Influence of household remittance on childhood stunting in Nepal

Thesis (Master's)--University of Washington, 2016-08

Mothers’ perception of recovery and satisfaction with patent medicine dealers’ treatment of childhood febrile conditions in rural communities

Background Infant mortality in rural areas of Nigeria can be minimized if childhood febrile conditions are treated by trained health personnel, deployed to primary healthcare centres (PHCs) rather than the observed preference of mothers for patent medicine dealers (PMDs). However, health service utilization/patronage is driven by consumer satisfaction and perception of services/product value. The objective of this study was to determine ‘mothers’ perception of recovery’ and ‘mothers’ satisfaction’ after PMD treatment of childhood febrile conditions, as likely drivers of mothers’ health-seeking behaviour, which must be targeted to reverse the trend. Methods Ugwuogo-Nike, in Enugu, Nigeria, has many PMDs/PHCs, and was selected based on high prevalence of childhood febrile conditions. In total, 385 consenting mothers (aged 15–45 years) were consecutively recruited at PMD shops, after purchasing drugs for childhood febrile conditions, in a cross-sectional observational study using a pre-tested instrument; 33 of them (aged 21–47 years) participated in focus group discussions (FGDs). Qualitative data were thematically analysed while a quantitative study was analysed with Z score and Chi square statistics, at p < 0.05. Results Most participants in FGDs perceived that their child had delayed recovery, but were satisfied with PMDs’ treatment of childhood febrile conditions, for reasons that included politeness, caring attitude, drug availability, easy accessibility, flexibility in pricing, shorter waiting time, their God-fearing nature, and disposition as good listeners. Mothers’ satisfaction with PMDs’ treatment is significantly (p < 0.05) associated with mothers’ perception of recovery of their child (χ2 = 192.94, df = 4; p < 0.0001; Cramer’s V = 0.7079). However, predicting mothers’ satisfaction with PMDs’ treatment from a knowledge of mothers’ perception of recovery shows a high accord (lambda[A from B] = 0.8727), unlike when predicting mothers’ perception of recovery based on knowledge of mothers’ satisfaction with PMDs’ treatment (lambda[A from B] = 0.4727). Conclusions Mothers’ satisfaction could be the key ‘driver’ of mothers’ health-seeking behaviour and is less likely to be influenced by mothers’ perception of recovery of their child. Therefore, mothers’ negative perception of their child’s recovery may not induce proportionate decline in mothers’ health-seeking behaviour (patronage of PMDs), which might be influenced mainly by mothers’ satisfaction with the positive attributes of PMDs’ personality/practice and sets an important agenda for PHC reforms.

Intestinal obstruction by giant Meckel's diverticulum. Case report

Most cases of Meckel’s diverticulum (MD) are asymptomatic and discovered by chance. Management of MD is controversial. The authors describe an exceptional case of intestinal obstruction caused by a giant MD in a patient who had previously undergone appendectomy. A review of the contradictory literature on this subject leads to the conclusion that careful consideration of clinical and morphological data (patient's age, ASA score, the surgical procedure to be performed, morphology and position of the MD, any fibrotic bands) is required before deciding whether or not to resect an asymptomatic MD.

Human Ezrin: Prediction of the 3D structure and interactions with mTOR

The protein Ezrin, is a member of the ERM family (Ezrin, Radixin and Moesin) that links the F-actin to the plasma membrane. The protein is made of three domains namely the FERM domain, a central α-helical domain and the CERMAD domain. The residues in Ezrin such as Ser66, Tyr145, Tyr353 and Tyr477 regulate the function of the protein through phosphorylation. The protein is found in two distinct conformations of active and dormant (inactive) state. The initial step during the conformation change is the breakage of intramolecular interaction in dormant Ezrin by phosphorylation of residue Thr567. The dormant structure of human Ezrin was predicted computationally since only partial active form structure was available. The validation analysis showed that 99.7% residues were positioned in favored, allowed and generously allowed regions of the Ramachandran plot. The Z-score of Ezrin was −7.36, G-factor was 0.1, and the QMEAN score of the model was 0.61 indicating a good model for human Ezrin. The comparison of the conformations of the activated and dormant Ezrin showed a major shift in the F2 lobe (residues 142-149 and 161-177) while changes in the conformation induced mobility shifts in lobe F3 (residues 261 to 267). The 3D positions of the phosphorylation sites Tyr145, Tyr353, Tyr477, Tyr482 and Thr567 were also located. Using targeted molecular dynamic simulation, the molecular movements during conformational change from active to dormant were visualized. The dormant Ezrin auto-inhibits itself by a head-to-tail interaction of the N-terminal and C-terminal residues. The trajectory shows the breakage of the interactions and mobility of the CERMAD domain away from the FERM domain. Protein docking and clustering analysis were used to predict the residues involved in the interaction between dormant Ezrin and mTOR. Residues Tyr477 and Tyr482 were found to be involved in interaction with mTOR.

