Search

Objectives/hypothesis Radiation-associated sarcomas of the head and neck (RASHN) are known but rare sequelae after radiation for squamous cell carcinoma. The purpose of this study was to characterize RASHN, estimate the risk of RASHN in head and neck squamous cell patients after therapeutic radiation, and compare their survival to that of patients with de novo sarcomas of the head and neck (dnSHN). Study design Retrospective database analysis. Methods RASHN and dnSHN cases were collected from the Surveillance, Epidemiology, and End Results Database to identify risk factors and calculate incidence and latency. Survival was compared between RASHN and dnSHN. Results The risk of RASHN was 20.0 per 100,000 person-years. The average latency period was 124.2 months (range 38-329). The cumulative incidence of RASHN at 20 years was 0.13%. Oral cavity and oropharynx primaries demonstrate increased risk. Five-year overall survival of RASHN was 22.4% compared to 64.5% for dnSHN. Conclusions RASHN are confirmed to be rare. RASHN have poor overall survival and worse survival compared to dnSHN. The impact of intensity-modulated radiation therapy protocols on this risk is unknown. Modifiable risk factors of smoking and alcohol consumption continue to dwarf radiation therapy as risk factors of second primary head and neck cancers. Level of evidence 3 Laryngoscope, 2021.

Background: Reading comprehension is a complex process influenced by many factors. However, the abilities that are known to influence reading comprehension may not contribute equally for children with different levels of oral language. Aims: Here we examined the relationship of two factors known to influence reading comprehension (morphology and syntax) in a group of children who varied in their levels of oral vocabulary. Method: Two hundred seventy-three typically developing Spanish-speaking fourth graders were assessed on non-verbal intelligence, word and pseudoword reading, oral vocabulary, morphological awareness and syntax, along with reading comprehension ability. Standardised oral language scores within this group ranged from the first to the 99th percentile. Mediated multiple regression with moderation was used to assess (1) whether the influence of oral vocabulary on reading comprehension was mediated by decoding, morphology or syntax and (2) whether the effects of syntax on reading comprehension varied as a function of oral vocabulary levels. Results: There was a direct positive relationship between vocabulary and reading comprehension, and this was mediated by word reading and syntax, but not by pseudoword reading or morphology. Furthermore, the relation between syntax and reading comprehension was moderated by oral vocabulary such that the strength of this relationship diminished as oral vocabulary levels increased. Conclusions: These findings suggest that longitudinal research is necessary to explore the possibility that a syntax intervention might be beneficial for readers with low oral vocabulary. FEDER 2014-2020 Consejería de Economía, Conocimiento, Empresas y Universidad US-1264792

Purpose Privately insured patients with head and neck cancer (HNC) typically have better outcomes; however, differential outcome among Medicaid versus the uninsured is unclear. We aimed to describe outcome disparities among HNC patients uninsured versus on Medicaid. Methods A cohort of 18-64-year-old adults (n = 57 920) with index HNC from the Surveillance, Epidemiology, and End Results 18 database (2007-2015) was analyzed using Fine and Gray multivariable competing risks proportional hazards models for HNC-specific mortality. Results Medicaid (sdHR = 1.65, 95% CI 1.58, 1.72) and uninsured patients (sdHR = 1.55, 95% CI 1.46, 1.65) had significantly greater mortality hazard than non-Medicaid patients. Medicaid patients had increased HNC mortality hazard than those uninsured. Conclusion Compared with those uninsured, HNC patients on Medicaid did not have superior survival, suggesting that there may be underlying mechanisms/factors inherent in this patient population that could undermine access to care benefits from being on Medicaid.

Glycaemic control is a key issue in the care of people with diabetes mellitus (DM). Periodontal disease is the inflammation and destruction of the underlying supporting tissues of the teeth. Some studies have suggested a bidirectional relationship between glycaemic control and periodontal disease. This review updates the previous version published in 2010.The objective is to investigate the effect of periodontal therapy on glycaemic control in people with diabetes mellitus.We searched the following electronic databases: the Cochrane Oral Health Group Trials Register (to 31 December 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library 2014, Issue 11), MEDLINE via OVID (1946 to 31 December 2014), EMBASE via OVID (1980 to 31 December 2014), LILACS via BIREME (1982 to 31 December 2014), and CINAHL via EBSCO (1937 to 31 December 2014). ZETOC (1993 to 31 December 2014) and Web of Knowledge (1990 to 31 December 2014) were searched for conference proceedings. Additionally, two periodontology journals were handsearched for completeness, Annals of Periodontology (1996 to 2003) and Periodontology 2000 (1993 to 2003). We searched the US National Institutes of Health Trials Registry (http://clinicaltrials.gov) and the WHO Clinical Trials Registry Platform for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases.We searched for randomised controlled trials (RCTs) of people with type 1 or type 2 DM (T1DM/T2DM) with a diagnosis of periodontitis. Interventions included periodontal treatments such as mechanical debridement, surgical treatment and antimicrobial therapy. Two broad comparisons were proposed:1. periodontal therapy versus no active intervention/usual care;2. periodontal therapy versus alternative periodontal therapy.For this review update, at least two review authors independently examined the titles and abstracts retrieved by the search, selected the included trials, extracted data from included trials and assessed included trials for risk of bias.Our primary outcome was blood glucose levels measured as glycated (glycosylated) haemoglobin assay (HbA1c).Our secondary outcomes included adverse effects, periodontal indices (bleeding on probing (BOP), clinical attachment level (CAL), gingival index (GI), plaque index (PI) and probing pocket depth (PPD)), cost implications and diabetic complications.We included 35 studies (including seven from the previous version of the review), which included 2565 participants in total. All studies used a parallel RCT design, and 33 studies (94%) only targeted T2DM patients. There was variation between studies with regards to included age groups (ages 18 to 80), duration of follow-up (3 to 12 months), use of antidiabetic therapy, and included participants' baseline HbA1c levels (from 5.5% to 13.1%).We assessed 29 studies (83%) as being at high risk of bias, two studies (6%) as being at low risk of bias, and four studies (11%) as unclear. Thirty-four of the studies provided data suitable for analysis under one or both of the two comparisons.Comparison 1: low quality evidence from 14 studies (1499 participants) comparing periodontal therapy with no active intervention/usual care demonstrated that mean HbA1c was 0.29% lower (95% confidence interval (CI) 0.48% to 0.10% lower) 3 to 4 months post-treatment, and 0.02% lower after 6 months (five studies, 826 participants; 95% CI 0.20% lower to 0.16% higher).Comparison 2: 21 studies (920 participants) compared different periodontal therapies with each other. There was only very low quality evidence for the multiple head-to-head comparisons, the majority of which were unsuitable to be pooled, and provided no clear evidence of a benefit for one periodontal intervention over another. We were able to pool the specific comparison between scaling and root planing (SRP) plus antimicrobial versus SRP and there was no consistent evidence that the addition of antimicrobials to SRP was of any benefit to delivering SRP alone (mean HbA1c 0.00% lower: 12 studies, 450 participants; 95% CI 0.22% lower to 0.22% higher) at 3-4 months post-treatment, or after 6 months (mean HbA1c 0.04% lower: five studies, 206 patients; 95% CI 0.41% lower to 0.32% higher).Less than half of the studies measured adverse effects. The evidence was insufficient to conclude whether any of the treatments were associated with harm. No other patient-reported outcomes (e.g. quality of life) were measured by the included studies, and neither were cost implications or diabetic complications.Studies showed varying degrees of success with regards to achieving periodontal health, with some showing high levels of residual inflammation following treatment. Statistically significant improvements were shown for all periodontal indices (BOP, CAL, GI, PI and PPD) at 3-4 and 6 months in comparison 1; however, this was less clear for individual comparisons within the broad category of comparison 2.There is low quality evidence that the treatment of periodontal disease by SRP does improve glycaemic control in people with diabetes, with a mean percentage reduction in HbA1c of 0.29% at 3-4 months; however, there is insufficient evidence to demonstrate that this is maintained after 4 months.There was no evidence to support that one periodontal therapy was more effective than another in improving glycaemic control in people with diabetes mellitus.In clinical practice, ongoing professional periodontal treatment will be required to maintain clinical improvements beyond 6 months. Further research is required to determine whether adjunctive drug therapies should be used with periodontal treatment. Future RCTs should evaluate this, provide longer follow-up periods, and consider the inclusion of a third 'no treatment' control arm.Larger, well conducted and clearly reported studies are needed in order to understand the potential of periodontal treatment to improve glycaemic control among people with diabetes mellitus. In addition, it will be important in future studies that the intervention is effective in reducing periodontal inflammation and maintaining it at lowered levels throughout the period of observation.

