Double outlet right atrium in a dog.

Double outlet right atrium is a rare congenital cardiac abnormality that has been previously reported in humans and cats, but not in dogs. A double outlet right atrium is typically characterized by the presence of a leftward deviation of the interatrial septum and atrial septal defect. Therefore, the right atrium drains into both ventricles. The unique features consistent with double outlet right atrium were identified by transthoracic echocardiography and computed tomography in a puppy. This case report describes the clinical, echocardiographic, and tomographic findings of a five-month-old Cocker Spaniel diagnosed with this rare congenital abnormality.

Epicardial pacemaker implantation and outcome in eight pet ferrets (Mustela putorius furo).

INTRODUCTION/OBJECTIVES: Minimal information exists regarding epicardial pacemaker (EP) implantation in pet ferrets (Mustela putorius furo). The objectives were to describe the indications, surgical technique, and outcome of EP implantation in ferrets for the treatment of advanced atrioventricular block (AVB). ANIMALS, MATERIALS, AND METHODS: Eight client-owned ferrets presenting to five veterinary referral centers. Signalment, physical exam findings, diagnostic tests, anesthesia protocols, surgical implantation techniques, postoperative treatment plans, and EP interrogations were reviewed. Intra- and postoperative, minor and major, and EP-related complications were established. Descriptive statistics were performed to report complication rates. Survival analyses were performed. RESULTS: All ferrets had advanced AVB: 3/8 had high-grade second-degree and 5/8 had third-degree. The primary clinical signs were collapse and weakness. Seven EP were implanted via a transdiaphragmatic approach and one via a left intercostal thoracotomy. Intraoperative complications occurred in 2/8 ferrets, both major. One ferret with severe comorbidities died during general anesthesia. Postoperative pacemaker-related complications were minor: inappropriate sinus beat sensing in 2/8 and occasional muscle fasciculations in 1/8. Two ferrets were alive at the time of manuscript submission, at 10 and 21 months postoperatively. The overall median survival time was 24 months. CONCLUSIONS: Implantation of EP was performed successfully in most ferrets for treatment of advanced AVB and was well tolerated. Ferrets with advanced AVB may experience resolution of clinical signs associated with their cardiac disease following EP implantation. Additional studies are warranted to investigate the effects of epicardial pacing on survival times in this species.

Non-cardiogenic pulmonary oedema complicating balloon valvuloplasty and stent angioplasty of severe pulmonary valve stenosis in four dogs.

In dogs, balloon valvuloplasty is considered the treatment of choice for severe pulmonary valve stenosis, and this technique is currently performed routinely in specialist referral practices with low morbidity and mortality. Stent angioplasty has also been recently proposed as a viable treatment option. The present case series describes the clinical course of four dogs with severe pulmonary valve stenosis, treated with balloon valvuloplasty or stent angioplasty at four different institutions, which developed non-cardiogenic pulmonary oedema perioperatively after apparently successful dilation of the pulmonary valve. In three cases, there was evidence of some degree of pulmonary hypertension before ballooning. Despite intensive care, the complication proved fatal in three cases. Clinicians should therefore be aware of this life-threatening complication, previously undescribed in dogs.

A novel hybrid stent technique to treat canine pulmonic stenosis.

Balloon valvuloplasty is routinely performed in dogs with severe pulmonic stenosis using a transvenous approach. We report a novel transventricular approach to stent the right ventricular outflow tract. An 18-month old Havanese with frequent syncope was referred with a diagnosis of severe valvular pulmonic stenosis. Transvenous approaches were unsuccessful; therefore, two Palmaz XL 29 mm by 12 mm transhepatic biliary stents were deployed across the valve using a direct right ventricular approach. The echocardiographically derived systolic pressure gradient decreased from 133 mmHg to 39 mmHg with resolution of clinical signs. The patient continues to do well after 3 years with occasional syncope when extremely excited despite pressure gradient increases to 130 mmHg at 12 months and 174 mmHg at 22 months.