Prevalence and factors associated with anthropometric failure, vitamin A and iron deficiency among adolescents in a Nigerian urban community.

Background: Under nutrition is a problem of severe magnitude in low income countries like Nigeria. Adolescent school children might also be vulnerable. The dearth of data hinders planning of school health and nutrition programmes for school children. Objective: To determine the prevalence of stunting, thinness; vitamin A and iron deficiencies among adolescent students in Nsukka urban, Nigeria and to determine factors that are associated with these nutritional problems. Methods: A total of 400 participants were randomly selected from 717 students aged 12 – 18 years in 3 randomly selected secondary schools. Questionnaires, anthropometric measurements, and blood analyses were the data collection methods employed. Results: The prevalence of stunting was 33.3% and thinness 31.0%. Neither overweight nor obesity was observed. While 64.0% were anaemic; 44.0% had vitamin A deficiency (VAD). A total of 48.0% had both anaemia and stunting, 42% had VAD + thinness; while 40% had anaemia + VAD. Household income was a predictor of vitamin A status. Children from medium/ high income households had higher odds of having VAD than those from low income households (AOR=0.14; 95% CI=0.031, 0.607; P=0.009). Household income (AOR=0.12; 95% CI=0.021, 0.671; P=0.016), and age (AOR=0.09; 95% CI=0.014, 0.587; P=0.012) were independent determinants of height-for-age status. Conclusion: Among urban adolescent students in Nigeria, stunting, thinness, anaemia and VAD were problems of public health significance. Age and household monthly income played major roles.

Epidometria de Calophyllum brasiliense Camb. em plantios comerciais

Tese (doutorado)—Universidade de Brasília, Faculdade de Tecnologia, Departamento de Engenharia Florestal, Programa de Pós-Graduação em Ciências Florestais, 2016.

Effects of a rhythmic and choreographic program in obese and overweight participants

Introduction: Currently there is a growing trend in the prevalence of overweight and obesity. This increased prevalence trend leads to an increase in the costs of health care. Objective: The aim of the present study was to analyze the effects on physical fitness and bone mineral density through an intervention program of physical activity based on rhythmic and choreographic activities in an overweight and obese population. Method: An 8-month physical activity based on rhythmic and choreographic activities was conducted in overweight and obese people. Thirty-four participants aged 50.43 ± 10.57 with a body mass index (BMI) 38.37 ± 4.82 took part in the physical activity program. This study assesses the effects of fitness, percentage of body fat and bone mineral density (BMD). Results: After an 8-month physical activity intervention program based on rhythmic and choreographic activities, significant differences were found in: percentage of body fat (p = 0.004), aerobic capacity (p = 0.023), flexibility of the lower limbs (flexibility in the right leg p = 0.029 and left leg p = 0.002), balance (p < 0.001), strength in lower limbs (p = 0..003) and strength in upper limbs (p < 0.001). Besides that, significant differences were found in parameters related with BMD such as T-Score (p = 0.025) and Z-Score (p = 0.012), Bone Quality Index (BQI) (p = 0.026) and an increase in Broadband Ultrasound Attenuation (BUA) although not a statistically significant one (p = 0.939). Conclusions: These findings suggest that a physical activity program based on rhythmic and choreographic activities can act as a preventive method of mobility and fragility, as well as preventing bone loss.

