Ella Terblanche RD, chair of the BDA’s Critical Care Specialist Group and Principal Dietitian for Critical Care at St George’s Hospital, London, has been made an MBE for her services to dietetics and in particular the response to COVID-19.
Ella said “This is a huge honour and such a surprise. I believe this award should also be viewed as recognition of all the dietitians, particularly those in critical care, who worked so hard to support the NHS and patients during the pandemic. Nutrition is such a vital part of a person’s treatment and recovery from coronavirus, and I’m hugely proud of the work all dietitians have done over the past six months to save lives and help get people back on their feet.”
Aside from her roles in the NHS and with the BDA, Ella has also been a leader in critical care dietetics, co-authoring key national guidance and standards and representing dietetics within the Intensive Care Society.
The BDA is delighted that our President, Dr Giles Yeo, has also received an MBE for services to Research, Science Communication and Engagement. Dr Yeo is a Geneticist and Principal Research Associate at the Metabolic Research Laboratories and MRC Metabolic Diseases Unit at Cambridge University.
His research particularly focuses on the study of brain control of body weight, and he is a champion for improving understanding of the complexities of obesity. Alongside his research and teaching roles, Dr Yeo is also a well-known from TV and from his work as an author, helping to explain to the public the complex relationships between genetics, appetite, and obesity.
Giles said “I can assure you that this was entirely unexpected. Because it was in times of COVID, the notification, instead of being on expensive official stationery, came via email, and I initially thought it was a phishing scam! Anyway, it wasn’t, and I’m deeply honoured to be recognised for my contributions to communicating and engagement in research. I am grateful to be working at an Institution which has allowed me to breathe and to follow my passion.”
Coeliac UK, the charity for people who need to live gluten-free, has been announced as the winner of the 2020 Memcom membership excellence awards, best use of an app category, for its Gluten Free on the Move app, that makes eating out on a gluten-free diet easier.
Last year, the charity won the award for its Gluten Free Food Checker app, which helps people when shopping for food and drink products. The Memcom awards celebrate the positive impact that professional bodies, trade associations, membership charities and other not-for-profit membership organisations have on public good.
Awarding Coeliac UK as the winner in the 2020 Best use of an app category, the judges said they were struck by the sheer scale and ambition of the Gluten Free on the Move app. They highlighted how it truly supports the membership community – as demonstrated by the huge take up – and it was really clear to see the intended benefits of the app for the coeliac community.
The app is exclusive to Coeliac UK’s members and helps people choose from over 7,000 venues across the UK that provide suitable gluten-free options, including those that hold Coeliac UK’s Gluten Free Accreditation as well as those recommended by the charity’s network of local groups. It makes life easier to find suitable venues when planning a meal for a special occasion, wanting to find something on the go when plans change unexpectedly or needing additional guidance when travelling abroad.
Hilary Croft, Coeliac UK CEO said: “Making life easier for those living gluten-free is at the heart of what we do. It is wonderful to have two of our flagship services recognised with a Memcom award which acknowledges our continuing efforts to make the content relevant to meet member needs.”
For further information on Coeliac UK, visit: www.coeliac.org.uk
Asthma and food hypersensitivity at age 12 is associated with an increased risk of having irritable bowel syndrome at 16, a new study presented today at UEG Week Virtual 2020 has found.
The research, conducted at the University of Gothenburg and the Karolinska Institute in Stockholm, Sweden, analysed the health of 2,770 children from birth to the age of 16. Those with IBS at 16 were almost twice as likely to have had asthma at the age of 12 (11.2% vs 6.7%). Almost half of children with IBS at 16 (40.7%) reported food hypersensitivity at 12 years (compared to 29.2% of children without IBS at 16). The research also showed that asthma, food hypersensitivity and eczema were all associated with an increased risk of concurrent IBS at 16 years.
The population-based cohort study was led by Dr Jessica Sjölund from the Institute of Medicine at the University of Gothenburg, Sweden. "The associations found in this large study suggest there's a shared pathophysiology between common allergy-related diseases and adolescent irritable bowel syndrome", she explained.
"We knew that allergy and immune dysregulation had been suggested to play a role in the development of irritable bowel syndrome, but previous studies on allergy-related diseases and irritable bowel syndrome are contradictory.
