Giant parathyroid lipoadenoma case report: A parathyroid phenomenon.

INTRODUCTION: Parathyroid lipoadenomas are a rare parathyroid phenomenon and an unusual cause of primary hyperparathyroidism. A difficult diagnosis to make, there are less than 100 cases in the literature since they were first described in 1958, and to our knowledge this is the largest parathyroid lipoadenoma to be reported. PRESENTATION OF CASE: A minimally-invasive parathyroidectomy with intraoperative parathyroid hormone monitoring was performed in the case of a male with a large neck mass and symptomatic primary hyperparathyroidism. A giant parathyroid lipoadenoma was excised, with an appropriate decrease in intraoperative parathyroid hormone level observed. DISCUSSION: This lesion poses a challenge to the surgeon, radiologist and pathologist alike and is an important addition to the scant literature available. Clinically it presents similarly to a simple adenoma. The high adipose content of this lesion leads to difficulty localising it on imaging, and the histology study can lead pathologists astray. CONCLUSION: We highlight the importance of having the parathyroid lipoadenoma as a differential diagnosis for patients who develop primary hyperparathyroidism.

Assessing Patient Risk, Benefit, and Outcomes in Drug Development: Insights From Afatinib Clinical Trials Across Diverse Cancer Indications.

PURPOSE: In 2013, afatinib was approved for non-small-cell lung cancer with subsequent indication expansion. We investigated published afatinib clinical trials to assess risk and benefit profiles for the drug in its approved indication of non-small-cell lung cancer as well as in off-label uses. Previous literature demonstrates excessive patient burden and limited benefit as afatinib has spread into more indications. A trial analysis is needed to establish efficacy and risk. METHODS: In this investigation, we screened literature databases and clinical trial registries for trials of afatinib as monotherapy or in combination interventions for cancer treatment. We extracted participant demographics, adverse event characteristics, as well as clinical and surrogate endpoints for each trial. Studies were deemed positive, negative, or indeterminate based on their achieving of primary endpoints as well as their safety. RESULTS: Our search yielded 2444 articles; we excluded 2352 articles for a final inclusion of 92 trials of 8859 patients. Our sample had 49 (53%) positive trials, 27 (29%) negative trials, and 16 (17%) indeterminate trials. The most common off-label indications for afatinib were breast cancer and squamous cell carcinoma of head and neck. The median OS for all trials was 8.4 months, median PFS 3.4 months, and the total ORR was 29.6%. Our study found that trials performed in disease states beyond the initial indications were largely negative with little patient benefit. The adverse events within our trial sample appear to be in line with expectations for toxicity. IMPLICATIONS: These results are consistent with other studies that present similar findings, such as in Carlisle et al which indicate limited efficacy in nonapproved indications. Future trials should keep this potential evidence and patient burden in mind before initiation of those trials. This study contributes to the understanding of afatinib's risk-benefit profile across many clinical applications.

Assessing patient risk, benefit, and outcomes in drug development: A decade of ramucirumab clinical trials.

OBJECTIVE: This study aims to evaluate published clinical trials of ramucirumab to assess the risk/benefit profile and burden over time for patients. BACKGROUND: The burden of oncologic drug development on patients paired with increasing clinical trial failure rates emphasizes the need for reform of drug development. Identifying and addressing patterns of excess burden can guide policy, ensure evidence-based protections for trial participants, and improve medical decision-making. METHODS: On May 25, 2023 a literature search was performed on Pubmed/MEDLINE, Embase, Cochrane CENTRAL, and ClinicalTrials.gov for clinical trials using ramucirumab as monotherapy or in combination with other interventions for cancer treatment. Authors screened titles and abstracts for potential inclusion in a masked, duplicate fashion. Following data screening, data was extracted in a masked, duplicate fashion. Trials were classified as positive when meeting their primary endpoint and safety, negative or indeterminate. RESULTS: Ramucirumab was initially approved for gastric cancer but has since been tested in 20 cancers outside of its FDA approved indications. In our analysis of ramucirumab trials, there were a total of 10,936 participants and 10,303 adverse events reported. Gains in overall survival and progression-free survival for patients were 1.5 and 1.2 months, respectively. FDA-approved indications have reported more positive outcomes in comparison to off-label indications. CONCLUSION: We found that FDA-approved indications for ramucirumab had better efficacy outcomes than non-approved indications. However, a concerning number of adverse events were observed across all trials assessed. Participants in ramucirumab randomized controlled trials saw meager gains in overall survival when evaluated against a comparison group. Clinicians should carefully weigh the risks associated with ramucirumab therapy given its toxicity burden and poor survival gains.

