Evaluation of different shape-memory staple configurations against crossed screws for first metatarsophalangeal joint arthrodesis: A biomechanical study.

BACKGROUND: The first metatarsophalangeal joint may be fused in order to treat arthritis or instability. The use of shape-memory staples for fixation is well recognised, but little work has been done into the optimal configuration of staples. METHODS: The structural behaviour of first metatarsophalangeal joint (MTPJ) arthrodeses using shape-memory staples or crossed screws was studied using cadaveric porcine joints. Five fixation configurations were tested: single vertical or horizontal staple, paired staples in dorsal-medial configuration (0-90° to the sagittal plane), paired staples in oblique orthogonal configuration (45-135°); or two crossed screws. Specimens were loaded in cyclical dorsiflexion for 1000 cycles. Plantar gapping and shearing were measured. Specimens were then loaded to failure. RESULTS: Cyclic testing caused more shear in the 45-135° staples than the crossed screws (1.0mm±0.5mm compared to 0.14mm±0.4mm, p<0.01). No significant difference was found in plantar gap formation. Single vertical and horizontal single staples failed at 15N and 19. CONCLUSIONS: N, respectively. Paired 0-90° staples failed at 43N±9N, significantly lower than the 45-135° staples (141N±25N; p<0.001) and crossed screws (180N±67N; p<0.001). There was no significant difference between the 45-135° staples and crossed screws. Screws failed by sudden cortical fracture; staples displayed gradual pull-out and shearing. First MTPJ arthrodeses fixed with single staples are not recommended. Arthrodeses fixed with staples at 0-90° to the sagittal plane were significantly less strong than two crossed screws. However, positioning oblique staples at 45-135° significantly improved stability, creating a construct as strong as, crossed screws. None of the constructs was strong enough for immediate weight bearing.

Maternal anxiety, risk factors and parenting in the first post-natal year.

BACKGROUND: The antecedents and consequences of maternal post-natal anxiety have received comparatively less attention than depression despite being one of the most frequently reported mental health difficulties experienced by parents following childbirth. The aim of this study was to extend emerging literature on post-natal anxiety by investigating the prevalence of maternal anxiety symptoms, and its relationship with parenting behaviours (i.e. warmth, hostility) and experiences (i.e. parenting efficacy and satisfaction) within the first post-natal year. The psychosocial risk factors for post-natal anxiety symptoms were also explored. METHODS: A community sample of 224 Australian mothers of infants (aged 0-12 months) completed a self-report questionnaire. RESULTS: Mothers in the current sample reported significantly more symptoms of anxiety compared with a normative sample. Approximately 18% of mothers reported mild to extremely severe symptoms of anxiety, with a high proportion experiencing co-morbid depressive symptoms. Maternal anxiety was associated with low parenting warmth, involvement, efficacy and satisfaction, and high parenting hostility. Yet, co-morbid depression and anxiety was more strongly associated with these parenting behaviours and experiences than anxiety alone. CONCLUSION: A range of psychosocial risk factors (e.g. education, sleep, relationship quality) were associated with maternal post-natal anxiety symptoms, providing opportunities for early identification and targeted early intervention.

First characterization of coherent optical vortices from harmonic undulator radiation.

We describe the experimental generation and measurement of coherent light that carries orbital angular momentum from a relativistic electron beam radiating at the second harmonic of a helical undulator. The measured helical phase of the light is shown to be in agreement with predictions of the sign and magnitude of the phase singularity and is more than 2 orders of magnitude greater than the incoherent signal. Our setup demonstrates that such optical vortices can be produced in modern free-electron lasers in a simple afterburner arrangement for novel two-mode pump-probe experiments.

Efficacy and tolerance of oral versus parenteral cyanocobalamin supplement in hypocobalaminaemic dogs with chronic enteropathy: a controlled randomised open-label trial.

