Dapagliflozin vs. metolazone in heart failure resistant to loop diuretics.

BACKGROUND AND AIMS: To examine the decongestive effect of the sodium-glucose cotransporter 2 inhibitor dapagliflozin compared to the thiazide-like diuretic metolazone in patients hospitalized for heart failure and resistant to treatment with intravenous furosemide. METHODS AND RESULTS: A multi-centre, open-label, randomized, and active-comparator trial. Patients were randomized to dapagliflozin 10 mg once daily or metolazone 5-10 mg once daily for a 3-day treatment period, with follow-up for primary and secondary endpoints until day 5 (96 h). The primary endpoint was a diuretic effect, assessed by change in weight (kg). Secondary endpoints included a change in pulmonary congestion (lung ultrasound), loop diuretic efficiency (weight change per 40 mg of furosemide), and a volume assessment score. 61 patients were randomized. The mean (±standard deviation) cumulative dose of furosemide at 96 h was 977 (±492) mg in the dapagliflozin group and 704 (±428) mg in patients assigned to metolazone. The mean (±standard deviation) decrease in weight at 96 h was 3.0 (2.5) kg with dapagliflozin compared to 3.6 (2.0) kg with metolazone [mean difference 0.65, 95% confidence interval (CI) -0.12,1.41 kg; P = 0.11]. Loop diuretic efficiency was less with dapagliflozin than with metolazone [mean 0.15 (0.12) vs. 0.25 (0.19); difference -0.08, 95% CI -0.17,0.01 kg; P = 0.10]. Changes in pulmonary congestion and volume assessment score were similar between treatments. Decreases in plasma sodium and potassium and increases in urea and creatinine were smaller with dapagliflozin than with metolazone. Serious adverse events were similar between treatments. CONCLUSION: In patients with heart failure and loop diuretic resistance, dapagliflozin was not more effective at relieving congestion than metolazone. Patients assigned to dapagliflozin received a larger cumulative dose of furosemide but experienced less biochemical upset than those assigned to metolazone. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04860011.

Retaining dermatology patients in primary care through dialogue with secondary care providers: A service evaluation.

BACKGROUND: There are long patient waiting lists for specialist care. A dermatology dialogue service between primary and secondary care (DDPS) was developed in eastern England. Primary care referrers uploaded patient images of skin conditions for review by and dialogue with consultant dermatologists in an attempt to retain patients in primary care rather than refer them to secondary care. METHODS: Evaluation of service performance against specific targets, including reduction in secondary care waiting list growth over the period April 2021-March 2022 inclusive. Service activity was summarized in terms of speed of resolution, case numbers, and dispositions. Clinician and patient satisfaction were assessed using structured questionnaires. Actual numbers of new referrals were compared to projections based on historical data. Waiting list growth was compared to other specialties and other commissioning areas. Waiting times to initial treatment were monitored. RESULTS: Over 3300 patients were enrolled and > 90% of dialogues were resolved within 36 hours. Clinician and patient satisfaction were high. Frequently asked questions and conditions were highlighted by dermatologists to design and deliver an educational event for primary care clinicians that was well received. Waiting list growth for dermatology patients in the commissioning area was smaller than for other major specialties, and generally smaller than growth for dermatology waiting lists commissioned by other NHS commissioners. There was no negative impact on the urgent priority (cancer pathway) waiting list. CONCLUSION: The DDPS was satisfactory for clinicians and patients and coincided with lower growth in dermatology waiting lists than might otherwise have been expected.

Analysis of complications and revisions after spine surgery in 270 multiple myeloma patients with spinal involvement.