Assessing Patient Risk, Benefit, and Outcomes in Drug Development: A Decade of Lenvatinib Clinical Trials: A Systematic Review.

IMPORTANCE: Chemotherapy agents are typically initially tested in their most promising indications; however, following initial US FDA approval, new clinical trials are often initiated in less promising indications where patients experience a worse burden-benefit ratio. The current literature on the burden-benefit profile of lenvatinib in non-FDA-approved indications is lacking. OBJECTIVE: This study aimed to evaluate published clinical trials of lenvatinib in order to determine the burden-benefit profile for patients over time. EVIDENCE REVIEW: On 25 May 2023, we searched the Pubmed/MEDLINE, Embase, Cochrane CENTRAL, and ClinicalTrials.gov databases for clinical trials of lenvatinib used to treat solid cancers. Eligible articles were clinical trials, containing adult participants, published in English, and involving solid tumors. Screening and data collection took place in a masked, duplicate fashion. For each eligible study, we collected adverse event data, trial characteristics, progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). Trials were classified as positive when meeting their primary endpoint and safety, negative (not meeting either criteria), or indeterminate (lacking prespecified primary endpoint). FINDINGS: Expansion of clinical trial testing beyond lenvatinib's initial FDA indication demonstrated a consistent rise in cumulative adverse events, along with a decline in drug efficacy. Lenvatinib was tested in 16 cancer indications, receiving FDA approval in 4. A total of 5390 Grade 3-5 adverse events were experienced across 6225 clinical trial participants. Expanded indication testing further demonstrated widely variable ORR (11-69%), OS (6.2-32 months), and PFS (3.6-15.7 months) across all indications. After initial FDA approval, clinical trial results in expanded indications were less likely to meet their primary endpoints, particularly among non-randomized clinical trials. CONCLUSION AND RELEVANCE: Our paper evaluated the effectiveness of lenvatinib for its FDA-approved indications; however, expansion of clinical trials into novel indications was characterized by diminished efficacy, while patients experienced a high burden of adverse events consistent with lenvatinib's established safety profile. Furthermore, clinical trials testing in novel indications was marked by repeated phase I and II clinical trials along with a failure to progress to phase III clinical trials. Future clinical trials using lenvatinib as an intervention should carefully evaluate the potential benefits and burden patients may experience.

Delayed discovery: the COVID-19 pandemic's influence on osteoarthritis clinical trials.

CONTEXT: The COVID-19 pandemic disrupted clinical research in many medical and surgical fields, resulting in research waste and loss of treatment for patients. Although other areas have been explored, the extent of the pandemic's influence on osteoarthritis (OA) trials is currently unknown. OBJECTIVES: This study aims to explore the reasons for termination of clinical trials investigating OA during the COVID-19 pandemic. METHODS: We searched ClinicalTrials.gov for OA trials and characterized their reason for discontinuation, noting where trialists directly cited the COVID-19 pandemic as the reason for trial discontinuation. We also coded other common reasons for trial discontinuation. Descriptive and inferential statistics were performed to determine the difference in enrollment, funding source, trial phase, allocation, and intervention type between the trials terminated early due to pandemic and nonpandemic reasons. RESULTS: Out of 135 clinical trials, 119 were included and 27 (22.7 %) of them reported the COVID-19 pandemic as a primary reason for discontinuation, which was the overall most common reason for OA trial discontinuation during the study period. We found statistically significant differences for trials discontinued due to pandemic vs. non-pandemic-related reasons, with trials having sites outside the United States, randomized allocation, and drug or device intervention type being most affected. However, there was no statistically significant difference between groups regarding trial phase, funding source, or enrollment. CONCLUSIONS: This study highlights the impact of the COVID-19 pandemic on the clinical trials related to OA. We found that many trials reported discontinuation directly due to the pandemic, which may lead to the loss or delay of novel treatments for OA. To avoid such discontinuation in the future, alternative methods for conducting OA-related clinical trials should be explored and implemented.

