Inner ear ossification and mineralization kinetics in human embryonic development - microtomographic and histomorphological study.

Little is known about middle and inner ear development during the second and third parts of human fetal life. Using ultra-high resolution Microcomputed Tomography coupled with bone histology, we performed the first quantitative middle and inner ear ossification/mineralization evaluation of fetuses between 17 and 39 weeks of gestational age. We show distinct ossification paces between ossicles, with a belated development of the stapes. A complete cochlear bony covering is observed within the time-frame of the onset of hearing, whereas distinct time courses of ossification for semicircular canal envelopes are observed in relation to the start of vestibular functions. The study evidences a spatio-temporal relationship between middle and inner ear structure development and the onset of hearing and balance, critical senses for the fetal adaptation to birth

Near Elimination of Ventricular Pacing in SafeR Mode Compared to DDD Modes: A Randomized Study of 422 Patients

Aims:SafeR performance versus DDD/automatic mode conversion (DDD/AMC) and DDD with a 250-ms atrioventricular (AV) delay (DDD/LD) modes was assessed toward ventricular pacing (Vp) reduction. Methods:After a 1-month run-in phase, recipients of dual-chamber pacemakers without persistent AV block and persistent atrial fibrillation (AF) were randomly assigned to SafeR, DDD/AMC, or DDD/LD in a 1:1:1 design. The main endpoint was the percentage of Vp (%Vp) at 2 months and 1 year after randomization, ascertained from device memories. Secondary endpoints include %Vp at 1 year according to pacing indication and 1-year AF incidence based on automatic mode switch device stored episodes. Results:Among 422 randomized patients (73.2 ± 10.6 years, 50% men, sinus node dysfunction 47.4%, paroxysmal AV block 30.3%, bradycardia-tachycardia syndrome 21.8%), 141 were assigned to SafeR versus 146 to DDD/AMC and 135 to DDD/LD modes. Mean %Vp at 2 months was 3.4 ± 12.6% in SafeR versus 33.6 ± 34.7% and 14.0 ± 26.0% in DDD/AMC and DDD/LD modes, respectively (P < 0.0001 for both). At 1 year, mean %Vp in SafeR was 4.5 ± 15.3% versus 37.9 ± 34.4% and 16.7 ± 28.0% in DDD/AMC and DDD/LD modes, respectively (P < 0.0001 for both). The proportion of patients in whom Vp was completely eliminated was significantly higher in SafeR (69%) versus DDD/AMC (15%) and DDD/LD (45%) modes (P < 0.0001 for both), regardless of pacing indication. The absolute risk of developing permanent AF or of remaining in AF for >30% of the time was 5.4% lower in SafeR than in the DDD pacing group (ns). Conclusions:In this selected patient population, SafeR markedly suppressed unnecessary Vp compared with DDD modes. PACE 2012; 35:392–402

The BKB_K Kaon Parameter in the Chiral Limit

We introduce four-point functions in the hadronic ladder resummation approach to large $N_c$ QCD Green functions. We determine the relevant one to calculate the $B_K$ kaon parameter in the chiral limit. This four-point function contains both the large momenta QCD OPE and the small momenta ChPT at NLO limits, analytically. We get $\hat B_K^\chi = 0.38 \pm 0.15$. We also give the ChPT result at NLO for the relevant four-point function to calculate $B_K$ outside the chiral limit, while the leading QCD OPE is the same as the chiral limit one.Comment: 17 page

Handling data quality issues to estimate the Spanish EQ-5D-5L value set using a hybrid interval regression approach

Background The Spanish five-level EuroQol five-dimensional questionnaire (EQ-5D-5L) valuation study was the first to use the EuroQol Valuation Technology protocol, including composite time trade-off (C-TTO) and discrete choice experiments (DCE). In this study, its investigators noticed that some interviewers did not fully explain the C-TTO task to respondents. Evidence from a follow-up study in 2014 confirmed that when interviewers followed the protocol, the distribution of C-TTO responses widened. Objectives To handle the data quality issues in the C-TTO responses by estimating a hybrid interval regression model to produce a Spanish EQ-5D-5L value set. Methods Four different models were tested. Model 0 integrated C-TTO and DCE responses in a hybrid model and models 1 to 3 altered the interpretation of the C-TTO responses: model 1 allowed for censoring of the C-TTO responses, whereas model 2 incorporated interval responses and model 3 included the interviewer-specific protocol violations. For external validation, the predictions of the four models were compared with those of the follow-up study using the Lin’s concordance correlation coefficient. Results This stepwise approach to modeling C-TTO and DCE responses improved the concordance between the valuation and follow-up studies (concordance correlation coefficient: 0.948 [model 0], 0.958 [model 1], 0.952 [model 2], and 0.989 [model 3]). We recommend the estimates from model 3, because its hybrid interval regression model addresses the data quality issues found in the valuation study. Conclusions Protocol violations may occur in any valuation study; handling them in the analysis can improve external validity. The resulting EQ-5D-5L value set (model 3) can be applied to inform Spanish health technology assessments