BACKGROUND CONTEXT: Patients with multiple myeloma (MM) are at increased risk of infections and suffer from poor bone quality due to their disseminated malignant bone disease. Therefore, postoperative complications may occur following surgical treatment of MM lesions. PURPOSE: In this study, we aimed to determine the incidence of postoperative complications and retreatments after spinal surgery in MM patients. Additionally, we sought to identify risk factors associated with complications and retreatments. STUDY DESIGN: Retrospective cohort study. PATIENT SAMPLE: In total, 270 patients with MM who received surgical treatment for spinal involvement between 2008 and 2021 were included. OUTCOME MEASURES: The incidence of perioperative complications within 6 weeks and reoperations within 2.5 years and individual odds ratios for factors associated with these complications and reoperations. METHODS: Data were collected through manual chart review. Hosmer and Lemeshow's purposeful regression method was used to identify risk factors for complications and reoperations. RESULTS: The median age of our cohort was 65 years (SD = 10.8), and 58% were male (n = 57). Intraoperative complications were present in 24 patients (8.9%). The overall 6-week complication rate after surgery was 35% (n = 95). The following variables were independently associated with 6-week complications: higher Genant grading of a present vertebral fracture (OR 1.41; 95% CI 1.04-1.95; p = .031), receiving intramuscular or intravenous steroids within a week prior to surgery (OR 3.97; 95% CI 1.79-9.06; p = .001), decompression surgery without fusion (OR 6.53; 95% CI 1.30-36.86; p = .026), higher creatinine levels (OR 2.18; 95% CI 1.19-5.60; p = .014), and lower calcium levels (OR 0.58; 95% CI 0.37-0.88; p = .013). A secondary surgery was indicated for 53 patients (20%), of which 13 (4.8%) took place within two weeks after the initial surgery. We additionally discovered factors associated with retreatments, which are elucidated within the manuscript. CONCLUSION: The goal of surgical treatment for MM bone disease is to enhance patient quality of life and reduce symptom burden. However, postoperative complication rates remain relatively high after spine surgery in patients with MM, likely attributable to both inherent characteristics of the disease and patient comorbidities. The risk for complications and secondary surgeries should be explored and a multidisciplinary approach is crucial.

"I did whatever they wanted me to do": a qualitative secondary analysis using reproductive justice to explore sexual violence among justice-involved Latina mothers.

BACKGROUND: One in three women experience sexual violence during their lifetime; however, little is known about this phenomenon with respect to justice-involved Latina mothers. Using the reproductive justice framework as a theoretical lens, we examined sexual violence in Latina mothers who had experienced incarceration and were thus involved in the justice system. METHODS: This was a secondary analysis of a qualitative data set. The reproductive justice framework provided a theoretical lens for examining the women's rights to bodily autonomy, to have or not have children, and to live in safe, sustainable environments given the intersection of incarceration and sexual violence. RESULTS: Women (N = 12) recounted their experiences of sexual violence after having been incarcerated. Incarceration and resulting sexual violence led to discrimination, limited bodily autonomy, sexual exploitation, substance use, depression, anxiety, re-traumatization, recidivism, underreporting of violence, underutilization of healthcare resources, strained relationships, family separation, and unsafe environments. CONCLUSIONS: More research is needed to understand the social, economic, and political contexts that perpetuate sexual violence among justice-involved women. Universal healthcare, participatory research, changing cultural mindsets, decriminalization of sex work, and more comprehensive tracking and prosecution of sexual predators may be key to ending sexual violence in justice-involved mothers.

Retrospective analysis of a STEM outreach event reveals positive influences on student attitudes toward STEM careers but not scientific methodology.

Substantial, involved, and expensive efforts to promote the dissemination of scientific knowledge and career interest in Science, Technology, Engineering, and Mathematics (STEM) are enthusiastically supported by many scientific, federal, and local organizations. The articulated underlying goals for these efforts include an enhanced public understanding of science and science-related policy, an increased diversity in STEM careers, and an increase in the future STEM workforce. This effort is primarily driven by an underperformance of the United States that includes poor test performance and limited number of students pursuing STEM degrees. Despite this investment, attitudes toward STEM have not notably changed. The goal of this project was to determine students' attitudes toward STEM in response to a previously established scientific outreach event. This event was used to address three common goals in STEM outreach: STEM literacy, diversity and inclusion, and career preparedness. We found there was a notable difference in the attitudes toward scientific activities and interest in pursuing a "Science Career" after participation in this event. Strikingly, interest in hypothesis development, the keystone of all STEM disciplines, was the least liked of all the activities offered during the event. Our data suggest that events designed to enhance interest in pursuing a STEM career may benefit from different elements compared with events designed to increase understanding of STEM literacy concepts, such as hypothesis development.

Maternal and fetal genetic contribution to gestational weight gain.

