and improve quality of care.

Impact of lipid-lowering therapy on the prevalence of dyslipidaemia in patients at high-risk of cardiovascular events in UK primary care - a retrospective database study.

AIMS: To estimate the prevalence of dyslipidaemias in high-risk patients new to lipid-modifying therapy (LMT), and establish the extent to which these lipid abnormalities are addressed by treatment in UK clinical practice. METHODS: The PRIMULA study was a retrospective analysis, conducted using the UK General Practice Research Database. Two periods were studied as follows: a pretreatment period, defined as the 12 months before initiation of LMT (the index date), and a follow-up period of at least 12 months. Patients included in the study (n = 25,011) had dyslipidaemia with at least one abnormal lipid measurement [total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) or triglycerides (TG)] in the pretreatment period. All patients were at high risk of cardiovascular events, which was defined as having a history of cardiovascular disease, a 10-year Framingham risk score higher than 20%, diabetes or hypertension, as defined by the Joint British Societies 2 guidelines. RESULTS: At the index date, 98% of patients were initiated on statin monotherapy. After 12 months of treatment, 15.2% (sub-group range: 11.0-22.9%) of all high-risk patients had no lipid abnormalities. The proportions of patients with high TC or LDL-C levels decreased from 98.8% to 68.9%, and from 99.2% to 68.7%, respectively, over 12 months. The prevalence of high TG levels decreased from 45.0% to 26.9%, whereas that of low HDL-C levels increased, from 16.6% to 18.0%. Risk factors for cardiovascular events were not consistently associated with the likelihood of attaining optimal lipid levels. CONCLUSIONS: Despite widespread use of statins, many individuals at high risk of cardiovascular events have persistently abnormal lipid levels, with over two-thirds of patients not achieving target levels of LDL-C or TC. Management of dyslipidaemia is therefore suboptimal in this important high-risk group in UK standard practice.

Using network analysis to detect associations between suspected painful health conditions and behaviour in dogs.

Pain associated with chronic health conditions in non-human animals is an important animal welfare issue. To identify animals in pain and develop an understanding of the mechanisms by which pain affects behaviour, it is therefore important to establish the direct behavioural effects of painful health conditions. We reanalyse data from a cross-sectional survey that considered the presence or absence of a painful condition in dogs and quantified their affective predispositions using the Positive and Negative Activation Scale (PANAS). By applying ideas from network theory, we conceptualise pain as a stressor that exerts direct effects on a network of interacting behavioural variables, and subsequently estimated a network model of conditional dependence relations. Painful health conditions were positively conditionally associated with age (posterior mean partial correlation, ρ = 0.34; standard deviation [SD]=0.05), and negatively conditionally associated with the item 'your dog is full of energy' (ρ = -0.14; SD=0.06). In turn, the energy item was conditionally associated with other PANAS items which were marginally associated with pain, such as items representing ease of excitability and persistence in play. This suggests these marginal effects might be indirectly mediated via the energy item. Further, utilising the posterior predictive distribution we estimated that the median conditional probability (95% credible interval) of a painful health condition given an answer of 'strongly agree' on the energy item was 0.08 (0.05, 0.11), which increased to 0.32 (0.09, 0.58), given a response of 'strongly disagree'. This provides a potentially clinically useful interpretation of the conditional dependencies detected in the network.

An ethological analysis of close-contact inter-cat interactions determining if cats are playing, fighting, or something in between.

