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Fat distribution and macro structure of white adipose tissue are important factors in predicting obesity-associated diseases, but cellular microstructure of white adipose tissue has been less explored. To investigate the relationship between adipocyte size and obesity-related traits, and their underlying disease-driving genetic associations, we performed the largest study of automatic adipocyte phenotyping linking histological measurements and genetics to date. We introduce deep learning based methods for scalable and accurate semantic segmentation of subcutaneous and visceral adipose tissue histology samples (N=2,667) across 5 independent cohorts, including data from 9,000 whole slide images, with over 27 million adipocytes. Estimates of mean size of adipocytes were validated against Glastonbury et al. 2020. We show that adipocyte hypertrophy correlates with an adverse metabolic profile with increased levels of leptin, fasting plasma glucose, glycated hemoglobin and triglycerides, and decreased levels of adiponectin and HDL cholesterol. We performed the largest GWAS (N Subcutaneous = 2066, N Visceral = 1878) and subsequent meta-analysis of mean adipocyte area, and find two genome-wide significant loci (rs73184721, rs200047724) associated with increased 95%-quantile adipocyte size in respectively visceral and subcutaneous adipose tissue. Stratifying by sex, in females we find two genome-wide significant loci, with one variant (rs140503338) associated with increased mean adipocyte size in subcutaneous adipose tissue, and the other (rs11656704) is associated with decreased 95%-quantile adipocyte size in visceral adipose tissue.

The NA62 experiment at CERN, configured in beam-dump mode, has searched for dark photon decays in flight to electron-positron pairs using a sample of 1.4×10^{17} protons on dump collected in 2021. No evidence for a dark photon signal is observed. The combined result for dark photon searches in lepton-antilepton final states is presented and a region of the parameter space is excluded at 90% confidence level, improving on previous experimental limits for dark photon mass values between 50 and 600  MeV/c^{2} and coupling values in the range 10^{-6} to 4×10^{-5}. An interpretation of the e^{+}e^{-} search result in terms of the emission and decay of an axionlike particle is also presented.

Sustained attention is pivotal for tasks like studying and working for which focus and low distractions are necessary for peak productivity. This study explores the effectiveness of adaptive transcranial direct current stimulation (tDCS) in either the frontal or parietal region to enhance sustained attention. The research involved ten healthy university students performing the Continuous Performance Task-AX (AX-CPT) while receiving either frontal or parietal tDCS. The study comprised three phases. First, we acquired the electroencephalography (EEG) signal to identify the most suitable metrics related to attention states. Among different spectral and complexity metrics computed on 3 s epochs of EEG, the Fuzzy Entropy and Multiscale Sample Entropy Index of frontal channels were selected. Secondly, we assessed how tDCS at a fixed 1.0 mA current affects attentional performance. Finally, a real-time experiment involving continuous metric monitoring allowed personalized dynamic optimization of the current amplitude and stimulation site (frontal or parietal). The findings reveal statistically significant improvements in mean accuracy (94.04 vs. 90.82%) and reaction times (262.93 vs. 302.03 ms) with the adaptive tDCS compared to a non-stimulation condition. Average reaction times were statistically shorter during adaptive stimulation compared to a fixed current amplitude condition (262.93 vs. 283.56 ms), while mean accuracy stayed similar (94.04 vs. 93.36%, improvement not statistically significant). Despite the limited number of subjects, this work points out the promising potential of adaptive tDCS as a tailored treatment for enhancing sustained attention.

Competing Interests: Conflicts of interest: All authors – none to declare.

This multicenter observational study included 171 COVID-19 adult patients hospitalized in the ICUs of nine hospitals in Lombardy (Northern Italy) from December, 1st 2021, to February, 9th 2022. During the study period, the Delta/Omicron variant ratio of cases decreased with a delay of two weeks in ICU patients compared to that in the community; a higher proportion of COVID-19 unvaccinated patients was infected by Delta than by Omicron whereas a higher rate of COVID-19 boosted patients was Omicron-infected. A higher number of comorbidities and a higher comorbidity score in ICU critically COVID-19 inpatients was positively associated with the Omicron infection as well in vaccinated individuals. Although people infected by Omicron have a lower risk of severe disease than those infected by Delta variant, the outcome, including the risk of ICU admission and the need for mechanical ventilation due to infection by Omicron versus Delta, remains uncertain. The continuous monitoring of the circulating SARS-CoV-2 variants remains a milestone to counteract this pandemic., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2023 SPLF and Elsevier Masson SAS. All rights reserved.)

