Making Sense of a New Transport System: An Ethnographic Study of the Cambridgeshire Guided Busway

An increase in public transport use has the potential to contribute to improving population health, and there is growing interest in innovative public transport systems. Yet how new public transport infrastructure is experienced and integrated (or not) into daily practice is little understood. We investigated how the Cambridgeshire Guided Busway, UK, was used and experienced in the weeks following its opening, using the method of participant observation (travelling on the busway and observing and talking to passengers) and drawing on Normalization Process Theory to interpret our data. Using excerpts of field notes to support our interpretations, we describe how the ease with which the new transport system could be integrated into existing daily routines was important in determining whether individuals would continue to use it. It emerged that there were two groups of passengers with different experiences and attitudes. Passengers who had previously travelled frequently on regular bus services did not perceive the new system to be an improvement; consequently, they were frustrated that it was differentiated from and not coherent with the regular system. In contrast, passengers who had previously travelled almost exclusively by car appraised the busway positively and perceived it to be a novel and superior form of travel. Our rich qualitative account highlights the varied and creative ways in which people learn to use new public transport and integrate it into their everyday lives. This has consequences for the introduction and promotion of future transport innovations. It is important to emphasise the novelty of new public transport, but also the ways in which its use can become ordinary and routine. Addressing these issues could help to promote uptake of other public transport interventions, which may contribute to increasing physical activity and improving population health. © 2013 Jones et al

Simultaneous chronic rupture of quadriceps tendon and contra-lateral patellar tendon in a patient affected by tertiary hyperparatiroidism

Spontaneous ruptures of the extensor mechanism of the knee are very rare. They tend to increase considerably in patients with metabolic diseases such as chronic renal failure, hyperparathyroidism, diabetes, gout, and systemic lupus erythematosus. The reported case regards a 48-year-old man with chronic, spontaneous and simultaneous quadriceps, and contra-lateral patellar tendon rupture. The patient suffered from chronic renal failure and for the past year from tertiary hyperparathyroidism. Ruptured tendons were repaired and both knee were evaluated monthly for the next 12 months. Good functional recovery was achieved on both knees without relapse. This case emphasizes the importance of long-term high parathyroid hormone level in the etiology of tendons ruptures

B-lymphocyte stimulator/a proliferation-inducing ligand heterotrimers are elevated in the sera of patients with autoimmune disease and are neutralized by atacicept and B-cell maturation antigen-immunoglobulin

Abstract Introduction B-lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL) are members of the tumor necrosis factor (TNF) family that regulate B-cell maturation, survival, and function. They are overexpressed in a variety of autoimmune diseases and reportedly exist in vivo not only as homotrimers, but also as BLyS/APRIL heterotrimers. Methods A proprietary N-terminal trimerization domain was used to produce recombinant BLyS/APRIL heterotrimers. Heterotrimer biologic activity was compared with that of BLyS and APRIL in a 4-hour signaling assay by using transmembrane activator and CAML interactor (TACI)-transfected Jurkat cells and in a 4-day primary human B-cell proliferation assay. A bead-based immunoassay was developed to quantify native heterotrimers in human sera from healthy donors (n = 89) and patients with systemic lupus erythematosus (SLE; n = 89) or rheumatoid arthritis (RA; n = 30). Heterotrimer levels were compared with BLyS and APRIL homotrimer levels in a subset of these samples. Results The recombinant heterotrimers consisted mostly of one BLyS and two APRIL molecules. Heterotrimer signaling did not show any significant difference compared with APRIL in the TACI-Jurkat assay. Heterotrimers were less-potent inducers of B-cell proliferation than were homotrimeric BLyS or APRIL (EC50, nMol/L: BLyS, 0.02; APRIL, 0.17; heterotrimers, 4.06). The soluble receptor fusion proteins atacicept and B-cell maturation antigen (BCMA)-immunoglobulin (Ig) neutralized the activity of BLyS, APRIL, and heterotrimers in both cellular assays, whereas B-cell activating factor belonging to the TNF family receptor (BAFF-R)-Ig neutralized only the activity of BLyS. In human sera, significantly more patients with SLE had detectable BLyS (67% versus 18%; P < 0.0001), APRIL (38% versus 3%; P < 0.0002), and heterotrimer (27% versus 8%; P = 0.0013) levels compared with healthy donors. Significantly more patients with RA had detectable APRIL, but not BLyS or heterotrimer, levels compared with healthy donors (83% versus 3%; P < 0.0001). Heterotrimer levels weakly correlated with BLyS, but not APRIL, levels. Conclusions Recombinant BLyS/APRIL heterotrimers have biologic activity and are inhibited by atacicept and BCMA-Ig, but not by BAFF-R-Ig. A novel immunoassay demonstrated that native BLyS/APRIL heterotrimers, as well as BLyS and APRIL homotrimers, are elevated in patients with autoimmune diseases

