Perinatal nutrition and gastrointestinal disorders : Working Group Report of the Second World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition

Metabolic programming during the perinatal period as a consequence of early nutrition is an emerging area of great interest. This concept is known as the "fetal origins of adult disease" theory (1). Numerous epidemiological studies published over the past 20 years or so have suggested that small body size at birth and during infancy and, more specifically, intrauterine growth retardation are associated later in life with lowered cognitive performance and increased rates of coronary heart disease and its major biological risk factors, ie, raised blood pressure, insulin resistance, coronary artery disease, and abnormalities in lipid metabolism. The molecular mechanisms that govern this phenomenon in humans, however, are unknown and need to be elucidated.

A Sketch of the Phonology and Grammar of Rajbanshi

This dissertation is a synchronic description of the phonology and grammar of two dialects of the Rajbanshi language (Eastern Indo-Aryan) as spoken in Jhapa, Nepal. I have primarily confined the analysis to the oral expression, since the emerging literary form is still in its infancy. The grammatical analysis is therefore based, for the most part, on a corpus of oral narrative text which was recorded and transcribed from three informants from north-east Jhapa. An informant, speaking a dialect from south-west Jhapa cross checked this text corpus and provided additional elicited material. I have described the phonology, morphology and syntax of the language, and also one aspect of its discourse structure. For the most part the phonology follows the basic Indo-Aryan pattern. Derivational morphology, compounding, reduplication, echo formation and onomatopoeic constructions are considered, as well as number, noun classes (their assignment and grammatical function), pronouns, and case and postpositions. In verbal morphology I cover causative stems, the copula, primary and secondary agreement, tense, aspect, mood, auxiliary constructions and non-finite forms. The term secondary agreement here refers to genitive agreement, dative-subject agreement and patient (and sometimes patient-agent) agreement. The breaking of default agreement rules has a range of pragmatic inferences. I argue that a distinction, based on formal, semantic and statistical grounds, should be made between conjunct verbs, derivational compound verbs and quasi-aspectual compound verbs. Rajbanshi has an open set of adjectives, and it additionally makes use of a restricted set of nouns which can function as adjectives. Various particles, and the emphatic and conjunctive clitics are also considered. The syntactic structures studied include: non-declarative speech acts, phrase-internal and clause-internal constituent order, negation, subordination, coordination and valence adjustment. I explain how the future, present and past tenses in Rajbanshi oral narratives do not seem to maintain a time reference, but rather to indicate a distinction between background and foreground information. I call this tense neutralisation .

Relocation of Intensive Agriculture to Northern Australia: The Case of the Rice Industry

Development of new agricultural industries in northern Australia is seen as a way to provide food security in the face of reduced water availability in existing regions in the south. This report aims to identify some of the possible economic consequences of developing a rice industry in the Burdekin region, while there is a reduction of output in the Riverina. Annual rice production in the Riverina peaked at 1.7 M tonnes, but the long-term outlook, given climate change impacts on that region and government water buy-backs, is more likely to be less than 800,000 tonnes. Growers are highly efficient water users by international standards, but the ability to offset an anticipated reduction in water availability through further efficiency gains is limited. In recent years growers in the Riverina have diversified their farms to a greater extent and secondary production systems include beef, sheep and wheat. Production in north Queensland is in its infancy, but a potentially suitable farming system has been developed by including rice within the sugarcane system without competition and in fact contributing to the production of sugar by increasing yields and controlling weeds. The economic outcomes are estimated a large scale, dynamic, computable general equilibrium (CGE) model of the world economy (Tasman Global), scaled down to regional level. CGE models mimic the workings of the economy through a system of interdependent behavioural and accounting equations which are linked to an input-output database. When an economic shock or change is applied to a model, each of the markets adjusts according to the set of behavioural parameters which are underpinned by economic theory. In this study the model is driven by reducing production in the Riverina in accordance with relationships found between water availability and the production of rice and replacement by other crops and by increasing ride production in the Burdekin. Three scenarios were considered: • Scenario 1: Rice is grown using the fallow period between the last ratoon crop of sugarcane and the new planting. In this scenario there is no competition between rice and sugarcane • Scenario 2: Rice displaces sugarcane production • Scenario 3: Rice is grown on additional land and does not compete with sugarcane. Two time periods were used, 2030 and 2070, which are the conventional time points to consider climate change impacts. Under scenario 1, real economic output declines in the Riverina by $45 million in 2030 and by $139 million in 2070. This is only partially offset by the increased real economic output in the Burdekin of $35 million and $131 million respectively.

