Invasive versus non-invasive paediatric home mechanical ventilation: review of the international evolution over the past 24 years.

BACKGROUND: Home mechanical ventilation (HMV) is the treatment for chronic hypercapnic alveolar hypoventilation. The proportion and evolution of paediatric invasive (IMV) and non-invasive (NIV) HMV across the world is unknown, as well as the disorders and age of children using HMV. METHODS: Search of Medline/PubMed for publications of paediatric surveys on HMV from 2000 to 2023. RESULTS: Data from 32 international reports, representing 8815 children (59% boys) using HMV, were analysed. A substantial number of children had neuromuscular disorders (NMD; 37%), followed by cardiorespiratory (Cardio-Resp; 16%), central nervous system (CNS; 16%), upper airway (UA; 13%), other disorders (Others; 10%), central hypoventilation (4%), thoracic (3%) and genetic/congenital disorders (Gen/Cong; 1%). Mean age±SD (range) at HMV initiation was 6.7±3.7 (0.5-14.7) years. Age distribution was bimodal, with two peaks around 1-2 and 14-15 years. The number and proportion of children using NIV was significantly greater than that of children using IMV (n=6362 vs 2453, p=0.03; 72% vs 28%, p=0.048), with wide variations among countries, studies and disorders. NIV was used preferentially in the preponderance of children affected by UA, Gen/Cong, Thoracic, NMD and Cardio-Resp disorders. Children with NMD still receiving primary invasive HMV were mainly type I spinal muscular atrophy (SMA). Mean age±SD at initiation of IMV and NIV was 3.3±3.3 and 8.2±4.4 years (p<0.01), respectively. The rate of children receiving additional daytime HMV was higher with IMV as compared with NIV (69% vs 10%, p<0.001). The evolution of paediatric HMV over the last two decades consists of a growing number of children using HMV, in parallel to an increasing use of NIV in recent years (2020-2023). There is no clear trend in the profile of children over time (age at HMV). However, an increasing number of patients requiring HMV were observed in the Gen/Cong, CNS and Others groups. Finally, the estimated prevalence of paediatric HMV was calculated at 7.4/100 000 children. CONCLUSIONS: Patients with NMD represent the largest group of children using HMV. NIV is increasingly favoured in recent years, but IMV is still a prevalent intervention in young children, particularly in countries indicating less experience with NIV.

Reevaluating the timing of Neanderthal disappearance in Northwest Europe.

Elucidating when Neanderthal populations disappeared from Eurasia is a key question in paleoanthropology, and Belgium is one of the key regions for studying the Middle to Upper Paleolithic transition. Previous radiocarbon dating placed the Spy Neanderthals among the latest surviving Neanderthals in Northwest Europe with reported dates as young as 23,880 ± 240 B.P. (OxA-8912). Questions were raised, however, regarding the reliability of these dates. Soil contamination and carbon-based conservation products are known to cause problems during the radiocarbon dating of bulk collagen samples. Employing a compound-specific approach that is today the most efficient in removing contamination and ancient genomic analysis, we demonstrate here that previous dates produced on Neanderthal specimens from Spy were inaccurately young by up to 10,000 y due to the presence of unremoved contamination. Our compound-specific radiocarbon dates on the Neanderthals from Spy and those from Engis and Fonds-de-Forêt demonstrate that they disappeared from Northwest Europe at 44,200 to 40,600 cal B.P. (at 95.4% probability), much earlier than previously suggested. Our data contribute significantly to refining models for Neanderthal disappearance in Europe and, more broadly, show that chronometric models regarding the appearance or disappearance of animal or hominin groups should be based only on radiocarbon dates obtained using robust pretreatment methods.

User-perceived impact of long-term mechanical assisted cough in paediatric neurodisability.

