Prediction of key milk biomarkers in dairy cows through milk mid-infrared spectra and international collaborations.

At the individual cow level, suboptimum fertility, mastitis, negative energy balance, and ketosis are major issues in dairy farming. These problems are widespread on dairy farms and have an important economic impact. The objectives of this study were (1) to assess the potential of milk mid-infrared (MIR) spectra to predict key biomarkers of energy deficit (citrate, isocitrate, glucose-6 phosphate [glucose-6P], free glucose), ketosis (ß-hydroxybutyrate [BHB] and acetone), mastitis (N-acetyl-ß-d-glucosaminidase activity [NAGase] and lactate dehydrogenase), and fertility (progesterone); (2) to test alternative methodologies to partial least squares (PLS) regression to better account for the specific asymmetric distribution of the biomarkers; and (3) to create robust models by merging large datasets from 5 international or national projects. Benefiting from this international collaboration, the dataset comprised a total of 9,143 milk samples from 3,758 cows located in 589 herds across 10 countries and represented 7 breeds. The samples were analyzed by reference chemistry for biomarker contents, whereas the MIR analyses were performed on 30 instruments from different models and brands, with spectra harmonized into a common format. Four quantitative methodologies were evaluated to address the strongly skewed distribution of some biomarkers. Partial least squares regression was used as the reference basis, and compared with a random modification of distribution associated with PLS (random-downsampling-PLS), an optimized modification of distribution associated with PLS (KennardStone-downsampling-PLS), and support vector machine (SVM). When the ability of MIR to predict biomarkers was too low for quantification, different qualitative methodologies were tested to discriminate low versus high values of biomarkers. For each biomarker, 20% of the herds were randomly removed within all countries to be used as the validation dataset. The remaining 80% of herds were used as the calibration dataset. In calibration, the 3 alternative methodologies outperform the PLS performances for the majority of biomarkers. However, in the external herd validation, PLS provided the best results for isocitrate, glucose-6P, free glucose, and lactate dehydrogenase (coefficient of determination in external herd validation [R2v] = 0.48, 0.58, 0.28, and 0.24, respectively). For other molecules, PLS-random-downsampling and PLS-KennardStone-downsampling outperformed PLS in the majority of cases, but the best results were provided by SVM for citrate, BHB, acetone, NAGase, and progesterone (R2v = 0.94, 0.58, 0.76, 0.68, and 0.15, respectively). Hence, PLS and SVM based on the entire dataset provided the best results for normal and skewed distributions, respectively. Complementary to the quantitative methods, the qualitative discriminant models enabled the discrimination of high and low values for BHB, acetone, and NAGase with a global accuracy around 90%, and glucose-6P with an accuracy of 83%. In conclusion, MIR spectra of milk can enable quantitative screening of citrate as a biomarker of energy deficit and discrimination of low and high values of BHB, acetone, and NAGase, as biomarkers of ketosis and mastitis. Finally, progesterone could not be predicted with sufficient accuracy from milk MIR spectra to be further considered. Consequently, MIR spectrometry can bring valuable information regarding the occurrence of energy deficit, ketosis, and mastitis in dairy cows, which in turn have major influences on their fertility and survival.

A comparison of 4 different machine learning algorithms to predict lactoferrin content in bovine milk from mid-infrared spectra.

Lactoferrin (LF) is a glycoprotein naturally present in milk. Its content varies throughout lactation, but also with mastitis; therefore it is a potential additional indicator of udder health beyond somatic cell count. Condequently, there is an interest in quantifying this biomolecule routinely. First prediction equations proposed in the literature to predict the content in milk using milk mid-infrared spectrometry were built using partial least square regression (PLSR) due to the limited size of the data set. Thanks to a large data set, the current study aimed to test 4 different machine learning algorithms using a large data set comprising 6,619 records collected across different herds, breeds, and countries. The first algorithm was a PLSR, as used in past investigations. The second and third algorithms used partial least square (PLS) factors combined with a linear and polynomial support vector regression (PLS + SVR). The fourth algorithm also used PLS factors, but included in an artificial neural network with 1 hidden layer (PLS + ANN). The training and validation sets comprised 5,541 and 836 records, respectively. Even if the calibration prediction performances were the best for PLS + polynomial SVR, their validation prediction performances were the worst. The 3 other algorithms had similar validation performances. Indeed, the validation root mean squared error (RMSE) ranged between 162.17 and 166.75 mg/L of milk. However, the lower standard deviation of cross-validation RMSE and the better normality of the residual distribution observed for PLS + ANN suggest that this modeling was more suitable to predict the LF content in milk from milk mid-infrared spectra (R2v = 0.60 and validation RMSE = 162.17 mg/L of milk). This PLS +ANN model was then applied to almost 6 million spectral records. The predicted LF showed the expected relationships with milk yield, somatic cell score, somatic cell count, and stage of lactation. The model tended to underestimate high LF values (higher than 600 mg/L of milk). However, if the prediction threshold was set to 500 mg/L, 82% of samples from the validation having a content of LF higher than 600 mg/L were detected. Future research should aim to increase the number of those extremely high LF records in the calibration set.

