PHYSIOCHEMICAL, PROXIMATE, AND SENSORY PROPERTIES OF UNFERMENTED AND FERMENTED SOY-CARROT BEVERAGES SWEETENED WITH SUGAR, DATE, AND HONEY

Objective: Physiochemical, proximate, and sensory properties of unfermented and fermented soy-carrot beverage sweetened with sugar, date, and honey were evaluated. Phytochemical content of soymilk, carrot juice, and their blend was also analyzed. Methods: Three sets of soy-carrot beverages were produced by homogenizing soy milk and carrot juice in a ratio of 2:1 and sweetened to 12% Brix. Each set was sweetened with sugar, date, and honey, respectively. A fourth set was unsweetened and served as control. After pasteurization, one part was fermented with pure culture of Lactobacillus acidophilus at 42°C for 24 h. Results: Fermentation significantly (p≤0.05) decreased pH (≥5.40–≤3.90), increased titratable acidity (≤0.55–≥0.90% lactic acid), and viscosity (≤0.65–≥0.87 Pa.S) of the soy-carrot beverages. Moisture, protein, fat, ash, carbohydrate, and energy content of unfermented beverages were 82.95– 93.95%, 2.15–2.87%, 0.42–1.21%, 0.10–0.20%, 3.21–12.55%, and 25.46–73.53 Kcal/g, respectively, while fermented beverages had 90.00–93.00%, 2.06–2.20%, 0.88–1.08%, 0.11–10.20%, 4.85–8.75%, and 36.76–52.20 Kcal/g, respectively. Total carotenoid, phenol, and DPPH radical scavenging activity varied, respectively, from 2.40–7.90, 14.81–26.59 mg tannic acid/ml, and 4.02–27.83% and were significantly (p≤0.05) highest in soy-carrot blend with carrot as major contributor. Degree of likeness of the sensory attributes for the sweetened and unfermented beverages was significantly (p≤0.05) higher than the fermented. Conclusion: Date and honey (12% Brix) can be used as sucrose alternatives in producing acceptable nutritious beverage from soymilk and carrot juice

Single-cycle viral gene expression, rather than progressive replication and oncolysis, is required for VSV therapy of B16 melanoma

A fully intact immune system would be expected to hinder the efficacy of oncolytic virotherapy by inhibiting viral replication. Simultaneously, however, it may also enhance antitumor therapy through initiation of proinflammatory, antiviral cytokine responses at the tumor site. The aim of this study was to investigate the role of a fully intact immune system on the antitumor efficacy of an oncolytic virus. In this respect, injection of oncolytic vesicular stomatitis virus (VSV) into subcutaneous B16ova melanomas in C57Bl/6 mice leads to tumor regression, but it is not associated with viral replicative burst in the tumor. In contrast, intratumoral delivery of VSV induces an acute proinflammatory reaction, which quickly resolves concomitantly with virus clearance. Consistent with the hypothesis that therapy may not be dependent on the ability of VSV to undergo progressive rounds of replication, a single-cycle VSV is equally effective as a fully replication-competent VSV, whereas inactivated viruses do not generate therapy. Even though therapy is dependent on host CD8+ and natural killer cells, these effects are not associated with interferon-γ-dependent responses against either the virus or tumor. There is, however, a strong correlation between viral gene expression, induction of proinflammatory reaction in the tumor and in vivo therapy. Overall, our results suggest that acute innate antiviral immune response, which rapidly clears VSV from B16ova tumors, is associated with the therapy observed in this model. Therefore, the antiviral immune response to an oncolytic virus mediates an intricate balance between safety, restriction of oncolysis and, potentially, significant immune-mediated antitumor therapy

Comparing Mutuality and Solidarity in Its Application to Disaster Ethics

Often it has been observed that in disaster situations, people (including victims) become altruistic and are very willing to listen, obey and act in a manner that would help bring an end to the situation. In this chapter, linking disaster ethics and human rights, it is argued that this indeed is how it should be, disaster or otherwise, and that we have moral duties to oneself and to others. An individual exhibiting solidarity, comradery and altruism during a disaster is indeed behaving as a reasonable Self, and exercising ethical individualism as per Gewirthian philosophy. It is the duty of the State and society to act as a supportive State and a caring society. In order to do this, we need to be conditioned for ethical rationality before any whiff of disaster arises, i.e. in our day-to-day conduct and decision-making, at a personal, institutional and transnational level. Our ethical resilience during disasters can only be as robust as our rational moral compass during ‘peace-time’. This chapter argues that Gewirthian solidarity ethics (GSE) should play a role in European policy and action in order to provide a system that conditions ethical rationality and in order to fulfil human rights. This involves addressing our current understanding of human rights as distinct categories of civil, political, economic, social and cultural rights and to effect a shift towards a more holistic understanding of human rights, whereby the hierarchy of fulfilment does not always prioritise civil and political rights.Peer reviewe

