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Studies find that same day registration (SDR) laws increase turnout, but less is known about which kinds of voters are most affected. Young people are disproportionately burdened by traditional reg...

The apoptosis-stimulating protein of p53 (ASPP) family of proteins can regulate apoptosis by interacting with the p53 family and have been identified to play an important role in cancer progression. Previously, we have demonstrated that ASPP2 downregulation can promote invasion and migration by controlling β-catenin- dependent regulation of ZEB1, however, the role of ASPP1 in colorectal cancer (CRC) remains unclear. We analyzed data from The Cancer Genome Atlas (TCGA) and coupled this to in vitro experiments in CRC cell lines as well as to experimental pulmonary metastasis in vivo. Tissue microarrays of CRC patients with information of clinical-pathological parameters were also used to investigate the expression and function of ASPP1 in CRC. Here, we report that loss of ASPP1 is capable of enhancing migration and invasion in CRC, both in vivo and in vitro. We demonstrate that depletion of ASPP1 could activate expression of Snail2 via the NF-κB pathway and in turn, induce EMT; and this process is further exacerbated in RAS-mutated CRC. ASPP1 could be a prognostic factor in CRC, and the use of NF-κB inhibitors may provide new strategies for therapy against metastasis in ASPP1-depleted CRC patients.

This article reflects on how offline and online everyday life coexists for encamped, young Karen living in protracted displacement. As part of the special issue ‘Cultures of (im)mobile entanglements’, edited by Earvin Cabalquinto and Koen Leurs, I centre the voices of young Karen living in Mae La refugee camp in Thailand and unpack how personal and social relationships are built and maintained physically in the camp, as well as in digitally mediated spaces. I focus on the tensions of (im)mobility and how life and presence were mediated before and during the Covid-19 pandemic. I emphasise the influence of culture, society, and infrastructure on my participants’ living trajectories and find how social media expands their lived reality far beyond the confinement of the camp.

Background Fluoropyrimidine plus platinum chemotherapy remains the standard first line treatment for gastric cancer (GC). Guidelines exist for the clinical interpretation of four DPYD genotypes related to severe fluoropyrimidine toxicity within European populations. However, the frequency of these single nucleotide polymorphisms (SNPs) in the Latin American population is low ( Methods Retrospectively, 224 clinical records of GC patient were screened, of which 93 patients were incorporated into the study. Eleven SNPs with minor allelic frequency above 5% in GSTP1, ERCC2, ERCC1, TP53, UMPS, SHMT1, MTHFR, ABCC2 and DPYD were assessed. Association between patient clinical characteristics and toxicity was estimated using logistic regression models and classification algorithms. Results Reported grade ≤ 2 and 3–4 toxicities were 64.6% (61/93) and 34.4% (32/93) respectively. Selected DPYD SNPs were associated with higher toxicity (rs1801265; OR = 4.20; 95% CI = 1.70–10.95, p = 0.002), while others displayed a trend towards lower toxicity (rs1801159; OR = 0.45; 95% CI = 0.19–1.08; p = 0.071). Combination of paired SNPs demonstrated significant associations in DPYD (rs1801265), UMPS (rs1801019), ABCC2 (rs717620) and SHMT1 (rs1979277). Using multivariate logistic regression that combined age, sex, peri-operative chemotherapy, 5-FU regimen, the binary combination of the SNPs DPYD (rs1801265) + ABCC2 (rs717620), and DPYD (rs1801159) displayed the best predictive performance. A nomogram was constructed to assess the risk of developing overall toxicity. Conclusion Pending further validation, this model could predict chemotherapy associated toxicity and improve GC patient quality of life.

