De novo assembly and annotation of the North American bison (Bison bison) reference genome and subsequent variant identification.

Genomic tools have improved the ability to manage bison populations and enhanced efforts to conserve this iconic species. These tools have been particularly useful for detecting introgression of cattle genome within bison herds but are limited by the need to use the cattle genome as a surrogate for mapping reads. This complicates efforts to distinguish the species of origin of chromosomal segments in individual bison at the genomic level. An assembly (Bison_UMD1.0) based on 75X genome coverage by Illumina and 454 reads was generated using the MaSuRCA assembler, generating a 2.81 Gigbases de novo reference genome from American bison. Comparison of bison and domestic cattle references identified 28 443 364 single nucleotide variants and 2 627 645 insertions/deletions distinguishing the species. Sequence alignment of an additional 12 modern bison samples and two historic bison samples to domestic cattle and bison references provides a dataset of genomic variants defining the different species and within-species variation. This first annotated draft assembly represents a resource for the management and conservation of bison, as well as a means to study the effects on the genome of interspecies hybridization. The comparisons of historical bison sequences with the new bison reference identified genomic differences between modern and pre-population bottleneck bison. The results support the application of genomics to enhance future research on disease, the establishment of satellite conservation herds and insight into bison and cattle speciation. The first genome assembly for bison and dataset provides a foundation that can be built upon as genetic technologies improve over the years.

The impact of a post-operative clinical care pathway on head and neck microvascular free tissue transfer outcomes.

OBJECTIVE: To study the impact of a clinical care pathway and computerised order set on short-term post-operative outcomes for patients undergoing head and neck free tissue transfer. METHODS: In this retrospective cohort study, patients who underwent head and neck free tissue transfer by a single reconstructive surgeon between January 2007 and July 2009 were assigned to one of two cohorts based on the timing of their surgery: pre- or post-clinical care pathway implementation. Measured outcomes included peri-operative complications and mortality, length of hospital stay and costs, unplanned reoperations, and readmissions within 30 days of discharge. RESULTS: The pre-clinical care pathway cohort included 81 patients and the post-clinical care pathway cohort comprised 46. Implementation of the clinical care pathway was associated with decreased variability in length of hospital stay (median (interquartile range) = 8 (6, 11) vs 7 (6, 9) days). The post-clinical care pathway cohort also had a significantly lower unplanned reoperation rate (15.2 vs 35.8 per cent, p = 0.01). CONCLUSION: A clinical care pathway is a successful means of standardising and improving complex patient care. In this study, care pathway implementation in head and neck free tissue transfer patients improved efficiency and the quality of patient care.

Using 3 Tesla magnetic resonance imaging in the pre-operative evaluation of tongue carcinoma.

OBJECTIVE: This study aimed to evaluate the role of 3 Tesla magnetic resonance imaging in predicting tongue tumour thickness via direct and reconstructed measures, and their correlations with corresponding histological measures, nodal metastasis and extracapsular spread. METHODS: A prospective study was conducted of 25 patients with histologically proven squamous cell carcinoma of the tongue and pre-operative 3 Tesla magnetic resonance imaging from 2009 to 2012. RESULTS: Correlations between 3 Tesla magnetic resonance imaging and histological measures of tongue tumour thickness were assessed using the Pearson correlation coefficient: r values were 0.84 (p < 0.0001) and 0.81 (p < 0.0001) for direct and reconstructed measurements, respectively. For magnetic resonance imaging, direct measures of tumour thickness (mean ± standard deviation, 18.2 ± 7.3 mm) did not significantly differ from the reconstructed measures (mean ± standard deviation, 17.9 ± 7.2 mm; r = 0.879). Moreover, 3 Tesla magnetic resonance imaging had 83 per cent sensitivity, 82 per cent specificity, 82 per cent accuracy and a 90 per cent negative predictive value for detecting cervical lymph node metastasis. CONCLUSION: In this cohort, 3 Tesla magnetic resonance imaging measures of tumour thickness correlated highly with the corresponding histological measures. Further, 3 Tesla magnetic resonance imaging was an effective method of detecting malignant adenopathy with extracapsular spread.

The safety and efficacy of pediatric lingual tonsillectomy.

