Filtration‐histogram based magnetic resonance texture analysis (Mrta) for the distinction of primary central nervous system lymphoma and glioblastoma

Primary central nervous system lymphoma (PCNSL) has variable imaging appearances, which overlap with those of glioblastoma (GBM), thereby necessitating invasive tissue diagnosis. We aimed to investigate whether a rapid filtration histogram analysis of clinical MRI data supports the distinction of PCNSL from GBM. Ninety tumours (PCNSL n = 48, GBM n = 42) were analysed using pre‐treatment MRI sequences (T1‐weighted contrast‐enhanced (T1CE), T2‐weighted (T2), and apparent diffusion coefficient maps (ADC)). The segmentations were completed with proprietary texture analysis software (TexRAD version 3.3). Filtered (five filter sizes SSF = 2–6 mm) and unfil-tered (SSF = 0) histogram parameters were compared using Mann‐Whitney U non‐parametric test-ing, with receiver operating characteristic (ROC) derived area under the curve (AUC) analysis for significant results. Across all (n = 90) tumours, the optimal algorithm performance was achieved using an unfiltered ADC mean and the mean of positive pixels (MPP), with a sensitivity of 83.8%, specificity of 8.9%, and AUC of 0.88. For subgroup analysis with >1/3 necrosis masses, ADC permit-ted the identification of PCNSL with a sensitivity of 96.9% and specificity of 100%. For T1CE‐derived regions, the distinction was less accurate, with a sensitivity of 71.4%, specificity of 77.1%, and AUC of 0.779. A role may exist for cross‐sectional texture analysis without complex machine learning models to differentiate PCNSL from GBM. ADC appears the most suitable sequence, especially for necrotic lesion distinction

Decision for reconstructive interventions of the upper limb in individuals with tetraplegia: the effect of treatment characteristics

Objective: To determine the effect of treatment characteristics on the\ud decision for reconstructive interventions for the upper extremities (UE) in\ud subjects with tetraplegia. - \ud Setting: Seven specialized spinal cord injury centres in the Netherlands. - \ud Method: Treatment characteristics for UE reconstructive interventions were\ud determined. Conjoint analysis (CA) was used to determine the contribution\ud and the relative importance of the treatment characteristics on the decision\ud for therapy. Therefore, a number of different treatment scenarios using these\ud characteristics were established. Different pairs of scenarios were presented\ud to subjects who were asked to choose the preferred scenario of each set. - \ud Results: forty nine subjects with tetraplegia with a stable C5, C6 or C7\ud lesion were selected. All treatment characteristics significantly influenced\ud the choice for treatment. Relative importance of treatment characteristics\ud were: intervention type (surgery or surgery with FES implant) 13%, number\ud of operations 15%, in patient rehabilitation period 22%, ambulant\ud rehabilitation period 9%, complication rate 15%, improvement of elbow\ud function 10%, improvement of hand function 15%. In deciding for therapy\ud 40% of the subjects focused on one characteristic. - \ud Conclusion: CA is applicable in Spinal Cord Injury medicine to study the\ud effect of health outcomes and non-health outcomes on the decision for\ud treatment. Non-health outcomes which relate to the intensity of treatment\ud are equally important or even more important than functional outcome in the\ud decision for reconstructive UE surgery in subjects with tetraplegia

The role of mutation rate variation and genetic diversity in the architecture of human disease

Background We have investigated the role that the mutation rate and the structure of genetic variation at a locus play in determining whether a gene is involved in disease. We predict that the mutation rate and its genetic diversity should be higher in genes associated with disease, unless all genes that could cause disease have already been identified. Results Consistent with our predictions we find that genes associated with Mendelian and complex disease are substantially longer than non-disease genes. However, we find that both Mendelian and complex disease genes are found in regions of the genome with relatively low mutation rates, as inferred from intron divergence between humans and chimpanzees, and they are predicted to have similar rates of non-synonymous mutation as other genes. Finally, we find that disease genes are in regions of significantly elevated genetic diversity, even when variation in the rate of mutation is controlled for. The effect is small nevertheless. Conclusions Our results suggest that gene length contributes to whether a gene is associated with disease. However, the mutation rate and the genetic architecture of the locus appear to play only a minor role in determining whether a gene is associated with disease

Study protocol: can a school gardening intervention improve children's diets?