AIM: To (1) compare the perceived benefit of long-term mechanical insufflation-exsufflation (MI-E) of children with neuromuscular disorders (NMDs) and central nervous system (CNS) disorders, including health care needs and treatment routines and (2) describe the children's health-related quality of life (HRQoL). METHOD: This cross-sectional study used a questionnaire and memory card data to assess the perceived benefit of MI-E via the Visual Analogue Scale (VAS; 10 maximum), willingness to pause treatment, level of health care needs before and after MI-E initiation, and the children's treatment routines. A DISABKIDS questionnaire assessed HRQoL (100 maximum). RESULTS: Seventy-three children using MI-E participated (42 males, median [interquartile range {IQR}] age 10 years 2 months [6 years 3 months-14 years 1 month]), 47 with NMDs (such as spinal muscular atrophy and Duchenne muscular dystrophy) and 26 with CNS disorders (such as cerebral palsy, encephalitis, neurometabolic and other diseases). The median (IQR) VAS score for the perceived benefit of MI-E therapy at stable state and respiratory tract infection were 9 (6-10) and 10 (8.5-10) respectively. Sixty-two per cent were reluctant or unwilling to pause MI-E therapy, with no NMD versus CNS disorder group difference. After MI-E initiation, fewer physician consultations and hospitalizations were reported by the group with NMDs. The MI-E routine was similar in both groups. The mean (SD) HRQoL score for 26 of 51 eligible children was 71 (16.7). INTERPRETATION: MI-E treatment was generally perceived as beneficial and performed equally in both diagnostic groups. HRQoL was in line with children with a moderate-to-severe chronic condition. WHAT THIS PAPER ADDS: Mechanical insufflation-exsufflation (MI-E) was generally perceived as beneficial by the children and parents. The reported benefit of MI-E was higher among daily than sporadic MI-E users. The MI-E treatment routine did not differ between diagnostic groups. The health-related quality of life in this neuropaediatric population was in line with that of children with other moderate-to-severe chronic conditions.

Building a home ventilation programme: population, equipment, delivery and cost.

Home mechanical ventilation (HMV) improves quality of life and survival in patients with neuromuscular disorders (NMD). Developing countries may benefit from published evidence regarding the prevalence, cost of equipment, technical issues and organisation of HMV in NMD, facilitating the development of local turn-key HMV programmes. Unfortunately, such evidence is scattered in the existing literature. We searched Medline for publications in English and French from 2005 to 2020. This narrative review analyses 24 international programmes of HMV. The estimated prevalence (min-max) of HMV is ±7.3/100 000 population (1.2-47), all disorders combined. The prevalence of HMV is associated with the gross domestic product per capita in these 24 countries. The prevalence of NMD is about 30/100 000 population, of which ±10% would use HMV. Nocturnal (8/24 hour), discontinuous (8-16/24 hours) and continuous (>16/24 hours) ventilation is likely to concern about 60%, 20% and 20% of NMD patients using HMV. A minimal budget of about 168€/patient/year (504€/100 000 population), including the cost of equipment solely, should address the cost of HMV equipment in low-income countries. When services and maintenance are included, the budget can drastically increase up to between 3232 and 5760€/patient/year. Emerging programmes of HMV in developing countries reveal the positive impact of international cooperation. Today, at least 12 new middle, and low-income countries are developing HMV programmes. This review with updated data on prevalence, technical issues, cost of equipment and services for HMV should trigger objective dialogues between the stakeholders (patient associations, healthcare professionals and politicians); potentially leading to the production of workable strategies for the development of HMV in patients with NMD living in developing countries.

Mechanical ventilation in Duchenne muscular dystrophy: A pilot project in Ukraine.

