Far from 'the magic of the mall': Retail (Change) in 'other places'

Abstract: A pre-occupation with the ‘new' and a focus on corporate retailers and spaces has led to a lack of consideration of change and issues in secondary or ‘other places' of retail. Using a longitudinal survey methodology, data on retail stock, churn, vacancy and use are considered for one such ‘other place' - Shettleston in Glasgow. The data show complex dimensions and aspects of vulnerability and resilience, compounded by reactions to exogenous retail and other economic and social changes. Far from being ‘seedy, pre-historical backwaters', Shettleston and similar ‘other' places can be vital, local centres playing a variety of useful roles. They require support and attention every bit as much as more high profile town centres and high streets

Using online patient feedback to improve NHS services : the INQUIRE multimethod study

Background Online customer feedback has become routine in many industries, but it has yet to be harnessed for service improvement in health care. Objectives To identify the current evidence on online patient feedback; to identify public and health professional attitudes and behaviour in relation to online patient feedback; to explore the experiences of patients in providing online feedback to the NHS; and to examine the practices and processes of online patient feedback within NHS trusts. Design A multimethod programme of five studies: (1) evidence synthesis and stakeholder consultation; (2) questionnaire survey of the public; (3) qualitative study of patients’ and carers’ experiences of creating and using online comment; (4) questionnaire surveys and a focus group of health-care professionals; and (5) ethnographic organisational case studies with four NHS secondary care provider organisations. Setting The UK. Methods We searched bibliographic databases and conducted hand-searches to January 2018. Synthesis was guided by themes arising from consultation with 15 stakeholders. We conducted a face-to-face survey of a representative sample of the UK population (n = 2036) and 37 purposively sampled qualitative semistructured interviews with people with experience of online feedback. We conducted online surveys of 1001 quota-sampled doctors and 749 nurses or midwives, and a focus group with five allied health professionals. We conducted ethnographic case studies at four NHS trusts, with a researcher spending 6–10 weeks at each site. Results Many people (42% of internet users in the general population) read online feedback from other patients. Fewer people (8%) write online feedback, but when they do one of their main reasons is to give praise. Most online feedback is positive in its tone and people describe caring about the NHS and wanting to help it (‘caring for care’). They also want their feedback to elicit a response as part of a conversation. Many professionals, especially doctors, are cautious about online feedback, believing it to be mainly critical and unrepresentative, and rarely encourage it. From a NHS trust perspective, online patient feedback is creating new forms of response-ability (organisations needing the infrastructure to address multiple channels and increasing amounts of online feedback) and responsivity (ensuring responses are swift and publicly visible). Limitations This work provides only a cross-sectional snapshot of a fast-emerging phenomenon. Questionnaire surveys can be limited by response bias. The quota sample of doctors and volunteer sample of nurses may not be representative. The ethnographic work was limited in its interrogation of differences between sites. Conclusions Providing and using online feedback are becoming more common for patients who are often motivated to give praise and to help the NHS improve, but health organisations and professionals are cautious and not fully prepared to use online feedback for service improvement. We identified several disconnections between patient motivations and staff and organisational perspectives, which will need to be resolved if NHS services are to engage with this source of constructive criticism and commentary from patient

Measurement of cortisol in saliva: a comparison of measurement error within and between international academic-research laboratories

Objective: Hundreds of scientific publications are produced annually that involve the measurement of cortisol in saliva. Intra- and inter-laboratory variation in salivary cortisol results has the potential to contribute to cross- study inconsistencies in findings, and the perception that salivary cortisol results are unreliable. This study rigor- ously estimates sources of measurement variability in the assay of salivary cortisol within and between established international academic-based laboratories that specialize in saliva analyses. One hundred young adults (Mean age: 23.10 years; 62 females) donated 2 mL of whole saliva by passive drool. Each sample was split into multiple- 100 µL aliquots and immediately frozen. One aliquot of each of the 100 participants’ saliva was transported to academic laboratories (N = 9) in the United States, Canada, UK, and Germany and assayed for cortisol by the same commercially available immunoassay. Results: 1.76% of the variance in salivary cortisol levels was attributable to differences between duplicate assays of the same sample within laboratories, 7.93% of the variance was associated with differences between laboratories, and 90.31% to differences between samples. In established-qualified laboratories, measurement error of salivary cortisol is minimal, and inter-laboratory differences in measurement are unlikely to have a major influence on the determined values

Preclinical and clinical evaluation of German-sourced ONC201 for the treatment of H3K27M-mutant diffuse intrinsic pontine glioma

Background Diffuse intrinsic pontine glioma (DIPG) is a fatal childhood brainstem tumor for which radiation is the only treatment. Case studies report a clinical response to ONC201 for patients with H3K27M-mutant gliomas. Oncoceutics (ONC201) is only available in the United States and Japan; however, in Germany, DIPG patients can be prescribed and dispensed a locally produced compound-ONC201 German-sourced ONC201 (GsONC201). Pediatric oncologists face the dilemma of supporting the administration of GsONC201 as conjecture surrounds its authenticity. Therefore, we compared GsONC201 to original ONC201 manufactured by Oncoceutics Inc. Methods Authenticity of GsONC201 was determined by high-resolution mass spectrometry and nuclear magnetic resonance spectroscopy. Biological activity was shown via assessment of on-target effects, in vitro growth, proliferation, and apoptosis analysis. Patient-derived xenograft mouse models were used to assess plasma and brain tissue pharmacokinetics, pharmacodynamics, and overall survival (OS). The clinical experience of 28 H3K27M+ mutant DIPG patients who received GsONC201 (2017-2020) was analyzed. Results GsONC201 harbored the authentic structure, however, was formulated as a free base rather than the dihydrochloride salt used in clinical trials. GsONC201 in vitro and in vivo efficacy and drug bioavailability studies showed no difference compared to Oncoceutics ONC201. Patients treated with GsONC201 (n = 28) showed a median OS of 18 months (P = .0007). GsONC201 patients who underwent reirradiation showed a median OS of 22 months compared to 12 months for GsONC201 patients who did not (P = .012). Conclusions This study confirms the biological activity of GsONC201 and documents the OS of patients who received the drug; however, GsONC201 was never used as a monotherapy