Molecular Characterization of Fibrotic Scarring in Kidneys with Congenital Nephrotic Syndrome of the Finnish type

Congenital nephrotic syndrome of the Finnish type (NPHS1, CNF) is an autosomal recessive disease, enriched in the Finnish population. NPHS1 is caused by a mutation in the NPHS1 gene. This gene encodes for nephrin, which is a major structural component of the slit diaphragm connecting podocyte foot processes in the glomerular capillary wall. In NPHS1, the genetic defect in nephrin leads to heavy proteinuria already in the newborn period. Finnish NPHS1 patients are nephrectomized at infancy, and after a short period of dialysis the patients receive a kidney transplant, which is the only curative therapy for the disease. In this thesis, we examined the cellular and molecular mechanisms leading to the progression of glomerulosclerosis and tubulointerstitial fibrosis in NPHS1 kidneys. Progressive mesangial expansion in NPHS1 kidneys is caused by mesangial cell hyperplasia and the accumulation of extracellular matrix proteins. Expansion of the extracellular matrix was caused by the normal mesangial cell component, collagen IV. However, no significant changes in mesangial cell phenotype or extracellular matrix component composition were observed. Endotheliosis was the main ultrastructural lesion observed in the endothelium of NPHS1 glomeruli. The abundant expression of vascular endothelial growth factor and its transcription factor hypoxia inducible factor-1 alpha were in accordance with the preserved structure of the endothelium in NPHS1 kidneys. Hypoperfusion of peritubular capillaries and tubulointerstitial hypoxia were evident in NPHS1 kidneys, indicating that these may play an important role in the rapid progression of fibrosis in the kidneys of NPHS1 patients. Upregulation of Angiotensin II was obvious, emphasizing its role in the pathophysiology of NPHS1. Excessive oxidative stress was evident in NPHS1 kidneys, manifested as an increase expression of p22phox, superoxide production, lipid oxide peroxidation and reduced antioxidant activity. In conclusion, our data indicate that mesangial cell proliferation and the accumulation of extracellular matrix accumulation are associated with the obliteration of glomerular capillaries, causing the reduction of circulation in peritubular capillaries. The injury and rarefaction of peritubular capillaries result in impairment of oxygen and nutrient delivery to the tubuli and interstitial cells, which correlates with the fibrosis, tubular atrophy and oxidative stress observed in NPHS1 kidneys.