This knowledge could open up for developing new treatment methods for adolescent IBS, targeting processes of low-grade inflammation seen in these allergy-related diseases."
During the study, children and parents were asked to complete questionnaires regarding asthma, allergic rhinitis, eczema and food hypersensitivity at ages 1, 2, 4, 8, 12 and 16 years. At 16, children answered questions based on the Rome III Questionnaire on Paediatric Gastrointestinal Symptoms, allowing participants to be categorised into IBS, functional abdominal pain and function dyspepsia groups.
IBS affects more than one in ten people and is the most common functional gastrointestinal disorder. It can be extremely disabling for patients, with abdominal cramps, bloating, diarrhoea, or constipation. There are often difficulties in diagnosing functional gastrointestinal disorders like IBS, and just one in three people with symptoms of IBS or constipation consult a healthcare professional.
Hans Törnblom, who was involved in the research and is one of Europe's leading IBS experts, comments: "Even though functional gastrointestinal disorders are common, many patients are, unfortunately, negatively stigmatised and labelled. The fact that many IBS sufferers do not seek medical advice should be of great concern. As well as dedicating resources to improve the physical elements of living with disorders like IBS, care and investment must be committed to providing psychological and emotional support for patients so they are comfortable in seeking medical advice."
To find out more about the UEG, visit: www.ueg.eu
Reference: Sjölund J (2020). Allergy-related Disease During Childhood and Risk of Irritable Bowel Syndrome at 16 Years: A Swedish birth cohort study. Presented at UEG Week Virtual 2020.
High vitamin A, E, and D intake may be linked to fewer respiratory complaints in adults, suggests an analysis of nationally representative long-term survey data, published online in the journal BMJ Nutrition Prevention & Health.
The findings warrant further study among different ethnic groups and geographies in view of the current coronavirus pandemic, suggest the researchers.
Nutrition has a key role in cutting the risk of several infections, although exactly how it boosts immunity is complex and not fully understood. Vitamins A, E, C and D have already been deemed to aid the normal functioning of the immune system in the European Union, and the American Nutrition Association suggests these vitamins may also help stave off respiratory infections.
The researchers wanted to explore whether the intake of these vitamins from both diet and supplements might be linked to the prevalence of respiratory complaints in a nationally representative sample of UK adults.
They drew on information provided by 6115 adult participants in the 2008–2016 National Diet and Nutrition Survey Rolling Programme (NDNS RP) who had completed three or more days of diet diaries. The NDNS RP is a rolling survey that collects information annually on all food and drink consumed from around 1000 randomly selected people living in private households across the UK. Respiratory complaints were reported by the participants and had not been diagnosed by a clinician. They were broadly defined, and included both infectious and non-infectious conditions, such as colds, chronic obstructive pulmonary disease, and asthma. The researchers looked at dietary intake only (continuous exposure) and that from diet and supplements (binary exposure), accounting for potentially influential factors, such as age, sex, weight (BMI), smoking, household income and total energy intake.
In all, there were 33 cases of respiratory complaints. These respondents were generally older and less likely to say they regularly took vitamins A, E, C or D supplements. There was no obvious association between BMI and vitamin intake, or between BMI and respiratory complaints. And it wasn’t possible to determine any associations with vitamin C supplements as none of the adults with respiratory complaints said they took them.
But vitamin A and E intake from both diet and supplements was associated with a lower prevalence of respiratory complaints in UK adults. Major dietary sources of vitamin A include liver, whole milk, and cheese, as well as carrots, dark green leafy vegetables, and orange-coloured fruits. Major dietary sources of vitamin E include vegetable oils, nuts, and seeds.
And vitamin D intake from supplements, but not from diet, was associated with fewer respiratory complaints, prompting the researchers to suggest that the findings add to the current scientific debate on the value of vitamin D supplementation.
“It is estimated that around a fifth of the general population in the UK have low vitamin D, and over 30% of older adults aged 65 years and above do not achieve the recommended nutrient intake,” they write.
“Our findings are consistent with the hypothesis that supplementation is critical to ensuring adequate vitamin D status is maintained and potentially indicate that intake of vitamin D from diet alone cannot help maintain adequate vitamin D status.”
This is an observational study, and as such, can’t establish cause, added to which the number of respiratory complaints was small, meaning that no inferences can be made in respect of the coronavirus pandemic, caution the researchers.