BACKGROUND: Home mechanical ventilation (HMV) prolongs survival in patients with Duchenne muscular dystrophy (DMD) until ±35 years of age. This study evaluates the implementation of a HMV pilot project in children with DMD in Ukraine. METHODS: Children with DMD were invited to Kirovograd Regional Children's Clinical Hospital, Kropyvnytskyi, Ukraine, for 5 days' training with non-invasive ventilation. Donated equipment comprised second-hand Covidien PB560 ventilators from Belgium. Due to the absence of carbon dioxide pressure and pulse oximetry monitoring, indications for HMV included sleep-related symptoms, restrictive lung function test, loss of ambulation for more than 1 year, or age greater than 17 years. Master class lectures on HMV were conducted for Ukrainian doctors in conjunction with patient training. RESULTS: Twelve Ukrainian physicians took part in face-to-face master classes and 50 Ukrainian physicians participated in online master classes. Simultaneously, eight Duchenne inpatients, mean age 15.4 (SD: 1.8) years and body mass index 25.8 (SD: 4.0), were included in the study. All patients chose nasal masks and volume-pressure-assisted control mode. After 6 weeks, one patient stopped HMV, two others used HMV partially during sleep, and 5/8 used nocturnal HMV increasingly with few complaints. Follow up via phone call was organized after hospitalization. CONCLUSIONS: Implementation of HMV is feasible in DMD inpatients in Ukraine. In the short term, the Ukrainian parliament should recognize official centers for HMV, and define the funding policy of equipment for HMV, and its maintenance. Local distributors should deliver equipment for HMV and devices for monitoring carbon dioxide pressure and pulse oximetry in specialized centers for HMV.

European Survey: Dysphagia Management in Patients with Neuromuscular Diseases.

Dysphagia is common in patients with neuromuscular diseases (NMDs). Its management differs by country and clinical setting. The purpose of this study was to describe current practices in the management of dysphagia in NMDs across Europe. An online survey of sixteen questions was developed, including basic information on facilities, existence of a management protocol, availability of dedicated therapists, tools used during screening, assessment, treatment stages, and treatment strategies. The survey was rolled out to European healthcare facilities providing care for NMDs. A total of 140 facilities across 25 European countries completed the survey. Substantial discrepancies in dysphagia management were identified among respondents. Seventy-two percent of the facilities reported having a protocol for at least one of the three management stages whereas only 39% had one for all. Speech and language therapists were reported as involved throughout the entire management stage while participation of other members from multidisciplinary teams varied depending on the stage. Clinical swallowing assessment was the most frequently reported tool in the assessment and treatment stages. For screening, questionnaires were the most frequently used while instrumental examinations were mainly reported in the assessment stage. For the treatment stage, adaptation strategies (diet, food, and posture) were the most reported approaches. In conclusion, the survey highlighted the absence of a defined protocol concerning the management of dysphagia in most of the surveyed healthcare facilities. Standardized training strategies and guidelines are necessary in the future to familiarize clinicians with each stage of the management of dysphagia.

Screening for oropharyngeal dysphagia in adult patients with neuromuscular diseases using the Sydney Swallow Questionnaire.

INTRODUCTION/AIMS: Oropharyngeal dysphagia is common in patients with neuromuscular diseases (NMDs). Its early recognition is vital for proper management. We tested a large cohort of adult NMD patients for oropharyngeal dysphagia using the Sydney Swallow Questionnaire (SSQ). We also looked for possible differences in characteristics of oropharyngeal dysphagia in various NMD groups and diseases. Finally, we compared results of this screening with those from their corresponding medical records for eventual "clinical history" of dysphagia. METHODS: We asked patients to fill in the SSQ during follow-up outpatient visits at our neuromuscular reference center. A total score above the cutoff score of 118.5 out of 1700 was indicative of oropharyngeal dysphagia. RESULTS: Of the 304 adult patients assessed for eligibility, 201 NMD patients (96 women and 105 men, aged 49.0 ± 16.2 years) were included and tested in this study. Oropharyngeal dysphagia was detected in 45% of all the NMD patients when using the SSQ, whereas only 12% had a positive medical record for dysphagia. The median SSQ scores for patients with myotonic syndromes (including myotonic dystrophy type 1), with amyotrophic lateral sclerosis, and with facioscapulohumeral dystrophy were above the cutoff score. The SSQ scores obtained revealed distinct oropharyngeal dysphagia characteristics in the different NMD groups and diseases. DISCUSSION: The SSQ tests positively for oropharyngeal dysphagia in a higher proportion of NMD patients compared with their medical records. The distinct oropharyngeal dysphagia characteristics we revealed in different NMD groups and diseases may help to elaborate adapted clinical approaches in the management of oropharyngeal dysphagia.

