Sustainable Market Involvement in Transport Infrastructure Management

The construction industry is going through hard times in many countries. This is certainly true in the Netherlands as all big Dutch contractors face disappointing results. The market policies of major (public) clients are held accountable by politics and the market for this situation. However, for the operation and development of transport infrastructure networks, a sustainable construction industry is essential. But how do public infrastructure network managers involve this industry in their network management? And does this involvement lead to the development of a sustainable construction market?In this paper we argue that the market policies of public transport infrastructure administrators (still) favour price competition and risk opportunism, thereby inhibiting a healthy development of the industry.This paper describes the reciprocal relation between public infrastructure network administrators (in their role as manager of the network and client) and the construction industry as a supplier of infrastructure hardware and services. It reveals that a sustainable development of the construction industry can only be achieved through the development of a value awarding mechanism, explicitly linked to the functions of the infrastructure network instead of to intermittent one-off projects. The paper will give practical recommendations for (public) infrastructure network administrators how to stimulate the creation of added network value through sustainable market involvement

Exertional rhabdomyolysis : relevance of clinical and laboratory findings, and clues for investigation

Some degree of exertional rhabdomyolysis (ER), striated muscle breakdown associated with strenuous exercise, is a well-known phenomenon associated with endurance sports. However in rare cases, severe and/or recurrent ER is a manifestation of an underlying condition, which puts patients at risk for significant morbidity and mortality. Selecting the patients that need a diagnostic work up of an acute rhabdomyolysis episode is an important task. Based on the diagnostic work up of three illustrative patients treated in our hospital, retrospectively using the 'RHABDO' screening tool, we discuss the clinical and biochemical clues that should trigger further investigation for an underlying condition. Finally, we describe the most common genetic causes of this clinical syndrome

Who participates in running events? : socio-demographic characteristics, psychosocial factors and barriers as correlates of non-participation : a pilot study in Belgium

In Western countries, the popularity of running events has increased exponentially during the last three decades. However, little is known about the profile of non-participants. This knowledge is crucial to tailor promotional actions towards people who are currently not participating. Therefore, this study aimed: (1) to examine which socio-ecological factors are related to participation in running events, (2) to give an overview of the barriers towards participation, and (3) to examine differences in barriers depending on gender, age and educational level. Flemish adults (n = 308) completed an online questionnaire about their socio-demographic and psychosocial characteristics, physical activity levels, participation in running events and barriers towards participation. Results showed that motivation, family social support, knowledge about running events and physical activity levels were associated with participation in running events. Among non-participants, the main barriers were bad physical condition, lack of time and lack of interest. In participants, lack of time, distance to the event and financial barriers were most prevalent. With some exceptions, barriers were relatively similar across socio-demographic subgroups. This study confirmed a democratization among participants of running events and provided evidence about which barriers should be tackled to increase participation among population subgroups that are currently underrepresented in such events

New insights on human T cell development by quantitative T cell receptor gene rearrangement studies and gene expression profiling

To gain more insight into initiation and regulation of T cell receptor (TCR) gene rearrangement during human T cell development, we analyzed TCR gene rearrangements by quantitative PCR analysis in nine consecutive T cell developmental stages, including CD34+ lin− cord blood cells as a reference. The same stages were used for gene expression profiling using DNA microarrays. We show that TCR loci rearrange in a highly ordered way (TCRD-TCRG-TCRB-TCRA) and that the initiating Dδ2-Dδ3 rearrangement occurs at the most immature CD34+CD38−CD1a− stage. TCRB rearrangement starts at the CD34+CD38+CD1a− stage and complete in-frame TCRB rearrangements were first detected in the immature single positive stage. TCRB rearrangement data together with the PTCRA (pTα) expression pattern show that human TCRβ-selection occurs at the CD34+CD38+CD1a+ stage. By combining the TCR rearrangement data with gene expression data, we identified candidate factors for the initiation/regulation of TCR recombination. Our data demonstrate that a number of key events occur earlier than assumed previously; therefore, human T cell development is much more similar to murine T cell development than reported before

The role of alcohol in constructing gender & class identities among young women in the age of social media

