Systematic comparisons of different quality control approaches applied to three large pediatric neuroimaging datasets.

INTRODUCTION: Poor quality T1-weighted brain scans systematically affect the calculation of brain measures. Removing the influence of such scans requires identifying and excluding scans with noise and artefacts through a quality control (QC) procedure. While QC is critical for brain imaging analyses, it is not yet clear whether different QC approaches lead to the exclusion of the same participants. Further, the removal of poor-quality scans may unintentionally introduce a sampling bias by excluding the subset of participants who are younger and/or feature greater clinical impairment. This study had two aims: (1) examine whether different QC approaches applied to T1-weighted scans would exclude the same participants, and (2) examine how exclusion of poor-quality scans impacts specific demographic, clinical and brain measure characteristics between excluded and included participants in three large pediatric neuroimaging samples. METHODS: We used T1-weighted, resting-state fMRI, demographic and clinical data from the Province of Ontario Neurodevelopmental Disorders network (Aim 1: n = 553, Aim 2: n = 465), the Healthy Brain Network (Aim 1: n = 1051, Aim 2: n = 558), and the Philadelphia Neurodevelopmental Cohort (Aim 1: n = 1087; Aim 2: n = 619). Four different QC approaches were applied to T1-weighted MRI (visual QC, metric QC, automated QC, fMRI-derived QC). We used tetrachoric correlation and inter-rater reliability analyses to examine whether different QC approaches excluded the same participants. We examined differences in age, mental health symptoms, everyday/adaptive functioning, IQ and structural MRI-derived brain indices between participants that were included versus excluded following each QC approach. RESULTS: Dataset-specific findings revealed mixed results with respect to overlap of QC exclusion. However, in POND and HBN, we found a moderate level of overlap between visual and automated QC approaches (rtet=0.52-0.59). Implementation of QC excluded younger participants, and tended to exclude those with lower IQ, and lower everyday/adaptive functioning scores across several approaches in a dataset-specific manner. Across nearly all datasets and QC approaches examined, excluded participants had lower estimates of cortical thickness and subcortical volume, but this effect did not differ by QC approach. CONCLUSION: The results of this study provide insight into the influence of QC decisions on structural pediatric imaging analyses. While different QC approaches exclude different subsets of participants, the variation of influence of different QC approaches on clinical and brain metrics is minimal in large datasets. Overall, implementation of QC tends to exclude participants who are younger, and those who have more cognitive and functional impairment. Given that automated QC is standardized and can reduce between-study differences, the results of this study support the potential to use automated QC for large pediatric neuroimaging datasets.

Safety of sequential immune checkpoint inhibitors after prior immune therapy.

BACKGROUND: The use of immune checkpoint inhibitors (ICI) has transformed cancer treatment. Subsequent ICI use has become increasingly common following disease progression. We aim to evaluate the safety and tolerability of the sequential ICI treatment modality. METHODS: Retrospective review of confirmed carcinoma from January 2014 to December 2018. Patients were categorized into "initial ICI arm" and "sequential ICI arm" defined as patients receiving single, dual or chemo-immunotherapy ICI following an initial ICI regimen. Primary outcome was the development of a new or recurrent immune related adverse event (irAE) during sequential therapy. Secondary outcomes were the number of cycles prior to the development of irAE and grade of irAE. RESULTS: A total of 483 patients received ICI during the timeframe. Of those, 22 patients received sequential ICI. The diagnoses included ten lung cancer, seven melanoma, four renal cell carcinoma and one bladder cancer. 16 patients received single agent ICI following the initial ICI, three patients received dual ICI following the initial ICI, one patient received chemotherapy-immunotherapy following initial ICI, and two patients received chemo-immunotherapy after dual ICI. Four patients developed new irAE and one patient developed the same irAE on sequential treatment. A higher proportion of patients experienced grade 3 irAE in the sequential arm compared to the initial ICI arm (p = 0.03). No statistical difference was found between the development of irAE and the number of cycles prior to development of irAE in either treatment groups (p = 0.5). CONCLUSION: Our data shows overall safety of sequencing ICI when close monitoring was employed.

Bayesian Decision Analysis: An Underutilized Tool in Veterinary Medicine.

