Demography and disorders of the French Bulldog population under primary veterinary care in the UK in 2013

Abstract Background Despite its Gallic name, the French Bulldog is a breed of both British and French origin that was first recognised by The Kennel Club in 1906. The French Bulldog has demonstrated recent rapid rises in Kennel Club registrations and is now (2017) the second most commonly registered pedigree breed in the UK. However, the breed has been reported to be predisposed to several disorders including ocular, respiratory, neurological and dermatological problems. The VetCompass™ Programme collates de-identified clinical data from primary-care veterinary practices in the UK for epidemiological research. Using VetCompass™ clinical data, this study aimed to characterise the demography and common disorders of the general population of French Bulldogs under veterinary care in the UK. Results French Bulldogs comprised 2228 (0.49%) of 445,557 study dogs under veterinary care during 2013. Annual proportional birth rates showed that the proportional ownership of French Bulldog puppies rose steeply from 0.02% of the annual birth cohort attending VetCompass™ practices in 2003 to 1.46% in 2013. The median age of the French Bulldogs overall was 1.3 years (IQR 0.6–2.5, range 0.0–13.0). The most common colours of French Bulldogs were brindle (solid or main) (32.36%) and fawn (solid or main) (29.9%). Of the 2228 French Bulldogs under veterinary care during 2013, 1612 (72.4%) had at least one disorder recorded. The most prevalent fine-level precision disorders recorded were otitis externa (14.0%, 95% CI: 12.6–15.5), diarrhoea (7.5%, 95% CI: 6.4–8.7), conjunctivitis (3.2%, 95% CI: 2.5–4.0), nails overlong (3.1%, 95% CI% 2.4–3.9) and skin fold dermatitis (3.0%, 95% CI% 2.3–3.8). The most prevalent disorder groups were cutaneous (17.9%, 95% CI: 16.3–19.6), enteropathy (16.7%, 95% CI: 15.2–18.3), aural (16.3%, 95% CI: 14.8–17.9), upper respiratory tract (12.7%, 95% CI: 11.3–14.1) and ophthalmological (10.5%, 95% CI: 9.3–11.9). Conclusions Ownership of French Bulldogs in the UK is rising steeply. This means that the disorder profiles reported in this study reflect a current young UK population and are likely to shift as this cohort ages. Otitis externa, diarrhoea and conjunctivitis were the most common disorders in French Bulldogs. Identification of health priorities based on VetCompass™ data can support evidence–based reforms to improve health and welfare within the breed

Validity and Reliability of Dermoscopic Criteria Used to Differentiate Nevi From Melanoma: A Web-Based International Dermoscopy Society Study.

IMPORTANCE: The comparative diagnostic performance of dermoscopic algorithms and their individual criteria are not well studied. OBJECTIVES: To analyze the discriminatory power and reliability of dermoscopic criteria used in melanoma detection and compare the diagnostic accuracy of existing algorithms. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective, observational study of 477 lesions (119 melanomas [24.9%] and 358 nevi [75.1%]), which were divided into 12 image sets that consisted of 39 or 40 images per set. A link on the International Dermoscopy Society website from January 1, 2011, through December 31, 2011, directed participants to the study website. Data analysis was performed from June 1, 2013, through May 31, 2015. Participants included physicians, residents, and medical students, and there were no specialty-type or experience-level restrictions. Participants were randomly assigned to evaluate 1 of the 12 image sets. MAIN OUTCOMES AND MEASURES: Associations with melanoma and intraclass correlation coefficients (ICCs) were evaluated for the presence of dermoscopic criteria. Diagnostic accuracy measures were estimated for the following algorithms: the ABCD rule, the Menzies method, the 7-point checklist, the 3-point checklist, chaos and clues, and CASH (color, architecture, symmetry, and homogeneity). RESULTS: A total of 240 participants registered, and 103 (42.9%) evaluated all images. The 110 participants (45.8%) who evaluated fewer than 20 lesions were excluded, resulting in data from 130 participants (54.2%), 121 (93.1%) of whom were regular dermoscopy users. Criteria associated with melanoma included marked architectural disorder (odds ratio [OR], 6.6; 95% CI, 5.6-7.8), pattern asymmetry (OR, 4.9; 95% CI, 4.1-5.8), nonorganized pattern (OR, 3.3; 95% CI, 2.9-3.7), border score of 6 (OR, 3.3; 95% CI, 2.5-4.3), and contour asymmetry (OR, 3.2; 95% CI, 2.7-3.7) (P < .001 for all). Most dermoscopic criteria had poor to fair interobserver agreement. Criteria that reached moderate levels of agreement included comma vessels (ICC, 0.44; 95% CI, 0.40-0.49), absence of vessels (ICC, 0.46; 95% CI, 0.42-0.51), dark brown color (ICC, 0.40; 95% CI, 0.35-0.44), and architectural disorder (ICC, 0.43; 95% CI, 0.39-0.48). The Menzies method had the highest sensitivity for melanoma diagnosis (95.1%) but the lowest specificity (24.8%) compared with any other method (P < .001). The ABCD rule had the highest specificity (59.4%). All methods had similar areas under the receiver operating characteristic curves. CONCLUSIONS AND RELEVANCE: Important dermoscopic criteria for melanoma recognition were revalidated by participants with varied experience. Six algorithms tested had similar but modest levels of diagnostic accuracy, and the interobserver agreement of most individual criteria was poor