Research suggests young women view drinking as a pleasurable aspect of their social lives but that they face challenges in engaging in a traditionally ‘masculine’ behaviour whilst maintaining a desirable ‘femininity’. Social network sites such as Facebook make socialising visible to a wide audience. This paper explores how young people discuss young women’s drinking practices, and how young women construct their identities through alcohol consumption and its display on social media. We conducted 21 friendship-based focus groups (both mixed and single sex) with young adults aged 18–29 years and 13 individual interviews with a subset of focus group respondents centred on their Facebook practices. We recruited a purposive sample in Glasgow, Scotland (UK) which included ‘middle class’ (defined as students and those in professional jobs) and ‘working class’ respondents (employed in manual/service sector jobs), who participated in a range of venues in the night time economy. Young women’s discussions revealed a difficult ‘balancing act’ between demonstrating an ‘up for it’ sexy (but not too sexy) femininity through their drinking and appearance, while still retaining control and respectability. This ‘balancing act’ was particularly precarious for working class women, who appeared to be judged more harshly than middle class women both online and offline. While a gendered double standard around appearance and alcohol consumption is not new, a wider online audience can now observe and comment on how women look and behave. Social structures such as gender and social class remain central to the construction of identity both online and offline

Evaluation of Staging Systems for Cancer of the Nasal Vestibule

Squamous cell carcinoma of the nasal vestibule is reported to account for less than one percent of all head and neck malignancies. It lacks a designated WHO ICD-O topography code, and multiple systems are available for the staging of this disease, which results in unwanted variability and the subsequent poor reliability of data. The aim of this study was to evaluate the currently available staging systems for cancer of the nasal vestibule, including the recently introduced classification by Bussu et al., which built on Wang's original concept but with clearer anatomical cutoffs. Different staging systems for cancer of the nasal vestibule (UICC nasal cavity, UICC skin cancer of the head and neck, Wang and Bussu et al.) were evaluated via a retrospective analysis of 148 patients. The staging system, per Bussu et al., had the most balanced allocation of patients among the stages. When using the Wang classification as a reference, stage migration occurred less frequently with the Bussu classification. The widespread adoption of a single staging system, as well as the introduction of a designated topography code for cancer of the nasal vestibule, could lead to more uniformity in data reporting and improve an understanding of the incidence and disease outcome. The newly proposed carcinoma of the nasal vestibule classification by Bussu et al. has the potential to improve the staging and allocation among stages. Further analysis of survival data is needed to assess which classification system is best suited for nasal vestibule carcinoma

The Additional Value of Somatostatin Receptor Positron Emission Computed Tomography ([68Ga]Ga-DOTATOC PET/CT) Compared with Magnetic Resonance Imaging of the Head and Neck Region in Paraganglioma Patients: A Pilot Study

The Dutch guideline for patients suspected of head and neck paragangliomas (HNPGLs) recommends magnetic resonance imaging (MRI) and/or computed tomography (CT) of the head and neck area. Additionally, it suggests considering additional nuclear imaging. The aim of this study was to evaluate the outcomes of [68Ga]Ga-DOTATOC PET/CT compared to MRI in patients with suspected HNPGLs and carriers of genetic variations. Methods: In this single-center pilot study, retrospective data were obtained from consecutive patients between 2016 and 2023. Both MRI and [68Ga]Ga-DOTATOC PET/CT were performed within 12 months. The primary outcome was the location of HNPGLs. Results: A total of 25 consecutive patients were included, and 7 patients (28.0%, p = 0.5) showed differences between the imaging modalities, of whom 5 patients had unexpected localizations with additional uptake by somatostatin receptors (SSTR) on the [68Ga]Ga-DOTATOC PET/CT. Conclusions: The authors recommend performing baseline imaging with [68Ga]Ga-DOTATOC PET/CT (if available) in variant carriers and using MRI/CT for follow-up according to the regional protocol, thereby shifting the gold standard for baseline imaging from MRI/CT to [68Ga]Ga-DOTATOC PET/CT

Clinico-Genetic, Imaging and Molecular Delineation of COQ8A-Ataxia: A Multicenter Study of 59 Patients.

