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Abstract Background Active school transport (AST) is a promising strategy to increase children’s physical activity. A systematic review published in 2011 found large heterogeneity in the effectiveness of interventions in increasing AST and highlighted several limitations of previous research. We provide a comprehensive update of that review. Methods Replicating the search of the previous review, we screened the PubMed, Web of Science, Cochrane, Sport Discus and National Transportation Library databases for articles published between February 1, 2010 and October 15, 2016. To be eligible, studies had to focus on school-aged children and adolescents, include an intervention related to school travel, and report a measure of travel behaviors. We assessed quality of individual studies with the Effective Public Health Practice Project quality assessment tool, and overall quality of evidence with the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach. We calculated Cohen’s d as a measure of effect size. Results Out of 6318 potentially relevant articles, 27 articles reporting 30 interventions met our inclusion criteria. Thirteen interventions resulted in an increase in AST, 8 found no changes, 4 reported inconsistent results, and 5 did not report inferential statistics. Cohen’s d ranged from −0.61 to 0.75, with most studies reporting “trivial-to-small” positive effect sizes. Three studies reported greater increases in AST over longer follow-up periods and two Safe Routes to School studies noted that multi-level interventions were more effective. Study quality was rated as weak for 27/30 interventions (due notably to lack of blinding of outcome assessors, unknown psychometric properties of measurement tools, and limited control for confounders), and overall quality of evidence was rated as low. Evaluations of implementation suggested that interventions were limited by insufficient follow-up duration, incomplete implementation of planned interventions, and limited access to resources for low-income communities. Conclusions Interventions may increase AST among children; however, there was substantial heterogeneity across studies and quality of evidence remains low. Future studies should include longer follow-ups, use standardized outcome measures (to allow for meta-analyses), and examine potential moderators and mediators of travel behavior change to help refine current interventions. Trial registration Registered in PROSPERO: CRD42016033252

Active school travel is in decline. An understanding of the potential determinants of health-enhancing physical activity during the school commute may help to inform interventions aimed at reversing these trends. The purpose of this study was to identify the physical environmental factors associated with health-enhancing physical activity during the school commute. Data were collected in 2009 on 166 children commuting home from school in Scotland. Data on location and physical activity were measured using global positioning systems (GPS) and accelerometers, and mapped using geographical information systems (GIS). Multi-level logistic regression models accounting for repeated observations within participants were used to test for associations between each land-use category (road/track/path, other man-made, greenspace, other natural) and moderate-to-vigorous physical activity (MVPA). Thirty-nine children provided 2,782 matched data points. Over one third (37.1%) of children’s school commute time was spent in MVPA. Children commuted approximately equal amounts of time via natural and man-made land-uses (50.2% and 49.8% respectively). Commuting via road/track/path was associated with increased likelihood of MVPA (Exp(B)=1.23, P via other manmade land-uses. No association was noted between greenspace use and MVPA, but travelling via other natural land-uses was associated with lower odds of MVPA (Exp(B)=0.32, P via man-made and natural land-uses, yet man-made transportation route infrastructure appears to provide greater opportunities for achieving health-enhancing physical activity levels.

Silicon photonics is one of the most dynamic fields within photonics, and it has seen huge progress in the last 20 years, addressing applications in data centers, autonomous cars, and sensing. It is mostly focused on the telecommunications wavelength range (1.3 and 1.55 µm), where silicon becomes transparent. In this range, there are excellent light sources and photodetectors, as well as optical fibers operating with extremely low losses and dispersion. It is a technology that hugely benefits from the availability of complementary metal–oxide–semiconductor (CMOS) fabrication infrastructure and techniques used for microelectronics. Silicon and germanium, as another CMOS compatible group IV material, are transparent beyond the wavelength of 2 µm. The mid-IR wavelength range (2–20 µm) is of particular importance as it contains strong absorption signatures of many molecules. Therefore, Si- and Ge-based platforms open up the possibility of small and cost-effective sensing in the fingerprint region for medical and environmental monitoring. In this paper, we discuss the current mid-IR silicon photonics landscape, future directions, and potential applications of the field.