Background: There is consistent evidence of social inequalities in dementia but the mechanisms underlying this association remain unclear. We examined the role of smoking in midlife in socioeconomic differences in dementia at older ages., Methods: Analyses were based on 9951 (67% men) participants, median age 44.3 [IQR=39.6, 50.3] years at baseline in 1985-1988, from the Whitehall II cohort study. Socioeconomic position (SEP) and smoking (smoking status (current, ex-, never-smoker), pack years of smoking, and smoking history score (combining status and pack-years)) were measured at baseline. Counterfactual mediation analysis was used to examine the contribution of smoking to the association between SEP and dementia., Findings: During a median follow-up of 31.6 (IQR 31.1, 32.6) years, 628 participants were diagnosed with dementia and 2110 died. Analyses adjusted for age, sex, ethnicity, education, and SEP showed smokers (hazard ratio [HR] 1.36 [95% CI 1.10-1.68]) but not ex-smokers (HR 0.95 [95% CI 0.79-1.14]) to have a higher risk of dementia compared to never-smokers; similar results for smoking were obtained for pack-years of smoking and smoking history score. Mediation analysis showed low SEP to be associated with higher risk of dementia (HRs between 1.97 and 2.02, depending on the measure of smoking in the model); estimate for the mediation effect was 16% for smoking status (Indirect Effect HR 1.09 [95% CI 1.03-1.15]), 7% for pack-years of smoking (Indirect Effect HR 1.03 [95% CI 1.01-1.06]) and 11% for smoking history score (Indirect Effect HR 1.06 [95% CI 1.02-1.10])., Interpretation: Our findings suggest that part of the social inequalities in dementia is mediated by smoking., Funding: NIH., Competing Interests: We declare no competing interests., (© 2022 The Author(s).)

Hematological patients at higher risk of severe COVID-19 were excluded from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine trials. In this single-center observational prospective study (NCT05074706), we evaluate immune response in the hematological patients followed at the Hematological Division of San Gerardo Hospital, Monza (Italy) deemed to be severely immunosuppressed after vaccination with two doses of the BNT162b2 vaccine. Anti-SARS-CoV-2 immunoglobulin G titers above the cutoff value of 33.8 BAU/ml were detected in 303 (80.2%) out of the 378 patients enrolled. Patients with lymphoproliferative disorders had a significant lower probability of immunization (43.2% vs. 88.4%, p  < 0.001). Patients treated with anti-CD20 showed a significantly lower probability of immunization compared to all other treatments (21.4%, p  < 0.0001). Among 69 patients who failed seroconversion, 15 patients (22.7%) showed a positive T-cell response. Patients previously treated with anti-CD20 were 2.4 times more likely to test positive for T-cell responses ( p  = 0.014). Within a follow-up of 9 months from the second COVID-19 vaccination, symptomatic SARS-CoV-2 infections were reported by 20 patients (5.3%) and four of them required hospitalization. Successful serological or T-cell-mediated immunization conferred protection from symptomatic COVID-19. Patients treated with anti-CD20 who were not seroconverted after vaccination might still be protected from COVID-19 due to the T-cell immune response., Competing Interests: The authors declare they have no conflicts of interest in relation to the work described., (© 2022 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)

Objective: To examine the association of midlife and late life multimorbidity, including severity of multimorbidity, with incident dementia., Design: Prospective cohort study., Setting: Civil service departments in London (Whitehall II study, study inception in 1985-88)., Participants: 10 095 participants, aged 35 to 55 at baseline., Main Outcome Measure: Incident dementia at follow-up between 1985 and 2019. Cause specific Cox proportional hazards regression was used to examine the association of multimorbidity overall and at age 55, 60, 65, and 70 with subsequent dementia, taking into account the competing risk of death., Results: The prevalence of multimorbidity (≥2 chronic diseases) was 6.6% (655/9937) at age 55 and 31.7% (2464/7783) at age 70; 639 cases of incident dementia occurred over a median follow-up of 31.7 years. After adjustment for sociodemographic factors and health behaviours, multimorbidity at age 55 was associated with subsequent risk of dementia (difference in incidence rate per 1000 person years 1.56, 95% confidence interval 0.62 to 2.77; hazard ratio 2.44, 95% confidence interval 1.82 to 3.26). The association weakened progressively with older age at onset of multimorbidity. At age 65, onset of multimorbidity before age 55 was associated with 3.86 (1.80 to 6.52) per 1000 person years higher incidence of dementia (hazard ratio 2.46, 1.80 to 2.26) and onset between 60 and 65 was associated with 1.85 (0.64 to 3.39) per 1000 person years higher incidence (1.51, 1.16 to 1.97). Severity of multimorbidity (≥3 chronic diseases) at age 55 was associated with a 5.22 (1.14 to 11.95) per 1000 person years higher incidence of dementia (hazard ratio 4.96, 2.54 to 9.67); the same analyses at age 70 showed 4.49 (2.33 to 7.19) per 1000 person years higher incidence (1.65, 1.25 to 2.18)., Conclusion: Multimorbidity, particularly when onset is in midlife rather than late life, has a robust association with subsequent dementia. The increasingly younger age at onset of multimorbidity makes prevention of multimorbidity in people with a first chronic disease important., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support for the Whitehall II study from the National Institute on Aging, NIH, and UK Medical Research Council; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Human motion analysis is gaining increased importance in several fields, from movement assessment in rehabilitation to recreational applications such as virtual coaching. Among all the technologies involved in motion capture, Magneto-Inertial Measurements Units (MIMUs) is one of the most promising due to their small dimensions and low costs. Nevertheless, their usage is strongly limited by different error sources, among which magnetic disturbances, which are particularly problematic in indoor environments. Inertial Measurement Units (IMUs) could, thus, be considered as alternative solution. Indeed, relying exclusively on accelerometers and gyroscopes, they are insensitive to magnetic disturbances. Even if the literature has started to propose few algorithms that do not take into account magnetometer input, their application is limited to robotics and aviation. The aim of the present work is to introduce a magnetic-free quaternion based Extended Kalman filter for upper limb kinematic assessment in human motion (i.e., yoga). The algorithm was tested on five expert yoga trainers during the execution of the sun salutation sequence. Joint angle estimations were compared with the ones obtained from an optoelectronic reference system by evaluating the Mean Absolute Errors (MAEs) and Pearson's correlation coefficients. The achieved worst-case was 6.17°, while the best one was 2.65° for MAEs mean values. The accuracy of the algorithm was further confirmed by the high values of the Pearson's correlation coefficients (lowest mean value of 0.86).Clinical Relevance- The proposed work validated a magnetic free algorithm for kinematic reconstruction with inertial units. It could be used as a wearable solution to track human movements in indoor environments being insensitive to magnetic disturbances, and thus could be potentially used also for rehabilitation purposes.

