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OBJECTIVE: Assess the utility of a Sub-Tenon's anesthesia (STA) protocol to provide suitable operating conditions for canine cataract surgery and compare it to an alternative low-dose neuromuscular blockade (LD-NMB) protocol used for canine cataract surgery. PROCEDURES: Clinical study of dog eyes undergoing cataract surgery with either an STA or LD-NMB protocol. While intraoperative vitreal expansion scores and intraoperative complications were collected prospectively, globe position, intraocular pressure, return of vision, and postoperative complications were collected retrospectively. Statistical testing was used to compare results between the STA and the LD-NMB groups for the data available. RESULTS: A total of 224 eyes from 126 dogs were assessed, with 133/224 (59.4%) eyes from 99/126 (78.6%) dogs receiving STA and 91/124 (40.6%) eyes from 72/126 (57.1%) dogs receiving LD-NMB. Forty-five of these dogs (45/126; 37.7%) received STA for one eye and LD-NMB for the other eye. There was no significant change in intraocular pressure measurements following STA administration. This was not measured for the LD-NMB group. The globe achieved a central position in 110/133 (82.7%) of eyes that received STA. This was not measured for the LD-NMB group. Intraoperative vitreal expansion scores were slightly higher in STA-treated eyes compared to LD-NMB-treated eyes. The intraoperative complication rate for STA-treated eyes was higher (73/133; 54.8%) compared to NMB-treated eyes (12/91; 13.2%). The most common intraoperative complication for STA was chemosis (64/133; 48.1%), the risk of which increased with an increase in the volume of local anesthetic injected. The post-operative complication rate was higher in STA-treated eyes (28/133; 21.1%) compared to NMB-treated eyes (16/91; 17.6%). Post-operative corneal ulceration was the most common postoperative complication in STA-treated eyes (6/133; 4.5%). CONCLUSION: The STA protocol described resulted in suitable operating conditions, but more intraoperative and postoperative complications compared to the LD-NMB protocol. Despite these complications, the STA protocol did not cause a significant deleterious impact on post-operative outcomes as defined in the present study.

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Bordetella pertussis, a slow-growing Gram-negative coccobacillus and the causative agent of whooping cough, is one of the leading causes of vaccine-preventable death and morbidity globally. A state of asymptomatic human carriage has not yet been demonstrated by population studies but is likely to be an important reservoir for community transmission of infection. Such a carriage state may be a target for future vaccine strategies. This chapter presents a short summary of the characteristics of B. pertussis, which should be taken into account when developing a human challenge model and any future experimental medicine interventions. Three studies involving deliberate infection with B. pertussis have been described to date. The first of these was a scientifically and ethically unacceptable paediatric challenge study involving four children in 1930. The second was an investigation of a putative live vaccine using a genetically modified and attenuated strain of B. pertussis. Finally, a systematically constructed human challenge model using a wild-type, potentially pathogenic strain has been established. The latter study has demonstrated that deliberate induction of asymptomatic colonisation in humans is safe and immunogenic, with colonised participants exhibiting seroconversion to pertussis antigens. It has also shown nasal wash to be a more sensitive method of detecting the presence of B. pertussis than either pernasal swab or throat swab, and that B. pertussis carriage can be cleared effectively with Azithromycin. The development of this wild-type B. pertussis human challenge model will allow the investigation of host-pathogen and facilitate future vaccine development.

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Rapid development of an effective vaccine for SARSCoV2 is a global priority. A controlled human infection model (CHIM) would accelerate the efficacy assessment of candidate vaccines. This strategy would require deliberate exposure of volunteers to SARSCoV2 with no currently available treatment and a small but definite risk of serious illness or death. This raises complex questions about the social and ethical acceptability of risk to individuals, given the potential benefit to the wider population, and as such, a study cannot be done without public involvement. We conducted a structured public consultation with 57 individuals aged 20-40 years to understand public attitudes to a CHIM, and pre-requisites for enrolment. The overall response to this strategy was positive, and many would volunteer altruistically. Carefully controlled infection is viewed as safer than natural exposure to wild virus. The prolonged social isolation required for the proposed CHIM is considered an obstacle but not insurmountable, with reasonable compensation and supportive care. Given the significant level of public interest, a CHIM should be done as open science with regular, controlled dissemination of information into the public domain. Importantly, there was a strong view that the final decision whether to conduct a CHIM should be in the hands of qualified and experienced clinician-scientists and the authorities.