Characterizing distinct components of tactical aircraft noise sources.

Noise from a tactical aircraft can impact operations due to concerns regarding military personnel noise exposure and community annoyance and disturbance. The efficacy of mission planning can increase when the distinct, complex acoustic source mechanisms creating the noise are better understood. For each type of noise, equivalent acoustic source distributions are obtained from a tied-down F-35B operating at various engine conditions using the hybrid method for acoustic source imaging of Padois, Gauthier, and Berry [J. Sound Vib. 333, 6858-6868 (2014)]. The source distributions for the distinct noise types are obtained using different sections of a 71 element, ground-based linear array. Using a subarray close to the nozzle exit plane, source distributions are obtained for fine-scale turbulent mixing noise and broadband shock-associated noise, although grating lobes complicate interpretations at higher frequencies. Results for a subarray spanning the maximum sound region show that the multiple frequency peaks in tactical aircraft noise appear to originate from overlapping source regions. The observation of overlapping spatial extent of competing noise sources is supported by the coherence properties of the source distributions for the different subarrays.

Variation in outcomes and use of laparoscopy in elective inguinal hernia repair.

Background: The early outcomes of inguinal hernia repair in routine practice and the extent to which the laparoscopic approach is used are unknown. The aims of this study were to identify national benchmarks for early reoperation and readmission rates, to identify the degree to which the laparoscopic approach is used for elective hernia surgery in England, and to identify whether there is any variation nationally. Methods: All adults who underwent publically funded elective inguinal hernia repair in England during the six financial years from 2011-2012 to 2016-2017 were identified in the Surgeon's Workload Outcomes and Research Database (SWORD). Patients were grouped according to whether they had a primary, recurrent or bilateral hernia, and according to sex. Overall rates of readmission, reoperation and laparoscopic approach were calculated, and variation was assessed using funnel plots. Results: Some 390 777 patients were included. Overall, 11 448 patients (2·9 per cent) were readmitted to hospital as an emergency within 30 days of surgery and 2872 (0·7 per cent) had a further operation. Laparoscopic repair was performed for 65·5 per cent of bilateral inguinal hernias compared with 17·1 per cent of primary unilateral inguinal hernias, 31·3 per cent of recurrent hernia repairs and 14·0 per cent of primary unilateral hernias in women. The unadjusted readmission, reoperation and laparoscopy rates varied significantly between hospitals. Conclusion: The likelihood of a patient being readmitted to hospital, having an emergency reoperation or undergoing laparoscopic inguinal hernia repair varies significantly depending on the hospital to which they are referred. Hospitals and service commissioners should use this data to drive service improvement and reduce this variation.

Validation of the acute cholecystectomy rate as a quality indicator for emergency general surgery using the SWORD database.

INTRODUCTION: Despite an increasing emphasis on data-driven quality improvement, few validated quality indicators for emergency surgical services have been published. The aims of this study therefore were: 1) to investigate whether the acute cholecystectomy rate is a valid process indicator; and 2) to use this rate to examine variation in the provision of acute cholecystectomy in England. MATERIALS AND METHODS: The Surgical Workload and Outcomes Research Database (SWORD), derived from the Hospital Episode Statistics database, was interrogated for the 2012-2017 financial years. All adult patients admitted with acute biliary pancreatitis, cholecystitis or biliary colic to hospitals in England were included and the acute cholecystectomy rate in each one examined. RESULTS: A total of 328,789 patients were included, of whom 42,642 (12.9%) underwent an acute cholecystectomy. The acute cholecystectomy rate varied significantly between hospitals, with the overall rate ranging from 1.2% to 36.5%. This variation was consistent across all disease groupings and time periods, and was independent of the annual number of procedures performed by each NHS trust. In 41 (29.9%) trusts, fewer than one in ten patients with acute gallbladder disease underwent cholecystectomy within two weeks. CONCLUSIONS: The acute cholecystectomy rate is easily measurable using routine administrative datasets, modifiable by local services and has a strong evidence base linking it to patient outcomes. We therefore advocate that it is an ideal process indicator that should be used in quality monitoring and improvement. Using it, we identified significant variation in the quality of care for acute biliary disease in England.