Prevalence of long-term mechanical insufflation-exsufflation in children with neurological conditions: a population-based study.

AIM: To determine the prevalence of long-term mechanical insufflation-exsufflation (MI-E) and concomitant mechanical ventilation in children with neurological conditions, with reported reasons behind the initiation of treatment. METHOD: This was a population-based, cross-sectional study using Norwegian national registries and a questionnaire. RESULTS: In total, 114 of 19 264 children with a neurological condition had an MI-E device. Seventy-three of 103 eligible children (31 females, 42 males), median (min-max) age of 10 years 1 month (1y 5mo-17y 10mo), reported their MI-E treatment initiation. Overall, 76% reported airway clearance as the main reason to start long-term MI-E. A prophylactic use was mainly reported by children with neuromuscular disorders (NMDs). Prevalence and age at initiation differed by diagnosis. In spinal muscular atrophy and muscular dystrophies, MI-E use was reported in 34% and 7% of children, of whom 83% and 57% respectively received ventilator support. One-third of the MI-E users were children with central nervous system (CNS) conditions, such as cerebral palsy and degenerative disorders, and ventilator support was provided in 31%. The overall use of concomitant ventilatory support among the long-term MI-E users was 56%. INTERPRETATION: The prevalence of MI-E in a neuropaediatric population was 6 per 1000, with two-thirds having NMDs and one-third having conditions of the CNS. The decision to initiate MI-E in children with neurological conditions relies on clinical judgment. WHAT THIS PAPER ADDS: The prevalence and age at initiation of mechanical insufflation/exsufflation (MI-E) differed between diagnoses. MI-E was most commonly used in spinal muscular atrophy, where it generally coincided with ventilatory support. One-third of MI-E devices were given to children with central nervous system conditions, and one-third also received ventilatory support.

Cough augmentation techniques for people with chronic neuromuscular disorders.

BACKGROUND: People with neuromuscular disorders may have a weak, ineffective cough predisposing them to respiratory complications. Cough augmentation techniques aim to improve cough effectiveness and mucous clearance, reduce the frequency and duration of respiratory infections requiring hospital admission, and improve quality of life. OBJECTIVES: To determine the efficacy and safety of cough augmentation techniques in adults and children with chronic neuromuscular disorders. SEARCH METHODS: On 13 April 2020, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, and ClinicalTrials.gov for randomised controlled trials (RCTs), quasi-RCTs, and randomised cross-over trials. SELECTION CRITERIA: We included trials of cough augmentation techniques compared to no treatment, alternative techniques, or combinations thereof, in adults and children with chronic neuromuscular disorders. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial eligibility, extracted data, and assessed risk of bias. The primary outcomes were the number and duration of unscheduled hospitalisations for acute respiratory exacerbations. We assessed the certainty of evidence using GRADE. MAIN RESULTS: The review included 11 studies involving 287 adults and children, aged three to 73 years. Inadequately reported cross-over studies and the limited additional information provided by authors severely restricted the number of analyses that could be performed. Studies compared manually assisted cough, mechanical insufflation, manual and mechanical breathstacking, mechanical insufflation-exsufflation, glossopharyngeal breathing, and combination techniques to unassisted cough and alternative or sham interventions. None of the included studies reported on the primary outcomes of this review (number and duration of unscheduled hospital admissions) or listed 'adverse events' as primary or secondary outcome measures. The evidence suggests that a range of cough augmentation techniques may increase peak cough flow compared to unassisted cough (199 participants, 8 RCTs), but the evidence is very uncertain. There may be little to no difference in peak cough flow outcomes between alternative cough augmentation techniques (216 participants, 9 RCTs). There was insufficient evidence to determine the effect of interventions on measures of gaseous exchange, pulmonary function, quality of life, general function, or participant preference and satisfaction. AUTHORS' CONCLUSIONS: We are very uncertain about the safety and efficacy of cough augmentation techniques in adults and children with chronic neuromuscular disorders and further studies are needed.