BACKGROUND: Clinical recommendations to limit gestational weight gain (GWG) imply high GWG is causally related to adverse outcomes in mother or offspring, but GWG is the sum of several inter-related complex phenotypes (maternal fat deposition and vascular expansion, placenta, amniotic fluid and fetal growth). Understanding the genetic contribution to GWG could help clarify the potential effect of its different components on maternal and offspring health. Here we explore the genetic contribution to total, early and late GWG. PARTICIPANTS AND METHODS: A genome-wide association study was used to identify maternal and fetal variants contributing to GWG in up to 10 543 mothers and 16 317 offspring of European origin, with replication in 10 660 mothers and 7561 offspring. Additional analyses determined the proportion of variability in GWG from maternal and fetal common genetic variants and the overlap of established genome-wide significant variants for phenotypes relevant to GWG (for example, maternal body mass index (BMI) and glucose, birth weight). RESULTS: Approximately 20% of the variability in GWG was tagged by common maternal genetic variants, and the fetal genome made a surprisingly minor contribution to explain variation in GWG. Variants near the pregnancy-specific beta-1 glycoprotein 5 (PSG5) gene reached genome-wide significance (P=1.71 × 10-8) for total GWG in the offspring genome, but did not replicate. Some established variants associated with increased BMI, fasting glucose and type 2 diabetes were associated with lower early, and higher later GWG. Maternal variants related to higher systolic blood pressure were related to lower late GWG. Established maternal and fetal birth weight variants were largely unrelated to GWG. CONCLUSIONS: We found a modest contribution of maternal common variants to GWG and some overlap of maternal BMI, glucose and type 2 diabetes variants with GWG. These findings suggest that associations between GWG and later offspring/maternal outcomes may be due to the relationship of maternal BMI and diabetes with GWG.

Risk evaluation mitigation strategy: impact of application of the Food and Drug Adminstration's strategy on use of erythropoiesis-stimulating agents and transfusion in patients with chemotherapy-induced anaemia.

WHAT IS KNOWN AND OBJECTIVE: The Food and Drug Administration (FDA) instituted a risk evaluation mitigation strategy (REMS) for erythropoiesis-stimulating agent (ESA) use in patients with cancer in February 2010. Implementation of REMS was considered likely to reduce ESA use and increase red blood cell transfusions. We aimed to quantify ESA and transfusion use pre- and post-REMS. METHODS: A retrospective data analysis was conducted using the Medicare 5% Sample Database from 2008 through 2011. Patients were 66 years of age or older and had lung and/or breast cancers along with chemotherapy-induced anaemia. Patients initiated chemotherapy in pre-REMS and post-REMS periods (1Q2008 through 4Q2009 and 1Q2010 through 4Q2011, respectively). Logistic regression was used to evaluate differences in proportions of patients receiving ESAs and transfusions pre-REMS and post-REMS. RESULTS AND DISCUSSION: The pre-REMS group included 1526 patients and the post-REMS group included 1689 patients. ESA use in patients with lung cancer decreased 30·2% from pre- to post-REMS and 33·1% in patients with breast cancer. Both decreases were statistically significant. Transfusion rates increased 22·1% from the pre-REMS period to the pre-REMS period in patients with breast cancer (P < 0·0001), but there was no statistically significant change over time in patients with lung cancer. WHAT IS NEW AND CONCLUSION: Erythropoiesis-stimulating agent use decreased in patients with both lung and breast cancer (P < 0·0001), and transfusion rates increased significantly post-REMS in patients with breast cancer (P < 0·0001) but not in those with lung cancer.

Metabolic effects of Carbon Dioxide (CO2) insufflation during laparoscopic surgery: changes in pH, arterial partial Pressure of Carbon Dioxide (PaCo2) and End Tidal Carbon Dioxide (EtCO2).