OBJECTIVE: Lingual tonsillar hypertrophy is recognized as a cause of persistent obstructive sleep apnea (OSA) after adenotonsillectomy in children. However, little has been reported regarding the complications, postoperative course and effectiveness of lingual tonsillectomy (LT). Our objective was to review the safety and effectiveness of LT in children. METHODS: Retrospective review of children undergoing LT from January 2009 to December 2015 at a tertiary children's hospital. Complications, postoperative course and polysomnographic (PSG) outcomes were recorded for all patients. RESULTS: We identified 92 children (mean age = 8.6 years, 50% female) who underwent LT; 43.5% had a syndromic diagnosis. The most common complications were emergency department presentation for bleeding (4.4%) and poor oral intake (3.3%). The readmission rate was 4.4% including 2 children (2.2%) who required operative control of hemorrhage. No children required unplanned reintubation or ICU admission. In children with PSG data (n = 18), the median apnea-hypopnea index (AHI) decreased from 8.5 to 3.8 events/hour (p = 0.022) and the median obstructive AHI (oAHI) decreased from 8.3 to 3.1 events/hour (p = 0.021). In addition, the oxygen saturation nadir increased from 83.8% to 89.0% (p = 0.0007). After surgery the percentage of patients with oAHI<5 events/hour increased from 27.8% to 61.1% (p = 0.08). CONCLUSIONS: Readmission and bleeding rates after lingual tonsillectomy in children were similar to that seen with tonsillectomy. Polysomnographic data showed that lingual tonsillectomy resulted in a significant reduction of both AHI and oAHI with a postoperative oAHI <5 achieved in 61% of patients.

Correlation of MRI Brain Injury Findings with Neonatal Clinical Factors in Infants with Congenital Diaphragmatic Hernia.

BACKGROUND AND PURPOSE: Infants with congenital diaphragmatic hernia are reported to have evidence of brain MR imaging abnormalities. Our study aimed to identify perinatal clinical factors in infants with congenital diaphragmatic hernia that are associated with evidence of brain injury on MR imaging performed before hospital discharge. MATERIALS AND METHODS: MRIs performed before hospital discharge in infants with congenital diaphragmatic hernia were scored for brain injury by 2 pediatric neuroradiologists. Perinatal variables and clinical variables from the neonatal intensive care unit stay were analyzed for potential associations with brain MR imaging findings. RESULTS: Fifty-three infants with congenital diaphragmatic hernia (31 boys) were included. At least 1 abnormality was seen on MR imaging in 32 infants (60%). The most common MR imaging findings were enlarged extra-axial spaces (36%), intraventricular hemorrhage (23%), ventriculomegaly (19%), white matter injury (17%), and cerebellar hemorrhage (17%). The MR imaging brain injury score was associated with extracorporeal membrane oxygenation (P = .0001), lack of oral feeding at discharge (P = .012), use of inotropes (P = .027), and gastrostomy tube placement before hospital discharge (P = .024). The MR imaging brain injury score was also associated with a large diaphragmatic defect size (P = .011). CONCLUSIONS: Most infants with congenital diaphragmatic hernia have at least 1 abnormality identified on MR imaging of the brain performed before discharge. The main predictors of brain injury in this population are a requirement for extracorporeal membrane oxygenation, large diaphragmatic defect size, and lack of oral feeding at discharge.

Donor human milk largely replaces formula-feeding of preterm infants in two urban hospitals.

OBJECTIVE: To determine acceptance of donor human milk (DM) for feeding preterm infants and whether offering DM, alters mothers' milk (MM) feeding. STUDY DESIGN: Infant feeding data were collected from medical records of 650 very preterm infants enrolled between 2006-2011 in two hospital level III neonatal intensive care units (NICUs) in Cincinnati, Ohio. The study was conducted during the implementation of a program offering 14 days of DM. RESULT: From 2006-2011, any DM use increased from 8 to 77% of infants, largely replacing formula for the first 2 weeks of life; provision of MM did not change. DM was more likely to be given in the first 2 weeks of life, if infants never received MM or were >1000 g birth weight, but DM use did not differ by sociodemographic factors. CONCLUSION: Offering DM dramatically increased human milk feeding and decreased formula use, but did not alter MM feeding in hospital.

Fetal and postnatal brain MRI in premature infants with twin-twin transfusion syndrome.