The Type and the Position of HNF1A Mutation Modulate Age at Diagnosis of Diabetes in Patients with Maturity-Onset Diabetes of the Young (MODY)-3

OBJECTIVE—The clinical expression of maturity-onset diabetes of the young (MODY)-3 is highly variable. This may be due to environmental and/or genetic factors, including molecular characteristics of the hepatocyte nuclear factor 1-α (HNF1A) gene mutation. RESEARCH DESIGN AND METHODS—We analyzed the mutations identified in 356 unrelated MODY3 patients, including 118 novel mutations, and searched for correlations between the genotype and age at diagnosis of diabetes. RESULTS—Missense mutations prevailed in the dimerization and DNA-binding domains (74%), while truncating mutations were predominant in the transactivation domain (62%). The majority (83%) of the mutations were located in exons 1- 6, thus affecting the three HNF1A isoforms. Age at diagnosis of diabetes was lower in patients with truncating mutations than in those with missense mutations (18 vs. 22 years, P = 0.005). Missense mutations affecting the dimerization/DNA-binding domains were associated with a lower age at diagnosis than those affecting the transactivation domain (20 vs. 30 years, P = 10−4). Patients with missense mutations affecting the three isoforms were younger at diagnosis than those with missense mutations involving one or two isoforms (P = 0.03). CONCLUSIONS—These data show that part of the variability of the clinical expression in MODY3 patients may be explained by the type and the location of HNF1A mutations. These findings should be considered in studies for the search of additional modifier genetic factors

Water-Soluble Fullerene (C60) Derivatives as Nonviral Gene-Delivery Vectors

A new class of water-soluble C60 transfecting agents has been prepared using Hirsch-Bingel chemistry and assessed for their ability to act as gene-delivery vectors in vitro. In an effort to elucidate the relationship between the hydrophobicity of the fullerene core, the hydrophilicity of the water-solubilizing groups, and the overall charge state of the C60 vectors in gene delivery and expression, several different C60 derivatives were synthesized to yield either positively charged, negatively charged, or neutral chemical functionalities under physiological conditions. These fullerene derivatives were then tested for their ability to transfect cells grown in culture with DNA carrying the green fluorescent protein (GFP) reporter gene. Statistically significant expression of GFP was observed for all forms of the C60 derivatives when used as DNA vectors and compared to the ability of naked DNA alone to transfect cells. However, efficient in vitro transfection was only achieved with the two positively charged C60 derivatives, namely, an octa-amino derivatized C60 and a dodeca-amino derivatized C60 vector. All C60 vectors showed an increase in toxicity in a dose-dependent manner. Increased levels of cellular toxicity were observed for positively charged C60 vectors relative to the negatively charged and neutral vectors. Structural analyses using dynamic light scattering and optical microscopy offered further insights into possible correlations between the various derivatized C60 compounds, the C60 vector/DNA complexes, their physical attributes (aggregation, charge) and their transfection efficiencies. Recently, similar Gd@C60-based compounds have demonstrated potential as advanced contrast agents for magnetic resonance imaging (MRI). Thus, the successful demonstration of intracellular DNA uptake, intracellular transport, and gene expression from DNA using C60 vectors suggests the possibility of developing analogous Gd@C60-based vectors to serve simultaneously as both therapeutic and diagnostic agents

Quantifying defects in graphene via Raman spectroscopy at different excitation energies.