Contributo da directiva-quadro da água 2000/60/CE para a melhoria do controlo de qualidade da água de consumo humano

Dissertação de mestrado, Tecnologia dos Alimentos, Instituto Superior de Engenharia, Universidade do Algarve, 2011

Configuring a Better Estimation of Kidney Size in Obese Children and Adolescents

Background: Obesity ignites numerous health and psychosocial problems and is associated with various comorbidities. Body mass index (BMI) is also independently associated with improved risk for numerous kidney disorders. As renal length is considered a vital parameter in the clinical assessment of renal patients, normal renal length has to be defined in accordance to BMI. Objectives: The aim of this study was to define normal kidney length in obese children, comparing ultrasound measurements of the kidney length in obese and non-obese children and adolescents, in order to reduce unnecessary evaluations for nephromegaly. Patients and Methods: Fifty obese children and adolescents and 50 non-obese children and adolescents, aged 1-19 years, were selected from patients of pediatric clinics in two hospitals (Rasoul-e-Akram and Shahid Fahmideh) in Tehran between June 2010 and 2012. After the nephrologist’s and endocrinologist’s approval, the largest longitudinal renal dimension was measured in deep inspiration position by abdomino-pelvic ultrasonography in both groups. Results: It was revealed that both kidneys in obese group were significantly larger than in control group (P = 0.044 and 0.040, respectively). Obesity status, height and age were proven to be significant and independent predictors of length of both kidneys. In both groups length of left kidney was significantly larger than that of right kidney (P < 0.001). Conclusions: A specific standard cut-point limit or norm gram has to be formulated for obese children and adolescents in order to facilitate the diagnosis of kidney diseases, including organomegaly, in these patients.

Aminoácidos y obesidad: relación de los niveles de homocisteína, aminoácidos de cadena ramificada y citrulina con sobrepeso-obesidad y resistencia insulínica en niños prepuberales