OBJECTIVE: To describe the findings on fetal and postnatal magnetic resonance imaging (MRI) in premature infants with twin-twin transfusion syndrome (TTTS) and to determine whether currently used staging systems and other fetal and postnatal factors correlate with brain injury in this population. STUDY DESIGN: We performed a prospective study of 22 premature infants with TTTS whose mothers had fetal MRIs. Postnatal brain MRI was performed at term equivalent age (38 to 44 weeks) and medical records were reviewed. Brain injury was scored on fetal and postnatal MRIs using an injury scale incorporating hemorrhagic and nonhemorrhagic injury. RESULT: The median (range) gestational age (GA) was 31 weeks (26 to 35) and birth weight (BW) was 1296 g (762 to 2330). In all, 5/22 patients (23%) had brain injury seen on fetal MRI and 15/22 patients (68%) had brain injury seen on postnatal MRI. Quintero stage was the only predictor variable that was significantly correlated with the total brain injury score (P=0.05). CONCLUSION: Postnatal brain injury in premature infants with TTTS is correlated with Quintero stage. GA and BW are not predictive of brain injury in this cohort of infants.

The lost art of intubation: assessing opportunities for residents to perform neonatal intubation.

OBJECTIVE: The objective of this study is to assess the opportunities afforded to and competence of pediatric residents in performing neonatal endotracheal intubations. STUDY DESIGN: The records of all intubations performed on neonates over a 3-year period at a university-based birthing hospital were reviewed to assess the relationships between outcomes, types of providers and the setting of intubations. RESULT: A total of 785 attempts were made during 362 intubations. Pediatric residents were given the opportunity to intubate 38% of the cohort (n=137) and were successful on 21% of the attempts. Residents were more likely to perform intubation in the neonatal intensive care unit (vs delivery room; P<0.001), in non-emergency situations (P<0.001), and on older (P<0.001) and larger (P=0.07) infants. CONCLUSION: Opportunities for residents to intubate neonates were few and their success rate was low. In the current care paradigm, it is doubtful if trainees can be sufficiently skilled in endotracheal intubation during residency. Residents that plan to pursue procedure-intensive subspecialties may benefit from other models for training.

Hospital and neurodevelopmental outcomes of extremely low-birth-weight infants with necrotizing enterocolitis and spontaneous intestinal perforation.

OBJECTIVE: We sought to determine the incidence of necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) in surviving extremely low-birth-weight (ELBW, <1000 g birth weight) infants and to establish the impact of NEC on outcomes by hospital discharge and at 18 to 22 months adjusted age in a large, contemporary, population-based practice. STUDY DESIGN: Hospital outcome data for all ELBW infants born in the greater Cincinnati region from 1998 to 2009 were extracted from the National Institute of Child Health Neonatal Research Network Database. Neurodevelopmental outcome at 18 to 22 months was assessed using Bayley Scales of Infant Development-II scores for Mental Developmental Index and Psychomotor Developmental Index. Multivariable logistic regression was used and adjusted odds ratios reported to control for confounders. RESULT: From 1998 to 2009, ELBW infants accounted for 0.5% of the 352 176 live-born infants in greater Cincinnati. The incidence of NEC was 12%, with a 50% case-fatality rate. Death before discharge, morbid complications of prematurity and neurodevelopmental impairment were all increased among infants diagnosed with NEC. Infants with surgical NEC and SIP had a higher incidence of death, but long-term neurodevelopmental outcomes were not different comparing surviving ELBW infants with medical NEC, surgical NEC and SIP. CONCLUSION: Although ELBW infants comprise a very small proportion of live-born infants, those who develop NEC and SIP are at an increased risk for death, morbid complications of prematurity and neurodevelopmental impairment. No significant differences in neurodevelopmental outcomes were observed between the medical and surgical NEC and SIP groups.

Maternal and neonatal factors impacting response to methadone therapy in infants treated for neonatal abstinence syndrome.