BACKGROUND: The current academic literature suggests there is a potential for using gardening as a tool to improve children's fruit and vegetable intake. This study is two parallel randomised controlled trials (RCT) devised to evaluate the school gardening programme of the Royal Horticultural Society (RHS) Campaign for School Gardening, to determine if it has an effect on children's fruit and vegetable intake. METHOD/DESIGN: Trial One will consist of 26 schools; these schools will be randomised into two groups, one to receive the intensive intervention as "Partner Schools" and the other to receive the less intensive intervention as "Associate Schools". Trial Two will consist of 32 schools; these schools will be randomised into either the less intensive intervention "Associate Schools" or a comparison group with delayed intervention. Baseline data collection will be collected using a 24-hour food diary (CADET) to collect data on dietary intake and a questionnaire exploring children's knowledge and attitudes towards fruit and vegetables. A process measures questionnaire will be used to assess each school's gardening activities. DISCUSSION: The results from these trials will provide information on the impact of the RHS Campaign for School Gardening on children's fruit and vegetable intake. The evaluation will provide valuable information for designing future research in primary school children's diets and school based interventions. TRIAL REGISTRATION: ISRCTN11396528

Transactivation of EGFR by LPS induces COX-2 expression in enterocytes

Necrotizing enterocolitis (NEC) is the leading cause of gastrointestinal morbidity and mortality in preterm infants. NEC is characterized by an exaggerated inflammatory response to bacterial flora leading to bowel necrosis. Bacterial lipopolysaccharide (LPS) mediates inflammation through TLR4 activation and is a key molecule in the pathogenesis of NEC. However, LPS also induces cyclooxygenase-2 (COX-2), which promotes intestinal barrier restitution through stimulation of intestinal cell survival, proliferation, and migration. Epidermal growth factor receptor (EGFR) activation prevents experimental NEC and may play a critical role in LPS-stimulated COX-2 production. We hypothesized that EGFR is required for LPS induction of COX-2 expression. Our data show that inhibiting EGFR kinase activity blocks LPS-induced COX-2 expression in small intestinal epithelial cells. LPS induction of COX-2 requires Src-family kinase signaling while LPS transactivation of EGFR requires matrix metalloprotease (MMP) activity. EGFR tyrosine kinase inhibitors block LPS stimulation of mitogen-activated protein kinase ERK, suggesting an important role of the MAPK/ERK pathway in EGFR-mediated COX-2 expression. LPS stimulates proliferation of IEC-6 cells, but this stimulation is inhibited with either the EGFR kinase inhibitor AG1478, or the selective COX-2 inhibitor Celecoxib. Taken together, these data show that EGFR plays an important role in LPS-induction of COX-2 expression in enterocytes, which may be one mechanism for EGF in inhibition of NEC

The Determinants of young Adult Social well-being and Health (DASH) study: diversity, psychosocial determinants and health.

Purpose: The Determinants of young Adult Social well-being and Health longitudinal study draws on life-course models to understand ethnic differences in health. A key hypothesis relates to the role of psychosocial factors in nurturing the health and well-being of ethnic minorities growing up in the UK. We report the effects of culturally patterned exposures in childhood. Methods: In 2002/2003, 6643 11–13 year olds in London, ~80 % ethnic minorities, participated in the baseline survey. In 2005/2006, 4782 were followed-up. In 2012–2014, 665 took part in a pilot follow-up aged 21–23 years, including 42 qualitative interviews. Measures of socioeconomic and psychosocial factors and health were collected. Results: Ethnic minority adolescents reported better mental health than White British, despite more adversity (e.g. economic disadvantage, racism). It is unclear what explains this resilience but findings support a role for cultural factors. Racism was an adverse influence on mental health, while family care and connectedness, religious involvement and ethnic diversity of friendships were protective. While mental health resilience was a feature throughout adolescence, a less positive picture emerged for cardio-respiratory health. Both, mental health and cultural factors played a role. These patterns largely endured in early 20s with family support reducing stressful transitions to adulthood. Education levels, however, signal potential for socio-economic parity across ethnic groups

Rapamycin Combined with Anti-CD45RB mAb and IL-10 or with G-CSF Induces Tolerance in a Stringent Mouse Model of Islet Transplantation

Background: A large pool of preexisting alloreactive effector T cells can cause allogeneic graft rejection following transplantation. However, it is possible to induce transplant tolerance by altering the balance between effector and regulatory T (Treg) cells. Among the various Treg-cell types, Foxp3 +Treg and IL-10-producing T regulatory type 1 (Tr1) cells have frequently been associated with tolerance following transplantation in both mice and humans. Previously, we demonstrated that rapamycin+IL-10 promotes Tr1-cell-associated tolerance in Balb/c mice transplanted with C57BL/6 pancreatic islets. However, this same treatment was unsuccessful in C57BL/6 mice transplanted with Balb/c islets (classified as a stringent transplant model). We accordingly designed a protocol that would be effective in the latter transplant model by simultaneously depleting effector T cells and fostering production of Treg cells. We additionally developed and tested a clinically translatable protocol that used no depleting agent. Methodology/Principal Findings: Diabetic C57BL/6 mice were transplanted with Balb/c pancreatic islets. Recipient mice transiently treated with anti-CD45RB mAb+rapamycin+IL-10 developed antigen-specific tolerance. During treatment, Foxp3 +Treg cells were momentarily enriched in the blood, followed by accumulation in the graft and draining lymph node, whereas CD4 +IL-10 +IL-4 - T (i.e., Tr1) cells localized in the spleen. In long-term tolerant mice, only CD4 +IL-10 +IL-4 - T cells remained enriched in the spleen and IL-10 was key in the maintenance of tolerance. Alternatively, recipient mice were treated with two compounds routinely used in the clinic (namely, rapamycin and G-CSF); this drug combination promoted tolerance associated with CD4 +IL-10 +IL-4 - T cells. Conclusions/Significance: The anti-CD45RB mAb+rapamycin+IL-10 combined protocol promotes a state of tolerance that is IL-10 dependent. Moreover, the combination of rapamycin+G-CSF induces tolerance and such treatment could be readily translatable into the clinic. © 2011 Gagliani et al