“Further research is required to assess the implications of the current study in the context of the current coronavirus disease 2019 pandemic using data from longitudinal cohorts,” they suggest.
“Our study also highlights the need for further data collection on nutrition and respiratory disorders to cover wider geographical areas and high-risk groups, including a focus on other ethnicities,” they add.
Shane McAuliffe, Science Communications Lead for the NNEdPro Nutrition & COVID-19 Taskforce, said: “While acknowledging the limitations of this data, it does add further to a growing body of interest and evidence for the role of vitamin D in respiratory health.
Given our knowledge of the extent of vitamin D deficiency in the population, balanced with the low cost and low risk of adverse events, it seems sensible to provide supplementation of this key vitamin, particularly to those most likely to be deficient.”
Professor Sumantra Ray, Executive Director of the NNEdPro Global Centre for Nutrition & Health in Cambridge and Visiting Professor of Public Health at Imperial College London, added: “Nationally representative data continue to remind us that micronutrient deficiencies are far from a thing of the past, even in higher income nations like the UK, and this trend is mirrored by comparable global data sources from lesser resourced countries to those with advanced health systems.
Despite this, micronutrient deficiencies are often overlooked as a key contributor to the burden of malnutrition and poor health, presenting an additional layer of challenge during the COVID-19 pandemic.”
Paper: Association between vitamin intake and respiratory complaints in adults from the UK National Diet and Nutrition Survey years 1–8. BMJ Nutrition Prevention & Health; https://nutrition.bmj.com/lookup/doi/10.1136/bmjnph-2020-000150
Early life risk factors in the first 1000 days cumulatively predict higher obesity and cardiometabolic risk in early adolescence, according to new research led by the Harvard Pilgrim Health Care Institute. The study is the first to evaluate the combined influence of early life risk factors with direct measures of adiposity (body mass index, fat-mass index) and metabolic risk in early adolescence.
The findings were published in the American Journal of Clinical Nutrition.
The rapid rise in the global prevalence of childhood obesity, a strong predictor of metabolic syndrome and related diseases such as type 2 diabetes mellitus, is an important public health challenge. The first 1000 days, spanning from conception to age 24 months, represents an important period of risk for the development of later childhood obesity. Certain prenatal and postpartum factors encompassing this period, such as maternal smoking, excessive gestational weight gain, maternal gestational diabetes, maternal diet during pregnancy, short breastfeeding duration, and short infant sleep duration have been shown to be associated with subsequent risk of childhood obesity.
"Most of these factors are modifiable and may provide insight into intervention strategies for childhood obesity prevention in early life," said lead author Izzuddin Aris, PhD, Assistant Professor of Population Medicine at the Harvard Pilgrim Health Care Institute and Harvard Medical School. "Our study assesses the impact of these risk factors in combination, which is more relevant to real-life behaviour, and could translate to a larger public health impact."
For this study, the research team studied 1038 mother-child pairs in Project Viva, a prospective, observational pre-birth cohort study of gestational factors, pregnancy outcomes, and offspring health, based in eastern Massachusetts. They measured six modifiable risk factors: smoking during pregnancy; gestational weight gain; sugar-sweetened beverage consumption during pregnancy; breastfeeding duration; timing of complementary food introduction and infant sleep duration.
After adjusting for sociodemographic characteristics and parental body mass index, the researchers found increases in indicators of adiposity such as body mass index and fat-mass index as well as increases in metabolic risk markers such as triglyceride levels and insulin resistance with increasing number of risk factors. Children with 5-6 risk factors versus those with 0-1 risk factors also had the highest risk of overweight or obesity and being in the highest metabolic risk score quartile in early adolescence.
"Our study findings not only suggest targets for future early life interventions, they also indicate that interventions to prevent later obesity and cardiometabolic risk may be more effective if conducted early in the life course and target multiple factors," said Emily Oken, Professor of Population Medicine at the Harvard Pilgrim Health Care Institute and Harvard Medical School and senior author of the study.
Paper: Hu Jiajin (2020). Longitudinal associations of modifiable risk factors in the first 1000 days with weight status and metabolic risk in early adolescence. American Journal of Clinical Nutrition: https://doi.org/10.1093/ajcn/nqaa297.
