<p>The breathing pattern of preterm infants is immature and is associated with a variety of reflexes. In a patient on the ventilator these reflexes interfere with spontaneous breathing. A better understanding of the immature control of breathing could lead to further improvements in ventilatory techniques. This thesis concerns studies of pulmonary stretch receptor (PSR) and phrenic nerve activity as part of the regulation of breathing in an animal model. </p><p>During assist/control ventilation with three different inspiratory pressure waveforms in animals with healthy lungs, squarewave pressure waveform<b> </b>strongly inhibits spontaneous inspiratory activity.</p><p>During partial liquid ventilation (PLV) in animals with healthy lungs, all PSRs studied maintained their phasic character, with increased impulse frequency during inspiration. PSR activity was not higher during PLV than during gas ventilation (GV), indicating that there was no extensive stretching of the lung during PLV.</p><p>During proportional assist ventilation (PAV) the applied airway pressure is servo-controlled proportionally to the ongoing breathing effort, thereby interacting with the activity of PSRs. Peak PSR activity was higher and occurred earlier during PAV than during CPAP. The regulation of breathing is maintained during PAV in surfactant-depleted animals before and early after surfactant instillation, with a higher ventilatory response and a lower breathing effort than during CPAP in both conditions.</p><p>Both lung mechanics and gas exchange influence the regulation of breathing. Inhibition of inspiratory activity occurred at a lower arterial pH and a higher PaCO₂ during PLV than during GV in animals with surfactant-depleted lungs, which might be related to recruitment of a larger number of pulmonary stretch receptors during PLV.</p><p>In summary, selected aspects of the regulation of breathing were studied in an animal model with different ventilatory techniques under different lung conditions similar to those that can occur in infants.</p>

Variation of diabetes incidence over time in countries with different incidence levels and socio-economic conditions, and in an age span beyond the childhood years, may give clues for diabetes causes. Materials: Data from prospective type 1 diabetes registers in Sweden and Lithuania in children (0-14 years) and young adults (15-34 and 15-39 years, respectively). Number of infections recorded in health care booklets (117 cases; 270 controls); interview about the dietary intake one-year before the diagnosis and routinely recorded growth data (99 cases; 180 controls). Results: The incidence of type 1 diabetes in Sweden and Lithuania differed most in the younger age groups, 28.9 and 7.5/100,000/year in 0-14-year group, respectively. During 1983-2000 incidence increased in 0-14-year old children in both countries, but the pattern of change differed. During 1983-1998 the incidence increased in Swedish children, but tended to decrease in young adults, with no increase in the age group below 35 years, indicating that the increase of childhood diabetes may be due to a shift towards a younger age at diagnosis. Within a low-incidence country Lithuania there was an urban-rural gradient of incidence, especially in the younger age groups, that seemed to follow poverty distribution: incidence in the 0-39-year group was 7.1, 9.0 and 8.8/100,000/year in rural areas, towns and cities, respectively, p&lt;0.001. Exposure to one or more non-specific infection during the first half-year of life reduced diabetes risk: odds ratios (95%-CI) in 0-14 and 5-14-year groups were (0.60; 0.37-0.98) and (0.47; 0.26-0.87), respectively. Higher energy intake and weight-for-age were independent diabetes risk factors: odds ratios for medium and high levels of energy were 1.33 (0.52-3.42) and 5.23 (1.67-16.38), and for weight-for-age 3.20 (1.30-7.88) and 3.09 (1.16-8.22), respectively. High intake of carbohydrates, disaccharides and sucrose in particular, increased diabetes risk independently of the high intake of energy. Conclusion: Environmental factors associated with socio-economic conditions in childhood may be important for the occurrence of type 1 diabetes. Lack of exposure to microbial antigens early in life, higher intake of energy and more rapid growth may contribute to the increase of childhood-onset diabetes observed in many countries.