Local excision after neoadjuvant chemoradiotherapy versus total mesorectal excision: a case-matched study in 110 selected high-risk patients with rectal cancer.

AIM: The aim of this comparative study was to report a 10-year experience of an organ preservation strategy by local excision (LE) in selected high-risk patients (aged patients and/or patients with severe comorbidity and/or indication for abdominoperineal excision) versus total mesorectal excision (TME) after neoadjuvant radiochemotherapy (RCT) for patients with locally advanced (T3-T4 and/or N+) low and mid rectal cancer with suspicion of complete tumour response (CTR) or near-CTR. METHOD: Thirty-nine patients with rectal cancer who underwent LE after RCT for suspicion of CTR were matched to 71 patients who underwent TME according to body mass index, gender, tumour location and ypTNM stage. Operative, oncological and functional results were compared between groups. RESULTS: In the LE group, ypT0, ypTis or ypT1N0R0 were noted in 28/39 (72%). Overall morbidity was observed in 10/39 (26%) in LE vs 46/71 in the TME group (65%) (P = 0.001). Severe morbidity (Clavien-Dindo ≥ 3) was noted in 1/39 patients from the LE group (3%) vs 3/71 (4%) from the TME group (P = 1.000). After a mean follow-up of 63 ± 4 months (range 56-70 months), local recurrence was noted in 2/39 (5%) from the LE group vs 2/71 (3%) from the TME group (P = 0.601). Definitive stoma was noted in 2/39 (6%) from the LE group vs 8/71 (12%) from the TME group (P = 0.489). Major low anterior resection syndrome was noted in 5/23 (22%) from LE group vs 11/33 (33%) from the TME group (P = 0.042). CONCLUSION: The accuracy of response prediction after RCT was 72% after LE. In high-risk patients, LE represents a safe alternative to TME with better functional results and the same long-term oncological outcome.

A Multinational Cost-Consequence Analysis of a Bone Conduction Hearing Implant System-A Randomized Trial of a Conventional vs. a Less Invasive Treatment With New Abutment Technology.

Background: It is hypothesized that, for patients with hearing loss, surgically placing an implant/abutment combination whilst leaving the subcutaneous tissues intact will improve cosmetic and clinical results, increase quality of life (QoL) for the patient, and reduce medical costs. Here, incremental costs and consequences associated with soft tissue preservation surgery with a hydroxyapatite (HA)-coated abutment (test) were compared with the conventional approach, soft tissue reduction surgery with an all-titanium abutment (control). Methods: A cost-consequence analysis was performed based on data gathered over a period of 3 years in an open randomized (1:1) controlled trial (RCT) running in four European countries (The Netherlands, Spain, France, and Sweden). Subjects with conductive or mixed hearing loss or single-sided sensorineural deafness were included. Results: During the first year, in the Netherlands (NL), France (FR), and Spain (ES) a net cost saving was achieved in favor of the test intervention because of a lower cost associated with surgery time and adverse event treatments [NL €86 (CI -50.33; 219.20), FR €134 (CI -3.63; 261.30), ES €178 (CI 34.12; 97.48)]. In Sweden (SE), the HA-coated abutment was more expensive than the conventional abutment, which neutralized the cost savings and led to a negative cost (SE €-29 CI -160.27; 97.48) of the new treatment modality. After 3 years, the mean cost saving reduced to €17 (CI -191.80; 213.30) in the Netherlands, in Spain to €84.50 (CI -117.90; 289.50), and in France to €80 (CI -99.40; 248.50). The mean additional cost in Sweden increased to €-116 (CI -326.90; 68.10). The consequences in terms of the subjective audiological benefit and Health-related quality of life (HRQoL) were comparable between treatments. A trend was identified for favorable results in the test group for some consequences and statistical significance is achieved for the cosmetic outcome as assessed by the clinician. Conclusions: From this multinational cost-consequence analysis it can be discerned that health care systems can achieve a cost saving during the first year that regresses after 3 years, by implementing soft tissue preservation surgery with a HA-coated abutment in comparison to the conventional treatment. The cosmetic results are better. (sponsored by Cochlear Bone Anchored Solutions AB; Clinical and health economic evaluation with a new Baha® abutment design combined with a minimally invasive surgical technique, ClinicalTrials.gov NCT01796236).

Can we refine the management of blunt liver trauma?

AIM: To describe the management of blunt liver injury and to study the potential relation between delayed complications, type of trauma mechanisms and liver lesions. PATIENTS AND METHODS: This is a retrospective single center study including 116 consecutive patients admitted with blunt liver injury between 2007 and 2015. RESULTS: Initial CT-scan identified an active bleeding in 33 (28%) patients. AAST (American Association for the Surgery of Trauma) grade was 1 to 3 in 82 (71%) patients and equal to 5 in 15 (13%) patients. Eighty (69%) patients had NOM, with a success rate of 96%. Other abdominal organ lesions were associated to invasive initial management. A follow-up CT-scan was useful to detect hepatic and extra-hepatic complications (46 complications in 80 patients), even without clinical or biological abnormalities. Subsequent hepatic complications such as bleeding, pseudo aneurysms, biloma and biliary peritonitis developed in 15 patients and were associated with the severity of blunt liver injury according to AAST classification (3.7±1.0 vs. 3.0±1.1, P=0.010). Total biliary complications occurred in 13 patients and were significantly more frequently observed in patients with injury of central segments 1, 4 and 9 (69% vs. 36%, P=0.033). CONCLUSIONS: Non-operative management is possible in most blunt liver injury with a success rate of 96%. A systematic CT-scan should be advocated during follow-up, especially when AAST grade is equal or superior to 3. Biliary complications should be suspected when lesions involve segments 1, 4 and 9.