Searches for the lepton number violating K^{+}→π^{-}μ^{+}e^{+} decay and the lepton flavor violating K^{+}→π^{+}μ^{-}e^{+} and π^{0}→μ^{-}e^{+} decays are reported using data collected by the NA62 experiment at CERN in 2017-2018. No evidence for these decays is found and upper limits of the branching ratios are obtained at 90% confidence level: B(K^{+}→π^{-}μ^{+}e^{+})<4.2×10^{-11}, B(K^{+}→π^{+}μ^{-}e^{+})<6.6×10^{-11} and B(π^{0}→μ^{-}e^{+})<3.2×10^{-10}. These results improve by 1 order of magnitude over previous results for these decay modes.

Wrist denervation is, by the way, one of the most performed and long-lasting surgical technique for wrist arthritis. Despite many progresses in upper extremity joint arthroplasty, wrist arthritis remains difficult to treat specially in young patients and heavy manual workers. The aim of this technical article is to describe a new outpatient's procedure in which applying pulsed radio frequency on nerve structure of the wrist could achieve similar clinical results of a wrist denervation without surgical incision., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

Developing long-term visions through participatory approaches can be very useful to explore different possible scenarios and pathways to reach desirable futures. This brief report describes a participatory process carried out in the Emilia-Romagna region (Italy) to develop a long-term vision for rural areas by 2040. This approach consisted of: (i) interviews and a focus group carried out with a multi-actor platform (MAP) composed of experts from science-society-policy sectors, and (ii) an on-line questionnaire addressing a larger number of rural stakeholders of the region. Mixing expert-based consultation through the MAP with a more inclusive consultation approach resulted in an effective method to build long-term visions in the very heterogeneous rural context of the Emilia-Romagna. However, this study only constitutes a preliminary step into a more elaborated backcasting approach., Competing Interests: No competing interests were disclosed., (Copyright: © 2021 Pellegrini E et al.)

Peripheral nerve stimulation (PNS) electrodes are used to treat intractable painful conditions involving peripheral nerves. Methods for performing PNS continue to evolve, from open surgical to minimally invasive placement of electrodes. A PNS system consisting of subcutaneously implanted leads with an integrated anchor and electrodes, and an external pulse generator to produce peripheral neuromodulation, is now available for use in the clinical setting. This novel system allows either surgical or percutaneous lead positioning, and avoids the use of long leads or extensions crossing the joints, which are exposed to mechanical stress and damage. To identify methods for successfully inserting these electrodes, we investigated if a cadaver model could be an effective educational tool for teaching PNS electrode placement using ultrasound guidance. Six cadavers were studied in an attempt to find an ideal approach for ultrasound-guided electrode placement into the upper and lower extremities and cervical spine, and to describe the unique anatomy of the peripheral nerves relative to percutaneous stimulation-electrode placement. The use of cadaveric model simulations offers opportunities to practice percutaneous placement of PNS electrodes under stress-free conditions without patient discomfort, to acquire skill and confidence in performing these surgical approaches. Ultrasound-guided percutaneous placement of PNS electrodes should be learned in a simulation laboratory before such placement is performed in actual patients.