To assess the impact of congenital malformations in Down syndrome (DS) on morbidity, mortality and outcome at birth, information on all children with DS born in the northern part of Sweden in 1973-80 (n=211) and 1995-98 (n=88) was collected. Most common were congenital heart defects (CHD), dominated by atrioventricular septal defects (AVSD). Up to age 10 years, morbidity and mortality were more than 10 times higher in DS children with CHD than in healthy DS children. The DS children seemed more vulnerable at birth than Swedish children in general: they had increased frequencies of Cesarean sections, premature birth, asphyxia, and low birthweight, and higher proportions of children small for gestational age, regardless of the presence of CHD. Infant mortality decreased from 14.2% to 2.3% between the two periods. All children with AVSD with and without DS born in Sweden 1973-1997 (n=801) were followed up retrospectively to 2001. Children with isolated AVSD without complex additional CHDs were studied more closely (n=502). A reduction in age at operation and postoperative mortality (from 28 to 1%) was observed. No significant difference in 5-year postoperative mortality between genders or between DS and non-DS children was found. The 5-year postoperative mortality in DS decreased from 35% in 1973-77 to about 10% in 1993-97. CHD had a major influence on morbidity, infectionrate and mortality in DS, but not on DS birth variables. The formerly high mortality in CHD is now reduced. In isolated AVSD measures seem equally successful in DS and non-DS children. Mortality is still 3 times higher in DS children with isolated AVSD than in healthy DS children.

The overall aim of this thesis was to study the implementation of guidelines, change processes and contextual variables from the perspective of improvements and neonatal nursing care’s endeavours to be more evidenced-based. Because health care is exposed to extensive change pressure and because the impact of effectiveness research on clinical practice is limited, it becomes urgent to understand how knowledge utilisation initiatives can be facilitated. Three studies involved managers and nurses at all neonatal units in Sweden. Two of these studies also included nurses from other healthcare organisations. The fourth study included all staff at four neonatal units. The study designs used were cross-sectional, comparative and prospective longitudinal surveys; questionnaires were used as data collection tools in all four studies. Evaluation of the utilisation of the neonatal nursing guidelines showed that the guidelines were known to the nurse managers and used at most of the units, though to varying degrees and in different ways. Fifteen months after guideline dissemination, 8 of 35 units had changed practice, of which 2 units had completed the implementation process of a guideline. Involvement in the preceding guideline project facilitated the completion of improvement projects compared with participation in training courses for quality improvement (QI) only. There was no difference between these two groups on long-standing involvement in improvement work. Nurses who continued QI work over a 4-year period were more active in seeking research and implementing research findings in clinical practice than those who ceased the improvement work. The QI-sustainable nurses reported better contextual support for research-related activities. In a separate study staff perceptions of organisational factors appeared stable over the course of one year at the aggregated level. Improvements in skills development and participatory management predicted higher overall organisational and staff well-being. The findings emphasize the importance of including both individual and organisational factors in the strategic planning for evidence-based nursing. Plans have to be long-term and consider that change is a slow process. Leadership commitment is essential and there are clear benefits in developing a learning and professional supportive environment as well as of involving staff in organisational decision making.

Fifty children with hematologic malignancies have been treated with autologous BMT in Uppsala. The aim was to describe late effects in this group with special reference to cataracts, reduced final height, and to hepatic, renal, and pulmonary late effects. Cataracts: All patients who received TBI in their conditioning developed posterior subcapsular cataract after BMT. A few patients with visual impairment affecting daily life needed cataract surgery, whereas the visual acuity was well preserved in most of the other patients. Final height: There was a decrease in final height relative both to height at BMT and to target height. This decrease was significant both in those who had received TBI only and in those who had been given cranial irradiation. Cranial irradiation, young age at BMT, and short duration of GH treatment were predictors of height loss. Hepatic function: Hepatic function was well preserved over a period of 10 years after BMT. TBI did not appear to be a risk factor for hepatic impairment. Renal function: Six months after BMT there was a decrease in renal function in patients who had received TBI. It then recovered, albeit incompletely, and stabilized. After the first year there was little change over a period of 10 years after BMT. TBI appeared to be the most important risk factor for the development of chronic renal impairment in a number of patients. Nephrotoxic antibiotics may have contributed. Pulmonary function: Six months after BMT there was a decrease in pulmonary function in those who received TBI. It then recovered and stabilized at the pretransplant level. After the first year there was little change over a period of 10 years after BMT. TBI appeared to be the most important risk factor for restrictive pulmonary disease in a number of patients whereas chemotherapy might also have been of importance for impaired gas exchange.