Respiratory morbidity in children with cerebral palsy: an overview.

Respiratory problems have a significant impact on morbidity and mortality in patients with cerebral palsy (CP). In particular, recurrent aspiration, impaired airway clearance, spinal and thoracic deformity, impaired lung function, poor nutritional status, and recurrent respiratory infections negatively affect respiratory status. Bronchopulmonary dysplasia may contribute to pulmonary problems, but asthma is not more common in CP than in the general population. We discuss treatment options for each of these factors. Multiple coexisting and interacting factors that influence the respiratory status of patients with CP should be recognized and effectively addressed to reduce respiratory morbidity and mortality. WHAT THIS PAPER ADDS: Respiratory problems are a significant cause of morbidity in patients with cerebral palsy (CP). Respiratory status in patients with CP is influenced by recurrent aspiration and impaired airway clearance. Spinal and thoracic deformity, impaired lung function, poor nutrition, and respiratory infections also negatively affect respiratory status. These factors should all be addressed to reduce respiratory problems in patients with CP.

MORBILIDAD RESPIRATORIA EN NIÑOS CON PARÁLISIS CEREBRAL: UNA VISIÓN GENERAL: Los problemas respiratorios tienen un impacto significativo sobre la morbilidad y mortalidad en pacientes con parálisis cerebral (PC). En particular, aspiraciones recurrentes, incapacidad para despejar la vía aérea, deformidades de la columna y del tórax, deterioro de la función pulmonar, un pobre estado nutricional e infecciones pulmonares recurrentes, afectan negativamente el estado respiratorio. La displasia broncopulmonar puede contribuir a estos problemas pulmonares, pero el asma no es más común en PC que en la población general. Discutimos las opciones terapéuticas para cada uno de estos factores. La coexistencia e interacción de múltiples factores que influencian el estado respiratorio de las pacientes con PC deben ser reconocidos y tratados efectivamente para reducir la morbilidad respiratoria y la mortalidad.

MORBIDADE RESPIRATÓRIA EM CRIANÇAS COM PARALISIA CEREBRAL: UM PANORAMA: Problemas respiratórios têm impacto significativo na morbidade e mortalidade em pacientes com paralisia cerebral (PC). Em particular, aspiração recorrente, limpeza deficiente das vias aéreas, deformidade espinhal e torácica, função pulmonar deficiente, pobre estado nutricional, e infecções respiratórias recorrentes podem afetar o estado respiratório negativamente. A displasia broncopulmonar pode contribuir para problemas pulmonares, mas a asma não é mais comum em PC do que na população geral. Nós discutimos opções de tratamento para cada um destes fators. Múltiplos fatores coexistentes ou que interagem e que influenciam o estado respiratório de pacientes com PC devem ser reconhecidos e efetivamente abordados para reduzir a morbidade e mortalidade respiratória.

Validation and Reliability of the French Version of the Sydney Swallow Questionnaire.