Impact of body mass index on post-thyroidectomy morbidity

BACKGROUND: The impact of obesity on total thyroidectomy (TT) morbidity (recurrent laryngeal nerve palsy and hypocalcaemia) remains largely unknown. METHODS: In a prospective study (NCT01551914), patients were divided into five groups according to their body mass index (BMI): underweight, normal weight, overweight, obese, and severely obese. Preoperative and postoperative serum calcium was measured. Recurrent laryngeal nerve (RLN) function was evaluated before discharge, and if abnormal, at 6 months. RESULTS: In total 1310 patients were included. Baseline characteristics were similar across BMI groups except for age and sex. Postoperative hypocalcaemia was more frequent in underweight compared to obese patients but the difference was not statistically significant in multivariate analysis. There was no difference between groups in terms of definitive hypocalcaemia, transient and definitive RLN palsy, and postoperative pain. CONCLUSION: Obesity does not increase intraoperative and postoperative morbidity of TT, despite a longer duration of the procedure

Advanced age does not increase morbidity after total thyroidectomy. Result of a prospective study

BACKGROUND: It is well known that total thyroidectomy is feasible on elderly patients but is linked to complications because of their underlying comorbidities. In this study we analyzed the specific risks linked to surgery, hypoparathyroidism and recurrent nerve palsy. METHODS: materials-methods:Prospective, multicentre trial conducted at 13 hospital sites. The primary endpoint was the percentage of patients with postoperative hypocalcaemia (albumin-corrected serum calcium level <2 mmol/L at day 2). Secondary endpoints included recurrent nerve palsy rate at day 2, the percentage of patients with hypocalcaemia (serum calcium level <2 mmol/L) and recurrent nerve palsy at month 6, operating durations and postoperative pain. Patients were separated in two groups: <70 years and ≥70 years old. RESULTS: In total, 1329 patients who underwent total thyroidectomy were included (median age 51.17 years [18.10; 80.90], 80% women, and hyperthyroidism in 20%, 101 ≥ 70 years old). Rates of hypocalcaemia at day 2 and month 6 were 20.02% and 1.98% respectively. Nasofibroscopy showed postoperative abnormal vocal cord motility in 9.92% cases (hypo-motility 5.76% - immobility 4.16%) and 0.95% at month 6 (hypo-motility 0.48%, immobility 0.48%). Patients ≥70 years had a lower (but non-significant) postoperative and definitive hypocalcaemia rate than patients < 70 years: 14.85% vs 20.44% at day 2 (p = 0.1773) and 0% vs 2.15% at month 6 respectively (p = 0.2557). Abnormal vocal cord motility rate was 12.00% in patients ≥70 years vs 9.75% in patients <70 years at day 2 (p = 0.4702), and 2.06% in patients ≥70 years vs 0.86% at month 6 (p = 0.2340). CONCLUSIONS: Total thyroidectomy in patients ≥70 years is feasible and safe. Age does not increase the morbidity. The study is registered with ClinicalTrials.gov number NCT01551914

Physics with the KLOE-2 experiment at the upgraded DAϕ\phiNE

Investigation at a $\phi$--factory can shed light on several debated issues in particle physics. We discuss: i) recent theoretical development and experimental progress in kaon physics relevant for the Standard Model tests in the flavor sector, ii) the sensitivity we can reach in probing CPT and Quantum Mechanics from time evolution of entangled kaon states, iii) the interest for improving on the present measurements of non-leptonic and radiative decays of kaons and eta/eta$^\prime$ mesons, iv) the contribution to understand the nature of light scalar mesons, and v) the opportunity to search for narrow di-lepton resonances suggested by recent models proposing a hidden dark-matter sector. We also report on the $e^+ e^-$ physics in the continuum with the measurements of (multi)hadronic cross sections and the study of gamma gamma processes.Comment: 60 pages, 41 figures; added affiliation for one of the authors; added reference to section

Epidemiology, practice of ventilation and outcome for patients at increased risk of postoperative pulmonary complications

BACKGROUND Limited information exists about the epidemiology and outcome of surgical patients at increased risk of postoperative pulmonary complications (PPCs), and how intraoperative ventilation was managed in these patients. OBJECTIVES To determine the incidence of surgical patients at increased risk of PPCs, and to compare the intraoperative ventilation management and postoperative outcomes with patients at low risk of PPCs. DESIGN This was a prospective international 1-week observational study using the ‘Assess Respiratory Risk in Surgical Patients in Catalonia risk score’ (ARISCAT score) for PPC for risk stratification. PATIENTS AND SETTING Adult patients requiring intraoperative ventilation during general anaesthesia for surgery in 146 hospitals across 29 countries. MAIN OUTCOME MEASURES The primary outcome was the incidence of patients at increased risk of PPCs based on the ARISCAT score. Secondary outcomes included intraoperative ventilatory management and clinical outcomes. RESULTS A total of 9864 patients fulfilled the inclusion criteria. The incidence of patients at increased risk was 28.4%. The most frequently chosen tidal volume (VT) size was 500 ml, or 7 to 9 ml kg1 predicted body weight, slightly lower in patients at increased risk of PPCs. Levels of positive end-expiratory pressure (PEEP) were slightly higher in patients at increased risk of PPCs, with 14.3% receiving more than 5 cmH2O PEEP compared with 7.6% in patients at low risk of PPCs (P < 0.001). Patients with a predicted preoperative increased risk of PPCs developed PPCs more frequently: 19 versus 7%, relative risk (RR) 3.16 (95% confidence interval 2.76 to 3.61), P < 0.001) and had longer hospital stays. The only ventilatory factor associated with the occurrence of PPCs was the peak pressure. CONCLUSION The incidence of patients with a predicted increased risk of PPCs is high. A large proportion of patients receive high VT and low PEEP levels. PPCs occur frequently in patients at increased risk, with worse clinical outcome