Detailed data on clinical presentations and outcomes of children with COVID-19 in Europe are still lacking. In this descriptive study, we report on 130 children with confirmed COVID-19 diagnosed by 28 centers (mostly hospitals), in 10 regions in Italy, during the first months of the pandemic. Among these, 67 (51.5%) had a relative with COVID-19 while 34 (26.2%) had comorbidities, with the most frequent being respiratory, cardiac, or neuromuscular chronic diseases. Overall, 98 (75.4%) had an asymptomatic or mild disease, 11 (8.5%) had moderate disease, 11 (8.5%) had a severe disease, and 9 (6.9%) had a critical presentation with infants below 6 months having significantly increased risk of critical disease severity (OR 5.6, 95% CI 1.3 to 29.1). Seventy-five (57.7%) children were hospitalized, 15 (11.5%) needed some respiratory support, and nine (6.9%) were treated in an intensive care unit. All recovered.Conclusion:This descriptive case series of children with COVID-19, mostly encompassing of cases enrolled at hospital level, suggest that COVID-19 may have a non-negligible rate of severe presentations in selected pediatric populations with a relatively high rates of comorbidities. More studies are needed to further understand the presentation and outcomes of children with COVID-19 in children with special needs. What is Known: • There is limited evidence on the clinical presentation and outcomes of children with COVID-19 in Europe, and almost no evidence on characteristics and risk factors of severe cases. What is New: • Among a case series of 130 children, mostly diagnosed at hospital level, and with a relatively high rate (26.2%) of comorbidities, about three-quarter had an asymptomatic or mild disease. • However, 57.7% were hospitalized, 11.5% needed some respiratory support, and 6.9% were treated in an intensive care unit.

The integration of different data sources is a widely discussed topic among both the researchers and the Official Statistics. Integrating data helps to contain costs and time required by new data collections. The non-parametric micro Statistical Matching (SM) allows to integrate 'live' data resorting only to the observed information, potentially avoiding the misspecification bias and speeding the computational effort. Despite these pros, the assessment of the integration goodness when we use this method is not robust. Moreover, several applications comply with some commonly accepted practices which recommend e.g. to use the biggest data set as donor. We propose a validation strategy to assess the integration goodness. We apply it to investigate these practices and to explore how different combinations of the SM techniques and distance functions perform in terms of the reliability of the synthetic (complete) data set generated. The validation strategy takes advantage of the relation existing among the variables pre-and-post the integration. The results show that 'the biggest, the best' rule must not be considered mandatory anymore. Indeed, the integration goodness increases in relation to the variability of the matching variables rather than with respect to the dimensionality ratio between the recipient and the donor data set., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2020 Informa UK Limited, trading as Taylor & Francis Group.)

Background: The literature suggests that optimal levels of gait symmetry might exist for lower-limb amputees. Not only these optimal values are unknown, but we also don't know typical symmetry ratios or which measures of symmetry are essential. Focusing on the symmetries of stance, step, first peak and impulse of the ground reaction force, the aim of this work was to answer to three methodological and three clinical questions. The methodological questions wanted to establish a minimum set of symmetry indexes to study and if there are limitations in their calculations. The clinical questions wanted to establish if typical levels of temporal and loading symmetry exist, and change with the level of amputation and prosthetic components., Methods: Sixty traumatic, K3-K4 amputees were involved in the study: 12 transfemoral mechanical knee users (TFM), 25 C-leg knee users (TFC), and 23 transtibial amputees (TT). Ninety-two percent used the Ossur Variflex foot. Ten healthy subjects were also included. Ground reaction force from both feet were collected with the Novel Pedar-X. Symmetry indexes were calculated and statistically compared with regression analyses and non-parametric analysis of variance among subjects., Results: Stance symmetry can be reported instead of step, but it cannot substitute impulse and first peak symmetry. The first peak cannot always be detected on all amputees. Statistically significant differences exist for stance symmetry among all groups, for impulse symmetry between TFM and TFC/TT, for first peak symmetry between transfemoral amputees altogether and TT. Regarding impulse symmetry, 25% of TFC and 43% of TT had a higher impulse on the prosthetic side. Regarding first peak symmetry, 59% of TF and 30% of TT loaded more the prosthetic side., Conclusions: Typical levels of symmetry for stance, impulse and first peak change with the level of amputation and componentry. Indications exist that C-leg and energy-storage-and-return feet can improve symmetry. Results are suggestive of two mechanisms related to sound side knee osteoarthritis: increased impulse for TF and increased first peak for TT. These results can be useful in clinics to set rehabilitation targets, understand the advancements of a patient during gait retraining, compare and chose components and possibly rehabilitation programs.