Bayesian inference and decision analysis can be used to identify the most probable differential diagnosis and use those probabilities to identify the best choice of diagnostic or treatment among several alternatives. In this retrospective case analysis, we surveyed three experts on the prior probability of several differential diagnoses, given the signalment and history of a ferret presenting for lethargy and anorexia, and the conditional probability of different clinical findings (physical, bloodwork, imaging, etc.), given a diagnosis. Using these data and utility estimates provided by other clinicians, we constructed a decision tree to retrospectively identify the optimal treatment choice between exploratory laparotomy and medical management. We identified medical management as the optimal choice, in contrast to the original clinical team which performed an exploratory laparotomy. We discuss the potential cognitive biases of the original clinical team. We also discuss the strengths, e.g., shared decision making, and limitations of a Bayesian decision analysis in the veterinary clinic. Bayesian decision analysis can be a useful tool for retrospective case analysis and prospective decision making, especially for deciding on invasive interventions or end-of-life care. The dissimilarity of expert-derived probability estimates makes Bayesian decision analysis somewhat challenging to apply, particularly in wide-ranging specialties like zoological medicine.

Geriatric Ferrets.

Ferrets are considered geriatric at 3 years of age. Twice-yearly physical examinations with additional testing finds problems and leads to prompt treatments that extend quality of life for the ferret. Bloodwork, urinalysis, dental examination, and imaging including radiographs and ultrasonography should be performed at least annually. Specialized testing includes echocardiography, electrocardiology, blood pressure, computed tomography scanning, and dental radiography depending on the ferret. Common problems include dental disease, cardiomyopathy, renal disease, musculoskeletal disorders, chronic gastrointestinal disorders, and neoplasias. Insulinoma, adrenal neoplasia, lymphoma, and skin tumors are commonly found neoplasias. Medical and surgical treatments and adjunctive complimentary therapies are discussed.

Using theory-based messages to motivate U.S. pregnant women to prevent cytomegalovirus infection: results from formative research.

BACKGROUND: An estimated 1 in 150 infants is born each year with congenital cytomegalovirus (CMV); nearly 1 in 750 suffers permanent disabilities. Congenital CMV is the result of a pregnant woman becoming infected with CMV. Educating pregnant women about CMV is currently the best approach to prevention. Limited research is available on how to effectively communicate with women about CMV. We conducted formative research on fear appeals theory-based messages about CMV and prevention with U.S. women. Fear appeal theories suggest that message recipients will take action if they feel fear. METHODS: First, we conducted in-depth interviews (N = 32) with women who had young children who tested positive for CMV. Second, we conducted eight focus groups (N = 70) in two phases and two cities (Phase 2: Atlanta, GA; Phase 3: San Diego, CA) with pregnant women and non-pregnant women who had young children. Few participants knew about CMV before the focus groups. Participants reviewed and gave feedback on messages created around fear appeals theory-based communication concepts. The following concepts were tested in one or more of the three phases of research: CMV is severe, CMV is common, CMV is preventable, CMV preventive strategies are similar to other behavior changes women make during pregnancy, CMV preventive strategies can be incorporated in moderation to reduce exposure, and CMV is severe but preventable. RESULTS: Participants recommended communicating that CMV is common by using prevalence ratios (e.g., 1 in 150) or comparing CMV to other well-known disabilities. To convey the severity of CMV, participants preferred stories about CMV along with prevention strategies. Participants also welcomed prevention strategies when it included a message about risk reduction. In general, participants said messages were motivating, even if they felt that it could be difficult to make certain behavior changes. CONCLUSIONS: Findings from this research can contribute to future efforts to educate pregnant women about CMV, especially regarding use of fear appeals-based messages. Pregnant women may face certain challenges to practicing prevention strategies but, overall, are motivated make changes to increase their chances of having a healthy baby.

Reproductive Disorders of Marsupials.

Marsupial reproduction differs significantly in anatomy and physiology from that of placental mammals. The gastrointestinal and urogenital tracts empty into a cloaca. Reproductive parameters include gestation and pouch time, as the fetus develops outside of the uterus. Captive marsupials discussed include sugar gliders), short-tailed opossums, Virginia opossums, and Tammar and Bennett's wallabies. Common disease conditions include joey eviction, pouch infections, mastitis, metritis, prostatitis, penile necrosis, and neoplasia. Common surgeries include penile amputation, castration, and ovario-vaginal-hysterectomy or ovario-hysterectomy. Therapeutics used for these conditions are presented.