Vertebrates form their skeletal tissues from three distinct origins (the neural crest, paraxial mesoderm, and lateral plate mesoderm) through two distinct modes of ossification (intramembranous and endochondral ossification). Since the paraxial mesoderm generates both intramembranous and endochondral bones, it is thought to give rise to both osteoprogenitors and osteo-chondroprogenitors. However, it remains unclear what directs the paraxial mesoderm-derived cells toward these different fates in distinct skeletal elements during human skeletal development. To answer this question, we need experimental systems that recapitulate paraxial mesoderm-mediated intramembranous and endochondral ossification processes. In this study, we aimed to develop a human pluripotent stem cell (hPSC)-based system that models the human intramembranous ossification process. We found that spheroid culture of the hPSC-derived paraxial mesoderm derivatives generates osteoprogenitors or osteo-chondroprogenitors depending on stimuli. The former induced intramembranous ossification, and the latter endochondral ossification, in mouse renal capsules. Transcriptional profiling supported the notion that bone signatures were enriched in the intramembranous bone-like tissues. Thus, we developed a system that recapitulates intramembranous ossification, and that enables the induction of two distinct modes of ossification by controlling the cell fate of the hPSC-derived paraxial mesoderm derivatives.

Abstract Background Interferon regulatory factor-8 (IRF8) and nuclear factor-activated T cells c1 (NFATc1) are two transcription factors that have an important role in osteoclast differentiation. Thanks to ChIP-seq technology, scientists can now estimate potential genome-wide target genes of IRF8 and NFATc1. However, finding target genes that are consistently up-regulated or down-regulated across different studies is hard because it requires analysis of a large number of high-throughput expression studies from a comparable context. Method We have developed a machine learning based method, called, Cohort-based TF target prediction system (cTAP) to overcome this problem. This method assumes that the pathway involving the transcription factors of interest is featured with multiple “functional groups” of marker genes pertaining to the concerned biological process. It uses two notions, Gene-Present Sufficiently (GP) and Gene-Absent Insufficiently (GA), in addition to log2 fold changes of differentially expressed genes for the prediction. Target prediction is made by applying multiple machine-learning models, which learn the patterns of GP and GA from log2 fold changes and four types of Z scores from the normalized cohort’s gene expression data. The learned patterns are then associated with the putative transcription factor targets to identify genes that consistently exhibit Up/Down gene regulation patterns within the cohort. We applied this method to 11 publicly available GEO data sets related to osteoclastgenesis. Result Our experiment identified a small number of Up/Down IRF8 and NFATc1 target genes as relevant to osteoclast differentiation. The machine learning models using GP and GA produced NFATc1 and IRF8 target genes different than simply using a log2 fold change alone. Our literature survey revealed that all predicted target genes have known roles in bone remodeling, specifically related to the immune system and osteoclast formation and functions, suggesting confidence and validity in our method. Conclusion cTAP was motivated by recognizing that biologists tend to use Z score values present in data sets for the analysis. However, using cTAP effectively presupposes assembling a sizable cohort of gene expression data sets within a comparable context. As public gene expression data repositories grow, the need to use cohort-based analysis method like cTAP will become increasingly important.

Abstract The osteogenic potential of bone marrow mesenchymal stem cells (BMSCs) declines dramatically with aging. By using a calvarial defect model, we showed that a senolytic cocktail (dasatinib+quercetin; D + Q) improved osteogenic capacity of aged BMSC both in vitro and in vivo. The study presented a model to assess strategies to improve bone-forming potential on aged BMSCs. D + Q might hold promise for improving BMSC function in aged populations.