A novel mechanism to produce and detect light dark matter in experiments making use of GeV electrons (and positrons) impinging on a thick target (beam dump) is proposed. The positron-rich environment produced by the electromagnetic shower allows us to produce an A^{'} via nonresonant (e^{+}+e^{-}→γ+A^{'}) and resonant (e^{+}+e^{-}→A^{'}) annihilation on atomic electrons. The latter mechanism, for some selected kinematics, results in a larger sensitivity with respect to limits derived by the commonly used A^{'}-strahlung. This idea, applied to beam-dump experiments and active beam-dump experiments, pushes down the current limits by an order of magnitude.

Introduction: Assessing the feasibility, technical implications, and clinical benefits of peripheral nerve stimulation (PNS) performed by an implantable pulse generator (IPG) located close to the stimulation site., Materials and Methods: Selected patients were affected by neuropathic pain associated with a documented peripheral nerve lesion, refractory to conventional surgical or pharmacological treatment. A PNS system specifically designed for peripheral placement (Neurimpulse, Padova, Italy) was implanted and followed for six months, recording the degree of patient's satisfaction (PGI-I questionnaire), the pain numerical rating scale (NRS) and the quality of life (SF36 questionnaire), as well as any change in drug regimen and work capability. The statistical significance of differences was determined by the paired Student's t-test., Results: A total of 58 patients were referred to permanent IPG implantation. Stimulation failure due to lead damage or dislocation was noticed in two cases (3.4%) in six months. At the follow-up end, the relative NRS reduction averaged -58 ± 30% (p < 10 -6 ) and was greater than 50% in 69% of the cases. Quality-of-life physical and mental indices were increased by 18% (p < 0.005) and 29% (p < 0.0005), respectively. The administration of antalgic drugs was stopped in 55% and reduced in 16% of the patients. Low-energy stimulation was possible in most cases, resulting in an IPG estimated life of 80 ± 35 months., Conclusions: Successful PNS was achieved with a stimulation system designed for peripheral location. This new technology reduced the incidence of lead-related adverse events and the energy cost of the treatment., (© 2016 International Neuromodulation Society.)

Background: During the last decade, the spread of Klebsiella pneumoniae -carbapenemase-producing Klebsiella pneumoniae (KPC- Kp ) has increased dramatically worldwide. In this scenario, growing interest has been addressed to genotyping of KPC- Kp strains, which emerged as an important tool for a better understanding of the epidemiological and clinical characteristics of the outbreaks., Methods: We performed a retrospective cohort study on patients infected with KPC- Kp during a 28-month outbreak period (January 2010-April 2012) at San Gerardo Hospital (Monza, Italy), investigating KPC- Kp genotypes by means of repetitive element sequence-based polymerase chain reaction (Rep-PCR)., Results: We enrolled 97 patients infected with KPC- Kp . Rep-PCR analysis identified 5 distinct clone types, with different distribution over time. During the first 12 months of the outbreak period, only 1 clone was detected (clone A, in 47 patients), while the 4 other clones were identified over the remaining 16 months (clones C, E, and F/L in 23, 24, and 3 patients respectively). Mechanical ventilation was less frequent in patients infected with clones C/E/F/L (OR = 0.14; 95% CI: 0.05-0.37) compared to clone A, and the Charlson comorbidity index (CI) was more likely to have a score >5 in patients infected with clones C/E/F/L (OR = 7.21; 95% CI: 2.24-23.14) compared to clone A.Overall mortality was higher in patients infected with clones C/E/F/L (13/20 patients, 65%) compared to those infected with clone A (7/20, 35%). Mortality in patients infected with clones C/E/F/L remained significantly higher even after adjusting for the potential confounding effect of comorbidities (ie, CI), with a hazard ratio (HR) of 4.65 (95% CI: 1.83-11.89)., Conclusions: Our results suggested a close relationship between strain genotype and clinical outcome., Competing Interests: All authors: No reported conflicts. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Clinical gait analysis (CGA) has shown potentials for the prosthetics field and has been found effective for scientific purposes and to design general rehabilitation models. However, intrinsic limitations of the "artificial" laboratory environment usually result in recording performances not representative patients' real-life gait. In order to promote the diffusion of CGA in the clinical decision-making process, a framework for developing novel, more ecological CGA applications is presented. Moreover, the Outwalk protocol, based on wearable sensors and developed within this framework guidelines, is described and validated for its inter-rater agreement on a population of transtibial amputees walking in a real-life scenario. Results show the possibility of drawing precise conclusions over different aspects of amputees' gait and prostheses' performance in every-day life conditions.

