Glucose transporter Glut-1 is detectable in pen-necrotic regions in many human tumor types but not normal tissues: Study using tissue microarrays

The hypoxic tumor microenvironment is associated with malignant progression and poor treatment response. The glucose transporter Glut-1 is a prognostic factor and putative hypoxia marker. So far, studies of Glut-1 in cancer have utilised conventional immunohistochemical analysis in a series of individual biopsy or surgical specimens. Tissue microarrays, however, provide a rapid, inexpensive means of profiling biomarker expression. To evaluate hypoxia markers, tissue cores must show architectural features of hypoxia, i.e. viable tissue surrounding necrotic regions. Glut-1 may be a useful biomarker to validate tissue microarrays for use in studies of hypoxia-regulated genes in cancer. In this study, we carried out immunohistochemical detection of Glut-1 protein in many tumor and normal tissue types in a range of tissue microarrays. Glut-1 was frequently found in peri-necrotic regions, occurring in 9/34 lymphomas, 6/12 melanomas, and 5/16 glioblastomas; and in 43/54 lung, 22/84 colon, and 23/60 ovarian tumors. Expression was rare in breast (6/40) and prostate (1/57) tumors, and in normal tissue, was restricted to spleen, tongue and CNS endothelium. In conclusion, tissue microarrays enable the observation of Glut-1 expression in peri-necrotic regions, which may be linked to hypoxia, and reflect previous studies showing differential Glut-1 expression across tumor types and non malignant tissue

How do dentists and their teams incorporate evidence about preventive care? An empirical study

Objectives: To identify how dentists and their teams adopt evidence-based preventive care. Methods: A qualitative study using grounded theory methodology was conducted. We interviewed 23 participants working in eight dental practices about their experience and work processes, while adopting evidence-based preventive care. During the study, Charmaz’s grounded theory methodology was employed to examine the social process of adopting preventive dental care in dental practices. Charmaz’s iteration of the constant comparative method was used during the data analysis. This involved coding of interview transcripts, detailed memo-writing and drawing diagrams. The transcripts were analysed as soon as possible after each round of interviews in each dental practice. Coding was conducted primarily by AS, supported by team meetings and discussions when researchers compared their interpretations. Results: Participants engaged in a slow process of adapting evidence-based protocols and guidelines to the existing logistics of the practices. This process was influenced by practical, philosophical, and historical aspects of dental care, and a range of barriers and facilitators. In particular, dentists spoke spontaneously about two deeply held ‘rules’ underpinning continued restorative treatment, which acted as barriers to provide preventive care: (i) dentists believed that some patients were too ‘unreliable’ to benefit from prevention; and (ii) dentists believed that patients thought that only tangible restorative treatment offered ‘value for money’. During the adaptation process, some dentists and teams transitioned from their initial state – selling restorative care – through an intermediary stage – learning by doing and educating patients about the importance of preventive care – and finally to a stage where they were offering patients more than just restorative care. Resources were needed for the adaptation process to occur, including: the ability to maintain the financial viability of the practice, appropriate technology, time, and supportive dental team relationships. Conclusions: The findings from this study show that with considerable effort, motivation and coordination, it is possible for dental practices to work against the dental ‘mainstream’ and implement prevention as their clinical norm. This study has shown that dental practice is not purely scientific, but it includes cultural, social, and economic resources that interfere with the provision of preventive care.NHMRC Project Grant 63271

Southern North Sea storm surge event of 5 December 2013: Water levels, waves and coastal impacts

The storm surge event that affected the coastal margins of the southern North Sea on 5–6 December 2013 produced the highest still water levels on record at several tide gauges on the UK east coast. On east-facing coasts south of the Humber estuary and north-facing Norfolk, water levels were higher than in the twentieth century benchmark surge event of 31 January–1 February 1953. Maximum significant wave heights were highest off the North Norfolk coast (peak Hs = 3.8 m offshore, 2.9 m inshore) and lowest off the Suffolk coast (Hs = 1.5–1.8 m inshore); comparable offshore wave heights in 1953 were 7–8 m and ca. 3 m. The lower wave heights, and their short duration, in 2013 explain both localised breaching, overtopping, and back-barrier flooding associated with gravel ridges and relatively low earthen banks as well as the lack of failure in more highly-engineered coastal defences. On barrier coasts and within estuaries, the signal of maximum runup was highly variable, reflecting the modification of the tide–surge–wave signal by inshore bathymetry and the presence of a range of coastal ecosystems. The landscape impacts of the December 2013 surge included the notching of soft rock cliffs and cliffline retreat; erosion of coastal dunes; and the augmentation or re-activation of barrier island washover deposits. Whilst surge event-related cliff retreat on the rapidly eroding cliffs of the Suffolk coast lay within the natural variability in inter-annual rates of retreat, the impact of the surge on upper beach/sand dune margins produced a pulse of shoreline translation landwards equivalent to about 10 years of ‘normal’ shoreline retreat. The study of east coast surges over the last 60 years, and the identification of significant phases of landscape change — such as periods of rapid soft rock cliff retreat and the formation of new gravel washovers on barrier islands — points to the importance of high water levels being accompanied by high wave activity. Future developments in early warning systems and evacuation planning require information on the variable impacts of such extreme events.This paper is a contribution to NERC BESS Consortium grant A hierarchical approach to the examination of the relationship between biodiversity and ecosystem service flows across coastal margins (grant reference NE/J015423/1). Table 5 incorporates information gathered as part of an EU FP7 Collaborative Project Resilience-Increasing Strategies for Coasts — toolkit (RISC_KIT).This is the final published version. It first appeared at http://www.sciencedirect.com/science/article/pii/S0012825215000628#