ABSTRACT Albright hereditary osteodystrophy (AHO) is caused by heterozygous inactivation of GNAS, a complex locus that encodes the alpha‐stimulatory subunit of heterotrimeric G proteins (Gsα) in addition to NESP55 and XLαs due to alternative first exons. AHO skeletal manifestations include brachydactyly, brachymetacarpia, compromised adult stature, and subcutaneous ossifications. AHO patients with maternally‐inherited GNAS mutations develop pseudohypoparathyroidism type 1A (PHP1A) with resistance to multiple hormones that mediate their actions through G protein‐coupled receptors (GPCRs) requiring Gsα (eg, parathyroid hormone [PTH], thyroid‐stimulating hormone [TSH], growth hormone–releasing hormone [GHRH], calcitonin) and severe obesity. Paternally‐inherited GNAS mutations cause pseudopseudohypoparathyroidism (PPHP), in which patients have AHO skeletal features but do not develop hormonal resistance or marked obesity. These differences between PHP1A and PPHP are caused by tissue‐specific reduction of paternal Gsα expression. Previous reports in mice have shown loss of Gsα causes osteopenia due to impaired osteoblast number and function and suggest that AHO patients could display evidence of reduced bone mineral density (BMD). However, we previously demonstrated PHP1A patients display normal‐increased BMD measurements without any correlation to body mass index or serum PTH. Due to these observed differences between PHP1A and PPHP, we utilized our laboratory's AHO mouse model to address whether Gsα heterozygous inactivation differentially affects bone remodeling based on the parental inheritance of the mutation. We identified fundamental distinctions in bone remodeling between mice with paternally‐inherited (GnasE1+/−p) versus maternally‐inherited (GnasE1+/−m) mutations, and these findings were observed predominantly in female mice. Specifically, GnasE1+/−p mice exhibited reduced bone parameters due to impaired bone formation and enhanced bone resorption. GnasE1+/−m mice, however, displayed enhanced bone parameters due to both increased osteoblast activity and normal bone resorption. These in vivo distinctions in bone remodeling between GnasE1+/−p and GnasE1+/−m mice could potentially be related to changes in the bone microenvironment driven by calcitonin‐resistance within GnasE1+/−m osteoclasts. Further studies are warranted to assess how Gsα influences osteoblast–osteoclast coupling. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Summary:. Injectable drug use in the upper extremity often leads to chronic wounds complicated by osteomyelitis. Conventional reconstructive options are often not feasible and/or are contraindicated in this patient population. We have started using a synthetic, biodegradable temporizing matrix (BTM) for the treatment of these patients. We hypothesize that BTM is a safe, low-risk, and low-morbidity alternative reconstructive option. We report outcomes after staged debridement and BTM application followed by split-thickness skin grafting for two patients with large, chronic bilateral forearm wounds with concomitant osteomyelitis confirmed by MRI and biopsy. No acute surgical complications were encountered and at a mean follow-up of 13 months, both patients had maintained stable soft-tissue coverage. Reconstruction using BTM is a novel treatment option that can simplify the reconstruction, reduce donor-site morbidity, and optimize success for patients with chronic wounds resulting from injectable drug use. Initial outcomes are promising; however, further comparative studies are needed to better evaluate long-term outcomes of this technique.

Recent advances suggest that miniaturised mid-infrared (MIR) devices could replace more time-consuming, laboratory-based techniques for clinical diagnostics. This work uses Fourier transform infrared spectroscopy to show that the MIR complex refractive index of whole blood varies across a range of haematocrit. This indicates that the use of an evanescent measurement is not sufficient to optically exclude the cellular content of blood in the MIR, as previously assumed. Here, spectral refractive index data is presented in two ways. First, it is given as whole blood with varying haematocrit. Second, it is given as the percentage error that haematocrit introduces to plasma. The maximum error in the effective plasma refractive index due to the haematocrit of healthy adults was 0.25% for the real part n and 11% for the imaginary part k. This implies that calibration measurements of haematocrit can be used to account for errors introduced by the cellular content, enabling plasma spectra and analyte concentrations to be indirectly calculated from a whole blood sample. This methodological advance is of clinical importance as plasma concentration of analytes such as drugs can be determined using MIR without the preprocessing of whole blood.