Pathophysiology of Congenital Nephrotic Syndrome of the Finnish type

Congenital nephrotic syndrome of the Finnish type (NPHS1) is an autosomal recessive disease which is highly enriched in the Finnish population. It is caused by mutations in the NPHS1 gene encoding for nephrin, which is a major component of the glomerular filtration barrier in the kidney. Patients with NPHS1 have heavy proteinuria and nephrotic syndrome (NS) from birth and develop renal fibrosis in early childhood. Renal transplantation (TX) is the only curative treatment for NPHS1. These patients form the largest group of pediatric kidney transplant children in our country. The NPHS1 kidneys are removed in infancy and they serve as an excellent human material for studies of the pathophysiology of proteinuric kidney diseases. Sustained proteinuria is a major factor leading to end-stage renal failure and understanding this process is crucial for nephrology. In this study we investigated the glomerular and tubulointerstitial changes that occur in the NPHS1 kidneys during infancy as well as the expression of nephrin in non-renal tissues. We also studied the pathology and management of recurrent proteinuria in kidney grafts transplanted to NPHS1 children. Severe renal lesions evolved in patients with NPHS1 during the first months of life. Glomerular sclerosis developed through progressive mesangial sclerosis, and capillary obliteration was an early consequence of this process. Shrinkage of the glomerular tuft was common, whereas occlusion of tubular opening or protrusion of the glomerular tuft into subepithelial space or through the Bowman's capsule were not detected. Few inflammatory cells were detected in the mesangial area. The glomerular epithelial cells (podocytes) showed severe ultrastructural changes and hypertrophy. Podocyte proliferation and apoptosis were rare, but moderate amounts of podocytes were detached and ended up in the urine. The results showed that endocapillary lesions not extracapillary lesions, as generally believed were important for the sclerotic process in the NPHS1 glomeruli. In the tubulointerstitium, severe lesions developed in NPHS1 kidneys during infancy. Despite heavy proteinuria, tubular epithelial cells (TECs) did not show transition into myofibroblasts. The most abundant chemokines in NPHS1 tissue were neutrophil activating protein-2 (NAP-2), macrophage inhibiting factor (MIF), and monocyte chemoattractant protein-1 (MCP-1). Interstitial inflammation and fibrosis were first detected in the paraglomerular areas and the most abundant inflammatory cells were monocytes/macrophages. Arteries and arterioles showed intimal hypertrophy, but the pericapillary microvasculature remained quite normal. However, excessive oxidative stress was evident in NPHS1 kidneys. The results indicated that TECs were relatively resistant to the heavy tubular protein load. Nephrin was at first thought to be podocyte specific, but some studies especially in experimental animals have suggested that nephrin might also be expressed in non-renal tissues such as pancreas and central nervous system. The knowledge of nephrin biology is important for the evaluation of nephrin related diseases. In our study, no significant amounts of nephrin protein or mRNA were detected in non-renal tissues of man and pig as studied by immunohistochemistry and in situ hybridization. The phenotype analysis of NPHS1 children, who totally lack nephrin, revealed no marked impairment in the neurological, testicular, or pancreatic function speaking against the idea that nephrin would play an important functional role outside the kidney. The NPHS1 kidneys do not express nephrin and antibodies against this major glomerular filter protein have been observed in NPHS1 children after renal TX most likely as an immune reaction against a novel antigen. These antibodies have been associated with the development of recurrent NS in the kidney graft of NPHS1 patients. In our study, a third of the NPHS1 patients homozygous for Fin-Major mutation developed recurrent NS in the transplanted graft. Re-transplantations were performed to patients who lost their graft due to recurrent NS and heavy proteinuria immediately developed in all cases. While 73% of the patients had detectable serum anti-nephrin antibodies, the kidney biopsy findings were minimal. Introduction of plasma exchange (PE) to the treatment of recurrent nephroses increased the remission rate from 54% to 89%. If remission was achieved, recurrent NS did not significantly deteriorate the long term graft function. In conclusion, the results show that the lack of nephrin in podocyte slit diaphragm in NPHS1 kidneys induces progressive mesangial expansion and glomerular capillary obliteration and inflicts interstitial fibrosis, inflammation, and oxidative stress with surprisingly little involvement of the TECs in this process. Nephrin appears to have no clinical significance outside the kidney. Development of antibodies against nephrin seems to be a major cause of recurrent NS in kidney grafts of NPHS1 patients and combined use of PE and cyclophosphamide markedly improved remission rates.

From drawing board to dining table: the success story of the GIFT project

As compared to crops and livestock, the genetic enhancement of fish is in its infancy. While significant progress has been achieved in the genetic improvement of temperate fish such as salmonids, no efforts were made until the late 1980s for the genetic improvement of tropical finfish, which account for about 90 percent of global aquaculture production. This paper traces the history of the Genetic Improvement of Farmed Tilapia (GIFT) project initiated in 1988 by the WorldFish Center and its partners for the development of methods for genetic enhancement of tropical finfish using Nile tilapia (Oreochromis niloticus) as a test species. It also describes the impacts of the project on the adoption of these methods for other species and the dissemination of improved breeds in several countries in Asia and the Pacific.

An ethnographic interpretation of the work environment within a creative culture in the advertising sector.