Management of otitis media with effusion in children. Société française d'ORL et de chirurgie cervico-faciale clinical practice guidelines.

The Société française d'ORL et de chirurgie cervico-faciale clinical practice guidelines concern the management of otitis media with effusion (OME) in children under the age of 12 years. They are based on extensive review of MEDLINE and Cochrane Library publications in English or French from 1996 to 2016 concerning the methods of diagnosis and assessment of otitis media with effusion, as well as the efficacy of tympanostomy tubes and medical and surgical treatments of OME.

International consensus (ICON) on management of otitis media with effusion in children.

Otitis media with effusion (OME) is a common childhood disease defined as the presence of liquid in the middle ear without signs or symptoms of acute ear infection. Children can be impacted mainly with hearing impairment and/or co-occurring recurrent acute otitis media (AOM) thus requiring treatment. Although many meta-analyses and national guidelines have been issued, management remains difficult to standardize, and use of surgical and medical treatments continue to vary. We convened an international consensus conference as part of the 2017 International Federation of Oto-rhino-laryngological Societies Congress, to identify best practices in OME management. Overall, regional differences were minor and consensual management was obtained on several important issues. At initial assessment, although a thorough medical examination is necessary to seek reflux, allergy or nasal obstruction symptoms; an age-appropriate auditory test is the only assessment required in children without abnormal history. Non-surgical treatments poorly address the underlying problem of an age-dependent dysfunctional Eustachian tube; auto-inflation seems to be the only beneficial, low-risk and low-cost non-surgical therapy. There was a clear international recommendation against using steroids, antibiotics, decongestants or antihistamines to treat OME, because of side-effects, cost issues and no convincing evidence of long-term effectiveness. Decisions to insert tympanostomy ventilation tubes should be based on an auditory test but also take into account the child's context and overall hearing difficulties. Tubes significantly improve hearing and reduce the number of recurrent AOM with effusion while in place. Adjuvant adenoidectomy should be considered in children over four years of age, and in those with significant nasal obstruction or infection.

Prediction of fatty acid profiles in cow, ewe, and goat milk by mid-infrared spectrometry.

Mid-infrared (MIR) spectrometry was used to estimate the fatty acid (FA) composition in cow, ewe, and goat milk. The objectives were to compare different statistical approaches with wavelength selection to predict the milk FA composition from MIR spectra, and to develop equations for FA in cow, goat, and ewe milk. In total, a set of 349 cow milk samples, 200 ewe milk samples, and 332 goat milk samples were both analyzed by MIR and by gas chromatography, the reference method. A broad FA variability was ensured by using milk from different breeds and feeding systems. The methods studied were partial least squares regression (PLS), first-derivative pretreatment + PLS, genetic algorithm + PLS, wavelets + PLS, least absolute shrinkage and selection operator method (LASSO), and elastic net. The best results were obtained with PLS, genetic algorithm + PLS and first derivative + PLS. The residual standard deviation and the coefficient of determination in external validation were used to characterize the equations and to retain the best for each FA in each species. In all cases, the predictions were of better quality for FA found at medium to high concentrations (i.e., for saturated FA and some monounsaturated FA with a coefficient of determination in external validation >0.90). The conversion of the FA expressed in grams per 100mL of milk to grams per 100g of FA was possible with a small loss of accuracy for some FA.

[Treatment of simple snoring by radiofrequency velar coblation]. / Traitement du ronflement simple par coblation vélaire.

OBJECTIVES: Short- and long-term evaluation of the efficacy and safety of radiofrequency velar coblation for simple snoring. MATERIAL AND METHODS: From February 2000 to May 2004, 175 patients underwent a single radiofrequency session for velar coblation. All patients suffered from snoring without sleep apnea. They presented modifications of the velo-pharyngeal region but did not have tonsillar or basilingual hypertrophy. Outcome was assessed in terms of pain, changes in snoring, secondary effects and complications at three months and one, two, and three years. Secondary uvulectomy was performed in 28 patients. RESULTS: At three months, snoring had decreased in 82% of patients with complete resolution in 12%. Outcome remained unchanged in 70% of patients at one, two, and three years. After uvulectomy, snoring declined in 96% of patients with complete resolution in 48%. Post-treatment pain lasted less than five days in 68% of patients. Mean duration was three days. Fifteen patients developed pharyngeal paresthesia which regressed at one year. Two patients had a nasal voice and three developed necrosis of the uvula. CONCLUSION: Velar coblation is a simple treatment for snoring which can be performed in a single session. The best results are achieved in patients whose body mass index is below 25 and after secondary uvulectomy.