Validation of quantitative magnetic resonance imaging techniques in head and neck healthy structures involved in the salivary and swallowing function: Accuracy and repeatability.

Background and Purpose: Radiation-induced damage to the organs at risk (OARs) in head-and-neck cancer (HNC) patient can result in long-term complications. Quantitative magnetic resonance imaging (qMRI) techniques such as diffusion-weighted imaging (DWI), DIXON for fat fraction (FF) estimation and T2 mapping could potentially provide a spatial assessment of such damage. The goal of this study is to validate these qMRI techniques in terms of accuracy in phantoms and repeatability in-vivo across a broad selection of healthy OARs in the HN region. Materials and Methods: Scanning was performed at a 3 T diagnostic MRI scanner, including the calculation of apparent diffusion coefficient (ADC) from DWI, FF and T2 maps. Phantoms were scanned to estimate the qMRI techniques bias using Bland-Altman statistics. Twenty-six healthy subjects were scanned twice in a test-retest study to determine repeatability. Repeatability coefficients (RC) were calculated for the parotid, submandibular, sublingual and tubarial salivary glands, oral cavity, pharyngeal constrictor muscle and brainstem. Additionally, a linear mixed-effect model analysis was used to evaluate the effect of subject-specific characteristics on the qMRI values. Results: Bias was 0.009x10-3 mm2/s for ADC, -0.7 % for FF and -7.9 ms for T2. RCs ranged 0.11-0.25x10-3 mm2/s for ADC, 1.2-6.3 % for FF and 2.5-6.3 ms for T2. A significant positive linear relationship between age and the FF and T2 for some of the OARs was found. Conclusion: These qMRI techniques are feasible, accurate and repeatable, which is promising for treatment response monitoring and/or differentiating between healthy and unhealthy tissues due to radiation-induced damage in HNC patients.

Wetness severity increases abrupt shifts in ecosystem functioning in arid savannas.

The accelerating pace of climate change has led to unprecedented shifts in surface temperature and precipitation patterns worldwide, with African savannas being among the most vulnerable regions. Understanding the impacts of these extreme changes on ecosystem health, functioning and stability is crucial. This paper focuses on the detection of breakpoints, indicative of shifts in ecosystem functioning, while also determining relevant ecosystem characteristics and climatic drivers that increase susceptibility to these shifts within the semi-arid to arid savanna biome. Utilising a remote sensing change detection approach and rain use efficiency (RaUE) as a proxy for ecosystem functioning, spatial and temporal patterns of breakpoints in the savanna biome were identified. We then employed a novel combination of survival analysis and remote sensing time series analysis to compare ecosystem characteristics and climatic drivers in areas experiencing breakpoints versus areas with stable ecosystem functioning. Key ecosystem factors increasing savanna breakpoint susceptibility were identified, namely higher soil sand content, flatter terrain and a cooler long-term mean temperature during the wet summer season. Moreover, the primary driver of changes in ecosystem functioning in arid savannas, as opposed to wetter tropical savannas, was found to be the increased frequency and severity of rainfall events, rather than drought pressures. This research highlights the importance of incorporating wetness severity metrics alongside drought metrics to comprehensively understand climate-ecosystem interactions leading to abrupt shifts in ecosystem functioning in arid biomes. The findings also emphasise the need to consider the underlying ecosystem characteristics, including soil, topography and vegetation composition, in assessing ecosystem responses to climate change. While this research primarily concentrated on the southern African savanna as a case study, the methodological robustness of this approach enables its application to diverse arid and semi-arid biomes for the assessment of climate-ecosystem interactions that contribute to abrupt shifts.

Long-term functional outcomes in tumour stage T2 glottic carcinoma after radiotherapy.