Rolandic epilepsy (RE) is the most common focal epilepsy syndrome in the pediatric age group with an onset between 3 and 13 years. The syndrome is defined by electro-clinically typical features and has been considered benign according to seizure remission before the age of 16 years. The aim of this thesis was to investigate children with typical RE with different methods and to discuss the delineation of the syndrome. Thirty-eight children, aged 6–14 years, participated in one up to four studies. Eighteen children were investigated with MRI. Hippocampal abnormalities were found in six (33%), volume asymmetry in five (28%) and high signal intensities on T2-weighted images in three (17%). Additionally, high signal intensities in T2-weighted images were revealed subcortically in temporal and frontal lobes bilaterally in five children (28%). The hippocampal region was evaluated metabolically using proton magnetic resonance spectroscopy (1H-MRS) in 13 children with RE and 15 matched controls. A metabolic asymmetry of the hippocampal regions was found in the patients compared to controls indicating an abnormal neuronal function. Seventeen children with RE and 17 matched controls were investigated with a neuropsychological test battery. The RE children showed lower performance in auditory-verbal tests and in executive functions compared to controls. Twenty RE children and 24 controls were assessed concerning their oromotor function. The RE children had greater problems concerning tongue movements including articulation. A dichotic listening test was also performed in a subgroup showing poorer results in the RE group. A simple classification is proposed with RE ‘pure’ as the main group and the frame for this study. In conclusion, these investigations disclosed various abnormalities in children with RE, challenging the benign concept during the active phase. It is assumed that maturational factors comprise causal mechanism to the deviant findings, which probably successively will normalize.

Background: The survival rates for very low birthweight (VLBW; birthweight ≤1500 g) children are increasing, but they run a greater risk than controls of developing neurosensory disabilities and other functional problems during childhood. However, there is a great need for more knowledge regarding long-term outcome to adulthood in VLBW subjects. Aims: To evaluate long-term outcomes in a regional cohort of VLBW children born in 1987-88 regarding hospital readmissions, morbidity, neurological conditions, cognitive function, reading skills, school achievements, behaviour, growth, general health, and social functioning in relation to gender, neonatal risk factors, disability and Magnetic Resonance Imaging (MRI) findings. Study design: Prospective longitudinal case-controlled long-term regional follow-up. Material and Methods: A total of 86 (80.4%) children (47 boys out of 60 and 39 girls out of 47 live-borns) survived the neonatal period and were recruited to the follow-up study. A total of 86 term controls (45 boys and 41 girls) were included from the newborn period. Readmissions, hospital diagnoses, need of habilitation and child psychiatric care were checked in registers to 15 years of age. The VLBW children were enrolled in the follow-up study at 40 weeks gestational age and at 4, 9, and 15 years of age in assessing neurological conditions. At 15 years of age, the groups were assessed in cognition (WISC III), reading skills, school outcome, behaviour, vision and growth. Fifty-nine (69%) VLBW children were examined using cerebral MRI. Physical and mental health, weight and height, education, and socio-economic situation were assessed at 20 years of age in 77/85 VLBW and 69/84 control subjects by means of postal questionnaires. Results: VLBW boys had three times more readmissions compared with control boys (p=0.003). Gestational age below 30 weeks, birthweight less than 1000 g, and mechanical ventilation were neonatal risk factors for readmissions. Five (5.8%) children had moderate/severe cerebral palsy, 5 (5.8%) had attention deficit hyperactivity disorder, and 1 was blind due to retinopathy of prematurity. VLBW children were inferior in neurological function in comparison with controls at 40 weeks of gestational age and 4 and 15 years of age. Fourteen of 56 (25%) VLBW children without overt disability had abnormal MRI