BACKGROUND The current study was conducted to determine whether the incidence of late-stage head and neck cancer (HNC) is decreasing and to estimate the risk of late-stage HNC diagnosis based on race and sex. METHODS Age-adjusted incidence rates for patients aged ≥18 years with stage IV HNC were abstracted from the Surveillance, Epidemiology, and End Results database (2004-2015). Rates were stratified by race, sex, and age. Joinpoint regression estimated annual percent changes (APCs) in rates over time, and logistic regression estimated adjusted odds ratios (aORs). RESULTS There were 57,118 patients with stage IV HNC in the current study cohort, with an average age of 61.9 years. From 2004 to 2015, the age-adjusted incidence rates for stage IV HNC significantly increased by 26.1% (6.11 per 100,000 person-years in 2004 to 7.70 per 100,000 person-years in 2015). White and Asian/Pacific Islander/American Indian/Alaska Native patients had significant increases in incidence (APC for white patients, 3.03 [P

OBJECTIVE To describe comorbidity burden and nonclinical factors associated with all-cause mortality of sinonasal cancer in the United States. METHODS The National Cancer Database (2004-2013) was queried for adult cases of sinonasal cancer (n = 10,518). Outcome of interest was all-cause mortality. Independent variables included comorbidity score and nonclinical factors such as age, gender, race, facility type, distance to facility, insurance, and income. Survival analysis was conducted via multivariable extended Cox regression with Heaviside adjustments. RESULTS Patients were mostly (79%), male (61%), and mean age of diagnosis was 63.5 years. Approximately one in five patients (18.7%) had a major comorbid condition (Charlson-Deyo score ≥ 1) at diagnosis. After adjusting for clinical factors, increasing comorbidity score was associated with a corresponding increase in hazard of mortality (aHR comorbidity score of 1 = 1.25; 95% CI, 1.16, 1.35), (aHR score of 2+ = 1.61; 95%, CI 1.41, 1.83). Hazard of mortality was also associated with being male (aHR = 1.11; 95% CI, 1.04, 1.17); black (aHR = 1.13, 95% CI, 1.03, 1.24); uninsured (aHR = 1.45; 95% CI, 1.25, 1.68) or on Medicaid (aHR = 1.50; 95% CI, 1.33, 1.69); residence in zip codes with lower median income quartile (aHR

Objectives Incidence trends and outcomes of head and neck cancer (HNC) among female patients are not well understood. The objective of this study was to estimate incidence trends and quantify the association between health insurance status, stage at presentation, and survival among females with HNC. Study design Retrospective cohort study. Methods The Surveillance, Epidemiology, and End Results database (2007-2014) was queried for females aged ≥18 years diagnosed with a malignant primary head and neck cancer (HNC) (n = 18,923). Incidence trends for stage at presentation were estimated using Joinpoint regression analysis. The association between health insurance status and stage at presentation on overall and disease-specific survival was estimated using Fine and Gray proportional hazards models. Results Incidence of stage IV HNC rose by 1.24% from 2007 to 2014 (annual percent change = 1.24, 95% CI 0.30, 2.20). Patients with Medicaid (adjusted odds ratio [aOR] = 1.59, 95% confidence interval [CI] 1.45, 1.74) and who were uninsured (aOR = 1.73, 95% CI 1.47, 2.04) were more likely to be diagnosed with advanced stage (stages III/IV) HNC. Similarly, patients with Medicaid (adjusted hazard ratio [aHR] = 1.47, 95% CI 1.38, 1.56) and who were uninsured (aHR =1.45, 95% CI 1.29, 1.63) were more likely to die from any cause compared to privately insured patients. Medicaid (aHR = 1.34, 95% CI 1.24, 1.44) and uninsured (aHR = 1.41, 95% CI 1.24, 1.60) patients also had a greater hazard of HNC-specific deaths compared to privately insured patients. Conclusions Incidence of advanced-stage presentation for female HNC patients in the United States has increased significantly since 2007, and patients who are uninsured or enrolled in Medicaid are more likely to present with late stage disease and die earlier. Level of evidence NA Laryngoscope, 130:385-391, 2020.

While there are a growing number of cancer survivors, this population is at increased risk of developing second primary malignancies (SPMs). We described the incidence, most common tumor sites, and trends in burden of SPM among survivors of the most commonly diagnosed smoking-related cancers. The current study was a population-based study of patients diagnosed with a primary malignancy from the top 10 smoking-related cancer sites between 2000 and 2014 from Surveillance, Epidemiology, and End Results data. SPM risks were quantified using standardized incidence ratios (SIRs) and excess absolute risks (EARs) per 10,000 person-years at risk (PYR). Trends in the burden of SPM were assessed using Joinpoint regression models. A cohort of 1,608,607 patients was identified, 119,980 (7.5%) of whom developed SPM (76% of the SPMs were smoking-related). The overall SIR of developing second primary malignancies was 1.51 (95% CI, 1.50-1.52) and the EAR was 73.3 cases per 10,000 PYR compared to the general population. Survivors of head and neck cancer had the highest risk of developing a SPM (SIR = 2.06) and urinary bladder cancer had the highest excess burden (EAR = 151.4 per 10,000 PYR). The excess burden of SPM for all smoking-related cancers decreased between 2000 and 2003 (annual percentage change [APC] = -13.7%; p = 0.007) but increased slightly between 2003 and 2014 (APC = 1.6%, p = 0.032). We show that 1-in-12 survivors of smoking-related cancers developed an SPM. With the significant increase in the burden of SPM from smoking-related cancers in the last decade, clinicians should be cognizant of long-term smoking-related cancer risks among these patients as part of their survivorship care plans.