OBJECTIVES: Determine comparative tolerance of daily oral and weekly parenteral cobalamin supplementation, in hypocobalaminaemic dogs with chronic enteropathy. Determine whether oral is as effective as parenteral supplementation at achieving eucobalaminaemia, in hypocobalaminaemic dogs with protein-losing enteropathy, severe hypocobalaminaemia or high canine inflammatory bowel disease activity index at inclusion. MATERIALS AND METHODS: Thirty-seven client-owned dogs with hypocobalaminaemia and clinical signs of chronic enteropathy were prospectively enrolled in three UK referral centres. Dogs were randomly allocated to daily oral for 12 weeks or weekly parenteral cobalamin supplementation for 6 weeks and one additional dose 4 weeks later. Serum cobalamin, body condition score, canine inflammatory bowel disease activity index and bodyweight were assessed at inclusion, weeks 7 and 13. Serum methylmalonic acid concentration was evaluated at inclusion and at week 13. Owners completed treatment adherence, palatability, tolerance and satisfaction questionnaires at week 13. RESULTS: Nineteen dogs completed the study. All dogs orally supplemented achieved normal or increased cobalaminaemia at weeks 7 and 13. There was no statistical difference in cobalamin concentration at week 13 in dogs treated with oral or parenteral supplementation, regardless of presence of protein-losing enteropathy, severity of hypocobalaminaemia or canine inflammatory bowel disease activity index at inclusion. Serum methylmalonic acid concentration was not significantly different between oral and parenteral groups, neither were treatment adherence, satisfaction, and tolerance scores at week 13. CLINICAL SIGNIFICANCE: Oral is as effective and as well-tolerated as parenteral cobalamin supplementation in hypocobalaminaemic dogs with chronic enteropathy and severe clinical or biochemical phenotypes, and should be considered as a suitable treatment option regardless of disease severity.

Demonstration of cascaded optical inverse free-electron laser accelerator.

We report on a proof-of-principle demonstration of a two-stage cascaded optical inverse free-electron laser (IFEL) accelerator in which an electron beam is accelerated by a strong laser pulse after being packed into optical microbunches by a weaker initial laser pulse. We show experimentally that injection of precisely prepared optical microbunches into an IFEL allows net acceleration or deceleration of the beam, depending on the relative phase of the two laser pulses. The experimental results are in excellent agreement with simulation. The demonstrated technique holds great promise to significantly improve the beam quality of IFELs and may have a strong impact on emerging laser accelerators driven by high-power optical lasers.

Single-shot coherent diffraction imaging of microbunched relativistic electron beams for free-electron laser applications.

With the advent of coherent x rays provided by the x-ray free-electron laser (FEL), strong interest has been kindled in sophisticated diffraction imaging techniques. In this Letter, we exploit such techniques for the diagnosis of the density distribution of the intense electron beams typically utilized in an x-ray FEL itself. We have implemented this method by analyzing the far-field coherent transition radiation emitted by an inverse-FEL microbunched electron beam. This analysis utilizes an oversampling phase retrieval method on the transition radiation angular spectrum to reconstruct the transverse spatial distribution of the electron beam. This application of diffraction imaging represents a significant advance in electron beam physics, having critical applications to the diagnosis of high-brightness beams, as well as the collective microbunching instabilities afflicting these systems.

Generation of coherent broadband photon pulses with a cascaded longitudinal space-charge amplifier.

The longitudinal space-charge amplifier has been recently proposed by Schneidmiller and Yurkov as an alternative to the free-electron laser instability for the generation of intense broadband radiation pulses [Phys. Rev. ST Accel. Beams 13, 110701 (2010)]. In this Letter, we report on the experimental demonstration of a cascaded longitudinal space-charge amplifier at optical wavelengths. Although seeded by electron beam shot noise, the strong compression of the electron beam along the three amplification stages leads to emission of coherent undulator radiation pulses exhibiting a single spectral spike and a single transverse mode. The on-axis gain is estimated to exceed 4 orders of magnitude with respect to spontaneous emission.

Description and outcome of dogs with primary immune-mediated polyarthritis: 73 cases (2012-2017).