Quantitative motion analysis protocols have been developed to assess the coordination between scapula and humerus. However, the application of these protocols to test whether a subject's scapula resting position or pattern of coordination is "normal", is precluded by the unavailability of reference prediction intervals and bands, respectively. The aim of this study was to present such references for the "ISEO" protocol, by using the non-parametric Bootstrap approach and two parametric Gaussian methods (based on Student's T and Normal distributions). One hundred and eleven asymptomatic subjects were divided into three groups based on their age (18-30, 31-50, and 51-70). For each group, "monolateral" prediction bands and intervals were computed for the scapulo-humeral patterns and the scapula resting orientation, respectively. A fourth group included the 36 subjects (42 ± 13 year-old) for whom the scapulo-humeral coordination was measured bilaterally, and "differential" prediction bands and intervals were computed, which describe right-to-left side differences. Bootstrap and Gaussian methods were compared using cross-validation analyses, by evaluating the coverage probability in comparison to a 90% target. Results showed a mean coverage for Bootstrap from 86% to 90%, compared to 67-70% for parametric bands and 87-88% for parametric intervals. Bootstrap prediction bands showed a distinctive change in amplitude and mean pattern related to age, with an increase toward scapula retraction, lateral rotation and posterior tilt. In conclusion, Bootstrap ensures an optimal coverage and should be preferred over parametric methods. Moreover, the stratification of "monolateral" prediction bands and intervals by age appears relevant for the correct classification of patients., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Symmetry and regularity of gait are essential outcomes of gait retraining programs, especially in lower-limb amputees. This study aims presenting an algorithm to automatically compute symmetry and regularity indices, and assessing the minimum number of strides for appropriate evaluation of gait symmetry and regularity through autocorrelation of acceleration signals., Methods: Ten transfemoral amputees (AMP) and ten control subjects (CTRL) were studied. Subjects wore an accelerometer and were asked to walk for 70 m at their natural speed (twice). Reference values of step and stride regularity indices (Ad1 and Ad2) were obtained by autocorrelation analysis of the vertical and antero-posterior acceleration signals, excluding initial and final strides. The Ad1 and Ad2 coefficients were then computed at different stages by analyzing increasing portions of the signals (considering both the signals cleaned by initial and final strides, and the whole signals). At each stage, the difference between Ad1 and Ad2 values and the corresponding reference values were compared with the minimum detectable difference, MDD, of the index. If that difference was less than MDD, it was assumed that the portion of signal used in the analysis was of sufficient length to allow reliable estimation of the autocorrelation coefficient., Results: All Ad1 and Ad2 indices were lower in AMP than in CTRL (P < 0.0001). Excluding initial and final strides from the analysis, the minimum number of strides needed for reliable computation of step symmetry and stride regularity was about 2.2 and 3.5, respectively. Analyzing the whole signals, the minimum number of strides increased to about 15 and 20, respectively., Conclusions: Without the need to identify and eliminate the phases of gait initiation and termination, twenty strides can provide a reasonable amount of information to reliably estimate gait regularity in transfemoral amputees.

Introduction: For the better understanding of the pathophysiological events occurring in the sequence inflammation-metaplasia-carcinoma in esophageal adenocarcinoma, an animal model would be desirable. In the past, several rat models have been used yielding conflicting results. Some demonstrated a sequence similar to the human situation whereas others failed to initiate true esophageal adenocarcinoma or even Barrett's metaplasia. For the study of the molecular events involved in the carcinogenesis of Barrett's carcinoma, a mouse model would be much more promising since most of the genetically altered animals are mice. However, as of now no such model exists, in the past predominately due to the high mortality involved with the surgical procedure to create a mixed duodenogastric reflux., Methods: Forty BALB-C mice weighing between 22 and 25 g underwent an esophagojejunostomy. The animals were sacrificed at 3, 4, and 5 months. Pathological evaluation was performed with HE staining., Results: Overall mortality was 17%. However, mortality within the first ten animals was 30%. Reasons were technical problems with the anastomosis, opening of the pleural cavity, or bleeding events. All animals had a severe esophagitis regardless of the time. Intestinal metaplasia could be found in 60% of the animals after 4 months and esophageal adenocarcinoma in 55% after 5 months. One animal showed multiple lung metastases., Conclusion: After a certain learning curve esophagojejunostomy is feasible in mice with an acceptable mortality rate and leads to esophageal adenocarcinoma.