Idiopathic pulmonary fibrosis (IPF) is the prototypic progressive fibrotic interstitial lung disease. Median survival is only 3 years, and treatment options are limited. IPF is thought to be a result of a combination of genetic and environmental factors with repetitive micro-injuries to alveolar epithelial cells playing a central role. IPF is characterised by aberrant extra cellular matrix (ECM) deposition by activated myofibroblasts. Epithelial-mesenchymal transition (EMT) is a process where polarised epithelial cells undergo molecular changes allowing them to gain a mesenchymal phenotype, with a subsequent enhanced ability to produce ECM components and increased migration and/or invasion. The source of myofibroblasts in IPF has been debated for many years, and EMT has been proposed as a source of these cells. However, lineage tracing in transgenic mice suggests the contribution of epithelial cells, which have undergone EMT, to the fibroblast population may be negligible. Instead, recent findings suggest that alveolar epithelial type II (ATII) cells undergoing EMT promote a pro-fibrotic microenvironment through paracrine signalling activating local fibroblasts. This review paper explores the contribution of ATII cells, which have undergone EMT, in the context of pulmonary fibrosis.

Background Recent guidelines in the UK have shaped Critical Care Units (CCUs) to bring the mental health needs of patients, and staff wellbeing to the forefront of service provision. A health board based in NHS Wales has trialled the secondment of a Mental Health Nurse (RMN) within a CCU to help service provision adhere to such guidelines. Methods Critical care staff were invited to attend focus groups to share their experiences of how the RMN influenced service provision. Results Thematic analysis identified five main themes; including ‘smoother care pathways’, ‘a holistic approach to care’, ‘co-production’, ‘knowledge and confidence’ and ‘staff wellbeing’. Each of these themes reflected how the RMN had both direct and indirect benefits on patient and staff wellbeing. Conclusion This qualitative exploration suggests that staff perceived value in the role of the RMN for both staff and patient outcomes, although further measures were considered necessary to improve staff-wellbeing within a critical care environment. This service evaluation supports recommendations for commissioning a RMN permanently in a CCU.

Despite the extensive study of MYCN-amplified neuroblastomas, there is a significant unmet clinical need in MYCN non-amplified neuroblastomas. In particular, the extent of heterogeneity within the MYCN non-amplified population is unknown. Here, we investigate whether transcriptional subtyping of MYCN non-amplified neuroblastomas can identify molecular subtypes with discrete prognosis and therapeutic vulnerabilities. Using tumour expression data and ConsensusClusterPlus, we demonstrate that MYCN non-amplified neuroblastomas are heterogeneous and can be classified into 3 subgroups based on their transcriptional signatures. Within these groups, subgroup 2 has the worst prognosis and this group shows a "MYCN" signature that is potentially induced by the overexpression of Aurora Kinase A (AURKA); whilst subgroup 3 is characterised by an "inflamed" gene signature. The clinical implications of this subtype classification are significant, as each subtype demonstrates unique prognosis and vulnerability to investigational therapies. We propose that matching baseline tumour subtype to therapy may enhance precision prognosis and therapy stratification for patients with MYCN non-amplified neuroblastomas.

Chronic pain affects 1 in 5 persons and contributes substantially to the global burden of disease. The 11th Revision of the International Classification of Diseases (ICD-11) includes a comprehensive classification of chronic pain. The aim of this ecological implementation field study was to evaluate the classification's interrater reliability and clinical utility in countries with different income levels. The study was conducted in 4 pain clinics in Cuba, India, and New Zealand. Twenty-one clinicians used the ICD-11 to diagnose and code n = 353 patients with chronic pain. Of these, 111 were assessed by 2 clinicians, and Fleiss' kappa was calculated to establish interrater reliability for any diagnosis assigned to ≥15 patients. The clinicians rated the clinical utility of all diagnoses. The interrater reliability could be calculated for 11 diagnoses. It was substantial for 10 diagnoses and moderate for 1 (kappa: 0.596-0.783). The mean clinical utility of the ICD-11 chronic pain diagnoses was rated as 8.45 ± 1.69/10. Clinical utility was rated higher for ICD-11 than for the commonly used classification systems (P < 0.001, η2 = 0.25) and differed between all centers (P < 0.001, η2 = 0.60). The utility of the ICD-11 diagnoses was rated higher than the commonly used diagnoses in Dunedin and Havana, and no difference was found in Kolkata and Hyderabad. The study showed the high interrater reliability of the new chronic pain diagnoses. The perceived clinical utility of the diagnoses indicates their superiority or equality compared with the classification systems currently used in pain clinics. These results suggest the global applicability of the classification in specialized pain treatment settings.

