Technology Development as a Normative Practice: A Meaning-Based Approach to Learning About Values in Engineering-Damming as a Case Study.

Engineering, as a complex and multidimensional practice of technology development, has long been a source of ethical concerns. These concerns have been approached from various perspectives. There are ongoing debates in the literature of the philosophy of engineering/technology about how to organize an optimized view of the values entailed in technology development processes. However, these debates deliver little in the way of a concrete rationale or framework that could comprehensively describe different types of engineering values and their multi-aspect interrelations in real engineering practices. Approaching engineering values from a meaning-based perspective, as in this paper, can be a reliable method of tackling such a controversial problem. This paper therefore proposes that technology development be considered a systemic normative practice and attempts to provide a comprehensive view of various built-in values, their different origins and features, and a way of prioritizing them in real engineering processes. Studying two cases of the Zayandeh Rood Dam and the Abbasi Dam will lead to practical insights into how to understand norms in technology development and incorporate them into engineering practice.

Water Management: Sacrificing Normative Practice Subverting the Traditions of Water Apportionment-'Whose Justice? Which Rationality?'.

Since current water governance patterns mandate cooperation and partnership within and between the actors in the hydrosystems, supplementary models are necessary to distinguish the roles and the rules of indoor actions which is why we extend a theory in the frameworks of philosophy of technology. This analysis is empirically grounded on the problematic hydrosystems of a river in central Iran, Zayandehrud. Following a modernist-holistic-based analysis, it illustrates how values in the water apportionment mechanisms are being reshaped. The article by using the theory of normative practice has scrutinised the tasks and the rules of the old and new water-management systems, Mirab. Subsequently according to such philosophical theory, it has argued that the conflicts over the cases are due to interference of structural and directional norms within them.

The clinical pattern of primary hyperoxaluria in pediatric patient at Queen Rania Abdulla Children Hospital.

INTRODUCTION: Hyperoxaluria is a metabolic disorder that can lead to end stage renal disease (ESRD). It can be either inherited or acquired. Primary hyperoxaluria (PHO) is more common and characterized by an excessive production of oxalate leading to recurrent urolithiasis and progressive nephrocalcinosis. Due to the high rate of consanguineous marriage in Jordan this disease is commonly diagnosed in pediatric nephrology clinics. We aimed to demonstrate the clinical pattern and progression to ESRD in pediatric patients with hyperoxaluria at Queen Rania Abdulla Children Hospital. METHODS: Medical records of all patients followed up in the pediatric nephrology clinic with the diagnosis of PHO during the period between September 2007 and March 2013 were reviewed. RESULTS: There were 70 patients with the diagnosis of PHO, 52.9% were males. The median age at presentation was 3 years ± 3 months with the youngest child being two months old. Diagnosis was made in the first year of life in 15.7% of patients. The most common presenting symptom was hematuria, while 14% of patients were asymptomatic and detected by family screening after the diagnosis of an index case. At the time of initial presentation, 15.7% of patients had ESRD and 25% had impaired renal function. Kidney stones were found in 57% of cases and nephrocalcinosis was found in 37%. CONCLUSION: High index of suspicion is needed to diagnose PHO in children presenting with kidney stone or unexplained hematuria. Twenty-four hour urine collection for oxalate are required to make the proper diagnosis. Family screening, when appropriate, is indicated for early detection of PHO.

A British Society of Paediatric Gastroenterology, Hepatology and Nutrition survey of the effectiveness and safety of adalimumab in children with inflammatory bowel disease.

BACKGROUND: Adalimumab is efficacious therapy for adults with Crohn's disease (CD). AIM: To summarise the United Kingdom and Republic of Ireland paediatric adalimumab experience. METHODS: British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) members with Inflammatory Bowel Disease (IBD) patients <18 years old commencing adalimumab with at least 4 weeks follow-up. Patient demographics and details of treatment were then collected. Response and remission was assessed using the Paediatric Crohn's Disease Activity Index (PCDAI)/Physicians Global Assessment (PGA). RESULTS: Seventy-two patients [70 CD, 1 ulcerative colitis (UC), 1 IBD unclassified (IBDU)] from 19 paediatric-centres received adalimumab at a median age of 14.8 (IQR 3.1, range 6.1-17.8) years; 66/70 CD (94%) had previously received infliximab. A dose of 80 mg then 40 mg was used for induction in 41(59%) and 40 mg fortnightly for maintenance in 61 (90%). Remission rates were 24%, 58% and 41% at 1, 6 and 12 months, respectively. Overall 43 (61%) went into remission at some point, with 24 (35%) requiring escalation of therapy. Remission rates were higher in those on concomitant immunosuppression cf. those not on immunosuppression [34/46 (74%) vs. 9/24 (37%), respectively, (χ(2) 8.8, P=0.003)]. There were 15 adverse events (21%) including four (6%) serious adverse events with two sepsis related deaths in patients who were also on immunosuppression and home parenteral nutrition (3% mortality rate). CONCLUSIONS: Adalimumab is useful in treatment of refractory paediatric patients with a remission rate of 61%. This treatment benefit should be balanced against side effects, including in this study a 3% mortality rate.