OBJECTIVE: To evaluate the long-term functional outcomes in patients who received primary radiotherapy for tumour-node stage T2N0 glottic carcinoma, stratified for tumour extension. METHODS: A cross-sectional study was performed on patients who were treated with radiotherapy for T2N0 glottic carcinoma. Four questionnaires were used to measure different aspects of functional outcome. In addition, objective evaluation and perceptual analysis were performed. RESULTS: Fourteen patients were included in this study. The median time between the start of radiotherapy and assessment was 42 months (range, 26-143 months). Patients reported high-level functioning, with low symptom scores and good swallowing function, and showed a median dysphonia grade of 1.5. The median Voice Handicap Index-30 score was 17.5. CONCLUSION: Patients with T2N0 glottic carcinoma treated with radiotherapy had good long-term quality of life, with low symptom scores, good swallowing functioning and slightly elevated voice outcome parameters.

Contralateral hearing loss in children with a unilateral enlarged vestibular aqueduct.

OBJECTIVE: To evaluate the long-term ipsi- and contralateral hearing of patients with a unilateral enlarged vestibular aqueduct (EVA). STUDY DESIGN: Multicenter retrospective cohort study. SETTING: Three tertiary otology and audiology referral centers. PATIENTS AND DIAGNOSTIC INTERVENTIONS: A total of 34 children with a unilateral enlarged vestibular aqueduct as identified on CT and/or MR imaging were evaluated with pure tone and speech perception audiometry. MEAN OUTCOME MEASURES: Radiologic measurements of the vestibular aqueduct, ipsi- and contralateral hearing loss, ipsi- and contralateral hearing loss progression over time and DNA test results. RESULTS: All patients in this cohort with unilateral EVA presented with hearing loss. Hearing loss was progressive in 38% of the ipsilateral ears. In 29% of the children, hearing loss was also found in the contralateral ear without EVA. In 90%, the contralateral hearing was stable, with a mean follow up of 4.2 years. We found a significant correlation between the severity of the hearing loss and the size of the EVA. A genetic diagnosis associated with EVA and/or SNHL was found in only 7%. CONCLUSION: About a third of the children with unilateral EVA are at risk of developing hearing loss in the contralateral ear. This indicates that at least in some patients with a unilateral EVA, a bilateral pathogenic process underlies the hearing loss, in contrary to what the imaging results suggest. These findings are important for counseling of EVA patients and their parents and have implications for follow up.

Value of Endolymphatic Hydrops and Perilymph Signal Intensity in Suspected Ménière Disease.

BACKGROUND AND PURPOSE: Ménière disease is characterized by endolymphatic hydrops, whereas perilymphatic enhancement on MR imaging has been suggested to be of additional value in diagnosing Ménière disease. This study evaluates the presence of endolymphatic hydrops and perilymphatic enhancement in patients with Ménière disease and with other vertigo-associated inner ear pathology. MATERIALS AND METHODS: A 3D-FLAIR sequence 4 hours after intravenous gadolinium injection was performed to visualize the endolymph and perilymph in 220 patients suspected of having Ménière disease. Patients' ears were retrospectively categorized as having Ménière disease (probable or definite) or other vertigo-associated inner ear pathology not attributable to Ménière disease. Endolymphatic hydrops was evaluated using a visual classification system, and perilymphatic enhancement was scored both visually and quantitatively. RESULTS: Endolymphatic hydrops was present in 137 (91.9%) of the definite Ménière disease ears and in 9 (7.0%) of the ears with other vertigo-associated inner ear pathology (P < .001). The combination of endolymphatic hydrops and visually increased perilymphatic enhancement was present in 122 (81.9%) definite Ménière disease ears compared with 4 (3.1%) ears with other vertigo-associated inner ear pathology (P < .001). This combination increases the positive predictive value from 0.94 for endolymphatic hydrops and 0.91 for perilymphatic enhancement to 0.97. The addition of measured perilymphatic enhancement leads to a moderate decrease in sensitivity from 0.92 for endolymphatic hydrops to 0.86. CONCLUSIONS: The combination of perilymphatic enhancement and endolymphatic hydrops in patients suspected of having Ménière disease increases the positive predictive value in the diagnosis of definite Ménière disease.