Assessing patient burden and benefit: A decade of cabozantinib clinical trials.

Drug development is complex and costly. Clinical trial participants take on risks, making it essential to maximize trial efficiency and maintain participant safety. Identifying periods of excessive burden during drug development can inform trial design, ensure patient benefit and prevent harm. This study aims to examine all published clinical trials for cabozantinib to assess patient benefit and burden over time. We conducted a retrospective cross-sectional review of interventional clinical trials of cabozantinib for solid cancer treatment. We searched PubMed/MEDLINE, Embase, Cochrane (CENTRAL) and ClinicalTrials.gov. We extracted adverse event rates, median progression-free survival (PFS), median overall survival and objective response rate (ORR) for each included trial. We calculated frequencies of trial characteristics, cumulative grade 3-5 adverse event rates and cumulative ORRs. Out of 1735 studies, 54 publications were included that involved 6372 participants and 21 cancers. Of the 54 studies in our sample, 31 (57.41%) were single-arm trials and 23 (42.60%) had negative results. Trials among and within various indications had conflicting results over time. Cumulative risk to participants increased over time, and clinical benefit decreased. The findings suggest that the risk profile of cabozantinib increased from 2011 to 2016 and has remained elevated but stable while benefit has decreased over time. The use of non-randomized and single-arm trials is concerning, and more methodologically rigorous trials are needed. The results of trials for different indications are inconsistent, and empirical administration may reduce the drug's efficacy.

Bird tolerance to humans in open tropical ecosystems.

Animal tolerance towards humans can be a key factor facilitating wildlife-human coexistence, yet traits predicting its direction and magnitude across tropical animals are poorly known. Using 10,249 observations for 842 bird species inhabiting open tropical ecosystems in Africa, South America, and Australia, we find that avian tolerance towards humans was lower (i.e., escape distance was longer) in rural rather than urban populations and in populations exposed to lower human disturbance (measured as human footprint index). In addition, larger species and species with larger clutches and enhanced flight ability are less tolerant to human approaches and escape distances increase when birds were approached during the wet season compared to the dry season and from longer starting distances. Identification of key factors affecting animal tolerance towards humans across large spatial and taxonomic scales may help us to better understand and predict the patterns of species distributions in the Anthropocene.

Trial Registry Searches in Plastic Surgery Systematic Reviews: A Meta-epidemiological Study.

INTRODUCTION: Clinical trial registry searches for unpublished clinical trial data are a means of mitigating publication bias within systematic reviews (SRs). The purpose of our study is to look at the rate of clinical trial registry searches conducted by SRs in the top five Plastic and Reconstructive Surgery journals. METHODS: We identified the top five plastic and reconstructive surgery journals using the Google h-5 index. We then searched Pubmed for SRs published in these journals and compared them to plastic surgery SRs published in the Cochrane Collaboration for SRs over the last 5 y. We included all SRs that were published within these top five journals and Cochrane between December 6, 2016 and December 6, 2021. We then conducted a secondary analysis on clinicaltrials.gov looking for unpublished clinical trials for 100 randomized SRs that did not conduct a clinical trial registry search. RESULTS: In SRs, 3.3% (17/512) from plastic surgery journals conducted trial registry searches. In comparison, 95.0% (38/40) of Cochrane Collaboration SRs conducted trial registry searches. Our secondary analysis found that 50% (50/100) of SRs could have included at least one unpublished clinical trial data set. CONCLUSIONS: We found that plastic surgery SRs rarely include searches for unpublished clinical trial data in clinical trial registries. To improve the data completeness of SRs in plastic surgery journals, we recommend journals alter their author guidelines to require a clinical trial registry search for unpublished literature.

Cemented vs Uncemented hemiarthroplasties for femoral neck fractures: An overlapping systematic review and evidence appraisal.