In many ways, American democracy seems to work better for older citizens than younger citizens, and one explanation is that young adults vote at much lower rates than their older counterparts. Yet while the existence of the age gap in turnout is well established, there remains uncertainty as to what drives it. In this paper, we explore age as a potentially important group identity and evaluate whether strength of age-group identity predicts political participation. Adapting established measures in the social identity literature, we surveyed a representative sample of American adults to gauge how strongly they identified with others in their age group. We find that, on average, younger adults identify less strongly than senior citizens with others their age. However, for young adults, age-group identity is as strong as another form of group identity that has gotten considerable attention in the literature: political party identity. The strength of age-group identity also predicts both voting and participating in climate change protests, especially for young adults. Age-group identity is a stronger predictor of climate protest participation for young Republicans than young Democrats—suggesting there may be potential for a bipartisan coalition of young people active on the issue of climate change.

Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer that lacks the oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2, making it difficult to target therapeutically. Targeting synthetic lethality is an alternative approach for cancer treatment. TNBC shows frequent loss of phosphatase and tensin homologue (PTEN) expression, which is associated with poor prognosis and treatment response. To identify PTEN synthetic lethal interactions, TCGA analysis coupled with a whole-genome siRNA screen in isogenic PTEN-negative and -positive cells were performed. Among the candidate genes essential for the survival of PTEN-inactive TNBC cells, WDHD1 (WD repeat and high-mobility group box DNA-binding protein 1) expression was increased in the low vs. high PTEN TNBC samples. It was also the top hit in the siRNA screen and its knockdown significantly inhibited cell viability in PTEN-negative cells, which was further validated in 2D and 3D cultures. Mechanistically, WDHD1 is important to mediate a high demand of protein translation in PTEN-inactive TNBC. Finally, the importance of WDHD1 in TNBC was confirmed in patient samples obtained from the TCGA and tissue microarrays with clinic-pathological information. Taken together, as an essential gene for the survival of PTEN-inactive TNBC cells, WDHD1 could be a potential biomarker or a therapeutic target for TNBC.

The COVID-19 crisis has generated interest in all-mail voting (AMV) as a potential policy solution for avoiding in-person elections. However, the quality of AMV implementation has varied greatly across states, leading to mixed results in previous research. We exploit the understudied 2014 implementation of AMV in Colorado to estimate the effect on turnout for all registered voters, along with age, racial, education, income and wealth, and occupational subgroups. Using large voter file data and a difference-in-differences design within individuals, we find a positive overall turnout effect of approximately 8 percentage points—translating into an additional 900,000 ballots being cast between 2014 and 2018. Effects are significantly larger among lower-propensity voting groups, such as young people, blue-collar workers, voters with less educational attainment, and voters of color. The results suggest that researchers and policymakers should look to Colorado's AMV approach as an effective model for boosting aggregate turnout and reducing voting disparities across subgroups.

Purpose The purpose of this paper is to explore whether the current forensic mental health inpatient population within a medium secure unit is more or less complex (i.e. clinical and risk presentations) than former years using the Health of the Nation Outcome Scale (HoNOS) secure. Additionally, the use of the HoNOS secure as a service-wide measure is discussed in terms of its usefulness. Clinical implications and recommendations are offered for the continued use of the HoNOS secure in services more widely. Design/methodology/approach A retrospective case review of completed HoNOS secure assessments for 130 patients over three time intervals 2012, 2015 and 2018 was used. A multivariate analysis was performed on the data using SPSS version 25. Findings The findings revealed that contrary to clinical opinion, inpatients’ clinical and risk presentations had not changed significantly overtime. Research limitations/implications The study shows the benefits of using the HoNOS secure at a service-wide level to explore and understand similarities and differences in inpatient admissions over time. It also highlights the usefulness of the HoNOS secure for considering different ward characteristics and the needs of patients residing in these environments. Originality/value Although much research exists surrounding the individual use of the HoNOS secure in relation to outcomes, there is limited research focusing on use of the HoNOS secure at the service level. The paper therefore provides evidence of the utility and value of the HoNOS secure as a service-level outcome measure.