Losing a few kilograms in weight almost halves people’s risk of developing Type 2 diabetes – according to a large-scale research study led by the Norfolk and Norwich University Hospital and the University of East Anglia.
A new study published in the international journal JAMA Internal Medicine shows how providing support to help people with prediabetes make small changes to their lifestyle, diet and physical activity can almost halve the risk of developing Type 2 diabetes. The findings come from the Norfolk Diabetes Prevention Study (NDPS) – the largest diabetes prevention research study in the world in the last 30 years. The NDPS clinical trial ran over eight years and involved more than 1,000 people with prediabetes at high risk of developing Type 2 diabetes.
The study found that support to make modest lifestyle changes, including losing two to three kilograms of weight and increased physical activity over two years, reduced the risk of Type 2 diabetes by 40 to 47 per cent for those categorised as having prediabetes. There are about eight million people with prediabetes in the UK and 4.5 million have already developed Type 2 diabetes.
The NDPS, funded by £2.5m from the National Institute for Health Research (NIHR), and NIHR CRN Eastern, was led by the Norfolk and Norwich University Hospital (NNUH) and University of East Anglia (UEA), together with colleagues from Ipswich Hospital, and the Universities of Birmingham and Exeter.
The research trial tested a simple lifestyle intervention, which helped people make small achievable lifestyle changes that led to a modest weight loss, and increases in physical activity.
Importantly these changes were sustained for at least two years and the weight lost was not put back on.
These findings are important as they show that a ‘real-world’ lifestyle programme really can make a difference in helping people reduce their risk of Type 2 (adult onset) diabetes.
Prof Mike Sampson, NDPS Chief Investigator and Consultant in Diabetes at NNUH, said: “We are delighted with the results of this trial, as until now no one was very sure if a real-world lifestyle programme prevented Type 2 diabetes in the prediabetes population we studied, as there have been no clinical trials that had shown this.
We have now shown a significant effect in Type 2 diabetes prevention, and we can be very optimistic that even a modest weight loss, and an increase in physical activity, in real world programmes like this have a big effect on the risk of getting Type 2 diabetes.
This is really great news for the eight million people in the UK with a prediabetes diagnosis. The results of this trial, show that diabetes prevention is possible in the same prediabetes populations being treated in the NHS national diabetes prevention programme.
This is important to know, as the clinical methods for diagnosing diabetes and prediabetes have changed a lot in recent years.”
The Norfolk Diabetes Prevention Study ran between 2011 and 2018 and worked with 135 GP practices in the East of England, and found 144,000 people who were at risk of developing Type 2 diabetes.
In screening sites across the East of England, 13,000 of these people then took a fasting glucose and glycosylated haemoglobin (HbA1c) blood test to detect prediabetes. More than 1,000 people with prediabetes were then entered into a randomised controlled trial, testing a pragmatic real-world lifestyle intervention, compared to a control group, with average follow-up of just over two years.
Earlier studies have used quite intense and expensive research interventions in different groups of prediabetes participants, but this is the first time a real-world group delivered intervention has been shown to reduce the risk of Type 2 diabetes.
NDPS also asked lay members of the public who had Type 2 diabetes themselves, to help support participants with prediabetes in the trial, but for this particular population this did not further reduce the risk of getting Type 2 diabetes. NDPS co-investigator Prof Max Bachmann, from UEA’s Norwich Medical School, said: “The NDPS intervention was delivered in groups which was far less expensive than individual-focused interventions which have previously shown to be effective under optimal conditions.
For every 11 people who received the NDPS intervention, one person was prevented from getting Type 2 diabetes, which is a real breakthrough."
Prof Colin Greaves from the University of Birmingham, who jointly led the development of the NDPS intervention, said: “If you have been diagnosed with prediabetes, this approach offers a way to take a different direction in your life – to get off the path to type 2 diabetes and onto the road to a healthier future.”
Dr Jane Smith, NDPS collaborator from the University of Exeter, said: “Type 2 diabetes is a huge health challenge globally. NDPS is an incredibly positive story for individuals and healthcare systems, and underlines the importance of providing national diabetes prevention programmes, which can use our research findings.”
Prof Jonathan Valabhji, National Clinical Director for Diabetes and Obesity for NHS England, said: “This study with similar referral criteria and a similar intensive lifestyle intervention to the NHS Diabetes Prevention Programme has surpassed expectations in preventing Type 2 diabetes. This is hugely encouraging for the NHS Diabetes Prevention Programme, and what participants might expect to achieve in the longer term.”