Abstract Mid-infrared (MIR) spectroscopy is a powerful tool for characterising the vibrations of molecular bonds and is therefore ideal for label-free detection of chemical species. Recent research into thin-film deposition and etching techniques for mid-infrared materials shows potential for realising miniaturised bedside biosensors for clinical diagnostics exploiting MIR spectroscopy, to replace laboratory based-techniques. However, lack of refractive index information for commonly encountered biological media and analytes hampers optimisation of biosensor performance for maximum sensitivity, especially for devices exploiting evanescent spectroscopy. Here we present refractive index data for human whole blood and several aqueous solutions of general interest to the clinical community: anticoagulants, analgesics and buffers. The refractive indices are generally dominated by the water content of each sample and the whole blood spectra exhibit additional strong features due to protein content. Furthermore, we present a generalised method for extracting complex refractive indices of aqueous solutions in the mid-infrared region using conventional attenuated total reflection Fourier transform spectroscopy (ATR-FTIR) without the need for collimated or polarised incident light, as is required for existing methods.

The latent state is a critical component of all herpesvirus infections, and its regulation remains one of the most active areas of Epstein-Barr Virus (EBV) research. In particular, identifying environmental factors that trigger EBV reactivation into a virus-productive state has become a central goal in EBV latency research. Recently, a category of chemicals known as inducers of the endoplasmic reticulum unfolded protein response (UPR) have been shown to trigger EBV lytic reactivation in various established EBV-associated lymphoma cell lines. This has led to the recent belief that UPR is a universal cellular signaling pathway that directly triggers EBV lytic reactivation irrespective of cell type. We tested the potency of several widely used UPR inducers for EBV lytic reactivation on virus-immortalized primary lymphoblastoid cell lines (LCLs) in vitro. We found that, with the exception of Thapsigargin (Tg), UPR inducers did not trigger significant increases in BZLF1 transcripts or changes in the numbers of EBV genomic copies/cell in our panel of primary LCLs. Further investigation revealed that induction of lytic reactivation by Tg appeared to be due to its ability to trigger intracellular Ca2+ mobilization rather than its ability to induce UPR, based on our observations in which UPR induction alone was not sufficient to trigger the EBV lytic cycle in our LCLs. EBV immortalized LCLs have rarely been included in the majority of the lytic reactivation studies yet the characteristics of latent infection in LCLs should resemble those of proliferating B cells in clinically encountered lymphoproliferative diseases. Based on these observations, we propose an alternative mechanism of action for Tg in triggering EBV lytic reactivation in LCLs, and suggest that the proposed use of any chemical inducers of UPR for a purpose of oncolytic/lytic induction therapy needs to be fully evaluated pre-clinically in a panel of LCLs.

The field of silicon photonics has experienced widespread adoption in the datacoms industry over the past decade, with a plethora of other applications emerging more recently such as light detection and ranging (LIDAR), sensing, quantum photonics, programmable photonics and artificial intelligence. As a result of this, many commercial complementary metal oxide semiconductor (CMOS) foundries have developed open access silicon photonics process lines, enabling the mass production of silicon photonics systems. On the other side of the spectrum, several research labs, typically within universities, have opened up their facilities for small scale prototyping, commonly exploiting e-beam lithography for wafer patterning. Within this ecosystem, there remains a challenge for early stage researchers to progress their novel and innovate designs from the research lab to the commercial foundries because of the lack of compatibility of the processing technologies (e-beam lithography is not an industry tool). The CORNERSTONE rapid-prototyping capability bridges this gap between research and industry by providing a rapid prototyping fabrication line based on deep-UV lithography to enable seamless scaling up of production volumes, whilst also retaining the ability for device level innovation, crucial for researchers, by offering flexibility in its process flows. This review article presents a summary of the current CORNERSTONE capabilities and an outlook for the future.