Hyperbaric oxygen (HBO) is widely applied to treat several hypoxia-related diseases. Previous studies have focused on the immediate effect of HBO-exposure induced oxidative stress on the lungs, but knowledge regarding the chronic effects from repetitive HBO exposure is limited, especially at the gene expression level. We found that repetitive HBO exposure did not alter the morphology of murine lungs. However, by deconvolution of RNA-seq from those mice lungs using CIBERSORTx and the expression profile matrices of 8 mesenchymal cell subtypes obtained from bleomycin-treated mouse lungs, we identify several mesenchymal cell subtype changes. These include increases in Col13a1 matrix fibroblasts, mesenchymal progenitors and mesothelial cell populations and decreases in lipofibroblasts, endothelial and Pdgfrb high cell populations. Our data suggest that repetitive HBO exposure may affect biological processes in the lungs such as response to wounding, extracellular matrix, vasculature development and immune response.

The development of immune checkpoint inhibitors is revolutionizing gastric cancer (GC) therapy. However, the presence of an immune-suppressive tumor microenvironment and redundancy between inhibitory immune checkpoints may be responsible for why a high percentage of patients without clinical benefit. An emerging checkpoint target is Tim-3, a membrane protein that enhances immunosuppression upon binding to its ligand Galectin-9 (Gal-9). Gal-9 is overexpressed in gastrointestinal cancers and expressed in both cancer and stromal cells such as the tumor endothelium. However the role of the Gal-9/Tim-3 pathway in the GC tumor microenvironment is still undeciphered, we hypothesize that this pathway mediates immune escape though enhancement of a immunosuppressive microenvironment. We performed a bioinformatic analysis of stomach adenocarcinoma (STAD) from the TCGA database (TIMER©, Cibersort and Xcell were used). To evaluate if Gal-9 had an impact on cancer cell phenotype we transfected Gal-9 into the gastric cancer cell line AGS and the gastric epithelium cell line GES-1. To assess the potential role in CG tumor microenvironment, Gal-9 was transfected or recombinant Gal-9 (rGal-9) was administrated to Human Umbilical Vein Endothelial Cells (HUVECs). Gal-9 biological effects were assessed by migration, invasion and Matrigel tube formation assay. Western blotting assessed Tim-3 expression and PDL-1 expression. Furthermore, we used lactose to block Gal-9 binding to Tim-3 to determine if the biological effects required receptor engagement. Results from TCGA analysis demonstrated that both Gal-9 and Tim-3 are upregulated in gastric tumors. Tim-3 mRNA is significantly increased in invasive adenocarcinomas. A positive correlation was observed between Gal-9, PDL-1 and Tim-3, which was consistent with in vitro experiments, where increased expression of Gal-9 resulted in increased PDL-1 and Tim-3. In addition, Gal-9 increased cancer cell invasion and promoted HUVEC migration and tubular like structure formation in vitro. Further bioinformatic analysis revealed strong positive correlation with CD8+ T cell, Treg and macrophage/monocyte gene signatures. Tim-3 and Gal-9 were more strongly associated with these gene signatures than PD1 and PDL-1. Interestingly, Gal-9 was associated with T cell dysfunction and Treg markers, suggesting that in GC Gal-9 could promote T cell dysfunction and Treg expansion. Our results suggest an association between the Gal-9/Tim-3 pathway with a more aggressive and increased immune suppressive microenvironment and GC. Funding: Fondecyt 118024, CONICYT-FONDAP 15130011, IMIIP09/16F, FONDECYT 1180173 Citation Format: Charlotte Nicole Hill, Maximiliano Arce Arata, Camille Cabrolier, Noymar Luque, Pamela Gonzalez, Gabriela Maita, Ana Maria Vega-Letter, Patricia Luz Crawford, Marcelo Garrido, Gareth I. Owen. Galectin 9 promotes invasion and angiogenesis in vitro and associates with an immune-suppressive microenvironment in gastric cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2792.