Description of the BRIGHTLIGHT cohort: the evaluation of teenage and young adult cancer services in England

Objective International recognition of the unique needs of young people with cancer is growing. Many countries have developed specialist age-appropriate cancer services believing them to be of value. In England, 13 specialist principal treatment centres (PTCs) deliver cancer care to young people. Despite this expansion of specialist care, systematic investigation of associated outcomes and costs has, to date, been lacking. The aim of this paper is to describe recruitment and baseline characteristics of the BRIGHTLIGHT cohort and the development of the bespoke measures of levels of care and disease severity, which will inform the evaluation of cancer services in England. Design Prospective, longitudinal, observational study. Setting Ninety-seven National Health Service hospitals in England. Participants A total of 1114 participants were recruited and diagnosed between July 2012 and December 2014: 55% (n=618) were men, mean age was 20.1 years (SD=3.3), most (86%) were white and most common diagnoses were lymphoma (31%), germ cell tumour (19%) and leukaemia (13%). Results At diagnosis, median quality of life score was significantly lower than a published control threshold (69.7 points); 40% had borderline to severe anxiety, and 21% had borderline to severe depression. There was minimal variation in other patient-reported outcomes according to age, diagnosis or severity of illness. Survival was lower in the cohort than for young people diagnosed during the same period who were not recruited (cumulative survival probability 4 years after diagnosis: 88% vs 92%). Conclusions Data collection was completed in March 2018. Longitudinal comparisons will determine outcomes and costs associated with access/exposure to PTCs. Findings will inform international intervention and policy initiatives to improve outcomes for young people with cancer

Diagnostic timeliness in adolescents and young adults with cancer: a cross-sectional analysis of the BRIGHTLIGHT cohort

© 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Background: Adolescents and young adults (AYAs) are thought to experience prolonged intervals to cancer diagnosis, but evidence quantifying this hypothesis and identifying high-risk patient subgroups is insufficient. We aimed to investigate diagnostic timeliness in a cohort of AYAs with incident cancers and to identify factors associated with variation in timeliness. Methods: We did a cross-sectional analysis of the BRIGHTLIGHT cohort, which included AYAs aged 12–24 years recruited within an average of 6 months from new primary cancer diagnosis from 96 National Health Service hospitals across England between July 1, 2012, and April 30, 2015. Participants completed structured, face-to-face interviews to provide information on their diagnostic experience (eg, month and year of symptom onset, number of consultations before referral to specialist care); demographic information was extracted from case report forms and date of diagnosis and cancer type from the national cancer registry. We analysed these data to assess patient interval (time from symptom onset to first presentation to a general practitioner [GP] or emergency department), the number of prereferral GP consultations, and the symptom onset-to-diagnosis interval (time from symptom onset to diagnosis) by patient characteristic and cancer site, and examined associations using multivariable regression models. Findings: Of 1114 participants recruited to the BRIGHTLIGHT cohort, 830 completed a face-to-face interview. Among participants with available information, 204 (27%) of 748 had a patient interval of more than a month and 242 (35%) of 701 consulting a general practitioner had three or more prereferral consultations. The median symptom onset-to-diagnosis interval was 62 days (IQR 29–153). Compared with male AYAs, female AYAs were more likely to have three or more consultations (adjusted odds ratio [OR] 1·6 [95% CI 1·1–2·3], p=0·0093) and longer median symptom onset-to-diagnosis intervals (adjusted median interval longer by 24 days [95% CI 11–37] , p=0·0005). Patients with lymphoma or bone tumours (adjusted OR 1·2 [95% CI 0·6–2·1] compared with lymphoma) were most likely to have three or more consultations and those with melanoma least likely (0·2 [0·1–0·7] compared with lymphoma). The adjusted median symptom onset-to-diagnosis intervals were longest in AYAs with bone tumours (51 days [95% CI 29–73] longer than for lymphoma) and shortest in those with leukaemia (33 days [17–49] shorter than for lymphoma). Interpretation: The findings provide a benchmark for diagnostic timeliness in young people with cancer and help to identify subgroups at higher risk of a prolonged diagnostic journey. Further research is needed to understand reasons for these findings and to prioritise and stratify early diagnosis initiatives for AYAs. Funding: National Institute for Health Research, Teenage Cancer Trust, and Cancer Research UK

Development and validation of the BRIGHTLIGHT Survey, a patient-reported experience measure for young people with cancer.