Breed does not affect the association between murmur intensity and disease severity in dogs with pulmonic or subaortic stenosis.

OBJECTIVES: To determine whether breed affects the ability of murmur intensity to predict the severity of stenosis in dogs with pulmonic stenosis or subaortic stenosis. MATERIALS AND METHODS: Retrospective multi-investigator study of dogs with pulmonic stenosis or subaortic stenosis. Murmur intensity, assessed by a four-level classification scheme, was compared with echocardiographically-determined pressure gradient across the affected valve. Breeds represented by at least 10 dogs at any murmur intensity were compared to determine the effect, if any, of breed. RESULTS: A total of 1088 dogs (520 with pulmonic stenosis and 568 with subaortic stenosis, representing 106 breeds and the mixed breed group) were included; 208 dogs had soft, 210 had moderate, 283 had loud and 387 had palpable murmurs. Fifteen breeds were represented by at least 10 dogs: five breeds with at least 10 dogs had soft murmurs (132 dogs), nine breeds had moderate murmurs (149 dogs), 10 breeds had loud murmurs (188 dogs), and 11 breeds had palpable murmurs (286 dogs). No breeds differed in stenosis severity from any other breeds within any murmur grade. Post hoc power calculations suggested that we would have been able to detect at least a moderate or large effect size, had one existed. Several dogs with soft murmurs had more-than-mild disease severity. CLINICAL SIGNIFICANCE: Despite anecdotally perceived differences in the detection of heart murmurs between breeds, which have been proposed to potentially affect the interpretation of stenosis severity, we found no obvious breed effect in the ability to predict severity of stenosis.

Stent angioplasty for treatment of canine valvular pulmonic stenosis.

Four dogs presented for evaluation and treatment of severe pulmonic valve stenosis and underwent stenting of the pulmonic valve annulus using bare-metal balloon-expandable stents. All dogs survived the procedure with immediate reduction of the transpulmonary valve pressure gradient and increase in activity levels. One dog had a stent fracture and migration 1 month after the intervention. This dog underwent a second procedure, in which multiple stents were used to alleviate the obstruction. The stents that were placed at the level of the right ventricular outflow tract fractured within 1 month of the procedure, and the patient died when a third (surgical) approach was attempted. The other three dogs remain alive 54, 42, and 29 months after the procedure. Stent angioplasty may be a viable option for dogs with valvular pulmonic stenosis in which routine balloon valvuloplasty does not provide a successful outcome. Aggressive attempts to diminish RVOT dynamic obstruction with high-dose beta blockade and avoiding deployment of the stent within the RVOT are recommended to prevent stent fracture and migration.

Subjective rating of the jet noise crackle percept.

Results of the first formal perceptual study of jet crackle are presented. Prior studies examined noise waveform properties believed to be linked to the jet crackle percept from a physics perspective or using signal processing and informal subjective evaluation. This investigation involves 31 listeners that rated 15 jet noise waveforms with a category subdivision scaling test. Results reveal a strong log-linear correlation between the pressure waveform time derivative's skewness and crackle rating. A regression analysis establishes practical derivative skewness bounds for a five-point categorical crackle scale and results in the suggested definition of the crepit as the unit of crackliness.

Absolute bacterial cell enumeration using flow cytometry.