Filaggrin loss-of-function variants are associated with atopic comorbidity in pediatric inflammatory bowel disease.

BACKGROUND: Pediatric inflammatory bowel disease (IBD) has a high prevalence of coexistent atopy. Filaggrin (FLG) loss-of-function variants (null-alleles) are associated with eczema and asthma in association with eczema. The aim was to assess the contribution of FLG null-alleles to pediatric IBD susceptibility and to coexistent atopy (eczema, asthma, allergic rhinitis, or food allergy). METHODS: FLG variants (R501X and 2282del4) were genotyped in 403 children with IBD, 683 parents, and 996 population controls. RESULTS: In all, 11% of IBD patients carried at least 1 FLG null-allele compared to 11% of population controls (P > 0.4). Carriage of 1 or more null-alleles in patients with atopy (present in 52% of IBD patients) differed from IBD patients without atopy (14% versus 6%, P = 0.01; odds ratio [OR] 2.4, 95% confidence interval [CI] 1.2-5.1). The effect of FLG null-alleles was strongest for eczema (19% versus 7%, P = 0.0003; OR 3.3, 95% CI 1.7-6.6) and food allergy (28% versus 8%, P = 0.0001; OR 4.5, 95% CI 2.0-10.0). The presence of more than 1 atopic disease tended to increase the associated OR: eczema + asthma (23% versus 7%, P = 0.001; OR 3.9, 95% CI 1.6-9.1), eczema + asthma + allergic rhinitis (29% versus 7%, P = 0.0006; OR 5.4, 95% CI 1.9-15.4) and eczema + asthma + allergic rhinitis + food allergy (45% versus 6%, P < 10(-4); OR 12.2, 95% CI 3.2-46.3). Logistic regression analysis of IBD cases confirmed the association of carriage of an FLG null-allele with atopy (P = 0.01; OR 2.4, 95% CI 1.2-5.1) and co-occurrence of different forms of atopy (P = 0.003; OR 3.5, 95% CI 1.5-8.1). CONCLUSIONS: Filaggrin null-alleles have no effect on IBD susceptibility but contribute to coexistent eczema and food allergy.

Anti-Saccharomyces cerevisiae antibodies status is associated with oral involvement and disease severity in Crohn disease.

OBJECTIVES: To determine anti-Saccharomyces cerevisiae antibodies (ASCA) status and its relation to disease phenotype in patients with inflammatory bowel disease (IBD). PATIENTS AND METHODS: A total of 301 Scottish patients with early-onset IBD-197 Crohn disease (CD), 76 ulcerative colitis (UC), 28 indeterminate colitis (IC)-and 78 healthy control individuals were studied. ASCA status (IgA, IgG) was determined by enzyme-linked immunosorbent assay. ASCA status was then analyzed in relation to CD phenotype. RESULTS: Patients with CD had a higher prevalence of ASCA than patients with UC and healthy controls: 82/197 versus 12/76, odds ratio (OR) 3.80 (1.93-7.50) and 82/197 versus 6/78, OR 8.56 (3.55-20.62), respectively. Univariate analysis showed that positive ASCA status was associated with oral CD (17/25 vs 59/153, OR 3.39 [1.38-8.34]), perianal CD (39/77 vs 38/108, OR 1.89 [1.04-3.44]) and the presence of granulomata (63/132 vs 15/52, OR 2.25 [1.13-4.48]) and also with markers of disease severity: raised C-reactive protein (44/90 vs 12/49, OR 2.95[1.36-6.37]), hypoalbuminemia (44/85 vs 20/74, OR 2.28[1.19-4.37]), and surgery (27/49 vs 54/147, OR 2.11 [1.10-4.06]). From multivariate analysis, the presence of oral disease (adjusted P = 0.001, OR 22.22 [3.41-142.86]) and hypoalbuminemia (adjusted P = 0.01, OR 4.78 [1.40-16.39]) was found to be independently associated with ASCA status. No association was demonstrated between ASCA and IBD candidate genes. CONCLUSIONS: Patients with CD had a higher prevalence of ASCA than did other patients with IBD. ASCA status described patients with CD who had a specific phenotype, showing an association with markers of disease severity and oral CD involvement.