Background: Acid base alterations occur during laparoscopy with carbon dioxide insufflation. The purpose of this study was to investigate the effects of low tidal volume ventilation on acid base status during pneumoperitonium. Materials and Methods: 30 patients undergoing laparoscopic surgery under General Anaesthesia were ventilated with tidal volume of 6 ml/kg and respiratory rate of 12 breaths/minute. Arterial blood gas analysis was done before, during and after C02 pneumoperitoneum. Arterial haemoglobin oxygen saturation by pulse oximetry (SPO2) and EtC02 were monitored continuously throughout the laparoscopy. Respiratory adjustments were done for EtCO2 levels above 60mmHg or SPO2 below 92% or adverse haemodynamic changes. Results: low tidal volume ventilation during pneumoperitoneum resulted in a significant elevation in PaCO2 (p<0.001) and a fall of pH (p <0.001), ion bicarbonate (HCO3-) (p = 0.011), and base excess (ABE) (p <0.001). A correlation was found between the EtCO2 and PaCO2 during pneumoperitoneum. Oxygenation was well maintained during pneumoperitoneum. No ventilatory adjustments were instituted on any of the patients as they maintained EtCO2 below 60mmHg throughout pneumoperitoneum. Conclusion: Ventilation with low tidal volume during pneumoperitoneum causes a mixed respiratory and metabolic acidosis. EtCO2 is still a good non-invasive monitor for estimation of PaCO2 during low tidal volume ventilation during pneumoperitoneum.

Cannabinoid WIN-55,212-2 mesylate inhibits interleukin-1ß induced matrix metalloproteinase and tissue inhibitor of matrix metalloproteinase expression in human chondrocytes.

OBJECTIVE: Interleukin-1ß (IL-1ß) is involved in the up-regulation of matrix metalloproteinases (MMPs) leading to cartilage degradation. Cannabinoids are anti-inflammatory and reduce joint damage in animal models of arthritis. This study aimed to determine a mechanism whereby the synthetic cannabinoid WIN-55,212-2 mesylate (WIN-55) may inhibit cartilage degradation. METHODS: Effects of WIN-55 were studied on IL-1ß stimulated production of MMP-3 and -13 and their inhibitors TIMP-1 and -2 in human chondrocytes. Chondrocytes were obtained from articular cartilage of patients undergoing total knee replacement. Chondrocytes were grown in monolayer and 3D alginate bead cultures. Real-time polymerase chain reaction (PCR) was used to determine the gene expression of MMP-3, -13, TIMP-1 and -2 and Enzyme Linked Immunosorbent Assay (ELISA) to measure the amount of MMP-3 and MMP-13 protein released into media. Immunocytochemistry was used to investigate the expression of cannabinoid receptors in chondrocyte cultures. RESULTS: Treatment with WIN-55 alone or in combination with IL-1ß, decreased or abolished MMP-3, -13, TIMP-1 and -2 gene expression in human chondrocyte monolayer and alginate bead cultures in both a concentration and time dependent manner. WIN-55 treatment alone, and in combination with IL-1ß, reduced MMP-3 and -13 protein production by chondrocytes cultured in alginate beads. Immunocytochemistry demonstrated the expression of cannabinoid receptors in chondrocyte cultures. CONCLUSION: Cannabinoid WIN-55 can reduce both basal and IL-1ß stimulated gene and protein expression of MMP-3 and -13. However WIN-55 also decreased basal levels of TIMP-1 and -2 mRNA. These actions of WIN-55 suggest a mechanism by which cannabinoids may act to prevent cartilage breakdown in arthritis.

miRNA-21 is dysregulated in response to vein grafting in multiple models and genetic ablation in mice attenuates neointima formation.

AIMS: The long-term failure of autologous saphenous vein bypass grafts due to neointimal thickening is a major clinical burden. Identifying novel strategies to prevent neointimal thickening is important. Thus, this study aimed to identify microRNAs (miRNAs) that are dysregulated during neointimal formation and determine their pathophysiological relevance following miRNA manipulation. METHODS AND RESULTS: We undertook a microarray approach to identify dysregulated miRNAs following engraftment in an interpositional porcine graft model. These profiling experiments identified a number of miRNAs which were dysregulated following engraftment. miR-21 levels were substantially elevated following engraftment and these results were confirmed by quantitative real-time PCR in mouse, pig, and human models of vein graft neointimal formation. Genetic ablation of miR-21 in mice or grafted veins dramatically reduced neointimal formation in a mouse model of vein grafting. Furthermore, pharmacological knockdown of miR-21 in human veins resulted in target gene de-repression and a significant reduction in neointimal formation. CONCLUSION: This is the first report demonstrating that miR-21 plays a pathological role in vein graft failure. Furthermore, we also provided evidence that knockdown of miR-21 has therapeutic potential for the prevention of pathological vein graft remodelling.