OBJECTIVES/HYPOTHESIS To 1) examine the characteristics of patients who develop second primary malignancies (SPMs) from an index human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) and HPV-unrelated HNSCC and to 2) compare overall survival between those with HPV-related and HPV-unrelated index HNSCC among patients who develop SPM. STUDY DESIGN Retrospective cohort analysis. METHODS A retrospective study was conducted of 113,259 patients who were diagnosed with HNSCC from 2000 to 2014. SPM was defined as the first subsequent primary cancer occurring at least 2 months after index cancer diagnosis, and HPV-relatedness was based on whether patients' index HNSCC was potentially HPV-related or HPV-unrelated. Multivariable Fine and Gray (FG) competing-risks regression models were used to estimate factors associated with risk of SPM by HPV-relatedness. Among patients with SPM, an adjusted Cox proportional hazards (PH) regression model was used to assess the association between HPV-relatedness and survival. RESULTS Approximately 13,900 patients (12.3%) developed SPM. In the FG model, patients with HPV-unrelated HNSCC had a 15% higher risk of developing SPM (adjusted hazard ratio: 1.15, 95% confidence interval: 1.10-1.20) than those with potentially HPV-related HNSCC, but the same characteristics were associated with SPM development. In the Cox PH model, patients with SPM whose index HNSCC was HPV-unrelated had higher risk of death than those whose index HNSCC was potentially HPV-related (adjusted hazard ratio: 1.06; 95% confidence interval: 1.02-1.11). CONCLUSIONS Patients with HPV-unrelated HNSCC have a higher risk of SPM development than do those with HPV-related HNSCC. Effective secondary disease-prevention strategies should be established to improve long-term patient outcomes. LEVEL OF EVIDENCE NA Laryngoscope, 129:1828-1835, 2019.

Objective To determine if there are differences in mortality from oral cavity squamous cell carcinoma (OCSCC) based on oral cavity (OC) subsites. Methods Using the Surveillance, Epidemiology, and End Results Program (SEER) 9 database, patients with sequence number 0 or 1 squamous cell OCSCC were analyzed by OC subsite for 5-year cause-specific mortality (CSM) from OCSCC. Proportional hazards regression determined the association between 5-year CSM and OC subsites while controlling for treatment modality, stage, and demographic characteristics using hazard ratios. Significance was set at alpha = 0.05. Results 20,647 OC patients were included in the regression analysis. The most commonly diagnosed sites were floor of mouth (34.4%) and oral tongue (34.3%). Floor of mouth, upper gum, and retromolar trigone were associated with lower CSM compared to oral tongue. Not receiving surgery and receiving radiation were associated with increased CSM, and CSM increased with cancer staging when distant or regional disease was compared to localized disease. Also, patients diagnosed at 60 years or older and black patients had increased CSM. Conclusion Among OCSCC patients, those with oral tongue cancer are more likely to experience CSM than patients with floor of mouth, upper gum, and retromolar trigone cancer. It is important to understand these mortality related differences in the management of OCSCC patients. Understanding subsite-specific mortality may benefit prognosis counseling of OCSCC patients and elicit subsite-directed research as a means to improve outcomes. Level of evidence NA Laryngoscope, 129:1400-1406, 2019.

Background Cancer survivors face psychosocial issues that increase their risk of suicide. This study examined the risk of suicide across cancer sites, with a focus on survivors of head and neck cancer (HNC). Methods The Surveillance, Epidemiology, and End Results 18-registry database (from 2000 to 2014) was queried for the top 20 cancer sites in the database, including HNC. The outcome of interest was suicide as a cause of death. The mortality rate from suicide was estimated for HNC sites and was compared with rates for 19 other cancer sites that were included in the study. Poisson regression was used to estimate adjusted rate ratios (aRRs) and 95% confidence intervals (CIs) for 1) HNC versus non-HNC sites (the other 19 cancer sites combined), and 2) HNC versus each individual cancer site. Models were stratified by sex, controlling for race, marital status, age, year, and stage at diagnosis. Results There were 404 suicides among 151,167 HNC survivors from 2000 to 2014, yielding a suicide rate of 63.4 suicides per 100,000 person-years. In this timeframe, there were 4493 suicides observed among 4219,097 cancer survivors in the study sample, yielding an incidence rate of 23.6 suicides per 100,000 person-years. Compared with survivors of other cancers, survivors of HNC were almost 2 times more likely to die from suicide (aRR, 1.97; 95% CI, 1.77-2.19). There was a 27% increase in the risk of suicide among HNC survivors during the period from 2010 to 2014 (aRR, 1.27; 95% CI, 1.16-1.38) compared with the period from 2000 to 2004. Conclusions Although survival rates in cancer have improved because of improved treatments, the risk of death by suicide remains a problem for cancer survivors, particularly those with HNC.

OBJECTIVE The literature on nasopharyngeal carcinoma survival in the United States has focused mostly on Whites or Asians and not much is known about survivorship in other minority racial and ethnic groups. We aimed to determine the disease-specific survival rate and prognostic factors for nasopharyngeal carcinoma survival across the minority United States population. DESIGN A retrospective cohort study. SETTING The Surveillance, Epidemiology and End Results (SEER) 13 database from 1992 to 2014 was queried for adult cases of nasopharyngeal carcinoma (n = 2549). PARTICIPANTS Eligible cases were Blacks, Hispanics, Asians/Pacific Islanders, American Indians/Alaska Natives; White patients were excluded. MAIN OUTCOMES MEASURE A multivariable competing risk survival analysis yielded hazard ratios (HR) for competing mortality and was used to identify independent prognostic factors for survival. RESULTS Non-Hispanic American Indians/Alaska Natives consistently had the worst cause-specific survival of any group and that non-Hispanic Asians/Pacific Islanders consistently had the best survival (P < 0.001). Even after adjusting for other poor prognostic factors in the study, including older age, keratinising histology, and lack of radiation treatment, non-Hispanic American Indians/Alaska Natives had more than double hazards of death from nasopharyngeal cancer compared with non-Hispanic Asians/Pacific Islanders (aHR = 2.63, 95% CI 1.67, 4.13). CONCLUSIONS There are disparities in nasopharyngeal carcinoma survival among racial and ethnic minority groups in the United States, with American Indians/Alaskan Natives faring worst. It is critical that future research focuses on nasopharyngeal carcinoma among this population to improve survivorship and mitigate cancer-related health disparities.