findings. Mechanical and/or intraventricular haemorrhages (IVH) were significantly related to less favourable neurological outcome. VLBW children performed significantly lower than their controls on a few reading variables and on WISC III. Half of them had IQ lower than 85. Ten VLBW children with IQ &lt; 70 had not been clinically identified earlier and a majority of these children attended mainstream school. Small head circumference correlated with low IQ. Mechanical ventilation and IVH correlated with lower IQ and poorer reading skills. At 20 years of age, the VLBW subjects did not differ significantly from the controls in self-perceived health, education, occupation and way of living. Conclusions: Most VLBW subjects were without major health problems up to 20 years of age and had attended mainstream schools. The presence of IVH and mechanical ventilation during the neonatal period negatively influenced health outcomes. VLBW children without overt neurological disability performed somewhat less well in neurological examinations in comparison with controls. VLBW children achieved poorer results in cognitive tests, but reading skills made a catch-up to 15 years of age. A majority of VLBW subjects managed transition to adulthood similar to that of controls. / Bakgrund: Överlevnaden för nyfödda barn med mycket låg födelsevikt (1500 g eller lägre; VLBW) har ökat avsevärt under de senaste årtionden och man finner nu att ca 90 % av barnen skrivs ut från neonatalavdelningar. Risken för cerebral pares (CP) har visat sig vara ökad jämfört med barn födda i fullgången tid. Studier visade att VLBW-barn som kommit upp i skolåldern hade högre frekvens av läs- och skrivsvårigheter, oftare behövde specialundervisning, samt hade högre grad av beteendeproblem jämfört med klasskamrater. Uppföljningsstudier var tidigare mestadels gjorda på populationer från större sjukhus, kontrollgrupp saknades eller inlemmades efter flera år, uppföljningstiden var kort och flera viktiga områden av barnets utveckling var ofullständigt undersökta. I Sverige saknades en studie med långtidsuppföljning av VLBW-barn födda under en tidsperiod då alltfler barn hade börjat erhålla andningshjälp med respirator. Socioekonomiska förhållanden i Sverige kan inte heller helt och hållet jämföras med flertalet andra länder. Syfte: Den här avhandlingens syfte var att studera hur det går för VLBW-barn upp till 15 års ålder avseende sjuklighet, motoriska funktioner, kognitiva funktioner, skolprestationer och beteende, samt vid 20 års ålder avseende hälsotillstånd, sysselsättning och boende. Undersökningsresultaten relaterades till nyföddhetsfaktorer och fynd vid magnet resonans-undersökning (MRI) av hjärnan vid 15 års ålder. Material och metoder: 86 överlevande VLBW-barn samt 86 barn födda i fullgången tid från 1/2 1987 till 30/4 1988 i sydöstra sjukvårdsregionen (Jönköpings, Kalmar och Östergötlands län) har ingått i studien. Uppgift om antalet sjukhusinläggningar och huvuddiagnos inhämtades från Slutenvårdsregistret, Epidemiologiskt centrum, Socialstyrelsen. Uppgifter om antalet barn med CP, ADHD, mental retardation och barnpsykiatriskt vårdbehov inhämtades från habiliteringscentraler och barnpsykiatriska kliniker i regionen. Information om skolbetyg från 9:e årskursen och skolgång inhämtades från kommunerna. Neurologiska och motoriska undersökningar utfördes på barn utan synligt handikapp enligt särskilda protokoll såväl neonatalt som vid 4, 9 och 15 års ålder. Vikt och längd, kognitiv test (WISC III), lästester och MRI undersökning (enbart VLBW-barn) gjordes vid 15 års ålder. Barn och föräldrar fick fylla i formulär om beteende. Vid 20 års ålder (december 2007) fick deltagarna tre frågeformulär: ett studiespecifikt med frågor om hälsa, vikt och längd, användning av tobak och alkohol, gymnasiestudier, nuvarande sysselsättning och boende; SF-36, som belyser fysisk kapacitet, allmän hälsa, vitalitet och psykiskt välbefinnande; samt KASAM (känsla av sammanhang), som belyser hur man upplever sitt eget sätt att fungera, uppdelat i begriplighet, hanterbarhet och meningsfullhet. Resultat: VLBW-barn (mest pojkar) vårdades oftare på sjukhus under första levnadsåren jämfört med kontroller. Infektioner och neurologiska sjukdomar dominerade för både VLBW-pojkar och -flickor. Fem (5.8 %) VLBW-barn hade måttlig/svår CP och fem hade ADHD. Hjärnblödning eller respiratorbehandling