Dr Elizabeth Robertson, Director of Research at Diabetes UK, said: “We welcome this new research showing that a group-based support programme can help people at high risk of developing type 2 diabetes reduce their risk.
This trial again highlights how achieving modest weight loss through diet and physical activity changes can lead to huge benefits for people at high risk of developing type 2. Type 2 diabetes is a serious condition, but with the right help many cases can be prevented or delayed.
Diabetes UK’s Know Your Risk’ tool helps people to determine their risk and take steps to reduce it, including by self-referring on to NHS England’s Diabetes Prevention Programme in their local area.”
Paper: Lifestyle Intervention With or Without Lay Volunteers to Prevent Type 2 Diabetes in People With Impaired Fasting Glucose and/or Nondiabetic Hyperglycemia. JAMA Internal Medicine; https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2772239.
In 2030, one in three people in Europe will be over the age of 65, and all of these people will want to enjoy their old age and lead an active lifestyle. To be able to do so, however, it is crucial that people maintain their physical and mental health.
Wanted: simple and inexpensive prevention
Published last year, the VITAL study in the US indicated that vitamin D and omega-3 fatty acids did not lower the risk of developing new cancer or major cardiovascular diseases in men and women aged between 50 and 60. Now, the largest European study on old age, DO-HEALTH, has investigated the effects of these supplements on aging. The EU-funded project is led by Heike A. Bischoff-Ferrari, professor of geriatric medicine and aging research at the University of Zurich, head of clinic at the University Hospital Zurich and senior physician at the university clinic for geriatrics at the Waid and Triemli hospitals in Zurich.
The first findings of the three-year clinical trial published by the international team of researchers has found no effects on lower extremity function, memory or bone fracture incidence. However, the study's findings suggest that, compared to the control group, some subgroups experienced increased benefits of vitamin D and omega-3 supplementation when it comes to lowering infection rates and systolic blood pressure.
Largest randomised double-blind study on old age
For their study, the researchers recruited 2,157 relatively healthy men and women aged 70 or older who lived at home and had no significant pre-existing conditions. About half of the participants came from Switzerland, followed by Austria, Germany, France and Portugal.
They were randomized into eight groups and received none, one, two or all three of the following interventions: supplementation of omega-3 fatty acids (1 gram/day), supplementation of vitamin D (2,000 IU/day) and/or a simple home-exercise program. Neither the trial centres nor the participants knew which group they were in. The control groups were given placebos and carried out control exercises focused on joint flexibility.
In each of the study's three years, the seven European trial centres conducted comprehensive full-day visits to observe participants' health and functions, while also carrying out extensive surveys over the phone every three months. The researchers examined, for example, bone and muscle density, blood pressure, memory functions, walking speed as well as important biomarkers. Moreover, they recorded events such as new diseases, infections, falls, visits to the doctor and hospital stays.
Significant positive effects for some subgroups only
"Our findings suggest that supplementation of vitamin D and omega-3s in adults aged 70 or older who lead an active lifestyle and have no pre-existing conditions does not provide any benefits when it comes to bone health, memory and muscle function. However, we believe there is an effect on infections, such as Covid-19," says Bischoff-Ferrari.
Omega-3s reduced the risk of infections by 11% in total, in particular for upper respiratory (10%) and urinary tract infections (62%), while vitamin D lowered systolic blood pressure in men by 2.5 mmHg and the risk of infections in younger participants (70 to 74-year-old) by 16%.
"Given the high safety and low costs of these supplements as well as the high mortality associated with infections in older adults, these findings are very relevant for the health of the general population," says Bischoff-Ferrari. The gender-specific effects of vitamin D on lowering systolic blood pressure also warrant additional research.
Placing findings in the right context
The researchers attribute the lack of effect on bone health, muscle function and memory to the relatively good health of the study's participants, most of whom took regular exercise. Moreover, about half of the participants were so-called healthy agers, with no pre-existing conditions or vitamin D insufficiency. In addition to the supplementation prescribed by the study, they were also allowed to take 800 IUs of vitamin D daily. "The results therefore do not contradict the Federal Office of Public Health's current recommendation on vitamin D supplementation and fall prevention for older people, nor the proven preventive effects of exercise programmes," says Bischoff-Ferrari.