Objectives/hypothesis Head and neck squamous cell carcinoma (HNSCC) prognosis strongly correlates with demographic factors. This study aimed to determine whether demographic predictors of HNSCC survival differ between age cohorts, with an emphasis on the growing elderly demographic. Study design Outcomes research. Methods Adults with squamous cell carcinoma of the upper aerodigestive tract were identified from the Surveillance, Epidemiology and End Results 18 database. Demographic and oncologic factors were compared between three age groups: 18 to 49, 50 to 74, and >75 years. Factors associated with cancer-specific survival were assessed in each cohort using subdistribution hazard ratio (sHR) and 95% confidence interval (CI) produced by multivariate competing risk models. Results A cohort of 69,098 patients included 10,588 (15.3%) 75 years or older and 9,882 (14.3%) less than 50 years old. Older patients were more often female (35.4% vs. 25.1% aged 18-49 years and 20.4% aged 50-74 years), white (78.7% vs. 69.4% and 75.9%), insured (63.5% vs. 46.5% and 56.8%), and married (56.6% vs. 53% and 51.1%), but received adequate treatment less often (72.0% vs. 86.3% and 82.7%). In the older cohort, male sex was associated with lower mortality (sHR: 0.92, 95% CI: 0.85-1.00), and unlike the younger cohorts, black race was no longer associated with mortality (sHR: 1.07, 95% CI: 0.94-1.22). Marriage was associated with lower mortality in all age groups but with diminishing effects (single sHR: young 1.52, middle 1.31, older 1.14). Conclusions Elderly HNSCC patients have distinct effects from demographic prognostic factors and should be considered a separate subgroup with unique epidemiology, risks, and preferences. Level of evidence 2c Laryngoscope, , 129:146-153, 2018.

Objective A pattern of disordered eating involving a pathological fixation with healthy food consumption, labeled orthorexia nervosa (ON), has recently generated attention; however, research has not yet investigated perceptions of ON-related behaviors. This study examined potential stigmatization of ON, compared with DSM-5 ED diagnoses. Method Participants (N = 505) were randomly assigned to read a vignette depicting a woman with anorexia nervosa (AN), bulimia nervosa (BN), binge-eating disorder (BED), or ON. They then answered questions about the individual depicted in the vignette. A series of MANOVAs investigated whether opinions and beliefs about the person depicted varied as a function of the disorder described in the vignette. Results Individuals with ON were perceived as less likely to “improve with treatment” than individuals with BN, and less likely to “pull themselves together,” than individuals with BED. Individuals with ON and AN were viewed as “hard[er] to talk to” and more of a “danger to others” compared with individuals with BED. ON was viewed as less distressing, less likely to evoke sympathy, and more acceptable than the other disorders. Finally, “poor living choices” were perceived as contributing more substantially to ON. Participants' attributions of various personality characteristics did not differ based on ED diagnosis. Discussion Results suggest that ON is viewed as less severe, more desirable, and more often the result of personal life choices. However, findings also imply that ON is associated with stigma, similar to DSM-5 EDs. These negative attitudes might reinforce ON behaviors, and limit awareness of their potential complications.

Hyperbaric oxygen therapy (HBOT) has been beneficial in treating people with nocardiosis. This report describes Nocardia spp. affecting a cat, with lesions confined to the skin. To the best of the authors' knowledge, this is the first report of HBOT, combined with amikacin, used to successfully treat feline cutaneous nocardiosis.

Background Cannabidiol (CBD) in hemp oil has become a widely used product in veterinary medicine. To date, there have been no reports of cutaneous adverse events associated with CBD-containing oil in the veterinary literature. Clinical summary A 4-year-old castrated male Labrador retriever presented with pad sloughing and rapidly progressive cutaneous and mucosal ulceration within five days of administering an oral CBD oil product. Histopathological findings in combination with cutaneous signs were consistent with Stevens-Johnson syndrome. All lesions completely resolved after discontinuation of the hemp oil in addition to a 12 day course of cephalexin and prednisone. Given the lack of alternative causes including other medications, an adverse drug event was deemed probable according to the Naranjo algorithm. Conclusions and clinical importance To the best of the authors' knowledge, this is the first report of suspected cutaneous adverse drug reaction to a CBD-containing hemp oil product.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the effects of topical treatments for athlete's foot (interdigital tinea pedis) caused by dermatophytes.

Deafness is the most frequent sensory disorder. With over 90 genes and 110 loci causally implicated in non-syndromic hearing loss, it is phenotypically and genetically heterogeneous. Here, we investigate the genetic etiology of deafness in four families of Iranian origin segregating autosomal recessive non-syndromic hearing loss (ARNSHL). We used a combination of linkage analysis, homozygosity mapping, and a targeted genomic enrichment platform to simultaneously screen 90 known deafness-causing genes for pathogenic variants. Variant segregation was confirmed by Sanger sequencing. Linkage analysis and homozygosity mapping showed segregation with the DFNB57 locus on chromosome 10 in two families. Targeted genomic enrichment with massively parallel sequencing identified causal variants in PDZD7: a homozygous missense variant (p.Gly103Arg) in one family and compound heterozygosity for missense (p.Met285Arg) and nonsense (p.Tyr500Ter) variants in the second family. Screening of two additional families identified two more variants: (p.Gly228Arg) and (p.Gln526Ter). Variant segregation with the hearing loss phenotype was confirmed in all families by Sanger sequencing. The missense variants are predicted to be deleterious, and the two nonsense mutations produce null alleles. This report is the first to show that mutations in PDZD7 cause ARNSHL, a finding that offers addition insight into the USH2 interactome. We also describe a novel likely disease-causing mutation in CIB2 and illustrate the complexity associated with gene identification in diseases that exhibit large genetic and phenotypic heterogeneity.

In this work, the influence of substrate surface charge on in vitro osteoblast cell proliferation on ferroelectric lithium niobate (LN) crystal surfaces is investigated. LN has a spontaneous polarization along the z-axis and is thus characterized by positive and negative bound polarization charge at the +z and -z surfaces. Biocompatibility of LN was demonstrated via culturing and fluorescence imaging of MC3T3 osteoblast cells for up to 11 days. The cells showed enhanced proliferation rates and improved osteoblast function through mineral formation on the positively and negatively charged LN surfaces compared to electrostatically neutral x-cut LN and a glass cover slip control. These results highlight the potential of LN as a template for investigating the role of charge on cellular processes.

To date, published studies of alluvial bar architecture in large rivers have been restricted mostly to case studies of individual bars and single locations. Relatively little is known about how the depositional processes and sedimentary architecture of kilometre-scale bars vary within a multi-kilometre reach or over several hundreds of kilometres downstream. This study presents Ground Penetrating Radar and core data from 11, kilometre-scale bars from the Río Paraná, Argentina. The investigated bars are located between 30 km upstream and 540 km downstream of the Río Paraná – Río Paraguay confluence, where a significant volume of fine-grained suspended sediment is introduced into the network. Bar-scale cross-stratified sets, with lengths and widths up to 600 m and thicknesses up to 12 m, enable the distinction of large river deposits from stacked deposits of smaller rivers, but are only present in half the surface area of the bars. Up to 90% of bar-scale sets are found on top of finer-grained ripple-laminated bar-trough deposits. Bar-scale sets make up as much as 58% of the volume of the deposits in small, incipient mid-channel bars, but this proportion decreases significantly with increasing age and size of the bars. Contrary to what might be expected, a significant proportion of the sedimentary structures found in the Río Paraná is similar in scale to those found in much smaller rivers. In other words, large river deposits are not always characterized by big structures that allow a simple interpretation of river scale. However, the large scale of the depositional units in big rivers causes small-scale structures, such as ripple sets, to be grouped into thicker cosets, which indicate river scale even when no obvious large-scale sets are present. The results also show that the composition of bars differs between the studied reaches upstream and downstream of the confluence with the Río Paraguay. Relative to other controls on downstream fining, the tributary input of fine-grained suspended material from the Río Paraguay causes a marked change in the composition of the bar deposits. Compared to the upstream reaches, the sedimentary architecture of the downstream reaches in the top ca 5 m of mid-channel bars shows: (i) an increase in the abundance and thickness (up to metre-scale) of laterally extensive (hundreds of metres) fine-grained layers; (ii) an increase in the percentage of deposits comprised of ripple sets (to >40% in the upper bar deposits); and (iii) an increase in bar-trough deposits and a corresponding decrease in bar-scale cross-strata (