Introducción: la obesidad infantil es uno de los problemas de Salud Pública más graves del s.XXI, sobre todo por las complicaciones cardiovasculares y endocrino-metabólicas asociadas. La prevalencia de obesidad se ha multiplicado por más de dos entre 1980 y 2014, estimándose que, a nivel mundial, más de 42 millones de niños tienen sobrepeso. En adultos hay estudios que reportan que la ingesta proteica conlleva efectos beneficiosos aunque altos niveles de determinados aminoácidos se relacionan con obesidad y resistencia insulínica; no obstante, en niños existen escasos estudios que confirmen tal asociación. Objetivos: analizar cómo se relacionan los niveles sanguíneos de los aminoácidos de cadena ramificada, la homocisteína y la citrulina con las variables que se utilizan en la práctica clínica habitual para diagnosticar obesidad en niños y adolescentes, así como estudiar si hay relación de éstos con la resistencia a la insulina. Material y métodos: estudio observacional analítico longitudinal prospectivo de una cohorte. Colaboración entre niveles asistenciales (atención hospitalaria y atención primaria). Se seleccionaron niños en diferentes centros de salud de Málaga entre 6-11 años, prepúberes (estadios de Tanner 1-2). Para conseguir un intervalo de confianza del 95% y siendo la prevalencia de sobrepeso-obesidad del 30%, se estimó que habría que incluir unos 100 sujetos. Criterios de exclusión: obesidad de causa secundaria, enfermedad orgánica añadida, ingesta crónica de medicamentos y antecedentes de diabetes personales o en familiares de primer grado. Se realizó: hoja de recogida de datos clínicos, epidemiológicos, encuesta de hábitos sociales, alimentarios y de ejercicio físico. Se extrajo una analítica sanguínea con bioquímica básica y ampliada (perfil lipídico, vitaminas B9 y B12, transaminasas, insulina…) y se determinaron aminoácidos de interés para el estudio (homocisteína, isoleucina, leucina, valina, citrulina, tirosina, fenilalanina y acilcarnitinas (C3 y C5)). La obesidad se define como IMC ≥2 SDS expresado en Z score (gráficas de Hernández). Para la resistencia insulínica se usó un índice HOMA mayor de 3. De los 100 sujetos de estudio en el momento basal completaron el seguimiento, a los 12 meses, 40 de ellos, repitiéndose todas las mediciones, para determinar si las variaciones clínico-analíticas se relacionaban con variaciones en los aminoácidos. Conclusiones: Los sujetos con exceso de peso presentaron niveles menores de colesterol-HDL y vitamina B12, y mayores niveles de triglicéridos, insulina e índice HOMA. No se observó relación entre el exceso de peso y el ácido fólico. Los factores epidemiológicos más asociados a niños con exceso de peso fueron: la presencia de sobrepeso en el progenitor “padre”; el elevado consumo de zumos, refrescos y snacks; la existencia de una mayor distancia del hogar al colegio; y el exceso de horas viendo la televisión o jugando a la consola. La resistencia insulínica se relacionó inversamente con los niveles plasmáticos de leucina e isoleucina, en el momento basal. Aunque la valina y la citrulina no obtuvieron significación estadística, sus datos fueron similares a los de la leucina e isoleucina. También se evidenció una relación directa entre la resistencia insulínica y el IMC y los TG, e inversa con el HDL, la vitamina B12 y el ácido fólico. La homocisteína no se correlacionó con datos antropométricos ni con resistencia insulínica. Los BCAA (valina, leucina e isoleucina) se relacionaron inversamente con el IMC y el perímetro abdominal, tanto en el momento basal como tras un año de seguimiento. La leucina e isoleucina obtuvieron asociación estadística con la resistencia insulínica, es decir, aquellos con HOMA >3 presentaron menores niveles de estos aminoácidos, a diferencia de los datos contrarios de otras publicaciones. Se constató la ausencia de diferencias, tras un año de evolución, entre los valores medios de los BCAA con respecto al desarrollo de resistencia insulínica. Sólo se apreciaron diferencias estadísticamente significativas para la arginina, siendo menores sus cifras en los que desarrollaron resistencia insulínica. Hay que resaltar que sólo la valina, al año de seguimiento, estuvo ligeramente aumentada en niños con índice HOMA > 3, aunque los datos no fueron significativos. Este hecho podría ser el primer indicio de las consecuencias de la resistencia insulínica en el metabolismo de los aminoácidos. La citrulina se relacionó inversamente con el perímetro abdominal y con el IMC. No hubo diferencias con la resistencia insulínica ni con el IMC al año. Bibliografía: a destacar: WHO. Overweight and obesity. (sitio web). Geneva, Switzerland: World Health Organization, 2006. (citado 5 agosto 2014). Disponible en: http://www.who.int/mediacentre/factsheets/fs311/en/index.html. Ice CL, Murphy E, Cottrell L, Neal WA. Morbidly obese diagnosis as an indicator of cardiovascular disease risk in children: results from the CARDIAC Project. Int J Pediatr Obes. 2011; 6:113-119. Carrascosa A, Yeste D. Complicaciones metabólicas de la obesidad infantil. An Pediatr (Barc). 2011; 75(2):135.e1-135.e9. De Farias AA, Camêlo A, Almeida GM, Da Silva MO, Teixeira A,Campos C et al. Homocysteine: cardiovascular risk factor in children and adolescents? Rev Assoc Med Bras. 2 0 1 3; 5 9(6):622-628. Lynch CJ, Adams SH. Branched-chain amino acids in metabolic signalling and insulin resistance. Nat. Rev. Endocrinol 2014; 10, 723-736. Fike CD, Summar M, Aschner JL. L-citrulline provides a novel strategy for treating chronic pulmonary hypertension in newborn infants. Acta Paediatr. 2014 Oct; 103(10):1019-26. doi: 10.1111/apa.12707. Epub 2014 Jun 20.

Au1to-reporte de la condición física relacionada con la salud en una muestra de escolares del distrito Bogotá: estudio FUPRECOL