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Three inherited autosomal dominant conditions-BRCA-related hereditary breast and ovarian cancer (HBOC), Lynch syndrome (LS) and familial hypercholesterolemia (FH)-have been termed the Centers for Disease Control and Prevention Tier 1 (CDCT1) genetic conditions, for which early identification and intervention have a meaningful potential for clinical actionability and a positive impact on public health1. In typical medical practice, genetic testing for these conditions is based on personal or family history, ethnic background or other demographic characteristics2. In this study of a cohort of 26,906 participants in the Healthy Nevada Project (HNP), we first evaluated whether population screening could efficiently identify carriers of these genetic conditions and, second, we evaluated the impact of genetic risk on health outcomes for these participants. We found a 1.33% combined carrier rate for pathogenic and likely pathogenic (P/LP) genetic variants for HBOC, LS and FH. Of these carriers, 21.9% of participants had clinically relevant disease, among whom 70% had been diagnosed with relevant disease before age 65. Moreover, 90% of the risk carriers had not been previously identified, and less than 19.8% of these had documentation in their medical records of inherited genetic disease risk, including family history. In a direct follow-up survey with all carriers, only 25.2% of individuals reported a family history of relevant disease. Our experience with the HNP suggests that genetic screening in patients could identify at-risk carriers, who would not be otherwise identified in routine care.

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A juvenile yellow-tailed black cockatoo (Calyptorhynchus funereus) was presented with paresis of the right wing, ptosis, and miosis of the right eye; feather erection of the right side of the head and neck; and a penetrating injury over the right pectoral muscle. Temporary reversal of ptosis, miosis, and feather erection after administration of phenylephrine drops confirmed a diagnosis of Horner syndrome. Computed tomographic imaging revealed a fractured rib, traumatic lung lesions, and subcutaneous emphysema. The right-sided Horner syndrome and wing paresis were attributed to a sympathetic nerve trauma of the eye and feathers and to the brachial plexus, respectively. This report describes the diagnosis and resolution of ptosis and miosis within 8 weeks and recovery of feather symmetry and wing function within 11 weeks of the cockatoo's initial presentation with a conservative-management treatment plan.

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OBJECTIVE: To analyze a study population of dogs with primary corneal endothelial degeneration (PCED) for information on the patterns of disease and to report the efficacy of superficial keratectomy (SK) for resolution of non-healing corneal ulcers associated with PCED. ANIMALS STUDIED: Primary corneal endothelial degeneration was diagnosed in 238 dogs between 1998 and 2017. Corneal ulceration associated with PCED was present in 89 dogs (109 eyes), of which 47 eyes were treated with SK. PROCEDURES: A retrospective assessment of medical records was performed to determine the signalment patterns of PCED, and the success rate of the SK procedure for resolving PCED-associated corneal ulceration. Descriptive statistics were reported on the signalment of PCED cases, with odd ratios and confidence intervals calculated to detect breed predispositions. RESULTS: Primary corneal endothelial degeneration was diagnosed in 238 dogs, 40.8% were female and 59.2% were male, with a mean age at diagnosis of 11.4 years. Dachshunds, Dalmatians, English Springer Spaniels, Welsh Springer Spaniels, Chihuahuas, Cocker Spaniels, and Golden Retrievers were significantly over-represented. All PCED-affected Dalmatians developed associated corneal ulceration. Follow-up information was available for 41/47 eyes treated with SK. At the first reassessment, 87.8% were healed which increased to 97.6% with subsequent monitoring. Four eyes (9.8%) had late corneal ulcer occurrence following SK, at a median time following SK of 182 weeks post-surgery. CONCLUSIONS: Superficial keratectomy was an effective option for resolving painful non-healing corneal ulcers associated with PCED. Dalmatians may be at increased risk of developing PCED-associated corneal ulceration.