Autophagy gene ATG16L1 influences susceptibility and disease location but not childhood-onset in Crohn's disease in Northern Europe.

BACKGROUND: The rs2241880A/G variant of the ATG16L1 gene has been associated with susceptibility to ileal Crohn's disease (CD) in adults. Our aim was to assess whether germline variation of ATG16L1 acts as an independent determinant of susceptibility to childhood-onset CD in the high-incidence Scottish population. METHODS: In all, 2195 subjects (361 children (inflammatory bowel disease [IBD] diagnosis <17 years), their parents (n = 634), 855 adult IBD patients, and 345 controls were genotyped. Case-control analysis was powered to detect effect sizes with an odds ratio (OR) >1.39 in pediatric CD. Case-control analysis, transmission disequilibrium testing (TDT), analysis of variance (ANOVA) of growth parameter z-scores, Kruskal-Wallis test (age at diagnosis), and multifactorial genotype-phenotype analysis (Montreal classification) were performed. 7.8% of pediatric CD patients and 37.2% of adult CD patients had pure ileal disease. RESULTS: We confirmed the association of the rs2241880G-allele with adult-onset CD (60.7% versus controls 53.9%, P = 0.01, OR 1.32, 95% confidence interval [CI] 1.07-1.63) in contrast to childhood-onset CD (54.1% versus controls, P = 0.95, OR 1.01, 95% CI 0.80-1.26). TDT analysis was negative. Genotype-phenotype analysis demonstrated an association of pure ileal disease with the rs2241880G-allele (P = 0.02, OR 1.34, 95% CI 1.03-1.74). Using binary logistic regression analysis we confirmed the effect of rs2241880 genotype (GG) on ileal disease versus colonic disease (P = 0.03, OR 2.43, 95% CI 1.05-5.65). ATG16L1 genotype did not influence age at CD diagnosis. ANOVA of z-scores of height, weight, and body mass index (BMI) at CD diagnosis in children showed no association with genotype. CONCLUSIONS: The ATG16L1 variant is associated with susceptibility to adult CD in Scotland, but not early-onset disease. These contrasting effects are primarily driven by differences in disease location between early-onset and adult-onset disease.

The contribution of the DLG5 113A variant in early-onset inflammatory bowel disease.

OBJECTIVE: To assess the contribution of the 113 G-->A missense mutation within the discs, large homolog 5 (DLG5) gene in childhood-onset inflammatory bowel disease (IBD) in Scotland. STUDY DESIGN: Two-hundred and ninety-six children with IBD were studied. Parental DNA was also collected for transmission disequilibrium testing (TDT) analysis. Genotyping was performed by TaqMan. Genotype-phenotype analysis was also undertaken. Socioeconomic status was assigned using a deprivation category (DepCat) score 1 through 7 (1 = most affluent). RESULTS: TDT analysis demonstrated a significant association with IBD (P = .045). On unifactorial analysis, 113A carriage was associated with: (1) higher social class (DepCat 1 compared with 2-7, and 1-2 compared with 3-7) (66.7% vs 22.6%, P = .0005, OR 6.84 [1.99-23.55] and 37.2% vs 22.2%, P = .03, OR 2.08 [1.04-4.17], respectively); (2) higher height centile (>75th centile vs <75th centile) (42.9% vs 23.1%, P = .01, OR 2.50 [1.18-5.28]); and (3) male sex in Crohn's disease (CD) (29.3% vs 16.9%, P = .04, OR 2.04 [1.01-4.11]). Multifactorial analysis demonstrated that higher social class (DepCat 1) was independently associated with carriage of variants of 113A (P = .001, OR = 6.92 [2.24-21.33]). CONCLUSIONS: DLG5 113A is associated with increased susceptibility to IBD in Scottish children. The effect may be most marked for those children living in relative affluence.

Contribution of the NOD1/CARD4 insertion/deletion polymorphism +32656 to inflammatory bowel disease in Northern Europe.