Anatomy and Disorders of the Oral Cavity of Ferrets and Other Exotic Companion Carnivores.

Exotic companion carnivores such as ferrets, skunks, fennec foxes, coatimundis, raccoons, and kinkajous presented in clinical practice share similar dental anatomy, function, and diseases. The domestic ferret serves as the representative species for this group with its anatomy, diseases, and conditions described in detail. Dog and cat guidelines for veterinary and home care seem to be relevant and applicable, including dental endodontic procedures. Annual or biannual dental examinations and prophylaxis are recommended. The most common dental and oral problems are tooth wear, plaque and calculus, teeth fractures, gingivitis and periodontitis, tooth loss, abscesses, oral ulceration, tonsillitis, and neoplasia.

Repeated measures study of weekly and daily cytomegalovirus shedding patterns in saliva and urine of healthy cytomegalovirus-seropositive children.

BACKGROUND: To better understand potential transmission risks from contact with the body fluids of children, we monitored the presence and amount of CMV shedding over time in healthy CMV-seropositive children. METHODS: Through screening we identified 36 children from the Atlanta, Georgia area who were CMV-seropositive, including 23 who were shedding CMV at the time of screening. Each child received 12 weekly in-home visits at which field workers collected saliva and urine. During the final two weeks, parents also collected saliva and urine daily. RESULTS: Prevalence of shedding was highly correlated with initial shedding status: children shedding at the screening visit had CMV DNA in 84% of follow-up saliva specimens (455/543) and 28% of follow-up urine specimens (151/539); those not shedding at the screening visit had CMV DNA in 16% of follow-up saliva specimens (47/303) and 5% of follow-up urine specimens (16/305). Among positive specimens we found median viral loads of 82,900 copies/mL in saliva and 34,730 copies/mL in urine (P=0.01), while the viral load for the 75th percentile was nearly 1.5 million copies/mL for saliva compared to 86,800 copies/mL for urine. Younger age was significantly associated with higher viral loads, especially for saliva (P<0.001). Shedding prevalence and viral loads were relatively stable over time. All children who were shedding at the screening visit were still shedding at least some days during weeks 11 and 12, and median and mean viral loads did not change substantially over time. CONCLUSIONS: Healthy CMV-seropositive children can shed CMV for months at high, relatively stable levels. These data suggest that behavioral prevention messages need to address transmission via both saliva and urine, but also need to be informed by the potentially higher risks posed by saliva and by exposures to younger children.

Captive marsupial nutrition.

Marsupials comprise an interesting group of mammals, which are increasingly being kept as pets. Few actual feeding trials have been published, although many anecdotal diets have years of usage with good success. Marsupials have dental and digestive tract adaptations that allow them to use specific niches in their environments. Knowing the diet in the wild is instrumental in designing diets used in captivity.

Ferret nutrition.

The domestic ferret (Mustela putorious furo) is a strict carnivore, also referred to as an obligate carnivore. Its dentition and gastrointestinal tract are adapted to a carnivorous diet. Its ancestor, the European polecat (Mustela putorius), feeds on birds and other small vertebrates. Domesticated ferrets have been fed mink feeds, cat foods, and now mostly subsist on commercial ferret diets formulated specifically to meet their needs.

Mycoplasmosis in ferrets.

We report an outbreak of severe respiratory disease associated with a novel Mycoplasma species in ferrets. During 2009-2012, a respiratory disease characterized by nonproductive coughing affected ≈8,000 ferrets, 6-8 weeks of age, which had been imported from a breeding facility in Canada. Almost 95% became ill, but almost none died. Treatments temporarily decreased all clinical signs except cough. Postmortem examinations of euthanized ferrets revealed bronchointerstitial pneumonia with prominent hyperplasia of bronchiole-associated lymphoid tissue. Immunohistochemical analysis with polyclonal antibody against Mycoplasma bovis demonstrated intense staining along the bronchiolar brush border. Bronchoalveolar lavage samples from 12 affected ferrets yielded fast-growing, glucose-fermenting mycoplasmas. Nucleic acid sequence analysis of PCR-derived amplicons from portions of the 16S rDNA and RNA polymerase B genes failed to identify the mycoplasmas but showed that they were most similar to M. molare and M. lagogenitalium. These findings indicate a causal association between the novel Mycoplasma species and the newly recognized pulmonary disease.