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OBJECTIVE: To test a sub-Tenon's anesthesia technique in dogs as an alternative to systemic neuromuscular blockade to aid in canine cataract surgery under general anesthesia. PROCEDURES: A prospective controlled clinical study was performed involving 12 dogs undergoing bilateral cataract surgery under general anesthesia. One eye was randomly assigned to have phacoemulsification and prosthetic lens implantation performed with sub-Tenon's anesthesia (STA), and the control eye had surgery performed with systemic neuromuscular blockade (NMB). Intraocular pressure (IOP) was measured immediately before and after STA administration. Globe position, globe rotation, pupillary dilation, and vitreal expansion were assessed for both STA and NMB eyes during surgery. RESULTS: Sub-Tenon's anesthesia produced a globe position suitable for cataract surgery with the degree of vitreal expansion not significantly different to control NMB eyes. STA produced greater anterior globe displacement than NMB in all cases. STA had no significant effect on IOP. CONCLUSION: Sub-Tenon's anesthesia was an effective alternative to systemic neuromuscular blockade for canine cataract surgery and may be beneficial for surgical exposure in deep orbited breeds.

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Evidence suggests that HIV-infected adolescents experience elevated levels of fatigue that impacts their functioning at school and other important aspects of their lives. Yet, fatigue has not been measured amongst this population group. In this cross-sectional, mixed-methods study we explored the psychometric properties of the 11-item Chalder Fatigue Questionnaire (CFQ) amongst 134 South African adolescents (11-18 years old) receiving antiretroviral therapy (ART) in the Western Cape. Using the Likert scoring method for the CFQ, the mean total score was 14.89 (SD=3.83) and about a quarter (n=33, 24.63%) of adolescents scored ≥ 18, indicating problematic levels of fatigue. The CFQ demonstrated good internal consistency with a Cronbach's alpha of 0.83 (0.84, with item 11 deleted), which is comparable to other validation studies. On the first iteration of the principal component analysis (PCA) with a Varimax rotation, three factors accounted for 59.15% of the variance. However, the third factor consisted of one item only which we chose to remove from the analysis. On the second iteration of the PCA, a two factor solution was retained that accounted for 54.24% of the variance. The first factor, 'Physical fatigue', represented the first eight items on the scale. The second factor 'Mental fatigue' represented items nine and ten. The CFQ also demonstrated modest content and construct validity. The CFQ is a short, easy-to-use and cost-effective measure of fatigue, and demonstrates reliability and validity amongst a South African sample of adolescents. Given the high rate of fatigue amongst our participants, we recommend that future interventions be developed to reduce fatigue among HIV-infected adolescents, which may ultimately lead to improvements in school performance and social functioning. Future research may include test-retest reliability of the CFQ in order to show stability over time.

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The most recent European guidelines and task force reports on hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) were published almost 10 years ago. Since then, further randomised clinical trials of HAP and VAP have been conducted and new information has become available. Studies of epidemiology, diagnosis, empiric treatment, response to treatment, new antibiotics or new forms of antibiotic administration and disease prevention have changed old paradigms. In addition, important differences between approaches in Europe and the USA have become apparent.The European Respiratory Society launched a project to develop new international guidelines for HAP and VAP. Other European societies, including the European Society of Intensive Care Medicine and the European Society of Clinical Microbiology and Infectious Diseases, were invited to participate and appointed their representatives. The Latin American Thoracic Association was also invited.A total of 15 experts and two methodologists made up the panel. Three experts from the USA were also invited (Michael S. Niederman, Marin Kollef and Richard Wunderink).Applying the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) methodology, the panel selected seven PICO (population-intervention-comparison-outcome) questions that generated a series of recommendations for HAP/VAP diagnosis, treatment and prevention.(AU)