Intraspecific social interactions in domestic cats are often categorised as affiliative or agonistic. However, public or professional assessment of encounters can have difficulty distinguishing rough-and-tumble play from true agonism. One possible issue is the potential occurrence of elements of both, play and agonism, within inter-cat play, for example when one cat wants to terminate a bout of play but the other seeks to continue the interaction, which subsequently may provoke more overt agonistic behaviour. To test this hypothesis, we conducted behavioural observations of 105 unique dyadic interactions of domestic cats (N = 210) captured on videos collected from owners and YouTube. We assessed cats for the frequency and duration of six behavioural elements. The dataset was reduced using PCA with a varimax rotation and factor scores were used to classify the population using hierarchical cluster analysis. To validate the identified clusters, the average scores of the constituent factors were compared and the data on interactions were labelled by four cat behaviour experts as "playful", "intermediate" or "agonistic". In addition, to evaluate properties of expert-labelled categories we used linear discriminant analysis followed by an ordinal regression. The results showed considerable convergent validity in factor distributions between clusters and expert-labelled groups: reciprocal wrestling was most closely associated with a group of playfully interacting cats, while vocalisation and chasing were associated with the agonistic group. The intermediate group, while having characteristics of both, was more closely related to the playful group than the agonistic group, with prolonged exchanges of interactive behaviours being a predominant feature. Thus, our findings support the suggestion of there being an intermediate category between mutual social play and agonism. This might escalate into a fully agonistic encounter, but does not necessarily reflect a break down in their social relationship but rather a short-term disagreement in social priorities.

Composite 3D printing of biomimetic human teeth.

Human teeth are mechanically robust through a complex structural composite organisation of materials and morphology. Efforts to replicate mechanical function in artificial teeth (typodont teeth), such as in dental training applications, attempt to replicate the structure and morphology of real teeth but lack tactile similarities during mechanical cutting of the teeth. In this study, biomimetic typodont teeth, with morphology derived from X-ray microtomography scans of extracted teeth, were 3D printed using an approach to develop novel composites. These composites with a range of glass, hydroxyapatite and porcelain reinforcements within a methacrylate-based photopolymer resin were compared to six commercial artificial typodont teeth. Mechanical performance of the extracted human teeth and 3D printed typodont teeth were evaluated using a haptic approach of measuring applied cutting forces. Results indicate 3D printed typodont teeth replicating enamel and dentine can be mechanically comparable to extracted human teeth despite the material compositions differing from the materials found in human teeth. A multiple parameter variable of material elastic modulus and hardness is shown to describe the haptic response when cutting through both human and biomimetic, highlighting a critical dependence between the ratio of material mechanical properties and not absolute material properties in determining tooth mechanical performance under the action of cutting forces.

Itinerant nature of atom-magnetization excitation by tunneling electrons.

We have performed single-atom magnetization curve (SAMC) measurements and inelastic scanning tunneling spectroscopy (ISTS) on individual Fe atoms on a Cu(111) surface. The SAMCs show a broad distribution of magnetic moments with 3.5 µB being the mean value. ISTS reveals a magnetization excitation with a lifetime of 200 fsec which decreases by a factor of 2 upon application of a magnetic field of 12 T. The experimental observations are quantitatively explained by the decay of the magnetization excitation into Stoner modes of the itinerant electron system as shown by newly developed theoretical modeling.

Selective inhibition of Erwinia amylovora by the herbicidally active germination-arrest factor (GAF) produced by Pseudomonas bacteria.

AIMS: The germination-arrest factor (GAF) produced by Pseudomonas fluorescens WH6, and identified as 4-formylaminooxyvinylglycine, specifically inhibits the germination of a wide range of grassy weeds. This study was undertaken to determine whether GAF has antimicrobial activity in addition to its inhibitory effects on grass seed germination. METHODS AND RESULTS: Culture filtrate from Ps. fluorescens WH6 had little or no effect on 17 species of bacteria grown in Petri dish lawns, but the in vitro growth of Erwinia amylovora, the causal agent of the disease of orchard crops known as fire blight, was strongly inhibited by the filtrate. The anti-Erwinia activity of WH6 culture filtrate was shown to be due to its GAF content, and a commercially available oxyvinylglycine, 4-aminoethoxyvinylglycine (AVG), exhibited anti-Erwinia activity similar to that of GAF. The effects of GAF on Erwinia were reversed by particular amino acids. CONCLUSIONS: The biological properties of GAF include a rather specific antimicrobial activity against Erw. amylovora. This may be a general property of oxyvinylglycines as AVG exhibited similar activity. The ability of particular amino acids to reverse GAF inhibition is consistent with a potential effect of this compound on the activity of aminotransferases. SIGNIFICANCE AND IMPACT OF THE STUDY: The results presented here demonstrate a novel antimicrobial activity of oxyvinylglycines and suggest that GAF and/or GAF-producing bacteria may have potential for the control of fire blight.