The effects of homelessness on Veterans' health care service use: an evaluation of independence from comorbidities.

OBJECTIVES: This study evaluates the prevalence of Multiple Comorbid Chronic Disease (MCCD) within homeless and non-homeless Veterans and the association between MCCD and inpatient medical care. METHODS: All individuals seen in the VA North Texas Health Care System between October 1, 2009 and September 30, 2010 (n = 102,034) were evaluated. Homelessness during the year and the number of common chronic diseases were evaluated for an association with likelihood of medical and psychiatric hospitalizations, bed days of care, inpatient substance treatment, rehabilitation admissions, and emergency department visits. RESULTS: Homeless Veterans had higher all-cause mortality rates and rates of use of almost all resources after controlling for chronic disease burden using the Charlson Comorbidity Index, psychiatric illnesses, substance use disorders, and demographic variables. CONCLUSIONS: Homelessness Veterans are vulnerable to a high use of resources and mortality, independent of medical and psychiatric conditions. This finding should focus additional attention on reducing homelessness.

Investigation of neutering status and age of neutering in female Dachshunds with thoracolumbar intervertebral disc extrusion.

OBJECTIVES: To evaluate neutering status and age of neutering in female Dachshunds with thoracolumbar intervertebral disc extrusion. We hypothesised that neutered Dachshunds presented with intervertebral disc extrusion at an earlier age, with a higher grade of neurological deficits and with more extensive extrusion of disc material compared with intact females. MATERIALS AND METHODS: Retrospective multi-centre study of client-owned female Dachshunds with surgically confirmed thoracolumbar intervertebral disc extrusion. Dogs were classified as early, late or not neutered (intact). Age, body condition score, duration of clinical signs before presentation, modified Frankel score at presentation, length of extruded disc material, maximum spinal cord compression and whether dogs presented for a subsequent intervertebral disc extrusion were recorded. RESULTS: One hundred and fifty-four dogs were included: 36 early neutered, 69 late neutered and 49 intact. No significant difference was found between early neutered, late neutered and entire female Dachshunds in any of the variables studied. CLINICAL SIGNIFICANCE: In this cohort of female dogs, neuter status and age of neutering were not found to affect age at onset nor severity of thoracolumbar intervertebral disc extrusion.

The ovine Booroola fecundity gene (FecB) is linked to markers from a region of human chromosome 4q.

The autosomal Booroola fecundity gene (FecB) mutation in sheep increases ovulation rate and litter size, with associated effects on ovarian physiology and hormone profiles. Analysis of segregation in twelve families (379 female progeny) identified linkage between the mutation, two microsatellite markers (OarAE101 and OarHH55, Zmax > 9.0) and epidermal growth factor (EGF) from human chromosome 4q25 (Zmax > 3.0). The marker OarAE101 was linked to secreted phosphoprotein 1 (SPP1, which maps to chromosome 4q21-23 in man) in the test pedigrees and independent families (Zmax > 9.7). The identification of linkage between the FecB mutation and markers from human chromosome 4q is an important step towards further understanding the control of ovulation rates in mammals.

Thyroid regulation in teleost embryonic and larval development - can it be a promise for aquaculture?

The role of thyroid hormones (THs) in fish development is often overlooked and particularly neglected for the embryonic and larval stages of fish. We used a set of experiments to elucidate the importance of TH in embryonic to early larval development in zebrafish. In the first set of experiments we used morpholino antisense oligonucleotides to knock down TH downstream genes and showed that the depletion of TH in early development resulted in severe deformities, developmental delay, and pigmentation, which could be quantitatively recovered by subsequent TH treatments. In the second set of experiments, blocking TH deposition into zebrafish eggs by treating parental fish with goitrogens resulted not only initial low TH content in eggs, but also subsequent loss of egg laying ability. Overall, these data strongly suggest a key role of TH in early development in fish, providing its worth to be investigated for effective use in reproduction and larviculture.

Neurologic Outcomes After Radiation Therapy for Severe Spinal Cord Compression in Multiple Myeloma: A Study of 162 Patients.