As the cause of fibromyalgia is controversial, communicating with patients can be challenging, particularly if the patient adopts the narrative ‘I am damaged and so I need a more powerful pain killer’. Research shows that providing patients with alternative narratives can be helpful, but it remains unclear what particular narratives are most acceptable to patients and at the same time provide a rationale for evidence based psychological and exercise interventions. This article described the development of a new narrative and the written comments made about the narrative by fibromyalgia patients. The narrative derives from a complexity theory model and provides an alternative to biogenic and psychogenic models. The model was presented to 15 patients whose comments about comprehensibility led to the final format of the narrative. In the final form, the body is presented as ‘a very, very clever computer’ where fibromyalgia is caused by a software rather than a hardware problem. The software problem is caused by the body adapting when people have to ‘keep going’ despite ‘stop signals’, such as pain and fatigue. The narrative provides a rationale for engaging in psychological and exercise interventions as a way of correcting the body’s software. This way of explaining fibromyalgia was evaluated by a further 25 patients attending a 7-week ‘body reprogramming’ intervention, where the therapy was presented as correcting the body’s software, and included both exercise and psychological components. Attendance at the course was 85%. Thematic analysis of written patient feedback collected after each session showed that patients found the model believable and informative, it provided hope and was empowering. Patients also indicated that they had started to implement lifestyle change with perceived benefit. Fibromyalgia patients appear to respond positively to a technology-derived narrative based on the analogy of the body as a computer.

Ventilator-associated pneumonia (VAP) is the leading cause of death with hospital-acquired infections, and preventing it is one of the Saving Lives initiatives ( Department of Health 2007 ). This article discusses the implementation of a purpose-designed VAP care bundle in a children's intensive care unit and examines the unique role of nurses in the management of the change process. A nurse-led VAP education, implementation and surveillance programme was set up. Nurse education was paramount, as nursing staff acceptance and involvement was a key feature. A multi-method training strategy was implemented, providing staff with multiple training opportunities and introducing VAP project education as a routine part of staff induction. Bundle compliance was monitored regularly and graphs of the results produced quarterly; feedback proved to be useful in keeping staff informed and engaged in VAP reduction. Comparison of VAP incidence before and after introduction of the care bundle showed a reduction after its implementation. With a co-ordinated, multidisciplinary approach, VAP care bundles can result in significant and sustained reductions in VAP rates in the paediatric intensive care unit. Effective co-ordination and leadership is crucial to successful implementation of the VAP bundle, and nurses are well placed to undertake this role.

Over half of organisations are expected to significantly increase their investment in biometric technologies to prevent fraud and combat organised cyber-crime groups, according to a recent Callcredit Fraud and Risk Report 1

Epithelial-mesenchymal transition (EMT) and autophagy are both known to play an important role in the development of cancer. Subsequently, these processes are now being utilised as targets for therapy. Cancer is globally one of the leading causes of death, and despite many advances in treatment options, patients still face many challenges. Drug-resistance in cancer-therapy is a large problem, and both EMT and autophagy have been shown to contribute. However, given the context-dependent role of these processes and the complexity of the interactions between them, elucidating how they both act alone and interact together is important. In this review, we will provide an insight into the current landscape of the interactions of autophagy and EMT in the context of malignancy, and how this ultimately may affect drug-resistance in cancer-therapy.