OBJECTIVES: To provide a description of primary idiopathic immune-mediated polyarthritis, including long-term outcome and relapse rates, for dogs starting treatment with corticosteroids alone or corticosteroids with a second immunosuppressant. MATERIALS AND METHODS: Medical records were reviewed between January 2012 and December 2017 to identify dogs diagnosed with primary immune-mediated polyarthritis. Data including signalment, clinicopathological findings, type and duration of treatment, relapse and outcome were recorded. RESULTS: Seventy-three dogs were included. Fifty-four dogs were started on corticosteroid monotherapy (an additional immunosuppressant was introduced later in 27/54 dogs) and 19 dogs were treated with multi-modal immunosuppression from the outset. Ninety-five percent (69/73) of dogs responded favourably to therapy although death was attributed to immune-mediated polyarthritis in 19% (14/73) of dogs. Relapse of clinical signs was reported in 53% (39/73) dogs (31/39 while on treatment), with multiple relapses observed in 17 dogs. Complete cure (permanent withdrawal of immunosuppressive medication) was achieved in 46 dogs (63%). Overall, 81% of dogs had a well-managed disease for an extended timeframe (≥1131 days). Fourteen of 19 (74%) dogs that started treatment with multi-modal immunosuppression and 32 of 54 (59%) started on corticosteroids alone achieved a complete cure. CLINICAL SIGNIFICANCE: This study provides extended follow-up information for a large cohort of dogs with primary immune-mediated polyarthritis. Immunosuppressive therapy was discontinued in the majority of dogs but disease-associated mortality remains high.

A survey on Shar Pei autoinflammatory disease in the United Kingdom.

OBJECTIVES: To characterise the fever episodes attributed to Shar Pei autoinflammatory disease and to identify common diagnostic and management strategies in the United Kingdom. A secondary objective was to determine risk factors associated with Shar Pei autoinflammatory disease fever episodes. METHODS: A retrospective survey was performed to characterise episodes of Shar Pei autoinflammatory disease fever and to identify commonly used treatments in affected dogs. Clinical data were collected from owners and veterinarians. Frequencies of previously proposed risk factors (skin thickness and folding, muzzle conformation) and comorbid conditions were compared between dogs that had exhibited fever episodes consistent with Shar Pei autoinflammatory disease and those who had not. RESULTS: At least one episode of fever attributed to Shar Pei autoinflammatory disease was reported in 52 of 106 (49%) Shar Pei. Nine other dogs had fever episodes consistent with Shar Pei autoinflammatory disease reported by their owners but not by veterinarians. Median rectal temperature at presentation for Shar Pei autoinflammatory disease fever was 40.1°C [104.2°F] (39.9 to 41.3°C [103.8 to 106.3°F]) and owners reported associated hyporexia (n=33, 63%) and vomiting (n=8, 15%) more frequently than veterinary records (n=22, 42% and n=0, 0%, respectively). The median number of veterinary appointments for Shar Pei autoinflammatory disease was two per dog (1 to 15) while owners reported a median of four episodes per dog per year. None of the assessed phenotypic variants or comorbidities were significantly associated with exhibiting Shar Pei autoinflammatory disease fever episodes. CLINICAL SIGNIFICANCE: Episodes of Shar Pei autoinflammatory disease fever were reported approximately twice as frequently by owners compared to veterinary records, suggesting the burden of this condition may be underestimated by veterinarians. Specific risk factors for Shar Pei autoinflammatory disease fever were not identified.

Evidence of high harmonics from echo-enabled harmonic generation for seeding x-ray free electron lasers.

Echo-enabled harmonic generation free electron lasers hold great promise for the generation of fully coherent radiation in x-ray wavelengths. Here we report the first evidence of high harmonics from the echo-enabled harmonic generation technique in the realistic scenario where the laser energy modulation is comparable to the beam slice energy spread. In this experiment, coherent radiation at the seventh harmonic of the second seed laser is generated when the energy modulation amplitude is about 2-3 times the slice energy spread. The experiment confirms the underlying physics of echo-enabled harmonic generation and may have a strong impact on emerging seeded x-ray free electron lasers that are capable of generating laserlike x rays which will advance many areas of science.

Generating periodic terahertz structures in a relativistic electron beam through frequency down-conversion of optical lasers.