BACKGROUND: Bone destruction is the most frequent disease-defining clinical feature of multiple myeloma (MM), resulting in skeletal-related events such as back pain, pathological fractures, or neurologic compromise including epidural spinal cord compression (ESCC). Up to 24% of patients with MM will be affected by ESCC. Radiation therapy has been proven to be highly effective in pain relief in patients with MM. However, a critical knowledge gap remains with regard to neurologic outcomes in patients with high-grade ESCC treated with radiation. METHODS: We retrospectively included 162 patients with MM and high-grade ESCC (grade 2 or 3) who underwent radiation therapy of the spine between January 2010 and July 2021. The primary outcome was the American Spinal Injury Association (ASIA) score after 12 to 24 months, or the last known ASIA score if the patient had had a repeat treatment or died. Multivariable logistic regression was used to assess factors associated with poor neurologic outcomes after radiation, defined as neurologic deterioration or lack of improvement. RESULTS: After radiation therapy, 34 patients (21%) had no improvement in their impaired neurologic function and 27 (17%) deteriorated neurologically. Thirty-six patients (22%) underwent either surgery or repeat irradiation after the initial radiation therapy. There were 100 patients who were neurologically intact at baseline (ASIA score of E), of whom 16 (16%) had neurologic deterioration. Four variables were independently associated with poor neurologic outcomes: baseline ASIA (odds ratio [OR] = 6.50; 95% confidence interval [CI] = 2.70 to 17.38; p < 0.001), Eastern Cooperative Oncology Group (ECOG) performance status (OR = 6.19; 95% CI = 1.49 to 29.49; p = 0.015), number of levels affected by ESCC (OR = 4.02; 95% CI = 1.19 to 14.18; p = 0.026), and receiving steroids prior to radiation (OR = 4.42; 95% CI = 1.41 to 16.10; p = 0.015). CONCLUSIONS: Our study showed that 38% of patients deteriorated or did not improve neurologically after radiation therapy for high-grade ESCC. The results highlight the need for multidisciplinary input and efforts in the treatment of high-grade ESCC in patients with MM. Future studies will help to improve patient selection for specific and standardized treatments and to clearly delineate which patients are likely to benefit from radiation therapy. LEVEL OF EVIDENCE: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Scotland's Knowledge Network: translating knowledge into action to improve quality of care.

The Knowledge Network (www.knowledge.scot.nhs.uk) is Scotland's online knowledge service for health and social care. It is designed to support practitioners to apply knowledge in frontline delivery of care, helping to translate knowledge into better health-care outcomes through safe, effective, person-centred care. The Knowledge Network helps to combine the worlds of evidence-based practice and quality improvement by providing access to knowledge about the effectiveness of clinical interventions ('know-what') and knowledge about how to implement this knowledge to support individual patients in working health-care environments ('know-how'). An 'evidence and guidance' search enables clinicians to quickly access quality-assured evidence and best practice, while point of care and mobile solutions provide knowledge in actionable formats to embed in clinical workflow. This research-based knowledge is complemented by social networking services and improvement tools which support the capture and exchange of knowledge from experience, facilitating practice change and systems improvement. In these cases, the Knowledge Network supports key components of the knowledge-to-action cycle--acquiring, creating, sharing and disseminating knowledge to improve performance and innovate. It provides a vehicle for implementing the recommendations of the national Knowledge into Action review, which outlines a new national approach to embedding knowledge in frontline practice and systems improvement.

Paroxysmal dyspnoea in asthma: Wheeze, ILO or dysfunctional breathing?

Paroxysms of dyspnoea in the general population are commonly reported and are frequently assumed to be asthma-related, especially if this diagnostic label has been previously applied. Often, this is not the case. Inducible Laryngeal Obstruction (ILO) and Dysfunctional Breathing (DB) are common comorbid conditions that go unrecognised in many difficult-to-treat asthmatics. On average, these patients have a delay in diagnosis of almost 5 years. This delay, along with ineffective, inappropriate escalation of asthma therapy, frequent hospital presentations for uncontrolled symptoms, and even intensive care admissions, magnifies patient morbidity and poor quality of life. ILO and DB have similar presentations and triggers to asthma. Differentiating between them can be challenging, especially in centres that do not have access to multidisciplinary subspecialty asthma services. Objectively confirming the diagnosis can likewise be challenging as symptoms fluctuate, and gold-standard investigations require extensive experience. This mini-review will summarise the clinical features of ILO and DB, with particular focus in the context of individuals treated for asthma. This narrative review will define each condition, highlight poignant aspects of the history and describe elements of the diagnostic pathway to gain objective confirmation.