BACKGROUND: The purpose of our study is to assess the methodology of overlapping systematic reviews related to cemented vs uncemented hip hemiarthroplasties for the treatment of femoral neck fractures to find the study with the best evidence. Also, we assess the gaps in methodology and information to help with direction of future studies. METHODS: A systematic search was conducted in September 2022 using Pubmed, Embase, and Cochrane Library. Clinical outcome data and characteristics of each study were extracted to see which treatment had better favorability. The outcomes and characteristics extracted from each study includes, first author, search date, publication journal and date, number of studies included, databases, level of evidence, software used, subgroup analyses that were conducted, and heterogeneity with the use of I2 statistics Methodological quality information was extracted from each study using four different methodologic scores (Oxford Levels of Evidence; Assessment of Multiple Systematic Reviews (AMSTAR); Quality of reporting of meta-analyses (QUROM); Oxman and Guyatt. After that, the Jadad decision algorithm was used to identify which studies in our sample contained the best available evidence. Finally, overlap of each systematic review was assessed using Corrected Covered Area (CCA) to look at redundancy and research waste among the systematic reviews published on the topic. RESULTS: After screening, 12 studies were included in our sample. For the Oxford Levels of Evidence, we found that all the studies were Level I evidence. For the QUORUM assessment, we had 1 study with the highest score of 18. Additionally, we did the Oxman and Guyatt assessment, where we found 4 studies with a maximum score of 6. Finally, we did an AMSTAR assessment and found 2 studies with a score of 9. After conducting the methodological scores; the authors determined that Li. L et al 2021 had the highest quality. In addition, it was found that the CCA found among the primary studies in each systematic review calculated to .22. Any CCA above .15 is considered "very high overlap". CONCLUSIONS: The best available evidence suggests that Cemented HAs are better at preventing Prosthesis-related complications. Conversely, the best evidence also suggests that Cemented HA also results in longer operative time and increased intraoperative blood loss. When conducting future systematic reviews related to the topic, we ask that authors restrict conducting another systematic review until new evidence emerges so as not to confuse the clinical decision-making of physicians.

Stylized versus voxel phantoms: quantification of internal organ chord length distances.

Dosimetric calculations, whether for radiation protection or nuclear medicine applications, are greatly influenced by the use of computational models of humans, called anthropomorphic phantoms. As anatomical models of phantoms have evolved and expanded, thus has the need for quantifying differences among each of these representations that yield variations in organ dose coefficients, whether from external radiation sources or internal emitters. This work represents an extension of previous efforts to quantify the differences in organ positioning within the body between a stylized and voxel phantom series. Where prior work focused on the organ depth distribution vis-à-vis the surface of the phantom models, the work described here quantifies the intra-organ and inter-organ distributions through calculation of the mean chord lengths. The revised Oak Ridge National Laboratory stylized phantom series and the University of Florida/National Cancer Institute voxel phantom series including a newborn, 1-, 5-, 10- and 15 year old, and adult phantoms were compared. Organ distances in the stylized phantoms were computed using a ray-tracing technique available through Monte Carlo radiation transport simulations in MCNP6. Organ distances in the voxel phantom were found using phantom matrix manipulation. Quantification of differences in organ chord lengths between the phantom series displayed that the organs of the stylized phantom series are typically situated farther away from one another than within the voxel phantom series. The impact of this work was to characterize the intra-organ and inter-organ distributions to explain the variations in updated internal dose coefficient quantities (i.e. specific absorbed fractions) while providing relevant data defining the spatial and volumetric organ distributions in the phantoms for use in subsequent internal dosimetric computations, with prospective relevance to patient-specific individualized dosimetry, as well as informing machine learning definition of organs using these reference models.

A VO2max Protocol for Young, Apparently Healthy Adults.