Add Health Wave IV Documentation: Measures of Inflammation and Immune Function

During Wave IV, Add Health collected biological specimens from a large, nationally representative sample of young adults. Given the size of the Wave IV sample, its geographic distribution, and in-home setting of the respondent interviews, biological specimen collection involved practical, relatively non-invasive, cost-efficient and innovative methods. These methods included collection of capillary whole blood via finger prick by trained and certified field interviewers, its in situ desiccation, then shipment, assay and archival of dried blood spots. The collection of capillary whole blood followed the collection of cardiovascular and anthropometric measures (Entzel et al, 2009) and saliva (Smolen et al, 2012). It preceded the collection of data on respondent use of prescription and select over-the-counter medications (Tabor et al, 2010). Further details on the design of Add Health Waves I-IV, are available elsewhere (Harris, 2011). Included in the Add Health Wave IV data are two measures of inflammation and immune function based on assay of the dried blood spots: • High Sensitivity C-Reactive Protein (hsCRP, mg/L) and • Epstein Barr Viral Capsid Antigen IgG (EBV, AU/ml) To facilitate analysis and interpretation of hsCRP and EBV, the restricted-use Add Health Wave IV data also include two data quality flags and 11constructed measures: • CRP_FLAG • EBV_FLAG • Classification of hsCRP (Pearson et al, 2003) • Count of Common Subclinical Symptoms (Vaidya et al, 2006) • Count of Common Infectious or Inflammatory Diseases • NSAID/Salicylate Medication Use in the Past 24 Hours • NSAID/Salicylate Medication Use in the Past 4 Weeks • Cox-2 Inhibitor Medication Use in the Past 4 Weeks • Inhaled Corticosteroid Medication Use in the Past 4 Weeks • Corticotropin/Glucocorticoid Medication Use in the Past 4 Weeks • Anti-rheumatic/Anti-psoriatic Medication Use in the Past 4 Weeks • Immunosuppressive Medication Use in the Past 4 Weeks • Anti-inflammatory Medication Use. This document summarizes the rationale, equipment, protocol, assay, internal quality control, data cleaning, external quality control, and classification procedures for each measure listed above. Measures of glucose homeostasis and candidate genes are documented elsewhere 3 (Whitsel et al, 2012; Smolen et al, 2012). Documentation of lipids will be provided in a separate report

Add Health Wave IV Documentation: Lipids

During Wave IV, Add Health collected biological specimens from a large, nationally representative sample of young adults. Given the size of the Wave IV sample, its geographic distribution, and in-home setting of the respondent interviews, biological specimen collection involved practical, relatively non-invasive, cost-efficient and innovative methods. These methods included collection of capillary whole blood via finger prick by trained and certified field interviewers, its in situ desiccation, then shipment, assay and archival of dried blood spots. The collection of capillary whole blood followed the collection of cardiovascular and anthropometric measures (Entzel et al. 2009) and saliva (Smolen et al. 2013). It preceded the collection of data on respondent use of prescription and select over-the-counter medications (Tabor et al. 2010). Further details on the design of Add Health Waves I-IV, are available elsewhere (Harris 2012; Harris et al. in press). Included in the Add Health Wave IV restricted use and public use data are thirteen constructed measures designed to facilitate analysis and interpretation of lipids results: • Total cholesterol decile • High-density lipoprotein cholesterol decile • Triglycerides decile • Total cholesterol measurement method • High-density lipoprotein cholesterol measurement method • Triglycerides measurement method • Low-density lipoprotein cholesterol decile • Non-high-density lipoprotein cholesterol decile • Total to high-density lipoprotein cholesterol ratio decile • Fasting duration • Fasted for nine hours or more • Antihyperlipidemic medication use • Hyperlipidemia. This document summarizes the rationale, equipment, protocol, assay, internal quality control, data cleaning, external quality control, and classification procedures for each measure listed above. Measures of glucose homeostasis, inflammation, immune function, and candidate genes are documented elsewhere (Whitsel et al. 2012a, 2012b; Smolen et al. 2013)