Macroautophagy/autophagy inhibition is a novel anticancer therapeutic strategy, especially for tumors driven by mutant RAS. Here, we demonstrate that autophagy inhibition in RAS-mutated cells induces epithelial-mesenchymal transition (EMT), which is associated with enhanced tumor invasion. This is at least partially achieved by triggering the NFKB/NF-κB pathway via SQSTM1/p62. Knockdown of ATG3 or ATG5 increases oncogenic RAS-induced expression of ZEB1 and SNAI2/Snail2, and activates NFKB activity. Depletion of SQSTM1 abolishes the activation of the NFKB pathway induced by autophagy inhibition in RAS-mutated cells. NFKB pathway inhibition by depletion of RELA/p65 blocks this EMT induction. Finally, accumulation of SQSTM1 protein correlates with loss of CDH1/E-cadherin expression in pancreatic adenocarcinoma. Together, we suggest that combining autophagy inhibition with NFKB inhibitors may therefore be necessary to treat RAS-mutated cancer. Abbreviations: 4-OHT: 4-hydroxytamoxifen; DIC: differential interference contrast; EMT: epithelial-mesenchymal transition; ESR: estrogen receptor; MAPK/ERK: mitogen-activated protein kinase; iBMK: immortalized baby mouse kidney epithelial cells; MET: mesenchymal-epithelial transition; PI3K: phosphoinositide 3-kinase; RNAi: RNA interference; TGFB/TGF-β: transforming growth factor beta; TNF: tumor necrosis factor; TRAF6: TNF receptor associated factor 6.

This year has already seen a multitude of companies propose and launch new systems and devices in the rapidly developing field of wearable biometrics. Smart wearable devices (SWDs) are becoming an increasingly popular form of identification using biometric measurements and are set to replace traditional password and chip and pin authentication methods while continuing to assist both the fitness and medical industries.

The contribution of epithelial-mesenchymal transition (EMT) to human lung fibrogenesis is controversial. Here we provide evidence that ZEB1-mediated EMT in human alveolar epithelial type II (ATII) cells contributes to the development of lung fibrosis by paracrine signalling to underlying fibroblasts. Activation of EGFR-RAS-ERK signalling in ATII cells induced EMT via ZEB1. ATII cells had extremely low extracellular matrix gene expression even after induction of EMT, however conditioned media from ATII cells undergoing RAS-induced EMT augmented TGFβ-induced profibrogenic responses in lung fibroblasts. This epithelial-mesenchymal crosstalk was controlled by ZEB1 via the expression of tissue plasminogen activator (tPA). In human fibrotic lung tissue, nuclear ZEB1 expression was detected in alveolar epithelium adjacent to sites of extracellular matrix (ECM) deposition, suggesting that ZEB1-mediated paracrine signalling has the potential to contribute to early fibrotic changes in the lung interstitium. Targeting this novel ZEB1 regulatory axis may be a viable strategy for the treatment of pulmonary fibrosis.

Background: The development of immune checkpoint inhibitors (immunotherapy, such as anti-PD1) that induce a sustained T-cell immune response with anti-tumor activity has been a breakthrough in oncology practice. However, in gastric cancer (GC), sustained responses to anti PD-1 therapy are only observed in approximately 20% of patients. The expression of alternative immune checkpoints such as Galectin 9 (Gal-9) and Tim3 has been associated to anti-PD1 resistance in other cancer types. In search of the factors that render gastric tumors resistant to immunotherapy, we hypothesized that Gal-9 expression in gastric cancer cells may enhance metastasis and immunosuppression. Methods: Bioinformatic analysis of gastric cancer data of patients with gastric adenocarcinoma from TCGA Database was performed. In vitro experiments with Gal-9 transfected gastric cancer cell line AGS were performed to elucidate Gal-9 gain of function effect on cell invasion and immune-suppressive proteins. Invasion assay using a matrigel coated transwell was performed within 24 hours of transfection. To determine changes in PDL1, E-Cadherin and N-Cadherin expression, cells were harvested 24h after transfection to analyze protein and mRNA levels through Western Blot and RT-PCR respectively. Results: TCGA database analysis demonstrate that Gal-9 expression is significantly correlated to PDL-1 expression in gastric cancer; furthermore, it was also positively correlated to immune cell markers such as FOXP3. In accordance, in vitro analysis demonstrates that exogenous expression of GAL9 results in an increase in PDL-1 protein and greater invasive potential of the AGS cell line. Conclusion: Taken together our results suggest that further studies should focus on the role played by Gal-9 is the establishment of an immune suppressive microenvironment in gastric tumors. FONDECYT 1180241, 1180173. CONICYT FONDAP 15130011, IMII P09/016F BMS CA209-8F3 Citation Format: Charlotte Hill, Camille Cabrolier, Elisa Cumsille, Maximiliano Arce, Mauricio P. Pinto, Maria Loreto Bravo, Matias Muñoz, Marcelo Garrido, Gareth I. Owen. Galectin 9 associates with PDL1 expression and promotes gastric cancer cell invasion [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1494.