The Bruce and Astrand treadmill protocols are commonly utilized when assessing maximal oxygen consumption (VO2max). However, the steep grade implemented in the protocols often leads to localized muscular fatigue, potentially causing participants prematurely to terminate the test prior to reaching their true VO2max. The purpose of this study was to evaluate a Novel VO2max protocol that may be better suited for young, apparently healthy populations. The Novel protocol starts at a higher speed and lower initial grade to limit lower extremity fatigue. Fifteen participants performed the Bruce, Astrand, and Novel protocols with the following maximal values recorded from each: VO2max, maximal ventilation (VEmax), respiratory exchange ratio (RER), heart rate (HR), rating of perceived exertion (RPE) and time to exhaustion (TTE). The Novel protocol displayed substantial agreement with both criterion protocols. Mean absolute percent error (MAPE) was less than 10% indicating that the Novel protocol is a valid measurement for VO2max values. Bland-Altman analysis revealed that the Novel protocol exhibited a low degree of bias, with tight limits of agreement when compared to the Bruce (bias ±95% LOA = 0.824 ± 3.163) and Astrand protocols (-0.153 ± 3.528) for VO2max. A paired samples t-test revealed no significant differences between Novel and criterion protocols for VO2max. Paired samples t-tests revealed that the Novel protocol had significantly lower TTE when compared to the Bruce and Astrand protocols and produced similar VO2max values to that of the Bruce and Astrand. The Novel protocol may be considered a valid and time-efficient protocol.

Australian primary health care nurses’ knowledge, practice and attitudes relating to preconception care: learnings for service implementation.

Preconception care (PCC) entails counselling and interventions to optimise health before pregnancy. Barriers to this service delivery include access and time. Primary healthcare nurses (PHCNs) are uniquely placed to deliver PCC. The aim of this study was to understand PHCNs' knowledge, practice and attitudes to PCC. A cross-sectional study was performed of a convenience sample of PHCNs in Australia who were seeing people of reproductive age. Recruitment was via the Australian Primary Health Care Nurses Association (APNA) electronic communication platforms. The 18-item, online, anonymous survey captured demographics, as well as PCC knowledge, practices and attitudes. Descriptive statistics were used to describe our findings. In all, 152 completed surveys were received. Of all respondents, 74% stated they discuss PCC in their practice, although only 13% do so routinely. Of these, more preconception discussions are held with women than with men. In total, 95% of respondents identified at least one barrier to delivery of PCC, with lack of time and knowledge being the most common. The findings of this study can inform targeted strategies, including education programs and resources, and consideration of incentives to support PHCNs deliver PCC. This study identifies areas for improvement at the individual, organisational and health system levels to enhance the role of PHCNs in PCC.

The role of MRI and CT of the brain in first episodes of psychosis and behavioural abnormality.

AIM: To investigate whether computed tomography (CT)/magnetic resonance imaging (MRI) brain imaging is associated with detection of structural causes of a first episode of psychosis (FEP) or first episode of behavioural abnormality (FEB) in the paediatric population, as this has not been previously documented in the literature. MATERIALS AND METHODS: Individuals with FEP/FEB but no neurological signs referred to a tertiary children's centre for cerebral MRI or CT were reviewed retrospectively. Individuals were evaluated independently with one technique (CT or MRI) only. RESULTS: Thirty-four consecutive cerebral MRI and six consecutive CT examinations were identified between 2017 and 2020. No patients were identified as having an organic cause for the psychosis at MRI or CT. Four patients (9%) had incidental findings on MRI, unrelated to the psychosis, such as prominent perivascular spaces, hypoplastic transverse sinus, and sinonasal mucosal wall thickening. No abnormal findings were seen on CT. There was therefore no obvious difference between MRI and CT imaging in detecting organic disease potentially responsible for FEP. CONCLUSION: Routine structural MRI or CT of the brain is unlikely to reveal disease leading to a significant change in management. MRI demonstrated only a few incidental findings, unrelated to the child's clinical history. Therefore, routine brain structural imaging of FEP/FEB in paediatric patients without focal neurology may not be routinely required. If imaging is requested, then there is no significant difference between CT and MRI in detecting clinically significant lesions.

Concordance between a neuroradiologist, a consultant radiologist and trained reporting radiographers interpreting MRI head examinations: An empirical study.