CT findings of the temporal bone in CHARGE syndrome: aspects of importance in cochlear implant surgery.

To provide an overview of anomalies of the temporal bone in CHARGE syndrome relevant to cochlear implantation (CI), anatomical structures of the temporal bone and the respective genotypes were analysed. In this retrospective study, 42 CTs of the temporal bone of 42 patients with CHARGE syndrome were reviewed in consensus by two head-and-neck radiologists and two otological surgeons. Anatomical structures of the temporal bone were evaluated and correlated with genetic data. Abnormalities that might affect CI surgery were seen, such as a vascular structure, a petrosquamosal sinus (13 %), an underdeveloped mastoid (8 %) and an aberrant course of the facial nerve crossing the round window (9 %) and/or the promontory (18 %). The appearance of the inner ear varied widely: in 77 % of patients all semicircular canals were absent and the cochlea varied from normal to hypoplastic. A stenotic cochlear aperture was observed in 37 %. The middle ear was often affected with a stenotic round (14 %) or oval window (71 %). More anomalies were observed in patients with truncating mutations than with non-truncating mutations. Temporal bone findings in CHARGE syndrome vary widely. Vascular variants, aberrant route of the facial nerve, an underdeveloped mastoid, aplasia of the semicircular canals, and stenotic round window may complicate cochlear implantation.

Measurement of head and neck paragangliomas: is volumetric analysis worth the effort? A method comparison study.

OBJECTIVES: The aim of this study was to assess the reproducibility of different measurement methods and define the most workable technique for measuring head and neck paragangliomas, to determine the best method for evaluating tumour growth. The evaluation of tumour growth is vital for a 'wait-and-scan' policy, a management strategy that became increasingly important. STUDY DESIGN: Method comparison study. SETTING AND PARTICIPANTS: Thirty tumours, including carotid body, vagal body, jugulotympanic tumours and conglomerates of multiple tumours, were measured in duplicate, using linear dimensions, manual area tracing and an automated segmentation method. MAIN OUTCOME MEASURES: Reproducibility was assessed using the Bland-Altman method. RESULTS: The smallest detectable difference using the linear dimension method was 11% for carotid body and 27% for vagal body tumours, compared with 17% and 20% for the manual area tracing method. Due to the irregular shape of paragangliomas in the temporal bone and conglomerates, the manual area tracing method showed better results in these tumours (26% and 8% versus 54% and 47%). The linear dimension method was significantly faster (median 4.27 versus 18.46 minutes, P < 0.001). The automatic segmentation method yielded smallest detectable differences between 39% and 75%, and although fast (2.19 ± 1.49 minutes), it failed technically. CONCLUSIONS: Due to a relatively good reproducibility, fast and easy application, we found the linear dimension method to be the most pragmatic approach for evaluation of growth of carotid and vagal body paragangliomas. For jugulotympanic tumours, the preferred method is manual area tracing. However, volumetric changes of these tumours may be of less clinical importance than changes in relation to surrounding anatomical structures.

Induction chemotherapy with docetaxel/cisplatin/5-fluorouracil followed by randomization to two cisplatin-based concomitant chemoradiotherapy schedules in patients with locally advanced head and neck cancer (CONDOR study) (Dutch Head and Neck Society 08-01): A randomized phase II study.