We report generation of density modulation at terahertz (THz) frequencies in a relativistic electron beam through laser modulation of the beam longitudinal phase space. We show that by modulating the energy distribution of the beam with two lasers, density modulation at the difference frequency of the two lasers can be generated after the beam passes through a chicane. In this experiment, density modulation around 10 THz was generated by down-converting the frequencies of an 800 nm laser and a 1550 nm laser. The central frequency of the density modulation can be tuned by varying the laser wavelengths, beam energy chirp, or momentum compaction of the chicane. This technique can be applied to accelerator-based light sources for generation of coherent THz radiation and marks a significant advance toward tunable narrow band THz sources.

Demonstration of the echo-enabled harmonic generation technique for short-wavelength seeded free electron lasers.

We report the first experimental demonstration of the echo-enabled harmonic generation technique, which holds great promise for generation of high-power, fully coherent short-wavelength radiation. In this experiment, coherent radiation at the 3rd and 4th harmonics of the second seed laser is generated from the so-called beam echo effect. The experiment confirms the physics behind this technique and paves the way for applying the echo-enabled harmonic generation technique for seeded x-ray free electron lasers.

Liquid-phase mega-electron-volt ultrafast electron diffraction.

The conversion of light into usable chemical and mechanical energy is pivotal to several biological and chemical processes, many of which occur in solution. To understand the structure-function relationships mediating these processes, a technique with high spatial and temporal resolutions is required. Here, we report on the design and commissioning of a liquid-phase mega-electron-volt (MeV) ultrafast electron diffraction instrument for the study of structural dynamics in solution. Limitations posed by the shallow penetration depth of electrons and the resulting information loss due to multiple scattering and the technical challenge of delivering liquids to vacuum were overcome through the use of MeV electrons and a gas-accelerated thin liquid sheet jet. To demonstrate the capabilities of this instrument, the structure of water and its network were resolved up to the 3 rd hydration shell with a spatial resolution of 0.6 Å; preliminary time-resolved experiments demonstrated a temporal resolution of 200 fs.

BASH: a tool for managing BeadArray spatial artefacts.

SUMMARY: With their many replicates and their random layouts, Illumina BeadArrays provide greater scope fordetecting spatial artefacts than do other microarray technologies. They are also robust to artefact exclusion, yet there is a lack of tools that can perform these tasks for Illumina. We present BASH, a tool for this purpose. BASH adopts the concepts of Harshlight, but implements them in a manner that utilizes the unique characteristics of the Illumina technology. Using bead-level data, spatial artefacts of various kinds can thus be identified and excluded from further analyses. AVAILABILITY: The beadarray Bioconductor package (version 1.10 onwards), www.bioconductor.org

Considerations for the processing and analysis of GoldenGate-based two-colour Illumina platforms.

Illumina's GoldenGate technology is a two-channel microarray platform that allows for the simultaneous interrogation of about 1,500 locations in the genome. GoldenGate has proved a flexible platform not only in the choice of those 1,500 locations, but also in the choice of the property being measured at them. It retains the desirable properties of Illumina's BeadArrays in that the probes (in this case 'beads') are randomly arranged across the microarray, there are multiple instances of each probe and many samples can be processed simultaneously. As for other Illumina technologies, however, these properties are not exploited as they might be. Here we review the various common adaptations of the GoldenGate platform, review the analysis methods that are associated with each adaptation and then, with the aid of a number of example data sets we illustrate some of the improvements that can be made over the default analysis.

Exogenous insulin treatment after hypofractionated radiotherapy in cats with diabetes mellitus and acromegaly.