Background: The aim of this study was to evaluate a method based on a single accelerometer for the assessment of gait symmetry and regularity in subjects wearing lower limb prostheses., Methods: Ten transfemoral amputees and ten healthy control subjects were studied. For the purpose of this study, subjects wore a triaxial accelerometer on their thorax, and foot insoles. Subjects were asked to walk straight ahead for 70 m at their natural speed, and at a lower and faster speed. Indices of step and stride regularity (Ad1 and Ad2, respectively) were obtained by the autocorrelation coefficients computed from the three acceleration components. Step and stride durations were calculated from the plantar pressure data and were used to compute two reference indices (SI1 and SI2) for step and stride regularity., Results: Regression analysis showed that both Ad1 well correlates with SI1 (R2 up to 0.74), and Ad2 well correlates with SI2 (R2 up to 0.52). A ROC analysis showed that Ad1 and Ad2 has generally a good sensitivity and specificity in classifying amputee's walking trial, as having a normal or a pathologic step or stride regularity as defined by means of the reference indices SI1 and SI2. In particular, the antero-posterior component of Ad1 and the vertical component of Ad2 had a sensitivity of 90.6% and 87.2%, and a specificity of 92.3% and 81.8%, respectively., Conclusions: The use of a simple accelerometer, whose components can be analyzed by the autocorrelation function method, is adequate for the assessment of gait symmetry and regularity in transfemoral amputees.

A protocol named "Outwalk" was recently proposed to measure the thorax-pelvis and lower-limb kinematics during gait in free-living conditions, by means of an inertial and magnetic measurement system (IMMS). The aim of this study was to validate Outwalk on four healthy subjects when it is used in combination with a specific IMMS (Xsens Technologies, NL), against a reference protocol (CAST) and measurement system (optoelectronic system; Vicon, Oxford Metrics Group, UK). For this purpose, we developed an original approach based on three tests, which allowed to separately investigate: (1) the consequences on joint kinematics of the differences between protocols (Outwalk vs. CAST), (2) the accuracy of the hardware (Xsens vs. Vicon), and (3) the summation of protocols' differences and hardware accuracy (Outwalk + Xsens vs. CAST + Vicon). In order to assess joint-angles similarity, the coefficient of multiple correlation (CMC) was used. For test 3, the CMC showed that Outwalk + Xsens and CAST + Vicon kinematics can be interchanged, offset included, for hip, knee and ankle flexion-extension, and hip ab-adduction (CMC > 0.88). The other joint-angles can be interchanged offset excluded (CMC > 0.85). Tests 1 and 2 also showed that differences in offset between joint-angles were predominantly induced by differences in the protocols; differences in correlation by both hardware and protocols; differences in range of motion by the Xsens accuracy. Results thus support the commencement of a clinical trial of Outwalk on transtibial amputees.

Purpose: In locally advanced (uT(3), N(+)) adenocarcinomas of the esophagus, neoadjuvant chemotherapy improves patient outcome. However, only a subgroup of patients responds. Therefore, in the present study, we evaluated whether the response to neoadjuvant chemotherapy can be predicted by a pretreatment tumor biopsy analysis., Experimental Design: Biopsies of 47 patients with locally advanced (uT(3), N(+)) adenocarcinoma of the esophagus were obtained during primary staging. All patients underwent neoadjuvant chemotherapy with cisplatin, 5-fluorouracil, and leucovorin and subsequent resection of the esophagus. Biopsies were used for microarray analysis. The predominance of tumor cells within the specimens was >70%. Affymetrix U133 plus 2.0 gene chips with 54675 probe sets were used. A statistical comparison of patients responding to chemotherapy versus nonresponding patients was done. All patients were examined with immunohistology against Ephrin B3 receptor and Ki-67., Results: A total of 86 genes were at least 2-fold differentially regulated comparing responding with nonresponding adenocarcinomas of the esophagus. The predominant genes encoded for the regulation of the cell cycle, transduction, translation, cell-cell interaction, cytoskeleton, and the signal transduction. The strongest difference was seen for the Ephrin B3 receptor. This result could be confirmed by immunhistology. A statistical significant correlation between the Ephrin B3 receptor, chemotherapy response, pathologic staging, and grading could be shown., Conclusions: There were significant differences in the gene profile between patients with adenocarcinoma of the esophagus responding to neoadjuvant chemotherapy compared with nonresponding patients. This suggests that it could be possible to characterize patients responding to chemotherapy even before starting the treatment using customized microarray analysis.

A protocol named Outwalk was developed to easily measure the thorax-pelvis and lower-limb 3D kinematics on children with cerebral palsy (CP) and amputees during gait in free-living conditions, by means of an Inertial and Magnetic Measurement System (IMMS). Outwalk defines the anatomical/functional coordinate systems (CS) for each body segment through three steps: (1) positioning the sensing units (SUs) of the IMMS on the subjects' thorax, pelvis, thighs, shanks and feet, following simple rules; (2) computing the orientation of the mean flexion-extension axis of the knees; (3) measuring the SUs' orientation while the subject's body is oriented in a predefined posture, either upright or supine. If the supine posture is chosen, e.g. when spasticity does not allow to maintain the upright posture, hips and knees static flexion angles must be measured through a standard goniometer and input into the equations that define Outwalk anatomical CSs. In order to test for the inter-rater measurement reliability of these angles, a study was carried out involving nine healthy children (7.9 +/- 2 years old) and two physical therapists as raters. Results showed RMS error of 1.4 degrees and 1.8 degrees and a negligible worst-case standard error of measurement of 2.0 degrees and 2.5 degrees for hip and knee angles, respectively. Results were thus smaller than those reported for the same measures when performed through an optoelectronic system with the CAST protocol and support the beginning of clinical trials of Outwalk with children with CP.