under nyföddhetsperioden var de faktorer som oftast var relaterade till sämre hälsotillstånd. Det var ingen skillnad i antal barn med behov av barnpsykiatrisk vård mellan grupperna. Det var ingen skillnad i summering av 9 slutbetyg mellan grupperna, men VLBW-pojkar hade lägre betyg i matematik och teknologi jämfört med sina kontroller. VLBW-barnen var lättare och kortare, men skillnaderna var störst mellan VLBW-flickor och deras kontroller. VLBW-barnen (fr.a. pojkarna) presterade lägre i neurologiska undersökningar, samt i kognitiva test. Tio av tolv av barnen som hade IQ under 70 var tidigare inte kända. Det fanns skillnader mellan grupperna i lästester, men signifikant enbart i ett test. Jämfört med lästester vid 9 års ålder hade VLBW-barnen gjort en upphämtning. Det framkom inga skillnader i beteende mellan grupperna, men VLBW-flickor uppgav färre beteendeproblem än sina kontroller. Vid 20 års ålder framkom inga skillnader i självuppskattad hälsa eller behov av vårdkontakter och läkemedel mellan grupperna. Tobaksanvändning var lika i grupperna, men fler i VLBW-gruppen var icke-användare av alkohol. Det var ingen signifikant skillnad i andel som gått ut gymnasiet, nuvarande sysselsättning eller boendeform mellan grupperna. Det var inga signifikanta skillnader i resultat på SF-36 och KASAM mellan grupperna. Konklusion: Hjärnblödning och respiratoranvändning under nyföddhetsperioden var de faktorer som hade störst inverkan på VLBW-barnens hälsotillstånd upp till 20 års ålder. CP och ADHD förekom hos relativt få, men lågt IQ var vanligt. VLBW-pojkar hade större sjukvårdsbehov, presterade lägre i neurologiska test och hade lägre skolbetyg än sina kontroller. VLBW-gruppen skilde sig inte från kontroll-gruppen avseende beteendeproblem. Självuppskattad hälsa vid 20 år skilde sig inte mellan grupperna. Särskilda uppföljningsprogram för VLBW-barn är nödvändigt där kognitiva tester ingår vilka bör utföras före skolstart.

Insulin pump treatment (CSII) is considered the most physiological way to imitate the healthy body’s insulin profile in adolescents with diabetes. However, despite the use of CSII, achieving the recommended disease control is difficult for adolescents. The aim of this thesis was to explore aspects of self-management of diabetes in adolescents using insulin pumps in order to describe conditions contributing to the recommended disease control. Three methods of bolusing (normal, dual-wave and square-wave) in connection with pasta meals were tested in a crossover study among 15 adolescents with diabetes to assess whether one method was superior in managing glucose levels. A cross-sectional study among 90 adolescents being treated with CSII was conducted to investigate the management of CSII, including the administration of bolus doses. Two qualitative interview studies, based on the grounded theory method, were performed to gain insight into the processes involved in taking bolus doses and to investigate reasons for missed bolus doses and strategies for avoiding missing them. Twelve adolescents, four parents and one diabetes specialist nurse were interviewed. No method of bolusing was found to be superior in managing the glucose levels after these meals. The post-prandial glucose peaks were &lt;10 mmol/L, in 48% of the cases, regardless of bolus methods. This indicates that adolescents can be encouraged to individually test which bolus method gives them the most normal post-prandial glucose levels. The cross-sectional study showed that adolescents were satisfied with CSII, but that 38% had missed more than 15% of the bolus doses the day under study. The frequency of bolus doses correlated with the disease control. Findings from the interview study revealed the need to clarify the responsibility for diabetes self-management in continuous negotiation between adolescents and parents to avoid insulin omission. The main reason for missed boluses was lost focus, and the strategies for remembering them were agreements involving reminders. The thesis describes that individual dose testing, clarification of responsibility and agreements involving reminders are conditions contributing to the recommended disease control. The thesis also describes that lost focus and a lack of responsibility can lead to insulin omission and be a hindrance to achieving disease control. / Anna Kernell avled maj 2010.