BACKGROUND: The optimal treatment for feline acromegaly has yet to be established. Surgical and medical therapies are minimally effective although radiotherapy might have greater efficacy. The purpose of this study was to review the response and outcome of cats with acromegaly and insulin-resistant diabetes mellitus (DM) to radiotherapy. HYPOTHESES: That radiotherapy improves glycemic control in cats with acromegaly and that improved glycemic control is due to remission of clinical acromegaly; demonstrated by a fall in serum insulin-like growth factor-1 (IGF-1) concentrations. ANIMALS: Fourteen cats with naturally occurring acromegaly. METHODS: Retrospective case review; records of all cats treated for acromegaly with radiotherapy were reviewed from 1997 to 2008. Cats were selected on the basis of compatible clinical signs, laboratory features, and diagnostic imaging findings. Fourteen cats received radiotherapy, delivered in 10 fractions, 3 times a week to a total dose of 3,700 cGy. RESULTS: Thirteen of 14 cats had improved diabetic control after radiotherapy. These improvements were sustained for up to 60 months. DM progressed in 2 cats and 1 did not respond. Seven cats responded before the final treatment. Ten cats were euthanized, 1 as a consequence of radiotherapy. In 8 cats in which IGF-1 was measured after treatment, changes in its concentration did not reflect the clinical improvement in glycemic control. CONCLUSIONS AND CLINICAL IMPORTANCE: Radiotherapy represents an effective treatment for cats with insulin-resistant DM resulting from acromegaly. IGF-1 concentration after treatment does not provide a suitable method by which remission from either acromegaly or insulin-resistant DM may be assessed.

Characterisation and outcome of idiopathic pyogranulomatous lymphadenitis in 64 English springer spaniel dogs.

OBJECTIVES: To describe the history, clinicopathological abnormalities, diagnostic imaging findings, lymph node cytological/histological appearance, treatment and outcome of English springer spaniels diagnosed with idiopathic pyogranulomatous lymphadenitis. MATERIALS AND METHODS: In this retrospective UK-based multicentre study, 64 dogs were recruited from 10 referral centres, 32 first-opinion practices and three histopathology/cytology laboratories, between 2010 and 2016. RESULTS: The median age at presentation was 6 years (range: 0.17 to 11.75). Neutered females were frequently affected. Pyrexia (83.8%), peripheral lymphadenomegaly (78.4%), dermatological lesions (72.9%), lethargy (67.6%), hyporexia (54%), diarrhoea (29.7%), coughing (24.3%), epistaxis, sneezing or nasal discharge (21.6%), ocular signs (21.6%) and vomiting (16.2%) were reported in dogs for which the history and physical examination records were available. Popliteal (45.3%), superficial cervical (35.9%) and submandibular (37.5%) lymphadenomegaly were frequently reported. Haematology and serum biochemistry revealed non-specific changes. When undertaken, testing for infectious diseases was negative in all cases. Lymph node cytology, histopathology or both demonstrated mixed inflammatory (27%), pyogranulomatous (24%), neutrophilic (20%) or granulomatous (11%) lymphadenitis. Treatment details were available for 38 dogs, with 34 receiving prednisolone for a median duration of 15 weeks (range: 1 to 28 weeks). A good to excellent clinical response was reported in all but one case. Ten dogs relapsed after discontinuing prednisolone. CLINICAL SIGNIFICANCE: Idiopathic pyogranulomatous lymphadenitis should be considered as a differential diagnosis for lymphadenopathy and pyrexia in English springer spaniels. The characteristics of the disease, absence of identifiable infectious aetiology and response to glucocorticoid therapy suggest an immune-mediated aetiology.

Effect of clinical signs, endocrinopathies, timing of surgery, hyperlipidemia, and hyperbilirubinemia on outcome in dogs with gallbladder mucocele.