BACKGROUND: NOD1/CARD4 and NOD2/CARD15 are both intracellular pattern-recognition receptors. The NOD1/CARD4 gene lies within a previously described inflammatory bowel disease (IBD) locus (7p14). An association has been suggested between the NOD1/CARD4+32656 deletion*1 variant of a complex deletion*1/insertion*2 polymorphism and IBD in 1 recent study in Europe. Our aim was to assess the influence of NOD1/CARD4+32656 on disease susceptibility and phenotype in the Scottish and Swedish IBD populations. METHODS: A total of 3,962 individuals (1,791 IBD patients, 522 parents, 1,649 healthy controls) from 2 independent populations (Scotland and Sweden) were genotyped for NOD1/CARD4+32656 A/C by TaqMan and direct sequencing. Case-control, Transmission Disequilibrium Testing (TDT) and detailed genotype-phenotype (Montreal) analyses were performed. The case-control analysis had 80% power to detect an effect size of odds ratio (OR) 1.21 for IBD. RESULTS: In case-control analyses in Scottish and Swedish patients, none of the genotypes studied in IBD, Crohn's disease (CD) or ulcerative colitis (UC), differed significantly from controls (deletion*1 allelic frequency 73.9%, 73.6%, 73.9%, and 73.6%, respectively: all P > 0.8). No epistatic interaction with NOD2/CARD15 was seen for CD susceptibility. TDT analysis in our Scottish early onset cohort was negative. CONCLUSIONS: This variant allele of NOD1/CARD4+32656 is not associated with a strong effect on susceptibility to IBD in children and adults in Northern Europe. A gene-wide haplotype-based approach may be preferable to analysis of individual variants to assess the contribution of the NOD1/CARD4 gene to IBD.

Analysis of the influence of OCTN1/2 variants within the IBD5 locus on disease susceptibility and growth indices in early onset inflammatory bowel disease.

BACKGROUND AND AIMS: The OCTN1 (SLC22A4 1672C-->T) and OCTN2 (SLC22A5 -207G-->C) variants within the IBD5 locus have been associated with susceptibility to adult onset Crohn's disease (CD), but their contribution in children has not been examined. METHODS: These OCTN1/2 variants and IBD5 marker single nucleotide polymorphisms (SNPs) (IGR2096a_1, IGR2198a_1, and IGR2230a_1) were examined in 299 Scottish children (200 with CD, 74 with ulcerative colitis (UC), and 25 with indeterminate colitis (IC)), together with 502 parents (for transmission disequilibrium testing) and 256 controls. RESULTS: All SNPs were in strong linkage disequilibrium (D' >0.94). TDT analysis showed association of the OCTN1 variant with inflammatory bowel disease (IBD) (p = 0.01) and CD (p = 0.04). Allele frequencies of the OCTN1/2 variants were significantly higher in IBD/CD cases (p<0.04). The homozygous mutant OCTN1/2 haplotype was increased in IBD (24.3% v 16.1%, p = 0.02) and UC (28.2% v 16.1%, p = 0.02) compared with controls. The OCTN1/2 variants were not independent of the background IBD5 risk haplotype in conferring disease susceptibility. Unifactorial analysis in CD patients showed that carriage of the TC haplotype was associated with lower weight, height, and BMI centile (<9(th) centile) at diagnosis (weight: 87.9% v 67.3% (p = 0.002), odds ratio (OR) = 3.52 (95% confidence interval, 1.51 to 8.22); height: 84.1% v 68.4% (p<0.05), OR = 2.44 (1.00 to 5.99); BMI: 79.6% v 61.1% (p = 0.02), OR = 2.49 (1.14 to 5.44)), and lower weight centile at follow up (87.5% v 64.6% (p = 0.03), OR = 3.83 (1.03 to 14.24)). Multifactorial binary logistic regression analysis confirmed association of the TC haplotype with lower weight centile at diagnosis (p = 0.02, OR = 3.41 (1.20 to 9.66)). CONCLUSIONS: These data implicate variants within the IBD5 haplotype, as determinants of disease susceptibility and growth indices in early onset IBD. The OCTN1/2 variants remain potential positional candidate genes, but require further analysis.

Pyloric balloon dilation for delayed gastric emptying in children.

Delayed gastric emptying may manifest with symptoms of epigastric pain, early satiety and delayed vomiting, and at times may be associated with failure to thrive. These symptoms and signs may improve following surgical pyloroplasty. To determine whether pyloric balloon dilation (PBD) is an effective therapy for children with these symptoms, hospital records of all children who underwent endoscopic PBD between October 1991 and March 1994 at British Columbia's Children's Hospital were reviewed. Excluded were children with chromosomal abnormalities, neurological disorders and erosive esophagitis. Through-the-scope balloons of diameter 15 or 18 mm were positioned in the pyloric channel and inflated with air to 2334 or 1815 mmHg respectively, for 2 min. Nineteen children with a mean age of 3.75 years (range eight months to 10 years) who presented with symptoms for more than three months (mean 11 months) were identified. Eleven children presented with failure to thrive, 14 with delayed vomiting and 10 with early satiety. Results of gastric emptying tests at 90 min ranged from 8% to 75% (mean 32%). The pylorus was difficult to intubate in 11 of 19 children, and in two the pylorus could not be passed before PBD. No complications were experienced with PBD. Thirteen children had complete resolution of symptoms, and five had transient improvement lasting four to eight weeks after PBD with subsequent complete resolution of symptoms following surgical pyloroplasty. One child continued to have mild symptoms after PBD but did not have further treatment. This study suggests that PBD is a safe and effective therapeutic option in children with symptoms and signs associated with delayed gastric emptying.