PURPOSE: To study the feasibility of induction chemotherapy added to concomitant cisplatin-based chemoradiotherapy (CRT) in patients with locally advanced head and neck cancer (LAHNC). PATIENTS AND METHODS: LAHNC patients were treated with 4 courses of docetaxel/cisplatin/5-fluorouracil (TPF) followed by randomization to either cisplatin 100 mg/m(2) with conventional radiotherapy (cis100 + RT) or cisplatin 40 mg/m(2) weekly with accelerated radiotherapy (cis40 + ART). Primary endpoint was feasibility, defined as receiving ≥ 90% of the scheduled total radiation dose. Based on power analysis 70 patients were needed. RESULTS: 65 patients were enrolled. The data safety monitoring board advised to prematurely terminate the study, because only 22% and 41% (32% in total) of the patients treated with cis100 + RT (n = 27) and cis40 + ART (n = 29) could receive the planned dose cisplatin during CRT, respectively, even though the primary endpoint was reached. Most common grade 3-4 toxicity was febrile neutropenia (18%) during TPF and dehydration (26% vs 14%), dysphagia (26% vs 24%) and mucositis (22% vs 57%) during cis100 + RT and cis40 + ART, respectively. For the patients treated with cis100 + RT and cis40 + ART, two years progression free survival and overall survival were 70% and 78% versus 72% and 79%, respectively. CONCLUSION: After TPF induction chemotherapy, cisplatin-containing CRT is not feasible in LAHNC patients, because the total planned cisplatin dose could only be administered in 32% of the patients due to toxicity. However, all but 2 patients received more than 90% of the planned radiotherapy. Clinical Trials Information: NCT00774319.

Vestibular function and temporal bone imaging in DFNB1.

DFNB1 is the most prevalent type of hereditary hearing impairment known nowadays and the audiometric phenotype is very heterogeneous. There is, however, no consensus in literature on vestibular and imaging characteristics. Vestibular function and imaging results of 44 DFNB1 patients were evaluated in this retrospective study. All patients displayed a response during rotational velocity step testing. In 65% of the cases, the caloric results were within normal range bilaterally. The video head impulse test was normal in all patients. In 34.4% of the CT scans one or more temporal bone anomalies were found. The various anomalies found, were present in small numbers and none seemed convincingly linked to a specific DFNB1genotype. The group of DFNB1 patients presented here is the largest thus far evaluated for their vestibular function. From this study, it can be assumed that DFNB1 is not associated with vestibular dysfunction or specific temporal bone anomalies.

Visualization of human inner ear anatomy with high-resolution MR imaging at 7T: initial clinical assessment.

BACKGROUND AND PURPOSE: In many centers, MR imaging of the inner ear and auditory pathway performed on 1.5T or 3T systems is part of the preoperative work-up of cochlear implants. We investigated the applicability of clinical inner ear MR imaging at 7T and compared the visibility of inner ear structures and nerves within the internal auditory canal with images acquired at 3T. MATERIALS AND METHODS: Thirteen patients with sensorineural hearing loss eligible for cochlear implantation underwent examinations on 3T and 7T scanners. Two experienced head and neck radiologists evaluated the 52 inner ear datasets. Twenty-four anatomic structures of the inner ear and 1 overall score for image quality were assessed by using a 4-point grading scale for the degree of visibility. RESULTS: The visibility of 11 of the 24 anatomic structures was rated higher on the 7T images. There was no significant difference in the visibility of 13 anatomic structures and the overall quality rating. A higher incidence of artifacts was observed in the 7T images. CONCLUSIONS: The gain in SNR at 7T yielded a more detailed visualization of many anatomic structures, especially delicate ones, despite the challenges accompanying MR imaging at a high magnetic field.

Otological aspects and surgical outcome in a consanguineous family with a novel ANKH gene mutation.