Gallbladder mucocele (GBM) is a common extra-hepatic biliary syndrome in dogs with death rates ranging from 7 to 45%. Therefore, the aim of this study was to identify the association of survival with variables that could be utilized to improve clinical decisions. A total of 1194 dogs with a gross and histopathological diagnosis of GBM were included from 41 veterinary referral hospitals in this retrospective study. Dogs with GBM that demonstrated abnormal clinical signs had significantly greater odds of death than subclinical dogs in a univariable analysis (OR, 4.2; 95% CI, 2.14-8.23; P<0.001). The multivariable model indicated that categorical variables including owner recognition of jaundice (OR, 2.12; 95% CI, 1.19-3.77; P=0.011), concurrent hyperadrenocorticism (OR 1.94; 95% CI, 1.08-3.47; P=0.026), and Pomeranian breed (OR, 2.46; 95% CI 1.10-5.50; P=0.029) were associated with increased odds of death, and vomiting was associated with decreased odds of death (OR, 0.48; 95% CI, 0.30-0.72; P=0.001). Continuous variables in the multivariable model, total serum/plasma bilirubin concentration (OR, 1.03; 95% CI, 1.01-1.04; P<0.001) and age (OR, 1.17; 95% CI, 1.08-1.26; P<0.001), were associated with increased odds of death. The clinical utility of total serum/plasma bilirubin concentration as a biomarker to predict death was poor with a sensitivity of 0.61 (95% CI, 0.54-0.69) and a specificity of 0.63 (95% CI, 0.59-0.66). This study identified several prognostic variables in dogs with GBM including total serum/plasma bilirubin concentration, age, clinical signs, concurrent hyperadrenocorticism, and the Pomeranian breed. The presence of hypothyroidism or diabetes mellitus did not impact outcome in this study.

A Remote Assay for Measuring Canine Platelet Activation and the Inhibitory Effects of Antiplatelet Agents.

BACKGROUND: Antiplatelet medications are increasingly used in dogs. Remote analysis of platelet activity is challenging, limiting assessment of antiplatelet drug efficacy. HYPOTHESIS/OBJECTIVES: To evaluate a method used in humans for stimulation and remote analysis of canine platelet activity. ANIMALS: Forty-five dogs of various ages without a coagulopathy or thrombocytopenia. Six were receiving antiplatelet medication. METHODS: Prospective observational study. Platelets were stimulated with combinations of arachidonic acid (AA) and epinephrine (Epi) or adenosine diphosphate (ADP) and the thromboxane A2 -mimetic U46619 (U4). PAMFix was added to the blood samples to facilitate delayed analysis of platelet activity. Activity was assessed by flow cytometric measurement of surface P-selectin (CD62P) expression. RESULTS: Canine platelets could be stimulated with both AA/Epi and ADP/U4. The levels of P-selectin were significantly greater than paired, unstimulated samples (P < 0.001). Inhibition of P-selectin expression occurred after this stimulation by adding antiplatelet drugs in vitro. The efficacy of antiplatelet drugs in samples from treated dogs was also measurable ex vivo using this method. Delayed analysis of platelet activity at time points up to 22 days demonstrated excellent correlation between respective mf values at each time point (r2  = 0.92, P < 0.0001). CONCLUSIONS AND CLINICAL IMPORTANCE: This study evaluated a new method to remotely assess canine platelet activity. It shows that PAMFix can be used for this purpose. This provides opportunities to interrogate the inhibitory action of antiplatelet drugs in clinical settings.

Gall bladder mucoceles in Border terriers.

BACKGROUND: Gall bladder mucoceles (GBM) are a leading cause of biliary disease in dogs with several breeds, including the Shetland Sheepdog, American Cocker Spaniel, Chihuahua, Pomeranian, and Miniature Schnauzer apparently predisposed. OBJECTIVE: To determine risk factors, clinical features, and response to treatment of GBM in Border terriers (BT). ANIMALS: Medical records of 99 dogs (including 51 BT) with an ultrasonographic (±histopathologic) diagnosis of GBM from three referral centers in the United Kingdom were collected. A control group of 87 similar-aged BT with no ultrasonographic evidence of gall bladder disease was selected for comparison. METHOD: Retrospective case-control study. Odds ratios were calculated to establish breed predisposition. Signalment, presence of endocrine disease, clinicopathologic results, and outcome were compared between the BT, other breeds, and control BTs. RESULTS: The odds of identifying a GBM in a BT in this hospital population was 85 times that of all other breeds (95% confidence interval 56.9-126.8). BT had similar clinical signs and clinicopathologic changes to other breeds with GBM. There was no evidence that endocrinopathies were associated with GBM in BT. CLINICAL SIGNIFICANCE: A robust breed predisposition to GBM is established for the BT.