Postoperative outcome of ambulatory dogs with intervertebral disc extrusion causing incontinence and/or tail dysfunction: 18 cases (2010-2020).

OBJECTIVES: To assess the recovery of urinary continence, faecal continence and tail function in ambulatory dogs with caudal lumbar intervertebral disc extrusion and to explore clinical factors that may be associated with recovery. MATERIALS AND METHODS: Medical records from January 2010 to December 2020 were searched to identify ambulatory dogs undergoing surgical treatment for a caudal lumbar intervertebral disc extrusion causing urinary incontinence, faecal incontinence and/or tail dysfunction. Signalment, history, presenting clinical signs, neurological examination findings, diagnostic test results, treatment and outcome were recorded for all dogs. RESULTS: Eighteen dogs with caudal lumbar intervertebral disc extrusion causing tail dysfunction, urinary and/or faecal incontinence were included. Urinary continence was recovered in 12 (86%) of 14 affected dogs, faecal continence recovered in nine (90%) of 10 affected dogs and tail function recovered in 13 (87%) of 15 affected dogs. Loss of tail nociception was recorded in three dogs on presentation; two made a full recovery and one showed mild persistent tail paresis. CLINICAL SIGNIFICANCE: The prognosis for functional recovery of urinary continence, faecal continence and tail function in ambulatory dogs with caudal lumbar intervertebral disc extrusion following surgical treatment is good. Larger studies are needed to identify prognostic factors associated with failure of recovery.

Third international challenge to model the medium- to long-range transport of radioxenon to four Comprehensive Nuclear-Test-Ban Treaty monitoring stations.

In 2015 and 2016, atmospheric transport modeling challenges were conducted in the context of the Comprehensive Nuclear-Test-Ban Treaty (CTBT) verification, however, with a more limited scope with respect to emission inventories, simulation period and number of relevant samples (i.e., those above the Minimum Detectable Concentration (MDC)) involved. Therefore, a more comprehensive atmospheric transport modeling challenge was organized in 2019. Stack release data of Xe-133 were provided by the Institut National des Radioéléments/IRE (Belgium) and the Canadian Nuclear Laboratories/CNL (Canada) and accounted for in the simulations over a three (mandatory) or six (optional) months period. Best estimate emissions of additional facilities (radiopharmaceutical production and nuclear research facilities, commercial reactors or relevant research reactors) of the Northern Hemisphere were included as well. Model results were compared with observed atmospheric activity concentrations at four International Monitoring System (IMS) stations located in Europe and North America with overall considerable influence of IRE and/or CNL emissions for evaluation of the participants' runs. Participants were prompted to work with controlled and harmonized model set-ups to make runs more comparable, but also to increase diversity. It was found that using the stack emissions of IRE and CNL with daily resolution does not lead to better results than disaggregating annual emissions of these two facilities taken from the literature if an overall score for all stations covering all valid observed samples is considered. A moderate benefit of roughly 10% is visible in statistical scores for samples influenced by IRE and/or CNL to at least 50% and there can be considerable benefit for individual samples. Effects of transport errors, not properly characterized remaining emitters and long IMS sampling times (12-24 h) undoubtedly are in contrast to and reduce the benefit of high-quality IRE and CNL stack data. Complementary best estimates for remaining emitters push the scores up by 18% compared to just considering IRE and CNL emissions alone. Despite the efforts undertaken the full multi-model ensemble built is highly redundant. An ensemble based on a few arbitrary runs is sufficient to model the Xe-133 background at the stations investigated. The effective ensemble size is below five. An optimized ensemble at each station has on average slightly higher skill compared to the full ensemble. However, the improvement (maximum of 20% and minimum of 3% in RMSE) in skill is likely being too small for being exploited for an independent period.