AIM: To evaluate a flow cytometry protocol that uses reference beads for the enumeration of live and dead bacteria present in a mixture. METHODS AND RESULTS: Mixtures of live and dead Escherichia coli with live:dead concentration ratios varying from 0 to 100% were prepared. These samples were stained using SYTO 9 and propidium iodide and 6-µm reference beads were added. Bacteria present in live samples were enumerated by agar plate counting. Bacteria present in dead samples were enumerated by agar plate counting before treatment with isopropanol. There is a linear relationship between the presented flow cytometry method and agar plate counts for live (R2  = 0·99) and dead E. coli (R2  = 0·93) concentrations of c. 104 to 108 bacteria per ml within mixtures of live and dead bacteria. CONCLUSIONS: Reliable enumeration of live E. coli within a mixture of both live and dead was possible for concentration ratios of above 2·5% live and for the enumeration of dead E. coli the lower limit was c. 20% dead. SIGNIFICANCE AND IMPACT OF THE STUDY: The ability to obtain absolute cell concentrations is only available for selected flow cytometers, this study describes a method for accurate enumeration that is applicable to basic flow cytometers without specialized counting features. By demonstrating the application of the method to count E. coli, we raised points of consideration for using this FCM counting method and aim to lay the foundation for future work that uses similar methods for different bacterial strains.

Testing two crackle criteria using modified jet noise waveforms.

The jet sound quality "crackle" has historically been studied and quantified using the statistics of the pressure waveform. Some investigators have suggested crackle, and its associated shock content, may be better quantified using the statistics of the time derivative of the waveform. Modified waveforms are used to evaluate crackle prediction criteria based on the skewness of each variable. The resultant waveforms are provided as direct evidence that the pressure distribution does not directly predict or quantify a crackling sound quality while the statistics of the derivative appear to do so.

Degenerative Valvular Disease in the Cavalier King Charles Spaniel: Results of the UK Breed Scheme 1991-2010.

BACKGROUND: Cavalier King Charles spaniels (CKCSs) are predisposed to degenerative mitral valve disease (DMVD) and studies have indicated a genetic cause. ANIMALS: A total of 8,860 CKCSs were examined at shows or private clinics from 1991 to 2010. OBJECTIVES: To analyze the effects of a breed scheme for CKCS on the age at which a murmur consistent with DMVD was first detected. METHODS: The presence or absence of a murmur consistent with mitral regurgitation was noted and age a murmur was first detected recorded. RESULTS: A total of 16,887 examinations were performed on 8,860 dogs. The median age dogs developed a murmur were slightly younger in male than female dogs (7.8 versus 8.3 years, 95% confidence interval [CI] 7.4-8.1 versus 8.0-8.4, P < .001) and cardiologists detected murmurs in younger dogs than did general practitioner (GP) veterinary surgeons (7.2 versus 8.6 years, 95% CI 7.0-7.4 versus 8.3-8.7 P < .001). In bitches examined by GP vets during the study, there was a significantly increased age of detection of murmurs over time (8.6-9.2 years, 95% CI 8.3-9.1 and 8.5-10.9, P = .001) but not for male dogs examined by GP vets or dogs of either sex examined by cardiologists. CONCLUSIONS AND CLINICAL IMPORTANCE: This study suggests that the age incidence of murmurs associated with DMVD might be increased by application of breeding guidelines based on auscultation alone. This benefit was only seen in a subgroup and compliance of breeders with this voluntary scheme was poor.

Extending sharpness calculation for an alternative loudness metric input.

Sound quality metrics help improve the psychoacoustic acceptability of devices and environments by modeling and thus enabling deliberate improvement of perceptual attributes. Sharpness as defined in DIN 45692 [(2009). Deutsches Institut für Normung, Berlin] requires inputs from Zwicker's loudness metric [ISO 532-1 (2017). International Organization for Standardization, Geneva]. This letter demonstrates that sharpness can be formulated to accept specific loudness values from Moore and Glasberg's loudness metric [ISO 532-2 (2017). International Organization for Standardization, Geneva; ANSI S3.4 (2007). American National Standards Institute, Inc., Washington, DC]. Sharpness calculations using the two loudness metrics produce similar results. This method thus enables evaluation of sharpness as a straightforward add-on to standard loudness calculations using Moore and Glasberg's metric, for which sharpness calculations were not previously available.