The frequency of early-onset neonatal sepsis without prophylaxis is 1-5/1.000 live births. Since year '70 the most frequent causative microorganism is the group B Streptococcus (S. agalactiae, GBS), followed by Escherichia coli. The mortality rate is now reduced to 4% due to the improvement of neonatal intensive care. In the USA, the incidence of GBS early-onset neonatal sepsis has been markedly reduced by the application of the guidelines released by the Centers for Disease Control (CDC). This strategy, however, is not effective on occurrence of late-onset neonatal group B streptococcal disease. In Italy, the application of CDC guidelines is not customary, and different, often complex, protocols of obstetrical-neonatological integrated approach are applied. The frequency of infectious risk has made the GBS a paramount problem for the neonatologist, even for the legal responsibility issues resulting from the multiplicity of possible options. To reach the best level of protection of the newborn against early-onset GBS infection, the working group of providers of prenatal, obstetric, and neonatal care of the functional area of Cuneo issued an integrated protocol, in order to perform the GBS screening with the optimal culture method suggested by CDC guidelines in the highest possible number of pregnant women, and to standardize the obstetrical and neonatal management.

The performance of different policy design strategies is a key issue in evaluating programmes for water quality improvement under the Water Framework Directive (60/2000). This issue is emphasised by information asymmetries between regulator and agents. Using an economic model under asymmetric information, the aim of this paper is to compare the cost-effectiveness of selected methods of designing payments to farmers in order to reduce nitrogen pollution in agriculture. A principal-agent model is used, based on profit functions generated through farm-level linear programming. This allows a comparison of flat rate payments and a menu of contracts developed through mechanism design. The model is tested in an area of Emilia Romagna (Italy) in two policy contexts: Agenda 2000 and the 2003 Common Agricultural Policy (CAP) reform. The results show that different policy design options lead to differences in policy costs as great as 200-400%, with clear advantages for the menu of contracts. However, different policy scenarios may strongly affect such differences. Hence, the paper calls for greater attention to the interplay between CAP scenarios and water quality measures.

Two antipsychotic drugs (clozapine and loxapine) and six metabolites, N-demethylclozapine, clozapine N-oxide, N-demethylloxapine (amoxapine), 7-hydroxyloxapine, 8-hydroxyloxapine, 8-hydroxyamoxapine, were separated by capillary zone electrophoresis. Variation of pH and ionic strength of the acidic phosphate buffer (pH below 4) did not enable the separation of loxapine and one of its metabolites. Resolution of the single parent drugs and their metabolites was possible in background electrolytes (phosphate, pH 3.5, 60 mmol/l) containing either 0.2% (w/v) polyvinylpyrrolidone as replaceable pseudo-stationary phase, or 0.75 mmol/l beta-cyclodextrin added as complex-forming agent. Full separation of the mixture with baseline resolution of all analytes was obtained with a background electrolyte with heptakis-6-sulfato-beta-cyclodextrin added as negatively charged complexation agent with improved separation selectivity.

Several strategies to improve the separation of 11 central nervous system drugs (antipsychotics and antidepressants) with capillary zone electrophoresis were applied: the variation of the pH of the buffering background electrolyte, its ionic strength, addition of inclusion-complex forming beta-cyclodextrin or polyvinylpyrrolidone (PVP), respectively, as a replaceable, soluble, polymeric pseudo-stationary phase. Best separation was achieved at pH 2.5 and 35 mmol/l ionic strength (phosphate buffer), with 0.5% (w/v) PVP.

Bejar et al. described increased concentrations of valine, leucine and isoleucine in the plasma of 2 patients with cerebral gigantism (Sotos-syndrome). We have recently investigated a group of 14 children with Sotos-syndrome. The data of the plasma amino-acid determinations were compared with those of aged-matched healthy controls, 9 children with benign muscular hypotonia, 10 children with Down's syndrome and finally with those of 13 children with familial tall stature. The mean concentration of serine, glutamic acid, valine, isoleucine, leucine and phenylalanine was lower in the patients with Sotos-syndrome when compared to the healthy control group. However, all patients with benign muscular hypotonia and Down's syndrome showed increased concentrations of proline, glycine, alanine, ornithine and lysine in the plasma whereas the mean values of the children with familial tall stature differed only slightly from those of the controls. The levels of the plasma-aminoacids in patients with Sotos-syndrome were only slightly different from those in patients with muscular hypotonia, but generally lower than in tall children. We conclude that the determination of plasma-aminoacids is of no value in the diagnosis of Sotos-syndrome.