OBJECTIVE: To foster trial-readiness of coenzyme Q8A (COQ8A)-ataxia, we map the clinicogenetic, molecular, and neuroimaging spectrum of COQ8A-ataxia in a large worldwide cohort, and provide first progression data, including treatment response to coenzyme Q10 (CoQ10). METHODS: Cross-modal analysis of a multicenter cohort of 59 COQ8A patients, including genotype-phenotype correlations, 3D-protein modeling, in vitro mutation analyses, magnetic resonance imaging (MRI) markers, disease progression, and CoQ10 response data. RESULTS: Fifty-nine patients (39 novel) with 44 pathogenic COQ8A variants (18 novel) were identified. Missense variants demonstrated a pleiotropic range of detrimental effects upon protein modeling and in vitro analysis of purified variants. COQ8A-ataxia presented as variable multisystemic, early-onset cerebellar ataxia, with complicating features ranging from epilepsy (32%) and cognitive impairment (49%) to exercise intolerance (25%) and hyperkinetic movement disorders (41%), including dystonia and myoclonus as presenting symptoms. Multisystemic involvement was more prevalent in missense than biallelic loss-of-function variants (82-93% vs 53%; p = 0.029). Cerebellar atrophy was universal on MRI (100%), with cerebral atrophy or dentate and pontine T2 hyperintensities observed in 28%. Cross-sectional (n = 34) and longitudinal (n = 7) assessments consistently indicated mild-to-moderate progression of ataxia (SARA: 0.45/year). CoQ10 treatment led to improvement by clinical report in 14 of 30 patients, and by quantitative longitudinal assessments in 8 of 11 patients (SARA: -0.81/year). Explorative sample size calculations indicate that ≥48 patients per arm may suffice to demonstrate efficacy for interventions that reduce progression by 50%. INTERPRETATION: This study provides a deeper understanding of the disease, and paves the way toward large-scale natural history studies and treatment trials in COQ8A-ataxia. ANN NEUROL 2020;88:251-263

Comparison of illumina versus nanopore 16s rRNA gene sequencing of the human nasal microbiota

Illumina and nanopore sequencing technologies are powerful tools that can be used to determine the bacterial composition of complex microbial communities. In this study, we compared nasal microbiota results at genus level using both Illumina and nanopore 16S rRNA gene sequencing. We also monitored the progression of nanopore sequencing in the accurate identification of species, using pure, single species cultures, and evaluated the performance of the nanopore EPI2ME 16S data analysis pipeline. Fifty-nine nasal swabs were sequenced using Illumina MiSeq and Oxford Nanopore 16S rRNA gene sequencing technologies. In addition, five pure cultures of relevant bacterial species were sequenced with the nanopore sequencing technology. The Illumina MiSeq sequence data were processed using bioinformatics modules present in the Mothur software package. Albacore and Guppy base calling, a workflow in nanopore EPI2ME (Oxford Nanopore Technologies—ONT, Oxford, UK) and an in-house developed bioinformatics script were used to analyze the nanopore data. At genus level, similar bacterial diversity profiles were found, and five main and established genera were identified by both platforms. However, probably due to mismatching of the nanopore sequence primers, the nanopore sequencing platform identified Corynebacterium in much lower abundance compared to Illumina sequencing. Further, when using default settings in the EPI2ME workflow, almost all sequence reads that seem to belong to the bacterial genus Dolosigranulum and a considerable part to the genus Haemophilus were only identified at family level. Nanopore sequencing of single species cultures demonstrated at least 88% accurate identification of the species at genus and species level for 4/5 strains tested, including improvements in accurate sequence read identification when the basecaller Guppy and Albacore, and when flowcell versions R9.4 (Oxford Nanopore Technologies—ONT, Oxford, UK) and R9.2 (Oxford Nanopore Technologies—ONT, Oxford, UK) were compared. In conclusion, the current study shows that the nanopore sequencing platform is comparable with the Illumina platform in detection bacterial genera of the nasal microbiota, but the nanopore platform does have problems in detecting bacteria within the genus Corynebacterium. Although advances are being made, thorough validation of the nanopore platform is still recommendable