OBJECTIVES: To report the hearing impairment in a new autosomal recessive metabolic disorder due to a mutation in the ANKH gene and to report the outcomes of exploratory tympanotomy. STUDY DESIGN: Retrospective chart study. SETTING: Tertiary referral center. PATIENTS: One large consanguineous family was examined. Three patients underwent exploratory tympanotomy. INTERVENTION: Exploratory tympanotomies in three patients. MAIN OUTCOME MEASURES: Medical and otological histories; postoperative hearing outcomes. RESULTS: In the patients who received tympanotomies, a postoperative hearing gain of between 5 and 20 dB was noted, with a residual air-bone gap of between 6 and 35 dB (follow-up between 4 and 67 months). The sensorineural component of the hearing impairment varies greatly, between 4 and 23 dB, and this factor might also affect the final hearing outcome. CONCLUSIONS: Exploratory tympanotomy might improve the hearing outcome in patients with this syndrome and therefore surgery has a limited audiometric benefit in general. Based on anatomical findings, a congenital origin for the ossicular chain anomaly seems likely. It remains unclear whether the sensorineural component of the hearing impairment is progressive and this should be investigated further.

Unraveling the microbiota of teat apices of clinically healthy lactating dairy cows, with special emphasis on coagulase-negative staphylococci.

Swab samples (n=72) obtained from the teat apex of lactating dairy cows without visual signs of inflammation (n=18) were gathered on 2 well-managed Flemish dairy herds (herds 1 and 2) during the same month to assess the bacterial diversity of teat apices before milking. A combination of both culture-dependent [plating and (GTG)(5)-PCR fingerprinting of the colonies] and culture-independent [denaturing gradient gel electrophoresis (PCR-DGGE)] techniques indicated that the teat apices contain a wide diversity of bacterial genera. Despite a low bacterial load, 20 bacterial genera of 3 phyla (Actinobacteria, Firmicutes, and Proteobacteria) were present. The most prevalent bacteria were the coagulase-negative staphylococci (CNS), encompassing a total of 15 species, which were identified to the species level using a combination of (GTG)(5)-PCR fingerprinting, gene sequencing (16S ribosomal RNA and rpoB genes), and a novel PCR-DGGE technique based on the tuf-PCR amplicon. Overall bacterial diversity did not differ significantly between the herds or between noninfected and subclinically infected quarters in herd 1. In herd 1, borderline significant lower CNS species diversity was found on teat apices of noninfected quarters compared with subclinically infected quarters. The most prevalent CNS species were Staphylococcus haemolyticus and Staphylococcus equorum in both herds and Staphylococcus carnosus in herd 2.

Short communication: Associations between teat dimensions and milking-induced changes in teat dimensions and quarter milk somatic cell counts in dairy cows.

Although many studies have examined the relation between a wide range of factors and quarter milk somatic cell count (qSCC), including physical characteristics of the teat and changes in teat tissue due to milking, the effect of short-term, milking-induced changes in teat dimensions on somatic cell count has not yet been investigated. To identify teat dimensions and milking-induced changes in teat dimensions associated with qSCC, we conducted a longitudinal study (n(herds)=6, n(cows)=72, n(measurements)=12). Parity, stage of lactation, teat barrel diameter, and changes in teat barrel diameter during milking were identified as factors associated with qSCC. Teats with wider barrels had higher qSCC. Negative changes in the diameter of the teat barrel during milking (i.e., thinner teats postmilking compared with premilking) were associated with lower qSCC, whereas positive changes (i.e., thicker teats postmilking compared with premilking) were associated with higher qSCC. Selection toward more optimal teat characteristics may therefore result in improved milk quality and udder health. However, a threshold might exist for the maximum reduction in teat barrel diameter below which udder health is negatively influenced. If so, changes in teat barrel diameter might serve as an indicator for suboptimal milking and incorrect choice of teatcup liner or milking machine settings and thus help improve management of the herd.

Left vein of Labbé thrombosis associated with ipsilateral dural sinus thrombosis: non-enhanced CT and contrast-enhanced CT (CTV) findings.

A rare case of aseptic thrombosis of the left vein of Labbé in a young woman is reported. Cerebral venous thrombosis was suggested by computed tomography and confirmed after intravenous administration of contrast by computed tomography venography. The combination of the clinical setting with the findings on the non-enhanced CT may favour the diagnosis of vein of Labbé thrombosis. The diagnosis can be confirmed on computed tomography venography.