Oropharyngeal dysphagia is frequently under-reported and early detection may lead to adapt strategies of rehabilitation and management decisions. The Sydney Swallow Questionnaire (SSQ), a self-reported questionnaire for the detection and quantification of oropharyngeal dysphagia, was previously adapted and validated in other languages but not in French. The purposes of this study were to develop and validate a French version of SSQ (SSQ-f) and to assess its psychometric properties. This SSQ-f, obtained by back-translation and cross-cultural adaptation, was validated in 27 patients with impaired swallowing and 27 healthy controls. After inclusion, patients filled in the SSQ-f and performed a videofluoroscopic swallow study. The penetration aspiration scale (PAS) and Dysphagia outcome and severity scale (DOSS) were assigned to assess construct validity. Sensitivity and specificity of cut-off scores for the SSQ-f were assessed by the receiver operating characteristic (ROC) curves. Moreover, the SSQ-f was repeated after 2 weeks to evaluate its test-retest reliability. The results supported that SSQ-f was considered understandable. Its total score was strongly correlated to the DOSS (r = - 0.873) and to the PAS (r = 0.738). It demonstrated acceptable internal consistency, with Cronbach's alpha values ranging from 0.744 to 0.956. The test-retest reliability was excellent. According to the ROC curve, cut-off scores of 118.5 or 218.5 were proposed for determining oropharyngeal dysphagia using DOSS as a reference and 755.0, using PAS as reference. No ceiling or floor effects were observed. In conclusion, the SSQ-f is a valid and reliable instrument to measure and detect oropharyngeal dysphagia in French-speaking subjects and can be used in a clinical setting.

The clinical use of mechanical insufflation-exsufflation in children with neuromuscular disorders in Europe.

Mechanical insufflation-exsufflation (MI-E) is a strategy to treat pulmonary exacerbations in neuromuscular disorders (NMDs). Pediatric guidelines for optimal setting titration of MI-E are lacking and the settings used in studies vary. Our objective was to assess the actual MI-E settings being used in current clinical treatment of children with NMDs and a survey was sent in July 2016 to European expertise centers. Ten centers from seven countries gave information on MI-E settings for 240 children aged 4 months to 17.8 years (mean 10.5). Settings varied greatly between the centers. Auto mode was used in 71%, triggering of insufflation in 21% and manual mode in 8% of the cases. Mean (SD) time for insufflation (Ti) and exsufflation (Te) were 1.9 (0.5) and 1.8 (0.6) s respectively, both ranging from 1 to 4s. Asymmetric time settings were common (65%). Mean (SD) insufflation (Pi) and exsufflation (Pe) pressures were 32.4 (7.8) and -36.9 (7.4), ranging 10 to 50 and -10 to -60cmH2O, respectively. Asymmetric pressures were as common as symmetric. Both Ti, Te, Pi and Pe increased with age (p < 0.001). In conclusion, pediatric MI-E settings in clinical use varied greatly and altered with age, highlighting the need of more studies to improve our knowledge of optimal settings in MI-E in children with NMDs.

Screening and evaluation tools of dysphagia in children with neuromuscular diseases: a systematic review.

AIM: Dysphagia is frequent in paediatric patients with neuromuscular diseases (pNMD). Its detection is important for initiating early diagnosis and treatment as well as for minimizing related complications. The aim of this study was to review the literature on dysphagia screening and evaluation tools in pNMD. METHOD: A systematic review was performed on the basis of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Three databases (PubMed, CINAHL, and ScienceDirect) were searched. Measurement properties of tools and the quality index developed by Downs and Black were considered. RESULTS: Our search yielded four studies and four different tools for paediatric patients with Duchenne muscular dystrophy (DMD). The Sydney Swallow Questionnaire, surface electromyography, Neuromuscular Disease Swallowing Status Scale, and videofluoroscopic swallow study showed interesting properties for DMD. No data were available for other NMD and children under 9 years. The mean total score for the quality index was 17.5. INTERPRETATION: We did not identify any superior validated tools, either for screening or for evaluation of dysphagia, and no widely accepted protocol. Further studies are needed to identify the simplest assessment with the best psychometric properties for pNMD. We recommend establishing a specific tool for pNMD.

The Late Neandertal permanent lower left third premolar from Walou Cave (Trooz, Belgium) and its context.

OBJECTIVES: We describe a hominin permanent lower left third premolar unearthed in 1997 at Walou Cave (Belgium), found in direct association with a Mousterian lithic industry, in a layer directly dated to 40-38,000 years BP. MATERIALS AND METHODS: The taxonomical attribution of the tooth is addressed through comparative morphometric analyses, and stable isotope analyses aimed at determining the diet of the individual. RESULTS: The Walou P3 plots within the Neandertal range of variation and is significantly different from recent modern humans in all morphometric assessments. The isotope data showed that like other Neandertals, the Walou individual acquired its dietary proteins primarily from terrestrial food sources. DISCUSSION: We discuss the implications of the existence of a clearly Neandertal premolar dating to the period of the Middle to Upper Paleolithic transition in the Meuse river basin.