INTRODUCTION: This study assessed agreement between MRI reporting radiographers and a consultant radiologist compared with an index neuroradiologist when reporting MRI head (brain/internal auditory meati [IAMs]) examinations. The effect on patient management of any discordant reports was also examined. METHODS: Two trained MRI reporting radiographers (RRs), a consultant radiologist (CR) and an index neuroradiologist (INR) reported on a random sample of 210 MRI examinations. The radiographers reported during clinical practice and the radiologists in clinical practice conditions. Two independent consultant physicians (neuro-rehabilitation and neuropsychiatry) compared these reports with the index neuroradiologist report for agreement and the clinical importance of discrepant reports. RESULTS: Overall observer agreement between the RRs and CR was comparable in relation to agreement with the INR: RR; 93/210 (44.3%); and the CR; 83/210 (39.4%) for all head MRI examinations (p = 0.32). For brain examinations the difference was similar: RR; 64/180 (35.6%); and CR; 54/190 (30.0%), p = 0.26. Agreement rates for the IAMs examinations were identical, 29/30 (97.7%). For all head MRI examinations (n = 210) there was a very small observed difference of <0.5% in mean agreement between the reporting radiographers and the consultant radiologist (p = 0.92) for examinations where a major disagreement would have been likely to have led to a change in patient management. CONCLUSION: MRI reporting radiographers reported during clinical practice on MRI head examinations to a level of agreement comparable with a consultant radiologist. IMPLICATIONS FOR PRACTICE: This is an area in which radiographers could provide additional reporting roles to the reporting service to increase capacity. Wider potential benefits include cost-effectiveness and role development/retention of radiographers.

Race, Natriuretic Peptides, and High-Carbohydrate Challenge: A Clinical Trial.

RATIONALE: Lower NP (natriuretic peptide) levels may contribute to the development of cardiometabolic diseases. Blacks have lower NP levels than middle-aged and older white adults. A high-carbohydrate challenge causes an upregulation of a negative ANP regulator microRNA-425 (miR-425), which reduces ANP (atrial-NP) levels in whites. OBJECTIVES: We designed a prospective trial to study racial differences in (1) NP levels among young adults, (2) NP response to a high-carbohydrate challenge, and (3) explore underlying mechanisms for race-based differences. METHODS AND RESULTS: Healthy self-identified blacks and whites received 3 days of study diet followed by a high-carbohydrate challenge. Gene expression from whole blood RNA was assessed in the trial participants. Additionally, atrial and ventricular tissue samples from the Myocardial Applied Genomics Network repository were examined for NP system gene expression. Among 72 healthy participants, we found that B-type-NP, NT-proBNP (N-terminal-pro-B-type NP), and MRproANP (midregional-pro-ANP) levels were 30%, 47%, and 18% lower in blacks compared with whites (P≤0.01), respectively. The decrease in MRproANP levels in response to a high-carbohydrate challenge differed by race (blacks 23% [95% CI, 19%-27%] versus whites 34% [95% CI, 31%-38]; Pinteraction<0.001), with no change in NT-proBNP levels. We did not observe any racial differences in expression of genes encoding for NPs (NPPA/NPPB) or NP signaling (NPR1) in atrial and ventricular tissues. NP processing (corin), clearance (NPR3), and regulation (miR-425) genes were ≈3.5-, ≈2.5-, and ≈2-fold higher in blacks than whites in atrial tissues, respectively. We also found a 2-and 8-fold higher whole blood RNA expression of gene encoding for Neprilysin (MME) and miR-425 among blacks than whites. CONCLUSIONS: Racial differences in NP levels are evident in young, healthy adults suggesting a state of NP deficiency exists in blacks. Impaired NP processing and clearance may contribute to race-based NP differences. Higher miR-425 levels in blacks motivate additional studies to understand differences in NP downregulation after physiological perturbations. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov/ct2/show/NCT03072602. Unique identifier: NCT03072602.

Identifying physiological measures of lifetime welfare status in pigs: exploring the usefulness of haptoglobin, C- reactive protein and hair cortisol sampled at the time of slaughter.