Characterization of coagulase-negative staphylococcus species from cows' milk and environment based on bap, icaA, and mecA genes and phenotypic susceptibility to antimicrobials and teat dips.

The aim of this study was to investigate whether the main coagulase-negative staphylococci (CNS) species involved in bovine intramammary infections (IMI) possess specific characteristics that promote colonization of the udder. Virulence markers associated with biofilm formation, antimicrobial resistance, and biocide tolerance were compared between typically contagious CNS species (Staphylococcus chromogenes, Staphylococcus epidermidis, Staphylococcus haemolyticus, and Staphylococcus simulans) and those rarely causing IMI (Staphylococcus sciuri, Staphylococcus equorum, and others) to find possible associations with pathogenicity. Coagulase-negative staphylococci isolates (n=366) belonging to 22 different species were analyzed by PCR for the presence of the biofilm-associated genes bap and icaA, and the methicillin resistance gene mecA. A selection of 82 isolates was additionally tested for their susceptibility to 5 antibiotics and 2 commercial teat dip products. Minimum inhibitory concentrations of antimicrobials were determined by Etest (AB bioMérieux, Marcy l'Etoile, France), and a microdilution method was optimized to determine minimum biocidal concentrations of teat dips. The bap, icaA, and mecA genes were detected significantly more in isolates from CNS species typically living in the cows' environment than in isolates from IMI-causing species. Antimicrobial resistance was mainly against erythromycin (23%) or oxacillin (16%), and was detected more often in the environmental species. The isolates least susceptible to the teat dips belonged to the IMI-causing species Staph. chromogenes and Staph. simulans. We concluded that carriage of biofilm genes and antimicrobial resistance were not associated with the ability to colonize the mammary gland because free-living CNS species constituted a more significant reservoir of biofilm and resistance determinants than did IMI-causing species. In contrast, increased tolerance to biocides may favor the establishment of bovine IMI by some CNS species.

Intra-species diversity and epidemiology varies among coagulase-negative Staphylococcus species causing bovine intramammary infections.

Although many studies report coagulase-negative staphylococci (CNS) as the predominant cause of subclinical bovine mastitis, their epidemiology is poorly understood. In the current study, the genetic diversity within four CNS species frequently associated with bovine intramammary infections, Staphylococcus haemolyticus, S. simulans, S. chromogenes, and S. epidermidis, was determined. For epidemiological purposes, CNS genotypes recovered from bovine milk collected on six Flemish dairy farms were compared with those from the farm environment, and their distribution within the farms was investigated. Genetic diversity was assessed by two molecular typing techniques, amplification fragment length polymorphism (AFLP) and random amplification of polymorphic DNA (RAPD) analysis. Subtyping revealed the highest genetic heterogeneity among S. haemolyticus isolates. A large variety of genotypes was found among environmental isolates, of which several could be linked with intramammary infection, indicating that the environment could act as a potential source for infection. For S. simulans, various genotypes were found in the environment, but a link with IMI was less obvious. For S. epidermidis and S. chromogenes, genetic heterogeneity was limited and the sporadic isolates from environment displayed largely the same genotypes as those from milk. The higher clonality of the S. epidermidis and S. chromogenes isolates from milk suggests that specific genotypes probably disseminate within herds and are more udder-adapted. Environmental sources and cow-to-cow transmission both seem to be involved in the epidemiology of CNS, although their relative importance might substantially vary between species.

Sources other than unused sawdust can introduce Klebsiella pneumoniae into dairy herds.