Technical Note: Guidelines for the digital computation of 2D and 3D enamel thickness in hominoid teeth.

The study of enamel thickness has received considerable attention in regard to the taxonomic, phylogenetic and dietary assessment of human and non-human primates. Recent developments based on two-dimensional (2D) and three-dimensional (3D) digital techniques have facilitated accurate analyses, preserving the original object from invasive procedures. Various digital protocols have been proposed. These include several procedures based on manual handling of the virtual models and technical shortcomings, which prevent other scholars from confidently reproducing the entire digital protocol. There is a compelling need for standard, reproducible, and well-tailored protocols for the digital analysis of 2D and 3D dental enamel thickness. In this contribution we provide essential guidelines for the digital computation of 2D and 3D enamel thickness in hominoid molars, premolars, canines and incisors. We modify previous techniques suggested for 2D analysis and we develop a new approach for 3D analysis that can also be applied to premolars and anterior teeth. For each tooth class, the cervical line should be considered as the fundamental morphological feature both to isolate the crown from the root (for 3D analysis) and to define the direction of the cross-sections (for 2D analysis).

Mechanically assisted cough strategies: user perspectives and cough flows in children with neurodisability.

Background: Mechanical insufflation-exsufflation (MI-E) is used to augment cough in children with neurodisability. We aimed to determine the user comfort and cough flows during three MI-E strategies, and to predict factors associated with improved comfort and cough flows. Methods: This multicentre, crossover trial was done at four regional hospitals in Norway. Children with neurodisability using MI-E long term via mask were enrolled. In randomised order, they tested three MI-E setting strategies (in-/exsufflation pressure (cmH2O)/in (In)- versus exsufflation (Ex) time): 1) "A-symmetric" (±50/In=Ex); 2) "B-asymmetric" (+25- +30)/-40, In>Ex); and 3) "C-personalised", as set by their therapist. The primary outcomes were user-reported comfort on a visual analogue scale (VAS) (0=maximum comfort) and peak cough flows (PCF) (L·min-1) measured by a pneumotachograph in the MI-E circuit. Results: We recruited 74 children median (IQR) age 8.1 (4.4-13.8) years, range 0.6-17.9, and analysed 218 MI-E sequences. The mean±sd VAS comfort scores were 4.7±2.96, 2.9±2.44 and 3.2±2.46 for strategies A, B and C, respectively (A versus B and C, p<0.001). The mean±sd PCF registered during strategies A, B and C were 203±46.87, 166±46.05 and 171±49.74 L·min-1, respectively (A versus B and C, p<0.001). Using low inspiratory flow predicted improved comfort. Age and unassisted cough flows increased exsufflation flows. Conclusions: An asymmetric or personalised MI-E strategy resulted in better comfort scores, but lower PCF than a symmetric approach utilising high pressures. All three strategies generated cough flows above therapeutic thresholds and were rated as slightly to moderately uncomfortable.

Dental evidence for ontogenetic differences between modern humans and Neanderthals.

Humans have an unusual life history, with an early weaning age, long childhood, late first reproduction, short interbirth intervals, and long lifespan. In contrast, great apes wean later, reproduce earlier, and have longer intervals between births. Despite 80 y of speculation, the origins of these developmental patterns in Homo sapiens remain unknown. Because they record daily growth during formation, teeth provide important insights, revealing that australopithecines and early Homo had more rapid ontogenies than recent humans. Dental development in later Homo species has been intensely debated, most notably the issue of whether Neanderthals and H. sapiens differ. Here we apply synchrotron virtual histology to a geographically and temporally diverse sample of Middle Paleolithic juveniles, including Neanderthals, to assess tooth formation and calculate age at death from dental microstructure. We find that most Neanderthal tooth crowns grew more rapidly than modern human teeth, resulting in significantly faster dental maturation. In contrast, Middle Paleolithic H. sapiens juveniles show greater similarity to recent humans. These findings are consistent with recent cranial and molecular evidence for subtle developmental differences between Neanderthals and H. sapiens. When compared with earlier hominin taxa, both Neanderthals and H. sapiens have extended the duration of dental development. This period of dental immaturity is particularly prolonged in modern humans.