OBJECTIVE: To identify maternal and neonatal factors that impact response to methadone therapy for neonatal abstinence syndrome. STUDY DESIGN: This is a retrospective review of 128 infants that received pharmacotherapy for opiate withdrawal to identify factors associated with favorable response to methadone therapy. Maternal and neonatal data were analyzed with univariate statistics and multivariate logistic regression. RESULT: Maternal methadone maintenance dose during pregnancy correlated with length of stay (P=0.009). There was an inverse correlation between the amount of mother's breast milk ingested and length of stay (ß=-0.03, P=0.02). Methadone was initiated later, tapered more rapidly and was more successful as monotherapy in preterm infants. Five percent of infants were admitted to hospital again for rebound withdrawal following reduction of breast milk intake. CONCLUSION: Severity of neonatal abstinence syndrome may be mitigated by titrating methadone to the lowest effective dose during pregnancy and by encouraging breast milk feeds, which should be weaned gradually.

Role of human milk in extremely low birth weight infants' risk of necrotizing enterocolitis or death.

OBJECTIVE: To determine the association between human milk (HM) intake and risk of necrotizing enterocolitis (NEC) or death among infants 401 to 1000 g birth weight. STUDY DESIGN: Analysis of 1272 infants in the National Institute of Child Health and Human Development Neonatal Network Glutamine Trial was performed to determine if increasing HM intake was associated with decreased risk of NEC or death. HM intake was defined as the proportion of HM to total intake, to enteral intake and total volume over the first 14 days. Known NEC risk factors were included as covariates in Cox proportional hazard analyses for duration of survival time free of NEC. RESULT: Among study infants, 13.6% died or developed NEC after 14 days. The likelihood of NEC or death after 14 days was decreased by a factor of 0.83 (95% confidence interval, CI 0.72, 0.96) for each 10% increase in the proportion of total intake as HM. Each 100 ml kg(-1) increase in HM intake during the first 14 days was associated with decreased risk of NEC or death (hazard ratio, HR 0.87 (95% CI 0.77, 0.97)). There appeared to be a trend towards a decreased risk of NEC or death among infants who received 100% HM as a proportion to total enteral intake (HM plus formula), although this finding was not statistically significant (HR 0.85 (95% CI 0.60, 1.19)). CONCLUSION: These data suggest a dose-related association of HM feeding with a reduction of risk of NEC or death after the first 2 weeks of life among extremely low birth weight infants.

Familial and herd-level associations with paratuberculosis enzyme-linked immunosorbent assay status in beef cattle.

A cross-sectional study was performed to determine the odds of having a positive paratuberculosis ELISA result if the dam was ELISA positive in Texas beef cattle, adjusted for individual and herd-level risk factors for seropositivity. Texas beef cattle (n = 2,621) were tested for paratuberculosis by using a commercial ELISA and microbiologic culture of feces for Mycobacterium avium subsp. paratuberculosis (MAP). Pedigree data were collected to identify dam-and sire-offspring pairs. Bayesian mixed-effects logistic regression was used to estimate the odds of seropositivity associated with age, dam ELISA status, sire ELISA status, herd size, herd history of clinical paratuberculosis, within-herd seroprevalence, within-herd fecal MAP prevalence, and within-herd fecal non-MAP Mycobacterium spp. prevalence. Herd of residence was included as a random effect to account for the correlation of observations within the same herd. Statistically probable associations were observed between ELISA status and herd fecal MAP prevalence [OR (odds ratio) 1.28 per 1% increase; P < 0.001] and herd seroprevalence (OR 1.21 per 1% increase; P < 0.001). The association with dam ELISA status was small (OR 1.35) and not highly probable (P = 0.69). Results indicate that use of dam ELISA status to make culling decisions in beef cattle may not improve the success of paratuberculosis control programs. Alternative strategies may be more effective for reducing the odds of seropositivity.

When is the vestibular aqueduct enlarged? A statistical analysis of the normative distribution of vestibular aqueduct size.

BACKGROUND AND PURPOSE: The size of vestibular aqueducts (VAs) seen on CT studies varies. The current practice of calling a VA enlarged when it exceeds a certain threshold (eg, 1.5 mm at the midpoint) is arbitrary. Our hypothesis was that statistical analysis of the range of VA widths in a normal-hearing population would lead to a mathematic definition of the upper-limit-of-normal VA width. MATERIALS AND METHODS: The VA midpoint and opercular widths were measured in 73 children with normal hearing. Statistical analysis yielded values of the 99 th, 97.5th, 95th, 90th, 75th, and 50th percentiles for this normal distribution. RESULTS: The upper-limit-of-normal (95th percentile) values for the VA midpoint and opercular widths were 0.9 and 1.9 mm, respectively. The VAs with greater widths may reasonably be considered enlarged. CONCLUSION: The VAs with midpoint or opercular widths of 1.0 and 2.0 mm or greater, respectively, are enlarged.