Anthropogenic climate change is a key threat to global biodiversity. To inform strategic actions aimed at conserving biodiversity as climate changes, conservation planners need early warning of the risks faced by different species. The IUCN Red List criteria for threatened species are widely acknowledged as useful risk assessment tools for informing conservation under constraints imposed by limited data. However, doubts have been expressed about the ability of the criteria to detect risks imposed by potentially slow-acting threats such as climate change, particularly because criteria addressing rates of population decline are assessed over time scales as short as 10 years. We used spatially explicit stochastic population models and dynamic species distribution models projected to future climates to determine how long before extinction a species would become eligible for listing as threatened based on the IUCN Red List criteria. We focused on a short-lived frog species (Assa darlingtoni) chosen specifically to represent potential weaknesses in the criteria to allow detailed consideration of the analytical issues and to develop an approach for wider application. The criteria were more sensitive to climate change than previously anticipated; lead times between initial listing in a threatened category and predicted extinction varied from 40 to 80 years, depending on data availability. We attributed this sensitivity primarily to the ensemble properties of the criteria that assess contrasting symptoms of extinction risk. Nevertheless, we recommend the robustness of the criteria warrants further investigation across species with contrasting life histories and patterns of decline. The adequacy of these lead times for early warning depends on practicalities of environmental policy and management, bureaucratic or political inertia, and the anticipated species response times to management actions.

The molecular mechanisms regulating G protein-coupled receptors (GPCRs) trafficking from their site of synthesis in the endoplasmic reticulum (ER) to their site of function (the cell surface) remain poorly characterized. Using a bioluminescence resonance energy transfer-based proteomic screen, we identified a novel GPCR-interacting protein; the human cornichon homologue 4 (CNIH4). This previously uncharacterized protein is localized in the early secretory pathway where it interacts with members of the 3 family of GPCRs. Both overexpression and knockdown expression of CNIH4 caused the intracellular retention of GPCRs, indicating that this ER-resident protein plays an important role in GPCR export. Overexpression of CNIH4 at low levels rescued the maturation and cell surface expression of an intracellularly retained mutant form of the β2-adrenergic receptor, further demonstrating a positive role of CNIH4 in GPCR trafficking. Taken with the co-immunoprecipitation of CNIH4 with Sec23 and Sec24, components of the COPII coat complex responsible for ER export, these data suggest that CNIH4 acts as a cargo-sorting receptor, recruiting GPCRs into COPII vesicles.

Aim Mire ecosystems are threatened by global climate change but have important roles in biodiversity conservation, carbon storage, landscape‐scale hydrological function and in providing ecosystem services. We aimed to: (1) estimate change in areas environmentally suitable for mires under future climates; (2) evaluate the sensitivities of projected change to uncertainties in future climate and model structure; (3) evaluate the effect of global mitigation actions on distribution change; (4) identify potential climate refuges for future adaptation actions. Methods We developed and evaluated correlative bioclimatic models for an Australian mire ecosystem by: (1) selecting environmental predictors representing ecological processes that mediate ecosystem occurrence and dynamics; (2) using a high‐performance modelling algorithm; (3) quantifying predictive performance by cross‐validation; (4) cross‐checking responses to predictor variables between different algorithms; (5) comparing the modelled responses with expected mechanistic responses; (6) evaluating extrapolation risks by quantifying the deviation between future and current environmental domains of the study area and by assessing the temporal constancy of correlations between variables; (7) using a geographically stratified cross‐validation to verify spatial consistency of the model; and (8) quantifying the robustness of predictions of climate change impacts to uncertainty in both climate and ecological models. Results All combinations of global circulation models and distribution model projected declines of at least 30% in both area and suitability of environments for the mire ecosystem and in projecting a contraction of range to the southwest. We identified a likely refuge in the south of the distribution and two less certain, emerging areas of suitable environment west and south of the current distribution. Main Conclusions We conclude that southern mire ecosystems are highly susceptible to climate change. Our approach will be useful for the prediction of climate impacts on other ecosystems for which there is enough knowledge to map distributions and develop plausible hypotheses about environmental factors that influence them.

There is a high demand for advanced, image-based, automated high-content screening (HCS) approaches to facilitate phenotypic screening in 3D cell culture models. A major challenge lies in retaining the resolution of fine cellular detail but at the same time imaging multicellular structures at a large scale. In this study, a confocal microscopy-based HCS platform in optical multiwell plates that enables the quantitative morphological profiling of populations of nonuniform spheroids obtained from HT-29 human colorectal cancer cells is described. This platform is then utilized to demonstrate a quantitative dissection of the penetration of synthetic nanoparticles (NP) in multicellular 3D spheroids at multiple levels of scale. A pilot RNA interference-based screening validates this methodology and identifies a subset of RAB GTPases that regulate NP trafficking in these spheroids. This technology is suitable for high-content phenotyping in 3D cell-based screening, providing a framework for nanomedicine drug development as applied to translational oncology.

This paper presents an integrated dataset of digital elevation models (DEMs) and ground penetrating radar (GPR) surveys from the sandy braided South Saskatchewan River, Canada. Data were collected from the same sites in 2004, 2005, 2006 and 2007, allowing the evolution of the surface morphology to be tied explicitly to its associated depositional record. The occurrence of a large flood in 2005 also allowed the influence of discharge to be assessed with respect to the process-product relationship. The data demonstrated that the morphology of the study reach evolved even with modest discharges and could become organized into planforms that were either more compound bar-dominated or unit bar-dominated. The large flood was a trigger for switching between states and caused more erosion than is normally the case. The GPR surveys quantified the extent to which the subsurface deposits (the ‘product’) were modified by the surface morphodynamics (the ‘process). They revealed that during the large flood there was an increase in the proportion of facies associated with bar margin accretion and larger dune sets. Conversely, in subsequent years these facies became truncated and replaced with facies associated with smaller dune sets. In particular, this analysis showed that unit bars generally become truncated vertically but especially laterally. Thus, they lose the high-angle bar margin deposits and the smaller-scale deposits found on their surfaces. As a result, commonly the only fragments that remain are dune sets, thus making identification of the original unit barform problematic. This unique datasets raises implications for what may ultimately become preserved in the rock record.