BACKGROUND: Patient experience is increasingly used as an indicator of high quality care in addition to more traditional clinical end-points. Surveys are generally accepted as appropriate methodology to capture patient experience. No validated patient experience surveys exist specifically for adolescents and young adults (AYA) aged 13-24 years at diagnosis with cancer. This paper describes early work undertaken to develop and validate a descriptive patient experience survey for AYA with cancer that encompasses both their cancer experience and age-related issues. We aimed to develop, with young people, an experience survey meaningful and relevant to AYA to be used in a longitudinal cohort study (BRIGHTLIGHT), ensuring high levels of acceptability to maximise study retention. METHODS: A three-stage approach was employed: Stage 1 involved developing a conceptual framework, conducting literature/Internet searches and establishing content validity of the survey; Stage 2 confirmed the acceptability of methods of administration and consisted of four focus groups involving 11 young people (14-25 years), three parents and two siblings; and Stage 3 established survey comprehension through telephone-administered cognitive interviews with a convenience sample of 23 young people aged 14-24 years. RESULT: Stage 1: Two-hundred and thirty eight questions were developed from qualitative reports of young people's cancer and treatment-related experience. Stage 2: The focus groups identified three core themes: (i) issues directly affecting young people, e.g. impact of treatment-related fatigue on ability to complete survey; (ii) issues relevant to the actual survey, e.g. ability to answer questions anonymously; (iii) administration issues, e.g. confusing format in some supporting documents. Stage 3: Cognitive interviews indicated high levels of comprehension requiring minor survey amendments. CONCLUSION: Collaborating with young people with cancer has enabled a survey of to be developed that is both meaningful to young people but also examines patient experience and outcomes associated with specialist cancer care. Engagement of young people throughout the survey development has ensured the content appropriately reflects their experience and is easily understood. The BRIGHTLIGHT survey was developed for a specific research project but has the potential to be used as a TYA cancer survey to assess patient experience and the care they receive

Diagnostic timeliness in adolescents and young adults with cancer: a cross-sectional analysis of the BRIGHTLIGHT cohort

Adolescents and young adults (AYAs) are thought to experience prolonged intervals to cancer diagnosis, but evidence quantifying this hypothesis and identifying high-risk patient subgroups is insufficient. We aimed to investigate diagnostic timeliness in a cohort of AYAs with incident cancers and to identify factors associated with variation in timeliness. Methods: We did a cross-sectional analysis of the BRIGHTLIGHT cohort, which included AYAs aged 12–24 years recruited within an average of 6 months from new primary cancer diagnosis from 96 National Health Service hospitals across England between July 1, 2012, and April 30, 2015. Participants completed structured, face-to-face interviews to provide information on their diagnostic experience (eg, month and year of symptom onset, number of consultations before referral to specialist care); demographic information was extracted from case report forms and date of diagnosis and cancer type from the national cancer registry. We analysed these data to assess patient interval (time from symptom onset to first presentation to a general practitioner [GP] or emergency department), the number of prereferral GP consultations, and the symptom onset-to-diagnosis interval (time from symptom onset to diagnosis) by patient characteristic and cancer site, and examined associations using multivariable regression models. Findings: Of 1114 participants recruited to the BRIGHTLIGHT cohort, 830 completed a face-to-face interview. Among participants with available information, 204 (27%) of 748 had a patient interval of more than a month and 242 (35%) of 701 consulting a general practitioner had three or more prereferral consultations. The median symptom onset-to-diagnosis interval was 62 days (IQR 29–153). Compared with male AYAs, female AYAs were more likely to have three or more consultations (adjusted odds ratio [OR] 1·6 [95% CI 1·1–2·3], p=0·0093) and longer median symptom onset-to-diagnosis intervals (adjusted median interval longer by 24 days [95% CI 11–37] , p=0·0005). Patients with lymphoma or bone tumours (adjusted OR 1·2 [95% CI 0·6–2·1] compared with lymphoma) were most likely to have three or more consultations and those with melanoma least likely (0·2 [0·1–0·7] compared with lymphoma). The adjusted median symptom onset-to-diagnosis intervals were longest in AYAs with bone tumours (51 days [95% CI 29–73] longer than for lymphoma) and shortest in those with leukaemia (33 days [17–49] shorter than for lymphoma). Interpretation: The findings provide a benchmark for diagnostic timeliness in young people with cancer and help to identify subgroups at higher risk of a prolonged diagnostic journey. Further research is needed to understand reasons for these findings and to prioritise and stratify early diagnosis initiatives for AYAs. Funding: National Institute for Health Research, Teenage Cancer Trust, and Cancer Research UK