The impact of COVID‐19 in Dravet syndrome: A UK survey

OBJECTIVES: To understand the risks, impact and outcome of COVID-19 in people affected by Dravet Syndrome (DS). MATERIALS AND METHODS: An anonymous cross-sectional online survey was conducted between June 17 and July 13, 2020, addressed to families of people with DS. RESULTS: A total of 116 responses were collected, from families of children (n = 86; 74%) and adults (30; 26%) with DS. The majority (106; 91%) were shielded at the family home during lockdown. Symptoms compatible with COVID-19 were reported in 22 (19%) individuals. Only four individuals with symptoms had a PCR swab test, none of which was positive. Only one symptomatic person had antibody testing (but not swab testing), which was positive. One person had repeatedly positive swab tests whilst in hospital for renal failure, but had no typical symptoms of COVID-19. In 50% of people with DS who developed possible or probable COVID-19 symptoms, seizure worsening was reported, in terms of increased seizure frequency or duration or both. Medical attention was required in 9/22 (41%), all of whom were children. CONCLUSIONS: In this cohort of people with DS, we observed an infection rate, determined by compatible symptoms, of 19%, with no deaths and benign outcome in most cases despite the underlying complex epilepsy although children often required medical attention. Early adoption of preventative measures, including testing of symptomatic individuals, regular surveillance for people living in residential care facilities, and shielding of individuals with comorbidities increasing the risk of severe outcome, may limit the impact of COVID-19

The impact of SARS-CoV-2 vaccination in Dravet Syndrome: A UK survey

Background: The COVID-19 pandemic led to the urgent need for accelerated vaccine development. Approved vaccines have proved to be safe and well tolerated across millions of people in the general population. Dravet Syndrome (DS) is a severe, early onset, developmental and epileptic encephalopathy. Vaccination is a precipitating factor for seizures. Whilst there is no evidence that vaccine-precipitated seizures lead to adverse outcomes in people with DS, fear surrounding vaccination can remain for caregivers of people with DS, in some cases resulting in rejection of recommended vaccinations, leaving individuals more vulnerable to the relevant infections. A greater understanding of the safety profile of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in this vulnerable group will help provide guidance for caregivers and clinicians when considering vaccination. / Methods: A cross‐sectional survey regarding COVID-19 and SARS-CoV-2 vaccine, in people with DS, was conducted by Dravet Syndrome UK (DSUK). Concomitantly, a review of individuals with DS who had recently received the SARS-CoV-2 vaccine, and who are resident at the Chalfont Centre for Epilepsy (CCE), or attend epilepsy clinics at the National Hospital for Neurology and Neurosurgery (NHNN), was undertaken. / Results: 38 people completed the DSUK survey. 37% of caregivers reported being concerned about someone with DS receiving the SARS-CoV-2 vaccine; with some reporting that they would decline a vaccine when offered. 77% had not received any advice from a health care professional about the SARS-CoV-2 vaccination. 18/38 were eligible for SARS-CoV-2 vaccination, of whom nine had received their first vaccine dose. Combining the results of the DSUK survey and the review of individuals monitored at CCE or NHNN, fifteen people with DS had received their first dose of the SARS-CoV-2 vaccine. 11/15 (73%) reported at least one side effect, the most common being fatigue (6/15; 40%) and fever (6/15; 40%). Three individuals (20%) reported an increase in seizure frequency after the first vaccine dose. No increase in seizure frequency or duration was reported after the second dose. / Conclusion: Overall, these results suggest that SARS-CoV-2 vaccines are safe and well tolerated in individuals with DS, as they are in most people without DS. In most people with DS, SARS-CoV-2 vaccine does not appear to be associated with an increase in the frequency or duration of seizures, even in those who develop fever post-vaccination. Many caregivers are concerned about a person with DS receiving a SARS-CoV-2 vaccine, with some reporting that they would decline a SARS-CoV-2 vaccine when offered. It is crucial that healthcare professionals are proactive in providing accurate information regarding the risks and benefits of vaccination in this population, given the potential for serious outcomes from infection