We present a Raman study of Ar(+)-bombarded graphene samples with increasing ion doses. This allows us to have a controlled, increasing, amount of defects. We find that the ratio between the D and G peak intensities, for a given defect density, strongly depends on the laser excitation energy. We quantify this effect and present a simple equation for the determination of the point defect density in graphene via Raman spectroscopy for any visible excitation energy. We note that, for all excitations, the D to G intensity ratio reaches a maximum for an interdefect distance ∼3 nm. Thus, a given ratio could correspond to two different defect densities, above or below the maximum. The analysis of the G peak width and its dispersion with excitation energy solves this ambiguity

Safety and immunogenicity of the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in children in Sierra Leone: a randomised, double-blind, controlled trial

Background—Children account for a substantial proportion of cases and deaths from Ebola virus disease. We aimed to assess the safety and immunogenicity of a two-dose heterologous vaccine regimen, comprising the adenovirus type 26 vector-based vaccine encoding the Ebola virus glycoprotein (Ad26.ZEBOV) and the modified vaccinia Ankara vectorbased vaccine, encoding glycoproteins from the Ebola virus, Sudan virus, and Marburg virus, and the nucleoprotein from the Tai Forest virus (MVA-BN-Filo), in a paediatric population in Sierra Leone. Methods—This randomised, double-blind, controlled trial was done at three clinics in Kambia district, Sierra Leone. Healthy children and adolescents aged 1–17 years were enrolled in three age cohorts (12–17 years, 4–11 years, and 1–3 years) and randomly assigned (3:1), via computer-generated block randomisation (block size of eight), to receive an intramuscular injection of either Ad26.ZEBOV (5 × 1010 viral particles; first dose) followed by MVA-BN-Filo (1 × 108 infectious units; second dose) on day 57 (Ebola vaccine group), or a single dose of meningococcal quadrivalent (serogroups A, C, W135, and Y) conjugate vaccine (MenACWY; first dose) followed by placebo (second dose) on day 57 (control group). Study team personnel (except for those with primary responsibility for study vaccine preparation), participants, and their parents or guardians were masked to study vaccine allocation. The primary outcome was safety, measured as the occurrence of solicited local and systemic adverse symptoms during 7 days after each vaccination, unsolicited systemic adverse events during 28 days after each vaccination, abnormal laboratory results during the study period, and serious adverse events or immediate reportable events throughout the study period. The secondary outcome was immunogenicity (humoral immune response), measured as the concentration of Ebola virus glycoprotein-specific binding antibodies at 21 days after the second dose. The primary outcome was assessed in all participants who had received at least one dose of study vaccine and had available reactogenicity data, and immunogenicity was assessed in all participants who had received both vaccinations within the protocol-defined time window, had at least one evaluable post-vaccination sample, and had no major protocol deviations that could have influenced the immune response. This study is registered at ClinicalTrials.gov, NCT02509494. Findings—From April 4, 2017, to July 5, 2018, 576 eligible children or adolescents (192 in each of the three age cohorts) were enrolled and randomly assigned. The most common solicited local adverse event during the 7 days after the first and second dose was injection-site pain in all age groups, with frequencies ranging from 0% (none of 48) of children aged 1–3 years after placebo injection to 21% (30 of 144) of children aged 4–11 years after Ad26.ZEBOV vaccination. The most frequently observed solicited systemic adverse event during the 7 days was headache in the 12–17 years and 4–11 years age cohorts after the first and second dose, and pyrexia in the 1–3 years age cohort after the first and second dose. The most frequent unsolicited adverse event after the first and second dose vaccinations was malaria in all age cohorts, irrespective of the vaccine types. Following vaccination with MenACWY, severe thrombocytopaenia was observed in one participant aged 3 years. No other clinically significant laboratory abnormalities were observed in other study participants, and no serious adverse events related to the Ebola vaccine regimen were reported. There were no treatment-related deaths. Ebola virus glycoprotein-specific binding antibody responses at 21 days after the second dose of the Ebola virus vaccine regimen were observed in 131 (98%) of 134 children aged 12–17 years (9929 ELISA units [EU]/mL [95% CI 8172–12 064]), in 119 (99%) of 120 aged 4–11 years (10 212 EU/mL [8419–12 388]), and in 118 (98%) of 121 aged 1–3 years (22 568 EU/mL [18 426–27 642]). Interpretation—The Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen was well tolerated with no safety concerns in children aged 1–17 years, and induced robust humoral immune responses, suggesting suitability of this regimen for Ebola virus disease prophylaxis in children