Screening of anti-mycobacterial compounds in a naturally infected zebrafish larvae model.

OBJECTIVES: Mycobacterium tuberculosis is a deadly human pathogen that causes the lung disease TB. M. tuberculosis latently infects a third of the world's population, resulting in ∼1.5 million deaths per year. Due to the difficulties and expense of carrying out animal drug trials using M. tuberculosis and rodents, infections of the zebrafish Danio rerio with Mycobacterium marinum have become a useful surrogate. However, the infection methods described to date require specialized equipment and a high level of operator expertise. METHODS: We investigated whether zebrafish larvae could be naturally infected with bioluminescently labelled M. marinum by immersion, and whether infected larvae could be used for rapid screening of anti-mycobacterial compounds using bioluminescence. We used rifampicin and a variety of nitroimidazole-based next-generation and experimental anti-mycobacterial drugs, selected for their wide range of potencies against M. tuberculosis, to validate this model for anti-mycobacterial drug discovery. RESULTS: We observed that five of the six treatments (rifampicin, pretomanid, delamanid, SN30488 and SN30527) significantly reduced the bioluminescent signal from M. marinum within naturally infected zebrafish larvae. Importantly, these same five treatments also retarded the growth of M. tuberculosis in vitro. In contrast, only three of the six treatments tested (rifampicin, delamanid and SN30527) retarded the growth of M. marinum in vitro. CONCLUSIONS: We have demonstrated that zebrafish larvae naturally infected with bioluminescent M. marinum M can be used for the rapid screening of anti-mycobacterial compounds with readily available equipment and limited expertise. The result is an assay that can be carried out by a wide variety of laboratories for minimal cost and without high levels of zebrafish expertise.

High-throughput screening to enhance oncolytic virus immunotherapy.

High-throughput screens can rapidly scan and capture large amounts of information across multiple biological parameters. Although many screens have been designed to uncover potential new therapeutic targets capable of crippling viruses that cause disease, there have been relatively few directed at improving the efficacy of viruses that are used to treat disease. Oncolytic viruses (OVs) are biotherapeutic agents with an inherent specificity for treating malignant disease. Certain OV platforms - including those based on herpes simplex virus, reovirus, and vaccinia virus - have shown success against solid tumors in advanced clinical trials. Yet, many of these OVs have only undergone minimal engineering to solidify tumor specificity, with few extra modifications to manipulate additional factors. Several aspects of the interaction between an OV and a tumor-bearing host have clear value as targets to improve therapeutic outcomes. At the virus level, these include delivery to the tumor, infectivity, productivity, oncolysis, bystander killing, spread, and persistence. At the host level, these include engaging the immune system and manipulating the tumor microenvironment. Here, we review the chemical- and genome-based high-throughput screens that have been performed to manipulate such parameters during OV infection and analyze their impact on therapeutic efficacy. We further explore emerging themes that represent key areas of focus for future research.

Spectrum and Sensitivity of Bacterial Keratitis Isolates in Auckland.

Background. The bacteria isolated from severe cases of keratitis and their antibiotic sensitivity are recognised to vary geographically and over time. Objectives. To identify the most commonly isolated bacteria in keratitis cases admitted over a 24-month period to a public hospital in Auckland, New Zealand, and to investigate in vitro sensitivity to antibiotics. Methods. Hospital admissions for culture-proven bacterial keratitis between January 2013 and December 2014 were identified. Laboratory records of 89 culture positive cases were retrospectively reviewed and antibiotic sensitivity patterns compared with previous studies from other NZ centres. Results. From 126 positive cultures, 35 species were identified. Staphylococcus was identified to be the most common isolate (38.2%), followed by Pseudomonas (21.3%). Over the last decade, infection due to Pseudomonas species, in the same setting, has increased (p ≤ 0.05). Aminoglycosides, cefazolin, ceftazidime, erythromycin, tetracycline, and doxycycline were 100% effective against tested isolates in vitro. Amoxicillin (41.6%), cefuroxime (33.3%), and chloramphenicol (94.7%) showed reduced efficacy against Gram-negative bacteria, whereas penicillin (51%) and ciprofloxacin (98.8%) showed reduced efficacy against Gram-positive bacteria. Conclusions. Despite a shift in the spectrum of bacterial keratitis isolates, antibiotic sensitivity patterns have generally remained stable and show comparability to results within the last decade from NZ centres.