Investigations of biogeochemical processes in semiarid environments have largely focused on either plot studies in the uplands or on in-stream and near stream reaction or transport studies. Recent research permits us to synthesize a conceptual model of how uplands and riparian systems are linked in semiarid climates specific to the San Pedro River basin in Arizona. These studies have demonstrated significant export of both dissolved and sediment associated carbon and nitrogen from the uplands into the channel network of semiarid river systems. Likewise research has demonstrated that riparian areas are biogeochemically active, with the potential to rapidly respire inputs of organic matter, releasing carbon back to the atmosphere and inorganic nitrogen into the water column or back to the atmosphere through denitrification. For the San Pedro, a total of more than 80% of both carbon and nitrogen export from the uplands that is observed in small catchments is not observed at the larger river system scale, indicating that this carbon and nitrogen must be either stored, taken up by vegetation or returned to the atmosphere at scales between the small catchment (1–1000 ha) and large river systems scale (∼320,000 ha). In summary, existing research shows that the uplands contribute significant amounts of material into the stream and near stream zone, and that this imported material influences nutrient conditions in aquatic systems. These conclusions point out significant gaps in developing a complete understanding of the reactions of carbon and nitrogen as material is transported from the uplands through ephemeral and perennial channel networks.

The rise in stream stage during high flow events (floods) can induce losing stream conditions, even along stream reaches that are gaining during baseflow conditions. The aquifer response to flood events can affect the geochemical composition of both near-stream groundwater and post-event streamflow, but the amount and persistence of recharged floodwater may differ as a function of local hydrogeologic forcings. As a result, this study focuses on how vertical flood recharge varies under different hydrogeologic forcings and the significance that recharge processes can have on groundwater and streamflow composition after floods. River and shallow groundwater samples were collected along three reaches of the Upper San Pedro River (Arizona, USA) before, during and after the 2009 and 2010 summer monsoon seasons. Tracer data from these samples indicate that subsurface floodwater propagation and residence times are strongly controlled by the direction and magnitude of the dominant stream–aquifer gradient. A reach that is typically strongly gaining shows minimal floodwater retention shortly after large events, whereas the moderately gaining and losing reaches can retain recharged floodwater from smaller events for longer periods. The moderately gaining reach likely returned flood recharge to the river as flow declined. These results indicate that reach-scale differences in hydrogeologic forcing can control (i) the amount of local flood recharge during events and (ii) the duration of its subsurface retention and possible return to the stream during low-flow periods. Our observations also suggest that the presence of floodwater in year-round baseflow is not due to long-term storage beneath the streambed along predominantly gaining reaches, so three alternative mechanisms are suggested: (i) repeated flooding that drives lateral redistribution of previously recharged floodwater, (ii) vertical recharge on the floodplain during overbank flow events and (iii) temporal variability in the stream–aquifer gradient due to seasonally varying water demands of riparian vegetation. Copyright © 2011 John Wiley & Sons, Ltd.

Design: Interviews about attitudes about psychotherapy with 12 undergraduate students who had never been in psychotherapy were analysed using consensual qualitative research. Results: Participants believed that the client role is to disclose, be receptive, and be motivated; that the therapist role is to listen, support, and give advice; and that the therapeutic relationship should be close and personal. Participants had ideas about the benefits (a healing therapeutic relationship, personal and interpersonal changes) and the barriers (self-stigma and public stigma, difficulty revealing, need to solve problems on own, cost) associated with seeking therapy, and they disliked the idea of being diagnosed. In contrast with participants who were securely attached, those who were insecurely attached more often wanted a professional therapeutic relationship, wanted the therapist to ask questions, mentioned fewer benefits to therapy, and thought that they would have difficulty disclosing to a therapist. Discussion:...

We evaluated the restoration of native plant assemblages by topsoil translocation in the Hunter Valley, south-east Australia. Species' responses were characterized by defining nine plant functional types (PFTs) based on combinations of four response mechanisms (seed bank persistence, germination cues, resprouting mechanisms, and longevity) through which species were predicted to persist or decline following translocation. The effects of community type and delay in topsoil restoration on restoration outcomes were tested in an orthogonal experiment. Changes in species' frequency were detected using Bayesian statistics with prior probabilities derived from pre-clearing data. Few species failed to reestablish following translocation; these were offset by recruitment of other native species not detected prior to clearing. Compositional changes were more pronounced when topsoil was stockpiled (cf direct reinstatement), although there was no trend related to the period of stockpiling. The PFT response model correctly predicted the rank probability of decline in three of the nine PFTs, while a further three were correctly placed in the top ranks but in the incorrect order. Three PFTs were incorrectly ranked because the response model was incorrect. Resprouters declined more frequently than seeders; however, species with physical seed dormancy declined less frequently than those with either transient seed banks or physiological, morphological, or morpho-physiological dormancy, irrespective of resprouting ability. Species with short juvenile periods were more likely to increase. We conclude that PFTs based on fire-response traits represent a practical means of predicting species' responses to translocation and a basis for prioritizing species for supplementary planting.

There is little empirical evidence showing a direct link between a capacity for statistical learning (SL) and proficiency with natural language. Moreover, discussion of the role of SL in language acquisition has seldom focused on literacy development. Our study addressed these issues by investigating the relationship between SL and reading ability in typically developing children and healthy adults. We tested SL using visually presented stimuli within a triplet learning paradigm and examined reading ability by administering the Wide Range Achievement Test (WRAT-4; Wilkinson & Robertson, 2006). A total of 38 typically developing children (mean age of 9;5 years, range 6;4–12;5) and 37 healthy adults (mean age of 21 years, range 18–34) were assessed. In children, SL was significantly related to reading ability. Importantly, this relationship was independent of grade and also age. The adult data, too, revealed that SL was significantly related to reading ability. A regression analysis of the combined child and adult data revealed that SL accounted for a unique amount of variance in reading ability, after age and attention had been taken into consideration. For the first time, this study provides empirical evidence that a capacity for more effective SL is related to higher reading ability in the general population.

The depositional stratigraphy of within-channel deposits in sandy braided rivers is dominated by a variety of barforms (both singular ‘unit’ bars and complex ‘compound’ bars), as well as the infill of individual channels (herein termed ‘channel fills’). The deposits of bars and channel fills define the key components of facies models for braided rivers and their within-channel heterogeneity, knowledge of which is important for reservoir characterization. However, few studies have sought to address the question of whether the deposits of bars and channel fills can be readily differentiated from each other. This paper presents the first quantitative study to achieve this aim, using aerial images of an evolving modern sandy braided river and geophysical imaging of its subsurface deposits. Aerial photographs taken between 2000 and 2004 document the abandonment and fill of a 1AE3 km long, 80 m wide anabranch channel in the sandy braided South Saskatchewan River, Canada. Upstream river regulation traps the majority of very fine sediment and there is little clay (

It is possible that statistical learning (SL) plays a role in almost every mental activity. Indeed, research on SL has grown rapidly over recent decades in an effort to better understand perception and cognition. Yet, there remain gaps in our understanding of how SL operates, in particular with regard to its (im)mutability. Here, we investigated whether participant-related variables (such as age) and task-related variables (such as speed of stimulus presentation) affect visual statistical learning (VSL) in typically developing children. We tested 183 participants ranging in age from 5 to 12 years and compared three speeds of presentation (using stimulus durations of 800, 400 and 200 msecs). A multiple regression analysis revealed significant effects of both age and speed of presentation - after attention during familiarization and gender had been taken into consideration. VSL followed a developmental trajectory whereby learning increased with age. The amount of learning increased with longer presentation times (as shown by Turk-Browne, Junge & Scholl, 2005, in their study of adults). There was no significant interaction between the two variables. These findings assist in elucidating the nature of statistical learning itself. While statistical learning can be observed in very young children and at remarkably fast presentation times, participant- and task-related variables do impact upon this type of learning. The findings reported here may serve to enhance our understanding of individual differences in the cognitive and perceptual processes that are thought to rely, at least in part, on SL (e.g. language processing and object recognition).