Background Deriving and validating local adjusted calcium equations is important for ensuring appropriate calcium status classification. We investigated the impact on our local adjusted calcium equation of a change in calcium method by the manufacturer from cresolphthalein complexone to NM-BAPTA. Methods Calcium and albumin results from general practice requests were extracted from the Laboratory Information Management system for a three-month period. Results for which there was evidence of disturbance in calcium homeostasis were excluded leaving 13,482 sets of results for analysis. The adjusted calcium equation was derived following least squares regression analysis of total calcium on albumin and normalized to the mean calcium concentration of the data-set. The revised equation (NM-BAPTA calcium method) was compared with the previous equation (cresolphthalein complexone calcium method). Results The switch in calcium assay resulted in a small change in the adjusted calcium equation but was not considered to be clinically significant. The calcium reference interval differed from that proposed by Pathology Harmony in the UK. Conclusions Local adjusted calcium equations should be re-assessed following changes in the calcium method. A locally derived reference interval may differ from the consensus harmonized reference interval.

2014 saw both positive developments and significant challenges for the biometrics industry in the educational sector. In the US, we saw Californian Governor Rick Scott pass a Bill in May 2014 (SB 188) that forbids the collection of biometric data in schools not only from its students, but also their parents and siblings as a response to privacy concerns. This is in addition to the collection of both political and religious affiliation and voting history, with Scott saying of the Bill, “The legislation I am signing today will set Florida students and families up for education success and prevent unnecessary collection of data.”

Syndecan 4 (Sdc4) is a cell-surface heparan sulfate proteoglycan (HSPG) that regulates gastrulation, neural tube closure and directed neural crest migration in Xenopus development. To determine whether Sdc4 participates in Wnt/PCP signaling during mouse development, we evaluated a possible interaction between a null mutation of Sdc4 and the loop-tail allele of Vangl2. Sdc4 is expressed in multiple tissues, but particularly in the non-neural ectoderm, hindgut and otic vesicles. Sdc4;Vangl2Lp compound mutant mice have defective spinal neural tube closure, disrupted orientation of the stereocilia bundles in the cochlea and delayed wound healing, demonstrating a strong genetic interaction. In Xenopus, co-injection of suboptimal amounts of Sdc4 and Vangl2 morpholinos resulted in a significantly greater proportion of embryos with defective neural tube closure than each individual morpholino alone. To probe the mechanism of this interaction, we overexpressed or knocked down Vangl2 function in HEK293 cells. The Sdc4 and Vangl2 proteins colocalize, and Vangl2, particularly the Vangl2Lp mutant form, diminishes Sdc4 protein levels. Conversely, Vangl2 knockdown enhances Sdc4 protein levels. Overall HSPG steady-state levels were regulated by Vangl2, suggesting a molecular mechanism for the genetic interaction in which Vangl2Lp/+ enhances the Sdc4-null phenotype. This could be mediated via heparan sulfate residues, as Vangl2Lp/+ embryos fail to initiate neural tube closure and develop craniorachischisis (usually seen only in Vangl2Lp/Lp) when cultured in the presence of chlorate, a sulfation inhibitor. These results demonstrate that Sdc4 can participate in the Wnt/PCP pathway, unveiling its importance during neural tube closure in mammalian embryos.