Purpose and rationale The purpose of the exploratory research is to provide a deeper understanding of how the work environment enhances or constrains organisational creativity (creativity and innovation) within the context of the advertising sector. The argument for the proposed research is that the contemporary literature is dominated by quantitative research instruments to measure the climate and work environment across many different sectors. The most influential theory within the extant literature is the componential theory of organisational creativity and innovation and is used as an analytical guide (Amabile, 1997; Figure 8) to conduct an ethnographic study within a creative advertising agency based in Scotland. The theory suggests that creative people (skills, expertise and task motivation) are influenced by the work environment in which they operate. This includes challenging work (+), work group supports (+), supervisory encouragement (+), freedom (+), sufficient resources (+), workload pressures (+ or -), organisational encouragement (+) and organisational impediments (-) which is argued enhances (+) or constrains (-) both creativity and innovation. An interpretive research design is conducted to confirm, challenge or extend the componential theory of organisational creativity and innovation (Amabile, 1997; Figure 8) and contribute to knowledge as well as practice. Design/methodology/approach The scholarly activity conducted within the context of the creative industries and advertising sector is in its infancy and research from the alternative paradigm using qualitative methods is limited which may provide new guidelines for this industry sector. As such, an ethnographic case study research design is a suitable methodology to provide a deeper understanding of the subject area and is consistent with a constructivist ontology and an interpretive epistemology. This ontological position is conducive to the researcher’s axiology and values in that meaning is not discovered as an objective truth but socially constructed from multiple realties from social actors. As such, ethnography is the study of people in naturally occurring settings and the creative advertising agency involved in the research is an appropriate purposive sample within an industry that is renowned for its creativity and innovation. Qualitative methods such as participant observation (field notes, meetings, rituals, social events and tracking a client brief), material artefacts (documents, websites, annual reports, emails, scrapbooks and photographic evidence) and focused interviews (informal and formal conversations, six taped and transcribed interviews and use of Survey Monkey) are used to provide a written account of the agency’s work environment. The analytical process of interpreting the ethnographic text is supported by thematic analysis (selective, axial and open coding) through the use of manual analysis and NVivo9 software Findings The findings highlight a complex interaction between the people within the agency and the enhancers and constraints of the work environment in which they operate. This involves the creative work environment (Amabile, 1997; Figure 8) as well as the physical work environment (Cain, 2012; Dul and Ceylan, 2011; Dul et al. 2011) and that of social control and power (Foucault, 1977; Gahan et al. 2007; Knights and Willmott, 2007). As such, the overarching themes to emerge from the data on how the work environment enhances or constrains organisational creativity include creative people (skills, expertise and task motivation), creative process (creative work environment and physical work environment) and creative power (working hours, value of creativity, self-fulfilment and surveillance). Therefore, the findings confirm that creative people interact and are influenced by aspects of the creative work environment outlined by Amabile (1997; Figure 8). However, the results also challenge and extend the theory to include that of the physical work environment and creative power. Originality/value/implications Methodologically, there is no other interpretive research that uses an ethnographic case study approach within the context of the advertising sector to explore and provide a deeper understanding of the subject area. As such, the contribution to knowledge in the form of a new interpretive framework (Figure 16) challenges and extends the existing body of knowledge (Amabile, 1997; Figure 8). Moreover, the contribution to practice includes a flexible set of industry guidelines (Appendix 13) that may be transferrable to other organisational settings.

The geography of Celtic personal names in the Latin inscriptions of the Roman Empire

Raybould, Marilynne, and Sims-Williams, Patrick, The geography of Celtic personal names in the Latin inscriptions of the Roman Empire (Aberystwyth: CMCS publications, 2007) RAE2008

The upstream enhancer elements of the G6PC promoter are critical for optimal G6PC expression in murine glycogen storage disease type Ia.

Glycogen storage disease type-Ia (GSD-Ia) patients deficient in glucose-6-phosphatase-α (G6Pase-α or G6PC) manifest impaired glucose homeostasis characterized by fasting hypoglycemia, growth retardation, hepatomegaly, nephromegaly, hyperlipidemia, hyperuricemia, and lactic acidemia. Two efficacious recombinant adeno-associated virus pseudotype 2/8 (rAAV8) vectors expressing human G6Pase-α have been independently developed. One is a single-stranded vector containing a 2864-bp of the G6PC promoter/enhancer (rAAV8-GPE) and the other is a double-stranded vector containing a shorter 382-bp minimal G6PC promoter/enhancer (rAAV8-miGPE). To identify the best construct, a direct comparison of the rAAV8-GPE and the rAAV8-miGPE vectors was initiated to determine the best vector to take forward into clinical trials. We show that the rAAV8-GPE vector directed significantly higher levels of hepatic G6Pase-α expression, achieved greater reduction in hepatic glycogen accumulation, and led to a better toleration of fasting in GSD-Ia mice than the rAAV8-miGPE vector. Our results indicated that additional control elements in the rAAV8-GPE vector outweigh the gains from the double-stranded rAAV8-miGPE transduction efficiency, and that the rAAV8-GPE vector is the current choice for clinical translation in human GSD-Ia.