Roles of hyaluronan in bone resorption

BACKGROUND: Hyaluronan, an unsulfated glycosaminoglycan, while being closely linked to osteoclast function several years ago, has received little attention lately. Given recent new knowledge of hyaluronan's possible cell binding abilities, it is important to re-examine the role of this polysaccharide in bone homeostasis. DISCUSSION: Previously published data demonstrating a linkage between induction of hyaluronan synthesis and osteoclast-mediated bone resorption are reviewed. Suggestions are made involving the cell binding ability of hyaluronan and its potential to mediate osteoclast binding to bone surfaces and its potential to serve as a diffusion barrier and participate in the sealing zone required for osteoclast-mediated bone resorption. SUMMARY: This brief article summarizes previous studies linking HA to bone resorption and suggests roles for hyaluronan in the process of bone resorption

Add Health Wave IV Documentation: Measures of Glucose Homeostasis

During Wave IV, Add Health collected biological specimens from a large, nationally representative sample of young adults. Given the size of the Wave IV sample, its geographic distribution, and in-home setting of the respondent interviews, biological specimen collection involved practical, relatively non-invasive, cost-efficient and innovative methods. These methods included collection of capillary whole blood via finger prick by trained and certified field interviewers, its in situ desiccation, then shipment, assay and archival of dried blood spots. The collection of capillary whole blood followed the collection of cardiovascular and anthropometric measures (Entzel et al., 2009) and saliva (in preparation). It preceded the collection of data on respondent use of prescription and select over-the-counter medications (Tabor et al., 2010). Further details on the design of Add Health Waves I-IV, are available elsewhere (Harris, 2011). Included in the Add Health Wave IV data are two measures of glucose homeostasis based on assay of the dried blood spots: • Glucose (mg/dl) and • Hemoglobin A1c (HbA1c, %). To facilitate analysis and interpretation of HbA1c, the restricted-use Add Health Wave IV data also include a trichotomous flag distinguishing the original (0) from two types (1,2) of inter-converted assay results (see Section 4.2.3.3): • Convert (0,1,2) Moreover, the restricted-use Add Health Wave IV data include six constructed measures: • Fasting duration (h) • Classification of fasting glucose (ADA, 2011) • Classification of non-fasting glucose (ADA, 2011) • Classification of HbA1c (ADA, 2011) • Anti-diabetic medication use • Joint classification of glucose, HbA1c, self-reported history of diabetes, and anti-diabetic medication use. This document summarizes the rationale, equipment, protocol, assay, internal quality control, data cleaning, external quality control, and classification procedures for each measure listed above. Documentation of other (metabolic; inflammatory; immune; genetic) measures based on assay of the dried blood spots and genotyping of DNA extracted from salivary buccal cells will be provided in separate reports

Dominant-negative variant in SLC1A4 causes an autosomal dominant epilepsy syndrome.

SLC1A4 is a trimeric neutral amino acid transporter essential for shuttling L-serine from astrocytes into neurons. Individuals with biallelic variants in SLC1A4 are known to have spastic tetraplegia, thin corpus callosum, and progressive microcephaly (SPATCCM) syndrome, but individuals with heterozygous variants are not thought to have disease. We identify an 8-year-old patient with global developmental delay, spasticity, epilepsy, and microcephaly who has a de novo heterozygous three amino acid duplication in SLC1A4 (L86_M88dup). We demonstrate that L86_M88dup causes a dominant-negative N-glycosylation defect of SLC1A4, which in turn reduces the plasma membrane localization of SLC1A4 and the transport rate of SLC1A4 for L-serine