Introducción y objetivo: La escala de auto-reporte de la condición física (IFIS) “The International FItness Scale”, fue creada como parte del proyecto financiado por la unión europea HELENA Study “Healthy Lifestyle in Europe by Nutrition in Adolescence”. A la fecha, no se conoce ningún estudio que haya examinado el auto-reporte de la condición física en un contexto distinto al Europeo. Este trabajo evalúa por auto-reporte la condición física relacionada con la salud (CFRS) en una muestra de niños y adolescentes del distrito de Bogotá pertenecientes al grupo FUPRECOL. Materiales y Método: Estudio transversal en 1.922 escolares (54.3% mujeres). Se aplicó de manera auto-administrada la escala “IFIS”. Se midió el peso, talla, circunferencia de cintura y se calculó el índice de masa corporal (IMC) en kg/m2. La capacidad aeróbica, el índice general de fuerza (z-score fuerza prensil + z-score salto de longitud), la velocidad/agilidad y la flexibilidad fueron como indicadores objetivos de la CFRS objetiva y directa. Resultados: La muestra estuvo conformada por 1.922 escolares, de los cuales 1.045 fueron mujeres (54.3%) y 877 hombres (45.6%). El análisis ANOVA mostró que los varones tenían mayores valores de peso (p<0.003), estatura (p<0.001), CC (p<0.001), capacidad aeróbica (p<0.001), velocidad/agilidad (p<0.001) e índice general de fuerza (p<0.001), mientras que las mujeres presentaron exceso de peso por IMC (sobrepeso y obesidad). En el componente de condición física general, las puntuaciones más altas en la escala “IFIS” se encontraron en la categoría buena (40%), seguido de aceptable (34%), mientras que la puntuación más baja se encontró en la categoría muy mala/mala (6%). En población general, relaciones lineales fueron observadas entre el auto-reporte de la CFRS por la escala “IFIS” y la mayoría de los indicadores del fitness evaluado objetivamente. El análisis post-hoc ajustado por sexo, edad y etapa de maduración reveló que los escolares que acusaron mejores valores en la auto-percepción de los dominios del “IFIS”, presentaron mejor desempeño en los indicadores de CFRS objetivos. Conclusión: Este trabajo describe por primera vez en población Latina, que el auto-reporte con la escala “IFIS”, es un instrumento válido para evaluar la CFRS, y además posee una adecuada capacidad para clasificar la aptitud física en población escolar de Bogotá, Colombia. Esta escala se encuentra disponible para otros investigadores interesados en evaluar la condición física muscular en América Latina.

Aplicação de cartas de controlo na monitorização de resultados de ensaios de comparação interlaboratorial

A norma NP EN ISO/IEC 17025 descreve os requisitos gerais para o reconhecimento da competência de um laboratório em realizar ensaios e/ou calibrações, incluindo amostragem, que é utilizada pelos laboratórios para desenvolver os seus sistemas de gestão da qualidade e para as atividades administrativas e técnicas. Além da referência aos procedimentos de controlo da qualidade para monitorizar a validade dos ensaios e calibrações realizadas, é referida a necessidade dos laboratórios participarem em Ensaios de Comparação Interlaboratorial (ECI) como garantia da fiabilidade dos resultados. Neste trabalho, apresentam-se resultados da aplicação de cartas de controlo de qualidade para monitorização da estatística z-score (diferença entre o resultado obtido pelo laboratório participante e o valor de referência dividida pelo erro). Quando os dados analisados apresentam autocorrelação, é testado um modelo apropriado de série temporal, ou seja, um modelo que remova a autocorrelação dos dados aplicando cartas de controlo aos resíduos

Creation of an Age-Adjusted, Dual-Energy X-ray Absorptiometry-Derived Trabecular Bone Score Curve for the Lumbar Spine in Non-Hispanic US White Women.

The trabecular bone score (TBS, Med-Imaps, Pessac, France) is an index of bone microarchitecture texture extracted from anteroposterior dual-energy X-ray absorptiometry images of the spine. Previous studies have documented the ability of TBS of the spine to differentiate between women with and without fractures among age- and areal bone mineral density (aBMD)-matched controls, as well as to predict future fractures. In this cross-sectional analysis of data collected from 3 geographically dispersed facilities in the United States, we investigated age-related changes in the microarchitecture of lumbar vertebrae as assessed by TBS in a cohort of non-Hispanic US white American women. All subjects were 30 yr of age and older and had an L1-L4aBMDZ-score within ±2 SD of the population mean. Individuals were excluded if they had fractures, were on any osteoporosis treatment, or had any illness that would be expected to impact bone metabolism. All data were extracted from Prodigy dual-energy X-ray absorptiometry devices (GE-Lunar, Madison, WI). Cross-calibrations between the 3 participating centers were performed for TBS and aBMD. aBMD and TBS were evaluated for spine L1-L4 but also for all other possible vertebral combinations. To validate the cohort, a comparison between the aBMD normative data of our cohort and US non-Hispanic white Lunar data provided by the manufacturer was performed. A database of 619 non-Hispanic US white women, ages 30-90 yr, was created. aBMD normative data obtained from this cohort were not statistically different from the non-Hispanic US white Lunar normative data provided by the manufacturer (p = 0.30). This outcome thereby indirectly validates our cohort. TBS values at L1-L4 were weakly inversely correlated with body mass index (r = -0.17) and weight (r = -0.16) and not correlated with height. TBS values for all lumbar vertebral combinations decreased significantly with age. There was a linear decrease of 16.0% (-2.47 T-score) in TBS at L1-L4 between 45 and 90 yr of age (vs. -2.34 for aBMD). Microarchitectural loss rate increased after age 65 by 50% (-0.004 to -0.006). Similar results were obtained for other combinations of lumbar vertebra. TBS, an index of bone microarchitectural texture, decreases with advancing age in non-Hispanic US white women. Little change in TBS is observed between ages 30 and 45. Thereafter, a progressive decrease is observed with advancing age. The changes we observed in these American women are similar to that previously reported for a French population of white women (r(2) > 0.99). This reference database will facilitate the use of TBS to assess bone microarchitectural deterioration in clinical practice.