First insights into human mobility in Neolithic Belgium using strontium isotopic analysis and proteomics: A case study of Grotte de La Faucille (Sclayn, province of Namur).

OBJECTIVES: So far, no 87 Sr/86 Sr mobility studies have been done for Neolithic remains from Belgium and information on the Sr isotopic variability in the region is scarce. This study aims to explore mobility in a Final Neolithic population from the funerary cave 'Grotte de La Faucille', contribute to the understanding of the isotopic composition of bioavailable Sr in Belgium, assess evidence for male mobility using proteomic analysis, and explore possible places of origin for nonlocal individuals. MATERIALS AND METHODS: The 87 Sr/86 Sr isotope ratio of dental enamel from six adults and six juveniles was determined. Liquid chromatography mass spectrometry-based protein analysis was employed to identify individuals of male biological sex. 87 Sr/86 Sr of micromammal teeth, snail shells, and modern plants from three geological areas in Belgium were measured to establish isotopic signatures for bioavailable strontium. Nonlocality was assessed by comparing human 87 Sr/86 Sr isotope ratios to the 87 Sr/86 Sr range for bioavailable Sr. RESULTS: Four individuals yielded 87 Sr/86 Sr isotope ratios consistent with a nonlocal origin. No statistical differences were found between adults and juveniles. Three males were detected in the sample set, of which two show nonlocal 87 Sr/86 Sr values. DISCUSSION: This study provides evidence for mobility in Final Neolithic Belgium. The four nonlocal 87 Sr/86 Sr signatures correspond with the 87 Sr/86 Sr of bio-available Sr in Dutch South Limburg, the Black Forest in Southwest Germany, and regions of France, such as parts of the Paris Basin and the Vosges. The results support the ruling hypothesis of connections with Northern France, brought to light by archeological research.

Variation in enamel thickness within the genus Homo.

Recent humans and their fossil relatives are classified as having thick molar enamel, one of very few dental traits that distinguish hominins from living African apes. However, little is known about enamel thickness in the earliest members of the genus Homo, and recent studies of later Homo report considerable intra- and inter-specific variation. In order to assess taxonomic, geographic, and temporal trends in enamel thickness, we applied micro-computed tomographic imaging to 150 fossil Homo teeth spanning two million years. Early Homo postcanine teeth from Africa and Asia show highly variable average and relative enamel thickness (AET and RET) values. Three molars from South Africa exceed Homo AET and RET ranges, resembling the hyper thick Paranthropus condition. Most later Homo groups (archaic European and north African Homo, and fossil and recent Homo sapiens) possess absolutely and relatively thick enamel across the entire dentition. In contrast, Neanderthals show relatively thin enamel in their incisors, canines, premolars, and molars, although incisor AET values are similar to H. sapiens. Comparisons of recent and fossil H. sapiens reveal that dental size reduction has led to a disproportionate decrease in coronal dentine compared with enamel (although both are reduced), leading to relatively thicker enamel in recent humans. General characterizations of hominins as having 'thick enamel' thus oversimplify a surprisingly variable craniodental trait with limited taxonomic utility within a genus. Moreover, estimates of dental attrition rates employed in paleodemographic reconstruction may be biased when this variation is not considered. Additional research is necessary to reconstruct hominin dietary ecology since thick enamel is not a prerequisite for hard-object feeding, and it is present in most later Homo species despite advances in technology and food processing.