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Molecular epidemiology has become a key tool for tracking infectious disease epidemics. Here, the spread of the most prevalent HIV-1 subtypes in Northern Alberta, Canada, was characterized with a Bayesian phylogenetic approach using 1146 HIV-1 pol sequences collected between 2007 and 2013 for routine clinical management purposes. Available patient metadata were qualitatively interpreted and correlated with onwards transmission using Fisher exact tests and logistic regression. Most infections were from subtypes A (n=36), B (n=815) and C (n=211). Africa is the dominant origin location for subtypes A and C while the subtype B epidemic was seeded from the USA and Middle America and, from the early 1990s onwards, mostly by interprovincial spread. Subtypes A (77.8%) and C (74.0%) were usually heterosexually transmitted and circulate predominantly among Blacks (61.1% and 85% respectively). Subtype B was mostly found among Caucasians (48.6%) and First Nations (36.8%), and its modes of transmission were stratified by ethnic origin. Compared to subtypes A (5.6%) and C (3.8-10.0%), a larger portion of subtype B patients were found within putative provincial transmission networks (20.3-29.5%), and this almost doubled when focusing on nationwide transmission clusters (37.9-57.5%). No clear association between cluster membership and particular patient characteristics was found. This study reveals complex and multi-faceted transmission dynamics of the HIV-1 epidemic in this otherwise low HIV prevalence population in Northern Alberta, Canada. These findings can aid public health planning.

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BACKGROUND: The models of mental disorders held by all mental health professionals are implicit in their attitudes and inform all aspects of theory and practice. The present study aims to explore the attitudes of trainee clinical psychologists towards mental disorders by building on a study conducted by Harland et al. () with psychiatrists. In so doing, the present study contributes to an evidence base that can inform the development of clinical training programs and multidisciplinary working. METHODS: The Maudsley Attitude Questionnaire was administered in an online survey of trainee clinical psychologists (n = 289). RESULTS: Analyses of variance revealed main effects of model, and of diagnostic category, and a significant interaction effect between model and diagnostic category. Principal component analysis revealed a biological-psychosocial continuum and cognitive/behavioural and psychodynamic/spiritual dimensions. Comparisons with Harland et al.'s () psychiatrists revealed large differences, particularly in biological and social constructionist model endorsement. CONCLUSION: Results suggest that the attitudes of psychologists and psychiatrists continue to sit at opposite ends of a biological-psychosocial continuum. However, an area of consensus regarding psychotherapeutic models was indicated. Training courses can be reassured that strong opinions tended to reflect the evidence base. Future research with similarly large representative samples from different disciplines would allow findings of the current study to be better contextualized. Copyright © 2016 John Wiley & Sons, Ltd. KEY PRACTITIONER MESSAGE: The models of mental disorders held by clinical psychologists are implicit in their attitudes and inform all aspects of theory and practice. We found that trainee clinical psychologists continue to favour psychosocial over biological understandings of mental disorders, giving the cognitive, behavioural and psychodynamic models equal value overall, and stronger attitudes were supported by the evidence base. We found that trainee clinical psychologists organized their attitudes around a biological-psychosocial continuum and cognitive/behavioural and psychodynamic/spiritual dimensions. These findings may be useful for those involved in developing clinical training programs and multidisciplinary working because they provide an insight into the attitudes of emerging clinical psychologists.

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Secreted WNT proteins control cell differentiation and proliferation in many tissues, and NOTUM is a secreted enzyme that modulates WNT morphogens by removing a palmitoleoylate moiety that is essential for their activity. To better understand the role this enzyme in development, the authors produced NOTUM-deficient mice by targeted insertional disruption of the Notum gene. The authors discovered a critical role for NOTUM in dentin morphogenesis suggesting that increased WNT activity can disrupt odontoblast differentiation and orientation in both incisor and molar teeth. Although molars in Notum(-/-) mice had normal-shaped crowns and normal mantle dentin, the defective crown dentin resulted in enamel prone to fracture during mastication and made teeth more susceptible to endodontal inflammation and necrosis. The dentin dysplasia and short roots contributed to tooth hypermobility and to the spread of periodontal inflammation, which often progressed to periapical abscess formation. The additional incidental finding of renal agenesis in some Notum (-/-) mice indicated that NOTUM also has a role in kidney development, with undiagnosed bilateral renal agenesis most likely responsible for the observed decreased perinatal viability of Notum(-/-) mice. The findings support a significant role for NOTUM in modulating WNT signaling pathways that have pleiotropic effects on tooth and kidney development.