Exercise during energy restriction mitigates bone loss but not alterations in estrogen status or metabolic hormones.

UNLABELLED: Energy restriction causes bone loss, increasing stress fracture risk. The impact of exercise during energy restriction on bone and endocrine factors is examined. Exercise with energy restriction did not influence endocrine factors, but did mitigate some bone loss seen with energy restriction in sedentary rats. INTRODUCTION: Chronic dietary energy restriction (ER) leads to bone loss and increased fracture risk. Strictly controlled trials of long-term ER with and without vigorous exercise are required to determine whether exercise loading can counterbalance ER-induced bone loss. The aim of this current project is to elucidate the impact of exercise and ER on bone mass, estrogen status, and metabolic hormones. METHODS: Twenty-four virgin female Sprague-Dawley rats (n = 8/group) were divided into three groups-ad libitum fed + exercise (Adlib + EX), 40 % energy restricted + exercise (ER + EX), and 40 % energy restricted + sedentary (ER + SED). Energy availability between ER groups was equal. Treadmill running was performed 4 days/week at 70 % VO2max for 12 weeks. RESULTS: Fat and lean mass and areal bone mineral density (aBMD) were lower after 12 weeks (p < 0.05) for ER + EX vs Adlib + EX, but ER + EX aBMD was higher than ER + SED (p < 0.0001). Serum leptin and a urinary estrogen metabolite, estrone-1-glucuronide (E1G), were lower at week 12 (p = 0.0002) with ER, with no impact of exercise. Serum insulin-like growth factor I (IGF-I) declined (p = 0.02) from baseline to week 12 in both ER groups. ER + EX exhibited higher cortical volumetric bone mineral density (vBMD) at the midshaft tibia (p = 0.006) vs ER + SED. CONCLUSION: Exercise during ER mitigated some, but not all, of the bone loss observed in sedentary ER rats, but had little impact on changes in urinary E1G and serum IGF-I and leptin. These data highlight the importance of both adequate energy intake and the mechanical loading of exercise in maintaining bone mass.

Clinical impact of FDG PET-CT on the management of patients with locally advanced cervical carcinoma.

AIM: To evaluate the impact of staging FDG PET-CT on the initial management of patients with locally advanced cervical carcinoma (LACC) and any prognostic variables predicting survival. MATERIALS AND METHODS: Retrospective analysis of consecutive patients undergoing FDG PET-CT for staging of LACC in a single tertiary referral centre, between April 2008 and August 2011. Comparison was made between MRI and PET-CT findings and any subsequent impact on treatment intent or radiotherapy planning was evaluated. RESULTS: Sixty-three patients underwent FDG PET-CT for initial staging of LACC. Major impact on management was found in 20 patients (32%), a minor impact in five (8%), and no impact in 38 (60%). In those patients where PET-CT had a major impact, 12 had more extensive local nodal involvement, five had occult metastatic disease, two had synchronous tumours, and one patient had equivocal lymph nodes on MRI characterized as negative. PET-positive nodal status at diagnosis was found to be a statistically significant predictor of relapse-free survival (p < 0.05). CONCLUSION: Staging FDG PET-CT has a major impact on the initial management of approximately one-third of patients with LACC by altering treatment intent and/or radiotherapy planning. PET-defined nodal status is a poor prognostic indicator.