Cyclosporine and 6-mercaptopurine for active, refractory Crohn's colitis in children.

OBJECTIVES: This prospective, open trial of treatment was conducted to determine whether cyclosporine A (CSA) is effective in inducing remission in children with severe, active Crohn's colitis refractory to other medical treatment and if remission may be maintained by 6-mercaptopurine (6-MP) and 5-aminosalicylic acid (5-ASA) after discontinuing CSA. METHODS: Ten children (five males, five females), ages 1.2-16 yr (mean 11), all had failed to respond to 4 wk of treatment with i.v. methylprednisolone and total parenteral nutrition/elemental diet; three were already receiving 6-mercaptopurine. CSA was initially given as a twice daily i.v. dosage and was switched to oral CSA when a clinical response was observed. At the same time, corticosteroids were switched to the oral route and tapered over the next 3 months. Patients were grouped by treatment outcome. "Responders" were those who achieved remission with i.v. CSA therapy, "relapsers" were those who achieved remission with i.v. CSA but relapsed later, and nonresponders had not achieved remission after 4 wk of i.v. CSA. Responders were given 6-MP with intent to discontinue CSA after 6 months and maintain remission by 6-MP and 5-ASA. RESULTS: There were seven responders to CSA. For all patients, the Pediatric Crohn's Disease Activity Index (PCDAI) (score range 0-100) had a mean value of 55 (range 40-65) just before treatment; PCDAI improved to a mean of 19 (range 5-42.5) after 2 wk of CSA therapy. Four of the seven responders discontinued CSA after 6 months and remain well on 6-MP and 5ASA alone for 22, 13, 8, and 3 months. One patient had massive GI bleeding (from active Crohn's colitis), which stopped within 48 h of CSA treatment. There were three relapsers (at 2-6 months of CSA), and three were nonresponders. Three patients who were already receiving 6-MP before CSA therapy either did not respond to CSA or relapsed while receiving it. The six nonresponders and relapsers required surgical resection. Transient side effects included hypertension responding to nifedipine in one child and hirsutism and tremors in another. CONCLUSIONS: We conclude that CSA offers a good remission rate for children with severe Crohn's colitis failing other medical treatment, although relapse was common especially if the child was already on 6-MP. In addition, CSA may offer "temporizing" therapy in severe, active Crohn's colitis; this may allow surgery to be performed electively, with time for psychosocial and nutritional preparation before surgery.

Effects of immediate modified feeding on infantile gastroenteritis.

BACKGROUND: Standard treatment of infants who are dehydrated as a result of acute gastroenteritis is to administer oral rehydration therapy (ORT). Traditionally, food has been withdrawn for 24-48 h, but there is no conclusive evidence that this is of any real benefit to the patient. Immediate modified feeding, in which an infant on ORT is not starved but administered a limited diet, may have benefits in the treatment of gastroenteritis, especially in children who are nutritionally compromised before they develop the illness. AIM: A pilot study was carried out to investigate the effects of giving infants suffering from acute gastroenteritis a limited modified diet in conjunction with ORT. METHOD: Infants recruited into the study by their general practitioner or by a research doctor in the hospital casualty unit of Bristol Children's Hospital were randomly allocated to receive ORT with or without immediate modified feeding. The duration of diarrhoea, weight change, and incidence of vomiting and lactose intolerance were measured in both treatment groups, and the results were compared. RESULTS: Of the infants studied, 27 received ORT and immediate modified feeding, and 32 ORT alone. The duration of diarrhoea, and incidence of vomiting or lactose intolerance were no greater in the group receiving immediate modified feeding. Patients who received ORT and immediate modified feeding appeared to gain more weight than the infants who were starved for 24-48 h, but this difference was not statistically significant. CONCLUSION: Immediate modified feeding is safe and effective, and may have nutritional advantages over traditional ORT with starvation. A similar but multicentre study using unmodified diet, i.e. child's normal diet, is being carried out by a working group of The European Society of Paediatrics, Gastroenterology and Nutrition (ESPGAN).