A longitudinal study was carried out to detect intramammary infections caused by Klebsiella pneumoniae and to identify potential sources of this bacterial species in the environment of the cows. The study was performed in 6 well-managed Belgian dairy herds from May 2008 to May 2009. Monthly (n=13), unused and used sawdust bedding samples as well as individual quarter milk and feces samples were collected from 10 randomly selected cohort cows in each herd. Cases of clinical mastitis of all lactating cows in the 6 herds were also sampled (n=64). From the 3,518 collected samples, 153 K. pneumoniae isolates were obtained, of which 2 originated from milk (clinical mastitis cases). In feces (n=728), used bedding (n=73), and unused bedding (n=73), respectively, 125 (17.2%), 20 (27.4%), and 6 (8.2%) isolates were found. The isolates were fingerprinted by means of pulsed field gel electrophoresis. In total, 109 different pulsotypes were differentiated, indicating a high degree of genetic diversity within the isolates. All isolates from unused bedding belonged to pulsotypes other than those from the other sources, suggesting that sources other than unused sawdust may introduce K. pneumoniae into the herd. Only 2 pulsotypes contained isolates originating from different sources. Pulsotype 10 was found in milk and used bedding and pulsotype 21 was found in feces and used bedding. The 2 milk isolates originated from 2 cows in the same herd but they belonged to a different pulsotype. The results indicate that K. pneumoniae can be prevalent in the environment without causing significant mastitis problems. Most cows were shedding K. pneumoniae in feces, substantiating findings under very different conditions (i.e., American dairy herds). Contamination of used bedding in the cubicles with K. pneumoniae from feces was confirmed, whereas unused bedding was not an important source of K. pneumoniae for the environment of the cows.

Distribution of coagulase-negative Staphylococcus species from milk and environment of dairy cows differs between herds.

In many parts of the world, coagulase-negative staphylococci (CNS) are the predominant pathogens causing intramammary infections (IMI) in dairy cows. The cows' environment is thought to be a possible source for CNS mastitis and this was investigated in the present paper. A longitudinal field study was carried out in 6 well-managed dairy herds to determine the distribution and epidemiology of various CNS species isolated from milk, causing IMI and living freely in the cows' environment, respectively. In each herd, quarter milk samples from a cohort of 10 lactating cows and environmental samples from stall air, slatted floor, sawdust from cubicles, and sawdust stock were collected monthly (n=13). Isolates from quarter milk samples (n=134) and the environment (n=637) were identified to species level using amplified fragment length polymorphism (AFLP) genotyping. Staphylococcus chromogenes, S. haemolyticus, S. epidermidis, and S. simulans accounted for 81.3% of all CNS milk isolates. Quarters were considered infected with CNS (positive IMI status) only when 2 out of 3 consecutive milk samples yielded the same CNS AFLP type. The species causing IMI were S. chromogenes (n=35 samples with positive IMI status), S. haemolyticus (n=29), S. simulans (n=14), and S. epidermidis (n=6). The observed persistent IMI cases (n=17) had a mean duration of 149.4 d (range 63.0 to 329.8 d). The CNS species predominating in the environment were S. equorum, S. sciuri, S. haemolyticus, and S. fleurettii. Herd-to-herd differences in distribution of CNS species were observed in both milk and the environment, suggesting that herd-level factors are involved in the establishment of particular species in a dairy herd. Primary reservoirs of the species causing IMI varied. Staphylococcus chromogenes and S. epidermidis were rarely found in the environment, indicating that other reservoirs were more important in their epidemiology. For S. haemolyticus and S. simulans, the environment was found as a reservoir, suggesting that IMI with these species were possibly environmental in origin.

Becker muscular dystrophy patients with deletions around exon 51; a promising outlook for exon skipping therapy in Duchenne patients.

Theoretically, 13% of patients with Duchenne muscular dystrophy may benefit from antisense-mediated skipping of exon 51 to restore the reading frame, which results in the production of a shortened dystrophin protein. We give a detailed description with longitudinal follow up of three patients with Becker muscular dystrophy with in-frame deletions in the DMD gene encompassing exon 51. Their internally deleted, but essentially functional, dystrophins are identical to those that are expected as end products in DMD patients treated with the exon 51 skipping therapy. The mild phenotype encourages further development of exon 51 skipping therapy.