PI3K/mTOR is a therapeutically targetable genetic dependency in diffuse intrinsic pontine glioma

Diffuse midline glioma (DMG), including tumors diagnosed in the brainstem (diffuse intrinsic pontine glioma; DIPG), are uniformly fatal brain tumors that lack effective treatment. Analysis of CRISPR/Cas9 loss-of-function gene deletion screens identified PIK3CA and MTOR as targetable molecular dependencies across patient derived models of DIPG, highlighting the therapeutic potential of the blood-brain barrier–penetrant PI3K/Akt/mTOR inhibitor, paxalisib. At the human-equivalent maximum tolerated dose, mice treated with paxalisib experienced systemic glucose feedback and increased insulin levels commensurate with patients using PI3K inhibitors. To exploit genetic dependence and overcome resistance while maintaining compliance and therapeutic benefit, we combined paxalisib with the antihyperglycemic drug metformin. Metformin restored glucose homeostasis and decreased phosphorylation of the insulin receptor in vivo, a common mechanism of PI3K-inhibitor resistance, extending survival of orthotopic models. DIPG models treated with paxalisib increased calcium-activated PKC signaling. The brain penetrant PKC inhibitor enzastaurin, in combination with paxalisib, synergistically extended the survival of multiple orthotopic patient-derived and immunocompetent syngeneic allograft models; benefits potentiated in combination with metformin and standard-of-care radiotherapy. Therapeutic adaptation was assessed using spatial transcriptomics and ATAC-Seq, identifying changes in myelination and tumor immune microenvironment crosstalk. Collectively, this study has identified what we believe to be a clinically relevant DIPG therapeutic combinational strategy

The semiology of changing brand image

This article considers the attempted change to the image of an established brand by studying the semiotics within the brand’s historical advertising campaigns. The use of semiotics to study the interpretation of messages is discussed, and the link between interpretation of messages and advertising effectiveness in changing brand image is explored. The authors deconstruct advertisements of a brand to provide a model containing opposing dialectics that may aid managers by highlighting alternative symbolic messages contained in advertisements. Oncwe identified, these alternative symbolic messages may be used to help change brand image and influence advertising effectiveness. Although the study focuses upon a major brand of beer, this is an industry in which there are numerous small firms, and many of those have constrained marketing budgets, and thus need to make sure that their advertising is effective. Equally, entrepreneurial marketing is not to found only in the small firm, and the case study discusses a radical and imaginative brand repositioning of a well established product

Polymorphisms near TBX5 and GDF7 are associated with increased risk for Barrett's esophagus.

BACKGROUND & AIMS: Barrett's esophagus (BE) increases the risk of esophageal adenocarcinoma (EAC). We found the risk to be BE has been associated with single nucleotide polymorphisms (SNPs) on chromosome 6p21 (within the HLA region) and on 16q23, where the closest protein-coding gene is FOXF1. Subsequently, the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) identified risk loci for BE and esophageal adenocarcinoma near CRTC1 and BARX1, and within 100 kb of FOXP1. We aimed to identify further SNPs that increased BE risk and to validate previously reported associations. METHODS: We performed a genome-wide association study (GWAS) to identify variants associated with BE and further analyzed promising variants identified by BEACON by genotyping 10,158 patients with BE and 21,062 controls. RESULTS: We identified 2 SNPs not previously associated with BE: rs3072 (2p24.1; odds ratio [OR] = 1.14; 95% CI: 1.09-1.18; P = 1.8 × 10(-11)) and rs2701108 (12q24.21; OR = 0.90; 95% CI: 0.86-0.93; P = 7.5 × 10(-9)). The closest protein-coding genes were respectively GDF7 (rs3072), which encodes a ligand in the bone morphogenetic protein pathway, and TBX5 (rs2701108), which encodes a transcription factor that regulates esophageal and cardiac development. Our data also supported in BE cases 3 risk SNPs identified by BEACON (rs2687201, rs11789015, and rs10423674). Meta-analysis of all data identified another SNP associated with BE and esophageal adenocarcinoma: rs3784262, within ALDH1A2 (OR = 0.90; 95% CI: 0.87-0.93; P = 3.72 × 10(-9)). CONCLUSIONS: We identified 2 loci associated with risk of BE and provided data to support a further locus. The genes we found to be associated with risk for BE encode transcription factors involved in thoracic, diaphragmatic, and esophageal development or proteins involved in the inflammatory response

A communal catalogue reveals Earth's multiscale microbial diversity

Our growing awareness of the microbial world's importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth's microbial diversity.Peer reviewe

A communal catalogue reveals Earth’s multiscale microbial diversity

Our growing awareness of the microbial world’s importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth’s microbial diversity