Introduction: Gut microbial composition has been associated with immune-mediated diseases. Breastfeeding yields a microbiota rich in bifidobacteria and promotes colonization by lactobacilli. Bifidobacteria and lactobacilli are considered health-promoting and are used as probiotics, i.e. live microbial food supplements which when ingested in adequate amounts confer a beneficial effect on the host. During weaning the developing gut immune system is exposed to an increasing variety of antigens from both foods and gut microbiota. Aims: We aimed to determine if daily feeding of 1x108 colony-forming units (CFU) of the probiotic Lactobacillus paracasei ssp. paracasei strain F19 (LF19) to healthy term infants from 4 to 13 months of age could maintain some of the beneficial effects conferred by breastfeeding on gut microbial composition, with possible effects on gut microbial function, T cell function, Th1/Th2 immune balance and eczema incidence. Study design: Infants were randomized to daily intake of cereals with (n=89) or without LF19 (n=90) from 4-13 months of age. Clinical outcome measures were monitored by diaries and a questionnaire. Stool and blood samples were obtained at 4, 6½, 9, 13 and 5½, 6½, 12 and 13 months of age, respectively. Stool samples were analyzed for lactobacilli counts by conventional culture methods and the presence of LF19 was verified by randomly amplified polymerase chain reaction (RAPD-PCR). Fecal short-chain fatty acid (SCFA) pattern, a proxy for gut microbial function, was determined by gas-liquid chromatography. After polyclonal or specific activation of T cells, the cytokine mRNA expression levels [interleukin 2 (IL2), IFN-, IL4 and IL10] were determined on isolated mRNA by quantitative real time reverse transcriptase-PCR. Serum concentrations of total and specific IgE antibodies, Haemophilus influenzae type b, diphtheria and tetanus toxoid specific IgG antibodies were analyzed by enzyme immunoassay. Results: Feeding LF19 maintained high fecal lactobacilli counts during weaning. Persistent colonization with LF19 induced differences in the fecal SCFA pattern. The cumulative incidence of eczema was lower in the probiotic group, in conjunction with a higher IFN-γ/IL4 mRNA ratio in polyclonally activated T cells. Even though there was an effect by LF19 on Th1/Th2 immune balance, there was no effect on IgE sensitization. Infants in both groups increased their capacity to express both Th1 and Th2 cytokines during the second half of infancy but the expression was still lower than that of adults. Infants in the probiotic group had lower IL2 levels after polyclonal T cell activation at 13 months of age compared with infants in the placebo group. Infants fed LF19 did not have fewer infections, but had fewer days with antibiotic prescription compared with infants fed placebo. In addition, compared to placebo, persistent colonization by LF19 enhanced specific vaccine responses to protein antigens during the course of vaccination. Conclusions: We conclude that feeding LF19 was safe, based on no observed adverse effects in our study. Infants in both groups demonstrated maturation of adaptive immune responses during weaning. Adding probiotics in complementary foods during weaning reduced the risk of eczema by 50%, with a concomitant shift towards an enhanced Th1/Th2 ratio. The reduction of eczema might be explained by probiotic effects on both T cell-mediated immune responses and reinforced gut microbial function.

Övervikt och fetma hos barn är ett allvarligt och växande problem. Det är ett tillstånd som för med sig många olika sjukdomar och i och med att antalet överviktiga barn ökar hastigt kommer det att vara en stor belastning för den framtida hälso- och sjukvården. Prevalensen är särskilt stor i vissa delar av världen och inom vissa grupper i samhället. Föräldrar spelar en väsentlig roll i huruvida barnen lever hälsosamma liv eftersom de bär ansvaret för barnen. Syftet med denna litteraturstudie var att undersöka föräldrars påverkan i utvecklingen av övervikt och fetma hos barn och genom en systematisk bearbetning av litteraturen granskades och bearbetades slutligen 19 vetenskapliga artiklar till resultatdelen i studien. Socioekonomiska faktorer, faktorer inom familjen och föräldrars roll var tre teman som utmärkte sig där det under varje rubrik beskrivs hur föräldrar påverkar med att bidra till eller motverka riskfaktorer till en ohälsosam viktstatus hos barn. Föräldrar har ett behov av stöd i form av information och kunskap och hälso- och sjukvården bär ett stort ansvar i att stödja föräldrar, förebygga sjukdom och främja hälsa. / Overweight and obesity in children are serious conditions, with many negative consequences to the health of individuals and the health care system as a whole. The prevalence is particularly great in certain groups of people and the frequency of these conditions is increasing at an alarming rate. Parents, as the primary caregivers, play a vital role in determining whether or not their children lead a healthy lifestyle. The aim of this literature review was to establish the influence that parents have on the development of overweight and obesity in their children. 19 articles were systematically reviewed and the results showed three main areas of influence; socio-economic factors, factors within the family and the role of the parent. In each of these areas, risk factors of developing overweight and obesity in children were identified. In general, parents lack information about these conditions and are in need of support from nurses and other health care professionals, who in turn carry the responsibility to support the parents, promote good health and prevent disease.