Rabbit respiratory system: clinical anatomy, physiology and disease.

Rabbits are obligate nose breathers due to their epiglottis positioned rostrally to the soft palate. Any obstruction within the nasal cavity will produce a respiratory wheeze with increased respiratory effort. Respiratory diseases are a major cause of morbidity and mortality in rabbits. This article focuses on these diseases and their causative pathogens.

Ferret respiratory system: clinical anatomy, physiology, and disease.

The upper and lower respiratory tracts of ferrets have several similarities to humans, and therefore have been used as a research model for respiratory function. This article describes the clinical anatomy and physiology, and common respiratory diseases of the ferret.

Emerging Ferret Diseases.

There are a number of newly described and emerging disease syndromes affecting the domestic ferret, and the purpose of this article is to make veterinarians aware of these diseases. A recently described systemic coronavirus infection appears to be a variant of the ferret enteric coronavirus and is currently termed "ferret infectious peritonitis." Disseminated immunopathologic myositis, aplastic anemia/bone marrow aplasia, acute hemorrhagic syndrome, and oral ulcerations are also described, although the exact etiologies for these diseases have yet to be determined. There appears to be at least 2 important amino acid metabolism deficiencies in ferrets: hindlimb weakness in older ferrets (L-carnitine) and cysteine urolithiasis. Ferrets have recently been found to be susceptible to H1N1 influenza, so knowledge regarding this zoonotic disease is essential for veterinarians working with these animals. A novel Mycoplasma spp. has also recently been identified in ferrets with chronic respiratory problems that originated from one breeding colony. Because these diseases are still being investigated, practitioners who treat a ferret patient exhibiting clinical signs consistent with any of the conditions mentioned are encouraged to contact people who are knowledgeable of that particular illness.

Parasites of captive nonhuman primates.

Parasites of captive nonhuman primates generally are more limited than those reported for field studies and in wild-caught primates. Captive primates include those in zoos, laboratory animal facilities, and private collections or pets. Primates kept indoors generally have few parasites, and those are easily eliminated. Outdoor housing presents problems in breaking life cycles of parasites, particularly those with invertebrate intermediate hosts. Decontamination of soils and substrates also makes total elimination of parasites nearly impossible. For outdoor-housed primates and those in social settings, control can be achieved through regular examination and appropriate administration of antiparasite medication. Because many of the parasites have zoonotic potential, practitioners must be vigilant and educate caretakers about the parasite life cycle and sanitation procedures.

Common procedures in hedgehogs, prairie dogs, exotic rodents, and companion marsupials.

Nondomesticated species are commonly being kept as companion animals. These include the African pygmy hedgehog (Atelerix albi-ventris), the North American black-tailed prairie dog (Cynomys lu-dovicianus), and exotic rodents such as the degu (Octodon degus)and duprasi or fat-tailed gerbil (Pachyuromys duprasi). Common companion marsupials include the sugar glider (Petaurus breviceps),Bennett's or Tammar (Dama) wallabies (Macropus rufogriseus rufo-griseus and Macropus eugenii, respectively), the Brazilian or South American gray short-tailed opossum (Monodelphis domestica), and the North American Virginia opossum (Didelphis virginiana). Although many of these animals are now bred domestically and are fairly docile when human-raised, they are essentially wild animals and hence have strong instincts to hide illness and pain.

Safety issues in the exotic pet practice.

Small animal practitioners are well versed in the potential zoonoses from dogs and cats. Although these account for the vast majority of documented cases of zoonotic disease in humans, there are documented as well as potential zoonotic diseases that the nontraditional companion animal is capable of transmitting. This article is a compilation of potential disease risks to veterinarians, staff, and owners of nontraditional companion animals. In addition, the article may serve as a training tool for veterinary practices.