Cell death by apoptosis is critical in myocardial diseases, and non-invasive detection of early, reversible apoptosis might be useful clinically. Exogenous Annexin-V (ANX) protein binds membrane phosphatidylserine, which is externalized in early apoptosis. A molecular MRI probe was constructed with superparamagnetic iron oxide (SPIO) conjugated to recombinant human ANX (ANX-SPIO). Apoptosis was induced with doxorubicin, a cardiotoxic cancer drug, in culture in neonatal rat ventricular myocytes, cardiac fibroblasts, and mesenchymal stem cells, and in vivo in the mouse heart. ANX-SPIO was validated using T2*-weighted 3T MRI. ANX-SPIO produced T2* signal loss, reflecting iron content, that correlated highly with independent apoptosis markers; bound with high affinity to apoptotic myocytes by competition assay (Ki 69nM); detected apoptosis in culture much earlier than did TUNEL stain; and revealed fibroblast resistance to apoptosis. With apoptosis in vivo, ANX-SPIO produced diffuse myocardial T2* signal loss that correlated with increased iron stain and caspase activity. Treatment with an alpha-1-adrenergic agonist in vivo reversed apoptosis and eliminated the ANX-SPIO MRI signal. It is concluded that cardiac MRI of ANX-SPIO detects early, non-ischemic cardiac apoptosis in culture and in vivo, and can identify reversibly injured cardiac cells in diseased hearts, when treatment is still possible.

Nanoparticles (NPs) are now used in numerous technologies and serve as carriers for several new classes of therapeutics. Studies of the distribution of NPs in vivo demonstrate that they can be transported through biological barriers and are concentrated in specific tissues. Here, transport behavior, and final destination of polystyrene NPs are reported in primary mouse cortical neurons and SH-SY5Y cells, cultured in two-compartmental microfluidic devices. In both cell types, negative polystyrene NPs (PS(-)) smaller than 100 nm are taken up by the axons, undergo axonal retrograde transport, and accumulate in the somata. Examination of NP transport reveals different transport mechanisms depending on the cell type, particle charge, and particle internalization by the lysosomes. In cortical neurons, PS(-) inside lysosomes and 40 nm positive polystyrene NPs undergo slow axonal transport, whereas PS(-) outside lysosomes undergo fast axonal transport. Inhibition of dynein in cortical neurons decreases the transport velocity and cause a dose-dependent reduction in the number of accumulated PS(-), suggesting that the fast axonal transport is dynein mediated. These results show that the axonal retrograde transport of NPs depends on the endosomal pathway taken and establishes a means for screening nanoparticle-based therapeutics for diseases that involve neurons.