The role and response of primary healthcare services in the delivery of palliative care in epidemics and pandemics : a rapid review to inform practice and service delivery during the COVID-19 pandemic

Background: The increased number of deaths in the community happening as a result of COVID-19 has caused primary healthcare services to change their traditional service delivery in a short timeframe. Services are quickly adapting to new challenges in the practical delivery of end-of-life care to patients in the community including through virtual consultations and in the provision of timely symptom control. Aim: To synthesise existing evidence related to the delivery of palliative and end-of-life care by primary healthcare professionals in epidemics and pandemics. Design: Rapid systematic review using modified systematic review methods, with narrative synthesis of the evidence. Data sources: Searches were carried out in Medline, Embase, PsychINFO, CINAHL and Web of Science on 7th March 2020. Results: Only five studies met the inclusion criteria, highlighting a striking lack of evidence base for the response of primary healthcare services in palliative care during epidemics and pandemics. All were observational studies. Findings were synthesised using a pandemic response framework according to ‘systems’ (community providers feeling disadvantaged in terms of receiving timely information and protocols), ‘space’ (recognised need for more care in the community), ‘staff’ (training needs and resilience) and ‘stuff’ (other aspects of managing care in pandemics including personal protective equipment, cleaning care settings and access to investigations). Conclusions: As the COVID-19 pandemic progresses, there is an urgent need for research to provide increased understanding of the role of primary care and community nursing services in palliative care, alongside hospices and community specialist palliative care providers

Cytogerontology since 1881: A reappraisal of August Weismann and a review of modern progress

Cytogerontology, the science of cellular ageing, originated in 1881 with the prediction by August Weismann that the somatic cells of higher animals have limited division potential. Weismann's prediction was derived by considering the role of natural selection in regulating the duration of an organism's life. For various reasons, Weismann's ideas on ageing fell into neglect following his death in 1914, and cytogerontology has only reappeared as a major research area following the demonstration by Hayflick and Moorhead in the early 1960s that diploid human fibroblasts are restricted to a finite number of divisions in vitro. In this review we give a detailed account of Weismann's theory, and we reveal that his ideas were both more extensive in their scope and more pertinent to current research than is generally recognised. We also appraise the progress which has been made over the past hundred years in investigating the causes of ageing, with particular emphasis being given to (i) the evolution of ageing, and (ii) ageing at the cellular level. We critically assess the current state of knowledge in these areas and recommend a series of points as primary targets for future research

Recommendations to improve physical activity among teenagers- A qualitative study with ethnic minority and European teenagers

<p>Abstract</p> <p>Background</p> <p>To understand the key challenges and explore recommendations from teenagers to promote physical activity with a focus on ethnic minority children.</p> <p>Methods</p> <p>Focus groups with teenagers aged 16-18 of Bangladeshi, Somali or Welsh descent attending a participating school in South Wales, UK. There were seventy four participants (18 Somali, 24 Bangladeshi and 32 Welsh children) divided into 12 focus groups.</p> <p>Results</p> <p>The boys were more positive about the benefits of exercise than the girls and felt there were not enough facilities or enough opportunity for unsupervised activity. The girls felt there was a lack of support to exercise from their family. All the children felt that attitudes to activity for teenagers needed to change, so that there was more family and community support for girls to be active and for boys to have freedom to do activities they wanted without formal supervision. It was felt that older children from all ethnic backgrounds should be involved more in delivering activities and schools needs to provide more frequent and a wider range of activities.</p> <p>Conclusions</p> <p>This study takes a child-focused approach to explore how interventions should be designed to promote physical activity in youth. Interventions need to improve access to facilities but also counteract attitudes that teenagers should be studying or working and not 'hanging about' playing with friends. Thus, the value of activity for teenagers needs to be promoted not just among the teenagers but with their teachers, parents and members of the community.</p