Diagnostic timeliness in teenagers and young adults with cancer: Cross-sectional findings from the BRIGHTLIGHT cohort

BACKGROUND: Adolescents and young adults (AYAs) are thought to experience prolonged intervals to cancer diagnosis, but evidence quantifying this hypothesis and identifying high-risk patient subgroups is insufficient. We aimed to investigate diagnostic timeliness in a cohort of AYAs with incident cancers and to identify factors associated with variation in timeliness. METHODS: We did a cross-sectional analysis of the BRIGHTLIGHT cohort, which included AYAs aged 12–24 years recruited within an average of 6 months from new primary cancer diagnosis from 96 National Health Service hospitals across England between July 1, 2012, and April 30, 2015. Participants completed structured, face-to-face interviews to provide information on their diagnostic experience (eg, month and year of symptom onset, number of consultations before referral to specialist care); demographic information was extracted from case report forms and date of diagnosis and cancer type from the national cancer registry. We analysed these data to assess patient interval (time from symptom onset to first presentation to a general practitioner [GP] or emergency department), the number of prereferral GP consultations, and the symptom onset-to-diagnosis interval (time from symptom onset to diagnosis) by patient characteristic and cancer site, and examined associations using multivariable regression models. FINDINGS: Of 1114 participants recruited to the BRIGHTLIGHT cohort, 830 completed a face-to-face interview. Among participants with available information, 204 (27%) of 748 had a patient interval of more than a month and 242 (35%) of 701 consulting a general practitioner had three or more prereferral consultations. The median symptom onset-to-diagnosis interval was 62 days (IQR 29–153). Compared with male AYAs, female AYAs were more likely to have three or more consultations (adjusted odds ratio [OR] 1·6 [95% CI 1·1–2·3], p=0·0093) and longer median symptom onset-to-diagnosis intervals (adjusted median interval longer by 24 days [95% CI 11–37], p=0·0005). Patients with lymphoma or bone tumours (adjusted OR 1·2 [95% CI 0·6–2·1] compared with lymphoma) were most likely to have three or more consultations and those with melanoma least likely (0·2 [0·1–0·7] compared with lymphoma). The adjusted median symptom onset-to-diagnosis intervals were longest in AYAs with bone tumours (51 days [95% CI 29–73] longer than for lymphoma) and shortest in those with leukaemia (33 days [17–49] shorter than for lymphoma). INTERPRETATION: The findings provide a benchmark for diagnostic timeliness in young people with cancer and help to identify subgroups at higher risk of a prolonged diagnostic journey. Further research is needed to understand reasons for these findings and to prioritise and stratify early diagnosis initiatives for AYAs

Specialist cancer services for teenagers and young adults in England: BRIGHTLIGHT research programme