Tacrolimus is a nonsteroidal alternative to treat noninfectious otitis externa (OE) in people. This 21-day study investigated whether twice daily application (0.2 mL/dose) of sterile olive oil based 0.1% tacrolimus suspension in ears of atopic beagle dogs without OE was associated with adverse local reactions, development of OE, change in otic cytology, vestibular dysfunction, or hearing loss detected by brainstem auditory evoked response (BAER). The study was randomized, double-blinded, and placebo-controlled. Twenty-two dogs matched for age and sex were randomized to tacrolimus or vehicle control treatment groups. Two investigators independently evaluated dogs for signs of adverse effects including OE the first 4 days of treatment, then every 3 days. A logistic regression model was fit for each investigator’s clinical scores (SAS, 9.2, 2008). Time (P = 0.0032) and group (P = 0.0167) were always significant for OE. Inter-observer reliability of clinical scores was strong, measured using Kappa coefficients and proportion of agreement. All nine exclusions (7/10 control- and 2/12 tacrolimus-treated dogs) were excluded for yeast OE. Inter-observer agreement to exclude was 100%. All dogs not excluded had normal BAER assessments before treatment, weekly during treatment, and after 21 days of treatment. None showed vestibular abnormalities at these times. Tacrolimus blood concentrations (Abbott IMx Tacrolimus II) were below detection limits (3 ng/mL) at baseline and after 21 days of treatment. Results suggest otic application of olive oil based tacrolimus suspension to canine ears with intact tympanic membranes is unlikely to result in hearing loss or vestibular dysfunction but yeast OE is a possible risk. Resume Le tacrolimus est une alternative therapeutique non-steroidienne de l’otite externe (OE) non-infectieuse de l’homme. Cette etude de 21 jours a evalue si une application biquotidienne (0.2 mL/dose) d’une suspension de 0.1% de tacrolimus dans de l’huile d’olive sterile dans les oreilles de Beagle atopiques ne presentant pas d’OE, etait associee a l’apparition de reactions indesirables locales, d’OE, de modifications dans la cytologie auriculaire, de dysfonctionnement vestibulaire ou de perte d’audition par analyse des potentiels auditifs evoques (BAER). L’etude etait randomisee, en double aveugle et contre placebo. Vingt-deux chiens couples par age et sexe ont ete repartis au hasard dans les groupes tacrolimus ou controle. Deux investigateurs ont evalues independamment les chiens pour les effets indesirables y compris l’OE au cours des 4 premiers jours de traitement puis tous les 3 jours. Un modele de regression logistique a ete adapte pour les scores cliniques de chaque investigateur (SAS, 9.2, 2008). La duree (P = 0.0032) et le groupe (P = 0.0167) etaient toujours significatifs pour l’OE. La fiabilite inter-observateur des scores cliniques etait forte, celle-ci etant mesuree par les coefficients de Kappa et la proportion d’agrement. Les neufs exclusions (7/10 controles et 2/12 traites au tacrolimus) etaient dues a des OE a levures. L’accord inter-observateur d’exclusion etait de 100%. Tous les chiens non-exclus avaient des BAER normaux avant traitement, chaque semaine au cours du traitement et apres 21 jours de traitement. Aucun animal ne montrait d’anomalies vestibulaires a ces moments. Les concentrations sanguines de tacrolimus (Abbott IMx Tacrolimus II) etaient en dessous des seuils limites de detection (3 ng/mL) au jour de reference et 21 jours apres traitement. Ces resultats suggerent qu’une application d’une suspension de tacrolimus dans de l’huile d’olive dans les oreilles de chiens avec un tympan intact n’entraine pas de perte d’audition ou de dysfonction vestibulaire mais le developpement d’OE a levure est un risque possible. Resumen El tacrolimus es un tratamiento no esteroide alternativo para la otitis externa no infecciosa (OE) en personas. Este estudio clinico de 21 dias de duracion investigo si la aplicacion dos veces al dia (0.2 mL/dosis) de una suspension al 0.1% de tacrolimus en aceite de oliva esteril en los oidos de perros Beagle atopicos sin OE se asociaba con efectos adversos locales, desarrollo de OE, cambios en la citologia auricular, disfuncion vestibular o perdida de capacidad auditiva detectada mediante respuesta auditiva inducida en la raiz cerebral (BAER). El estudio fue al azar, doble ciego y controlado por placebo. Veintidos perros de edad y sexo equivalentes se asignaron al azar a los grupos de tacrolimus o vehiculo control. De manera independiente dos investigadores evaluaron los perros por signos de efectos adversos, incluida OE en los primeros cuatro dias de tratamiento y despues cada 3 dias. Se creo un modelo de regresion logistica para los valores clinicos de cada investigador (SAS, 9.2, 2008). El tiempo (P = 0.0032) y el grupo (0.016) fueron siempre significativos para la produccion de OE. Hubo una correlacion elevada en la fiabilidad de los valores entre investigadores, medidos utilizando coeficientes Kappa y proporcion de acuerdo. Las nueve exclusiones (7/10 controles y 2/12 tratados con tracrolimus) fueron por OE asociada con levaduras. El acuerdo entre investigadores para la exclusion fue del 100%. Todos los perros no excluidos tenian valores BAER normales antes del tratamiento, semanalmente durante el tratamiento, y tras 21 dias de tratamiento. Ninguno mostro anormalidades vestibulares en esos tiempos. Las concentraciones de tacrolimus en sangre (Abbot IMx Tacrolimus II) estuvieron por debajo de los limites detectables (3 ng/mL) en el dia 0 y tras 21 dias de tratamiento. Los resultados indican que la aplicacion de la suspension de tacrolimus en aceite de oliva en oidos caninos intactos con membranas timpanicas no danadas es poco probable que resulte en perdida de capacidad auditiva o disfuncion vestibular, pero OE por levaduras es un posible riesgo. Zusammenfassung Tacrolimus ist eine nicht-steroidale Alternative, um eine nicht-infektiose Otitis externa (OE) beim Menschen zu behandeln. Diese 21 Tage dauernde Studie untersuchte, ob eine zweimal tagliche Applikation (0.2mL/Dosis) von 0.1%iger Tacrolimus-Suspension in sterilem Olivenol in Ohren von atopischen Beagles ohne OE mit lokalen Nebenwirkungen, der Entwicklung von OE, einer Veranderung des Zytologiebefundes der Ohren, vestibularer Dysfunktion oder Verlust des Gehors, welches durch eine BAER Hirnstamm Audiometrie gemessen wurde, in Zusammenhang gebracht werden konnte. Die Studie war randomisiert, doppelblind und Plazebo-kontrolliert. Zweiundzwanzig Hunde, die bezuglich Alter und Geschlecht ubereinstimmten, wurden zufallig der Behandlungsgruppe mit Tacrolimus oder der Kontrollgruppe, wo nur Tragermedium verwendet wurde, zugeteilt. In den ersten vier Tagen der Behandlung, und dann alle drei Tage, beurteilten zwei Untersucher voneinander unabhangig die Hunde auf Anzeichen von Nebenwirkungen, inklusive OE. Ein logistisches Regressionsmodell wurde an die klinischen Beurteilungen eines jeden Untersuchers angepasst (SAS, 9.2, 2008). Zeit (P = 0.0032) und Gruppe (P = 0.0167) waren immer signifikant fur OE. Die Bestandigkeit bezuglich der klinischen Bewertungen zwischen den Untersuchern war gut – gemessen wurde sie durch den Kappa Koeffizienten und das Mas der Ubereinstimmung. Alle neun Hunde (7/10 Kontrollhunde und 2/12 mit Takrolimus behandelte Hunde), die aus der Studie ausgeschlossen wurden, wurden wegen einer Hefepilz-Otitis ausgeschlossen. Die Ubereinstimmung zwischen den Untersuchern, die Hunde auszuschliesen, betrug 100%. Alle Hunde, die nicht ausgeschlossen wurden, hatten vor der Behandlung, wochentlich wahrend der Behandlung und 21 Tage nach der Behandlung eine normale BAER Bewertung. Keiner der Hunde zeigte zu diesen Zeitpunkten vestibulare Abweichungen. Die Blutkonzentrationen von Tacrolimus (Abbott IMx Tacrolimus II) waren unter der Nachweisgrenze (3 ng/mL) am Anfang und 21 Tage nach der Behandlung. Die Ergebnisse lassen darauf schliesen, dass eine ins Ohr instillierte Tacrolimus-Suspension in Olivenolbasis bei Hundeohren mit intaktem Trommelfell eher nicht in Horverlust oder einer vestibularen Dysfunktion resultiert, dass jedoch eine Hefepilz-Otitis ein mogliches Risiko darstellt.

BACKGROUND Lokivetmab neutralizes IL-31, a cytokine that plays an important role in the pathogenesis of atopic dermatitis (AD) in dogs. OBJECTIVE To review experience of one year of treatment with lokivetmab for the control of pruritus in dogs with allergic dermatitis. ANIMALS Eighty dogs diagnosed with AD, ten with concurrent adverse food reaction and AD and 45 with allergic dermatitis of undetermined cause. Three dogs were lost to follow- up. METHODS AND MATERIALS Retrospective analysis of medical records of dogs with allergic dermatitis treated with lokivetmab from November 2015 to October 2016. Treatment success for owner-assessed pruritus was empirically defined as ≥2 cm reduction in Visual Analog Scale (pVAS) from baseline. A ≥50% reduction in pVAS also was recorded. RESULTS Pruritus improvement was achieved in 116 of 132 dogs (87.8%) following initial lokivetmab administration at 1.8 to 3.7 mg/kg (P

Historical archives of grey-scale river channel imagery are extensive. Here, we present and test a methodology to extract detailed quantitative topographic date from such imagery of sand-bed rivers. Extracting elevation information from rivers is difficult as they are characterized by a low relative relief (less than 4 m); the area of interest may be spatially extensive (e.g. active channel widths > 500 m in large braided rivers); the rate of change of surface elevation is generally low except in the vicinity of individual channel banks where the rate of change is very high: there is the complication that comes from innundation: and there may be an added complication caused by blockage of the field of view by vegetation. Here, we couple archival photogrammetric techniques with image processing methods and test these for quantification of sand-bed braided river dynamics, illustrated for a 500 m wide, 3 km long reach of the Spouth Sasketchewan River, Canada. Digitial photogrammetry was used to quantify dry areas and water edge elevations. A methodology was then used to calibrate the special signature of inundated areas by combining established two media digital photogrammetric methods and image matching. This allowed determination of detailed depth maps for inundated area and, when combined with dry area data, creation of depths detectable from sequential digital elevation models. The result was a series of elevation models that demonstrate the potential for acquiring detailed and precise elevation data from any historical aerial imagery of rivers without needing associated calibration data, provided that imagery is of the necessary scale to capture the features of interest. We use these data to highlight several aspects of channel change on the South Saskatchewan River, including bar movement, bank erosion and channel infilling.