Detection of mitochondrial DNA from domestic cattle in bison on Santa Catalina Island.

In 1924, 14 American bison (Bison bison) were introduced to Santa Catalina Island, California and sporadically supplemented thereafter with additional animals. To reduce the herd and its impact on native vegetation, over 2000 animals have been exported during the past four decades. Today, the herd is estimated to contain around 250 individuals. Genetic analysis was performed on 98 animals removed from the island in 2004. Forty-four samples (45%) had domestic cattle mitochondrial DNA (mtDNA), 12 (12%) had previously reported bison haplotypes and 42 (43%) had a new haplotype differing by one base pair from a previously reported bison haplotype. A complement of five restriction enzymes was found to be useful in identifying bison with domestic cattle mtDNA.

Valence and magnetic ordering in intermediate valence compounds: TmSe versus SmB(6).

The intermediate valence systems TmSe and SmB(6) have been investigated up to 16 and 18 GPa by ac microcalorimetry with a pressure (p) tuning realized in situ at low temperature. For TmSe, the transition from an antiferromagnetic insulator for p<3 GPa to an antiferromagnetic metal at higher pressure has been confirmed. A drastic change in the p variation of the Néel temperature (T(N)) is observed at 3 GPa. In the metallic phase (p>3 GPa), T(N) is found to increase linearly with p. A similar linear p increase of T(N) is observed for the quasitrivalent compound TmS, which is at ambient pressure equivalent to TmSe at p∼7 GPa. In the case of SmB(6) long range magnetism has been detected above p∼8 GPa, i.e. at a pressure slightly higher than the pressure of the insulator to metal transition. However a homogeneous magnetic phase occurs only above 10 GPa. The magnetic and electronic properties are related to the renormalization of the 4f wavefunction either to the divalent or the trivalent configurations. As observed in SmS, long range magnetism in SmB(6) occurs already far below the pressure where a trivalent Sm(3+) state will be reached. It seems possible to describe roughly the physical properties of the intermediate valence equilibrium by assuming formulae for the Kondo lattice temperature depending on the valence configuration. Comparison is also made with the appearance of long range magnetism in cerium and ytterbium heavy fermion compounds.

GJB2 mutations and additional disabilities in a pediatric cochlear implant population.

BACKGROUND: Children with severe to profound sensorineural hearing loss due to GJB2 mutations have often been deemed good cochlear implant candidates. Studies on children with GJB2 mutations and cochlear implants have typically excluded children with additional disabilities. OBJECTIVE: To investigate the presence of additional disabilities among children with and without GJB2 mutations in a cochlear implant population. METHODS: A retrospective chart review was performed of children with non-syndromic sensorineural hearing loss (SNHL) who received a cochlear implant between 1993 and 2004. RESULTS: Among 108 children within the cochlear implant database; 46 patients met the inclusion criteria of idiopathic non-syndromic hearing loss. Sixteen children had GJB2 mutations, 12 were GJB2 negative, and 17 did not receive GJB2 testing but had no other identifiable etiology or risk factor contributing to hearing loss. The proportion of children with additional disabilities that would affect either pre-operative assessments or post-operative results in the GJB2 positive group was 44% compared to 33% of children in the GJB2 negative. Additional disabilities were present in 41% of the children who did not receive GJB2 testing. The disabilities in the GJB2 positive group included specific learning disability, apraxia, epileptiform aphasia, attention deficit disorder, global developmental delay, and gross motor delay. The GJB2 negative and those children not receiving GJB2 testing had motor delays, language delay, autism, specific learning disability, and attention deficit disorder. The proportion of children with at least 6 months CI use who relied on oral communication was 62% in the GJB2 positive group, 66% in the GJB2 negative group, and 38% in the untested group. A majority of the genetic alleles were 35delG (81%) and 10 of 16 (63%) patients with GJB2 mutations were homozygous 35delG. The rate of developmental diagnoses was similar in patients with homozygous GJB2 compared to compound heterozygous genotypes. CONCLUSIONS: The presence of biallelic GJB2 mutations does not rule out non-hearing related disorders that can have an effect on speech, language and learning. Forty-four percent of children with GJB2 mutations had other conditions that could directly affect pre-implant evaluation and post-implant performance. This rate is similar to the reported prevalence among the overall population of children with hearing loss. All children should have a comprehensive evaluation of development and behavior regardless of the etiology of hearing loss.