Unique database for research on old age
The study team is now expecting the results on the DO-HEALTH interventions when it comes to cancer prevention, cholesterol levels, cardiovascular diseases, falls, frailty and health costs. "Then we'll be able to fully assess the role of supplementation in preventive geriatrics," says Bischoff-Ferrari. Going forward, the comprehensive database and biobank set up for the DO-HEALTH study is also expected to help assess the aging process and health risks for each person early on and individually, with the aim of personalized prevention. "Ultimately, the goal of DO-HEALTH is to enable more people to age in a healthy and active way," says Bischoff-Ferrari.
Significantly higher numbers of Generation Z boys and girls in the UK are dieting to lose weight, and are likely to overestimate their own weight, finds a new UCL-led study.
The research, published in JAMA Pediatrics, found that girls who are trying to lose weight are also more likely to experience depressive symptoms than in previous years.
In 2015, 42% of 14-year-old girls and boys said they currently were trying to lose weight, compared to 30% in 2005.
Lead author Dr Francesca Solmi (UCL Psychiatry) said: "Our findings show how the way we talk about weight, health and appearance can have profound impacts on young people's mental health, and efforts to tackle rising obesity rates may have unintended consequences.
An increase in dieting among young people is concerning because experimental studies have found that dieting is generally ineffective in the long-term at reducing body weight in adolescents, but can instead have greater impacts on mental health. We know, for instance, that dieting is a strong risk factor in the development of eating disorders."
The research team reviewed data from 22,503 adolescents in the UK, in three different decades, who are part of different cohort studies: the British Cohort Study (of people born in 1970; data was collected in 1986), the Children of the 90s study (born 1991-92, data collected in 2005), and Millennium Cohort Study (born 2000-02, data collected in 2015).
The adolescents were all asked questions about whether they were, or had been, trying to lose weight, whether they had dieted or exercised to lose weight, whether they perceived themselves to be underweight, about the right weight or overweight (which was compared to their actual height and weight measurements), and they filled out questionnaires that gauged depressive symptoms. The researchers found that in 2015, 44% and 60% of all participants had dieted or exercised to lose weight, respectively, compared to 38% and 7% in 1986.
The researchers say other evidence suggests that engagement in vigorous physical activity has remained relatively stable among adolescents over the past few decades.
Senior author Dr Praveetha Patalay (Centre for Longitudinal Studies and MRC Unit for Lifelong Health & Ageing, UCL) said: "It seems that young people are exercising for different reasons than they did before – more adolescents seem to be thinking of exercise predominantly as a means to lose weight rather than exercising for fun, socialising and feeling healthy. We suspect that recent controversial calls to add 'exercise-equivalent' labels on food packaging may exacerbate this."
While girls have consistently been more likely to diet to lose weight, the researchers found a greater increase over the years among boys, who were also becoming more likely to be trying to gain weight.
Dr Patalay said: "Societal pressures for girls to be thin have been around for decades, but body image pressures on boys may be a more recent trend. Our findings underscore the impact that societal pressures and public health messaging around weight can have on children's health behaviours, body image and mental health."
Both girls and boys also became more likely to over-estimate their weight from 1986 to 2005, and even more so by 2015, which the researchers say adds to their concerns that increased efforts to lose weight are not necessarily due to increased obesity rates.
The reported weight-related behaviours and weight misperception were associated with depressive symptoms, and among girls, this relationship was becoming even stronger over the three decades examined in this study. The findings could possibly be part of the explanation for increases in adolescent depressive symptoms that have been observed in recent decades.
Dr Solmi said: "Media portrayals of thinness, the rise of the fitness industry and the advent of social media may all partly explain our results, and public health messaging around calorie restriction and exercise might also be causing unintended harm.
Public health campaigns around obesity should consider adverse mental health effects, and ensure they avoid weight stigma. By promoting health and wellbeing, as opposed to focusing on 'healthy weight', they could have positive effects on both mental and physical health."
Paper: Solmi F, et al. (2020). Changes in the Prevalence and Correlates of Weight-Control Behaviors and Weight Perception in Adolescents in the UK, 1986-2015. JAMA Pediatr.; doi:10.1001/jamapediatrics.2020.4746.