Generation and validation of a normative, age-specific reference curve for lumbar spine trabecular bone score (TBS) in French women.

Age-related changes in lumbar vertebral microarchitecture are evaluated, as assessed by trabecular bone score (TBS), in a cohort of 5,942 French women. The magnitude of TBS decline between 45 and 85 years of age is piecewise linear in the spine and averaged 14.5 %. TBS decline rate increases after 65 years by 50 %. INTRODUCTION: This study aimed to evaluate age-related changes in lumbar vertebral microarchitecture, as assessed by TBS, in a cohort of French women aged 45-85 years. METHODS: An all-comers cohort of French Caucasian women was selected from two clinical centers. Data obtained from these centers were cross-calibrated for TBS and bone mineral density (BMD). BMD and TBS were evaluated at L1-L4 and for all lumbar vertebrae combined using GE-Lunar Prodigy densitometer images. Weight, height, and body mass index (BMI) also were determined. To validate our all-comers cohort, the BMD normative data of our cohort and French Prodigy data were compared. RESULTS: A cohort of 5,942 French women aged 45 to 85 years was created. Dual-energy X-ray absorptiometry normative data obtained for BMD from this cohort were not significantly different from French prodigy normative data (p = 0.15). TBS values at L1-L4 were poorly correlated with BMI (r = -0.17) and weight (r = -0.14) and not correlated with height. TBS values obtained for all lumbar vertebra combined (L1, L2, L3, L4) decreased with age. The magnitude of TBS decline at L1-L4 between 45 and 85 years of age was piecewise linear in the spine and averaged 14.5 %, but this rate increased after 65 years by 50 %. Similar results were obtained for other region of interest in the lumbar spine. As opposed to BMD, TBS was not affected by spinal osteoarthrosis. CONCLUSION: The age-specific reference curve for TBS generated here could therefore be used to help clinicians to improve osteoporosis patient management and to monitor microarchitectural changes related to treatment or other diseases in routine clinical practice.

[factors Impacting The Growth And Nutritional Status Of Cystic Fibrosis Patients Younger Than 10 Years Of Age Who Did Not Undergo Neonatal Screening.]

The aim of this study was to evaluate by clinical and laboratory parameters how cystic fibrosis (CF) affects growth and nutritional status of children who were undergoing CF treatment but did not receive newborn screening. A historical cohort study of 52 CF patients younger than 10 years of age were followed in a reference center in Campinas, Southeast Brazil. Anthropometric measurements were abstracted from medical records until March/2010, when neonatal screening program was implemented. Between September/2009 and March/2010, parental height of the 52 CF patients were also measured. Regarding nutritional status, four patients had Z-scores ≤ -2 for height/age (H/A) and body mass index/age (BMI/A). The following variables were associated with improved H/A ratio: fewer hospitalizations, longer time from first appointment to diagnosis, longer time from birth to diagnosis and later onset of respiratory disease. Forced vital capacity [FVC(%)], forced expiratory flow between 25-75% of FVC [FEF25-75(%)], forced expiratory volume in the first second [FEV1(%)], gestational age, birth weight and early respiratory symptoms were associated with IMC/A. Greater number of hospitalizations, diagnosis delay and early onset of respiratory disease had a negative impact on growth. Lower spirometric values, lower gestational age, lower birth weight, and early onset of respiratory symptoms had negative impact on nutritional status. Malnutrition was observed in 7.7% of cases, but 23% of children had nutritional risk.