BACKGROUND: Physiological measures indicative of the welfare status of animals during rearing could form part of an abattoir-based animal health and welfare assessment tool. A total of 66 pigs were used in this study, the aim of which was to assess how serum concentrations of haptoglobin (Hp) and C-reactive protein (CRP) (assessed in 51 pigs), and hair concentrations of cortisol (assessed in 65 pigs), measured at or close to slaughter, reflected welfare-related indicators recorded from the animal during its lifetime. These indicators were recorded at intervals between 7 and 21 weeks of age and included assigning scores for levels of tail and skin lesions, recording the presence or absence of certain health issues, and conducting qualitative behavioural assessments (QBA). RESULTS: Pigs recorded as having tail lesions during their lifetime had higher hair cortisol levels than those with no tail lesions (tail lesions: 47.87 ± 3.34 pg/mg, no tail lesions: 42.20 ± 3.29 pg/mg, P = 0.023), and pigs recorded as having moderate or severe tail lesions had higher Hp levels than those with no or mild tail lesions (moderate/severe: 1.711 mg/ml ± 0.74, none/mild: 0.731 mg/ml ±0.10, P = 0.010). Pigs recorded as being lame during their lifetime tended to have higher hair cortisol levels than non-lame pigs (lame: 52.72 pg/mg ± 3.83, not lame: 43.07 pg/mg ± 2.69, P = 0.062). QBA scores were not associated with any of the physiological measures (P > 0.05). Receiver Operator Curve (ROC) analysis was also carried out to get a better understanding of the usefulness of the physiological measures in discriminating animals that had had welfare-related issues recorded during their lifetime from those that had not. Hair cortisol was determined as having 'moderate' accuracy in discriminating pigs that were tail bitten on-farm from unbitten pigs (AUC: 0.748) while Hp and CRP were determined to have no meaningful discriminatory ability (AUC < 0.600). CONCLUSION: This research should be repeated on a larger scale, but the results suggest that hair cortisol measured at slaughter could provide insight into the welfare status of pigs during their lifetime. Hp may be a useful indicator of tail lesions in pigs. However, further research utilising a greater proportion of severely bitten pigs is required before conclusions can be drawn.

Media pH and media type can significantly affect the reliability of in vitro copper tolerance assessments of Pseudomonas syringae pv. tomato.

AIMS: There are inconsistencies with in vitro copper tolerance screening methodology for Pseudomonas syringae pv. tomato in the current literature, particularly in relation to the appropriate medium to use, copper tolerance thresholds and reporting medium pH and/or pH adjustment steps. This study investigates the effect of medium and pH on copper tolerance results, including the potential use of 2-(N-morpholino)ethanesulfonic acid (MES) buffer to stabilize medium pH. METHODS AND RESULTS: Copper tolerance methodology was investigated through in vitro and in vivo testing of P. syringae pv. tomato. Four different media were tested, nutrient agar, Casitone yeast extract glycerol agar, King's B medium and potato dextrose agar. Highly variable copper tolerance profiles were observed for different isolates on the media tested. A pH range of 5·8-7·0 produced consistent copper tolerance data; outside of this range the data were unreliable. Addition of MES to media buffered the pH to within the acceptable levels. CONCLUSIONS: Copper tolerance thresholds with different media can vary significantly and the lowering effect of copper sulphate on media pH must be considered in media preparation. SIGNIFICANCE AND IMPACT OF THE STUDY: Methodology presented in the study can be extrapolated to copper tolerance testing for other pathogenic plant bacteria, particularly other pseudomonads.

European and Mediterranean hydroclimate responses to tropical volcanic forcing over the last millennium.

Volcanic eruptions have global climate impacts, but their effect on the hydrologic cycle is poorly understood. We use a modified version of superposed epoch analysis, an eruption year list collated from multiple datasets, and seasonal paleoclimate reconstructions (soil moisture, precipitation, geopotential heights, and temperature) to investigate volcanic forcing of spring and summer hydroclimate over Europe and the Mediterranean over the last millennium. In the western Mediterranean, wet conditions occur in the eruption year and the following 3 years. Conversely, northwestern Europe and the British Isles experience dry conditions in response to volcanic eruptions, with the largest moisture deficits in post-eruption years 2 and 3. The precipitation response occurs primarily in late spring and early summer (April-July), a pattern that strongly resembles the negative phase of the East Atlantic Pattern. Modulated by this mode of climate variability, eruptions force significant, widespread, and heterogeneous hydroclimate responses across Europe and the Mediterranean.