Relationship between transducer type and low-frequency hearing loss for patients with ventilation tubes.

OBJECTIVE: To determine the relationship between the type of transducer used to perform pure-tone audiometry and the appearance of low-frequency hearing loss at 250Hz and 500Hz for patients with ventilation tubes. METHODS: Air conduction thresholds at 250Hz and 500Hz were measured using Telephonics TDH-49 supra-aural headphones and EARTONE 3-A insert earphones for patients with normal ears (N=16) and patients with ventilation tubes (N=114). Tympanometry was performed on each patient prior to audiometric testing. Audiometric test results obtained in normal ears were compared to results for patients with ventilation tubes. For analysis, the ventilation tube patients were separated into two groups, representative of ventilation tube type. RESULTS: Audiometric results obtained using the two transducer types at 250Hz and 500Hz revealed significant differences in threshold for patients with ventilation tubes. Thresholds obtained using insert earphones were generally worse than thresholds obtained using supra-aural headphones for this group. On average, difference in threshold was 14.15dB worse with insert earphones at 250Hz and 9.75dB worse with insert earphones at 500Hz for patients with Sheehy tubes. Average difference in threshold for patients with Donaldson tubes was 13.93dB worse with insert earphones at 250Hz and 8.93dB worse with insert earphones at 500Hz. In addition, thresholds were more variable for patients with ventilation tubes than normal ears at 500Hz. There were no significant differences in threshold for normal ears using both transducers. CONCLUSIONS: When performing pure-tone audiometry, choice of transducer can influence the accurate identification of a low-frequency hearing loss in patients with ventilation tubes. Low-frequency thresholds were generally worse using insert-style earphones to test subjects with tubes, resulting in the apparent identification of a hearing loss. However, with supra-aural headphones, no low-frequency hearing loss existed. There were no significant differences in threshold values using either transducer in normal ears.

High-pressure ground state of SmB6: electronic conduction and long range magnetic order.

High-pressure 149Sm nuclear forward scattering of synchrotron radiation and specific heat measurements have been performed on the intermediate valent Kondo insulator SmB6. The results show that at a critical pressure p(c) approximately = 6 GPa, where the charge gap closes, a first order transition occurs to a magnetically ordered state, which shows typical features of trivalent samarium compounds. The similarity with SmS stresses the role of local correlations and gives important insight into the debate on the local or itinerant character of the f electrons in heavy fermion systems.

Bison PRNP genotyping and potential association with Brucella spp. seroprevalence.

The implication that host cellular prion protein (PrP(C)) may function as a cell surface receptor and/or portal protein for Brucella abortus in mice prompted an evaluation of nucleotide and amino acid variation within exon 3 of the prion protein gene (PRNP) for six US bison populations. A non-synonymous single nucleotide polymorphism (T50C), resulting in the predicted amino acid replacement M17T (Met --> Thr), was identified in each population. To date, no variation (T50; Met) has been detected at the corresponding exon 3 nucleotide and/or amino acid position for domestic cattle. Notably, 80% (20 of 25) of the Yellowstone National Park bison possessing the C/C genotype were Brucella spp. seropositive, representing a significant (P = 0.021) association between seropositivity and the C/C genotypic class. Moreover, significant differences in the distribution of PRNP exon 3 alleles and genotypes were detected between Yellowstone National Park bison and three bison populations that were either founded from seronegative stock or previously subjected to test-and-slaughter management to eradicate brucellosis. Unlike domestic cattle, no indel polymorphisms were detected within the corresponding regions of the putative bison PRNP promoter, intron 1, octapeptide repeat region or 3'-untranslated region for any population examined. This study provides the first evidence of a potential association between nucleotide variation within PRNP exon 3 and the presence of Brucella spp. antibodies in bison, implicating PrP(C) in the natural resistance of bison to brucellosis infection.