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Bacterial meningitis and meningococcal sepsis are rare conditions with high case fatality rates. Early recognition and prompt treatment saves lives. In 1999 the British Infection Society produced a consensus statement for the management of immunocompetent adults with meningitis and meningococcal sepsis. Since 1999 there have been many changes. We therefore set out to produce revised guidelines which provide a standardised evidence-based approach to the management of acute community acquired meningitis and meningococcal sepsis in adults. A working party consisting of infectious diseases physicians, neurologists, acute physicians, intensivists, microbiologists, public health experts and patient group representatives was formed. Key questions were identified and the literature reviewed. All recommendations were graded and agreed upon by the working party. The guidelines, which for the first time include viral meningitis, are written in accordance with the AGREE 2 tool and recommendations graded according to the GRADE system. Main changes from the original statement include the indications for pre-hospital antibiotics, timing of the lumbar puncture and the indications for neuroimaging. The list of investigations has been updated and more emphasis is placed on molecular diagnosis. Approaches to both antibiotic and steroid therapy have been revised. Several recommendations have been given regarding the follow-up of patients.

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BACKGROUND: The quality of melanoma surgery needs to be assessed by oncological outcome and complication rates. There is no published consensus on complication rates for common melanoma surgeries, namely wide excision (WE), sentinel node biopsy (SNB) and regional lymph node dissection (RLND). Consequently there are no agreed standards by which surgeons can audit their practices. METHODS: Surgical standards were proposed in 2008 following review of the literature and from expert opinion. Melanoma Institute Australia (MIA) self-reported audit data from 2011 and 2012 were compared with these standards. To quality check the self-reported audit, RLND data were extracted from the MIA database. RESULTS: Six surgeons performed a mean of 568 surgeries each quarter; with a mean of 106 major procedures. Following WE with primary closure or flap repair, wound infection or dehiscence occurred in <1% of cases. When skin grafting was required non-take of >20% of the grafted area was observed in 5.9% of cases. Following SNB wound infection and significant seroma occurred in 1.8% of cases. RLND node counts were below the 90% standard in 4 of 409 procedures. In comparison, data extraction identified 405 RLNDs, with node counts below the 90% standard in eight procedures. Two of these patients had previously undergone surgery removing nodes from the field and two had gross coalescing disease with extensive extra-nodal spread. CONCLUSION: The quality standards proposed in 2008 have been validated long-term by high volume caseloads. The data presented provide standards by which melanoma surgeons can audit their surgical performance.

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Data were extracted from the case records of UK patients admitted with laboratory-confirmed influenza A(H1N1)pdm09. White and non-White patients were characterized by age, sex, socioeconomic status, pandemic wave and indicators of pre-morbid health status. Logistic regression examined differences by ethnicity in patient characteristics, care pathway and clinical outcomes; multivariable models controlled for potential confounders. Whites (n = 630) and non-Whites (n = 510) differed by age, socioeconomic status, pandemic wave of admission, pregnancy, recorded obesity, previous and current smoking, and presence of chronic obstructive pulmonary disease. After adjustment for a priori confounders non-Whites were less likely to have received pre-admission antibiotics [adjusted odds ratio (aOR) 0·43, 95% confidence interval (CI) 0·28-0·68, P < 0·001) but more likely to receive antiviral drugs as in-patients (aOR 1·53, 95% CI 1·08-2·18, P = 0·018). However, there were no significant differences by ethnicity in delayed admission, severity at presentation for admission, or likelihood of severe outcome.

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GREMLIN 2 (GREM2)--formerly, protein related to Dan and cerberus (PRDC)-is a potent antagonist of the bone morphogenetic proteins 2 and 4, but little else in known about its functions. We found that Grem2(-/-) mice developed small deformed mandibular and maxillary incisors, indicating that GREMLIN2 is required for normal tooth morphogenesis. Although DEXA scans suggested that bone mineral density might be increased in Grem2(-/-) mice, histology did not reveal any evident bone phenotype. Grem2(-/-) mice did not display any other notable phenotypes evaluated in a high-throughput screening process that encompassed a range of immunologic, metabolic, ophthalmic, and behavioral parameters. Our findings indicate that Grem2 can be added to the growing list of genes that affect tooth development in mice.

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