Background: When cancer occurs in teenagers and young adults, the impact is far beyond the physical disease and treatment burden. The effect on psychological, social, educational and other normal development can be profound. In addition, outcomes including improvements in survival and participation in clinical trials are poorer than in younger children and older adults with similar cancers. These unique circumstances have driven the development of care models specifically for teenagers and young adults with cancer, often focused on a dedicated purpose-designed patient environments supported by a multidisciplinary team with expertise in the needs of teenagers and young adults. In England, this is commissioned by NHS England and delivered through 13 principal treatment centres. There is a lack of evaluation that identifies the key components of specialist care for teenagers and young adults, and any improvement in outcomes and costs associated with it. / Objective: To determine whether or not specialist services for teenagers and young adults with cancer add value. / Design: A series of multiple-methods studies centred on a prospective longitudinal cohort of teenagers and young adults who were newly diagnosed with cancer. / Settings: Multiple settings, including an international Delphi study of health-care professionals, qualitative observation in specialist services for teenagers and young adults, and NHS trusts. / Participants: A total of 158 international teenage and young adult experts, 42 health-care professionals from across England, 1143 teenagers and young adults, and 518 caregivers. / Main outcome measures: The main outcomes were specific to each project: key areas of competence for the Delphi survey; culture of teenagers and young adults care in the case study; and unmet needs from the caregiver survey. The primary outcome for the cohort participants was quality of life and the cost to the NHS and patients in the health economic evaluation. / Data sources: Multiple sources were used, including responses from health-care professionals through a Delphi survey and face-to-face interviews, interview data from teenagers and young adults, the BRIGHTLIGHT survey to collect patient-reported data, patient-completed cost records, hospital clinical records, routinely collected NHS data and responses from primary caregivers. / Results: Competencies associated with specialist care for teenagers and young adults were identified from a Delphi study. The key to developing a culture of teenage and young adult care was time and commitment. An exposure variable, the teenagers and young adults Cancer Specialism Scale, was derived, allowing categorisation of patients to three groups, which were defined by the time spent in a principal treatment centre: SOME (some care in a principal treatment centre for teenagers and young adults, and the rest of their care in either a children’s or an adult cancer unit), ALL (all care in a principal treatment centre for teenagers and young adults) or NONE (no care in a principal treatment centre for teenagers and young adults). The cohort study showed that the NONE group was associated with superior quality of life, survival and health status from 6 months to 3 years after diagnosis. The ALL group was associated with faster rates of quality-of-life improvement from 6 months to 3 years after diagnosis. The SOME group was associated with poorer quality of life and slower improvement in quality of life over time. Economic analysis revealed that NHS costs and travel costs were similar between the NONE and ALL groups. The ALL group had greater out-of-pocket expenses, and the SOME group was associated with greater NHS costs and greater expense for patients. However, if caregivers had access to a principal treatment centre for teenagers and young adults (i.e. in the ALL or SOME groups), then they had fewer unmet support and information needs. / Limitations: Our definition of exposure to specialist care using Hospital Episode Statistics-determined time spent in hospital was insufficient to capture the detail of episodes or account for the variation in specialist services. Quality of life was measured first at 6 months, but an earlier measure may have shown different baselines. / Conclusions: We could not determine the added value of specialist cancer care for teenagers and young adults as defined using the teenage and young adult Cancer Specialism Scale and using quality of life as a primary end point. A group of patients (i.e. those defined as the SOME group) appeared to be less advantaged across a range of outcomes. There was variation in the extent to which principal treatment centres for teenagers and young adults were established, and the case study indicated that the culture of teenagers and young adults care required time to develop and embed. It will therefore be important to establish whether or not the evolution in services since 2012–14, when the cohort was recruited, improves quality of life and other patient-reported and clinical outcomes. / Future work: A determination of whether or not the SOME group has similar or improved quality of life and other patient-reported and clinical outcomes in current teenage and young adult service delivery is essential if principal treatment centres for teenagers and young adults are being commissioned to provide ‘joint care’ models with other providers. / Funding: This project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 9, No. 12. See the NIHR Journals Library website for further project information

Structural and functional conservation of non-lumenized lymphatic endothelial cells in the mammalian leptomeninges

The vertebrate CNS is surrounded by the meninges, a protective barrier comprised of the outer dura mater and the inner leptomeninges, which includes the arachnoid and pial layers. While the dura mater contains lymphatic vessels, no conventional lymphatics have been found within the brain or leptomeninges. However, non-lumenized cells called Brain/Mural Lymphatic Endothelial Cells or Fluorescent Granule Perithelial cells (muLECs/BLECs/FGPs) that share a developmental program and gene expression with peripheral lymphatic vessels have been described in the meninges of zebrafish. Here we identify a structurally and functionally similar cell type in the mammalian leptomeninges that we name Leptomeningeal Lymphatic Endothelial Cells (LLEC). As in zebrafish, LLECs express multiple lymphatic markers, containing very large, spherical inclusions, and develop independently from the meningeal macrophage lineage. Mouse LLECs also internalize macromolecules from the cerebrospinal fluid, including Amyloid-β, the toxic driver of Alzheimer's disease progression. Finally, we identify morphologically similar cells co-expressing LLEC markers in human post-mortem leptomeninges. Given that LLECs share molecular, morphological, and functional characteristics with both lymphatics and macrophages, we propose they represent a novel, evolutionary conserved cell type with potential roles in homeostasis and immune organization of the meninges