Language experience shapes the development of the mutual exclusivity bias

Halberda (2003) demonstrated that 17-month-old infants, but not 14- or 16-month-olds, use a strategy known as mutual exclusivity (ME) to identify the meanings of new words. When 17-month-olds were presented with a novel word in an intermodal preferential looking task, they preferentially fixated a novel object over an object for which they already had a name. We explored whether the development of this word-learning strategy is driven by children's experience of hearing only one name for each referent in their environment by comparing the behavior of infants from monolingual and bilingual homes. Monolingual infants aged 17–22 months showed clear evidence of using an ME strategy, in that they preferentially fixated the novel object when they were asked to "look at the dax." Bilingual infants of the same age and vocabulary size failed to show a similar pattern of behavior. We suggest that children who are raised with more than one language fail to develop an ME strategy in parallel with monolingual infants because development of the bias is a consequence of the monolingual child's everyday experiences with words.

Psychometric properties of the parent-infant caregiving touch scale

Recent work in animals suggests that the extent of early tactile stimulation by parents of offspring is an important element in early caregiving. We evaluate the psychometric properties of a new parent-report measure designed to assess frequency of tactile stimulation across multiple caregiving domains in infancy. We describe the full item set of the Parent-Infant Caregiving Touch Scale (PICTS) and, using data from a UK longitudinal Child Health and Development Study, the response frequencies and factor structure and whether it was invariant over two time points in early development (5 and 9 weeks). When their infant was 9 weeks old, 838 mothers responded on the PICTS while a stratified subsample of 268 mothers completed PICTS at an earlier 5 week old assessment (229 responded on both occasions). Three PICTS factors were identified reflecting stroking, holding and affective communication. These were moderately to strongly correlated at each of the two time points of interest and were unrelated to, and therefore distinct from, a traditional measure of maternal sensitivity at 7-months. A wholly stable psychometry over 5 and 9-week assessments was not identified which suggests that behavior profiles differ slightly for younger and older infants. Tests of measurement invariance demonstrated that all three factors are characterized by full configural and metric invariance, as well as a moderate degree of evidence of scalar invariance for the stroking factor. We propose the PICTS as a valuable new measure of important aspects of caregiving in infancy.

Participation of the liver gluconeogenesis in the glibenclamide-induced hypoglycaemia in rats

We previously demonstrated an increased liver gluconeogenesis (LG) during insulin-induced hypoglycaemia. Thus, an expected effect of sulphonylureas induced hypoglycaemia (SIH) could be the activation of LG. However, sulphonylureas infused directly in to the liver inhibits LG. Considering these opposite effects we investigated herein LG in rats submitted to SIH. For this purpose, 24 h fasted rats that received glibenclamide (10 mg kg(-1)) were used (SIH group). Control group received oral saline. Glycaemia at 30, 60, 90, 120 and 150 min after oral administration of glibenclamide were evaluated. Since the lowest glycaemia was obtained 120 min after glibenclamide administration, this time was chosen to investigate LG in situ perfused livers. The gluconeogenesis from precursors that enters in this metabolic pathway before the mitochondrial step, i.e. L-alanine (5 mM), L-lactate (2 mM), pyruvate (5 mM) and L-glutamine were decreased (p < 0.05). However, the gluconeogenic activity using glycerol (2 mM), which enters in the gluconeogenesis after the mitochondrial step was maintained. Taken together, the results suggest that the inhibition of LG promoted by SIH overcome the activation of this metabolic pathway promoted by IIH and could be attributed, at least in part, to its effect on mitochondrial function. Copyright (C) 2011 John Wiley & Sons, Ltd.

The kidney in different stages of the cardiovascular continuum

Patients with chronic kidney disease are at higher risk of developing cardiovascular disease. The complex, interaction between the kidney and the cardiovascular system is incompletely understood, particularly at the early stages of the cardiovascular continuum. The overall aim of this thesis was to clarify novel aspects of the interplay between the kidney and the cardiovascular system at different stages of the cardiovascular continuum; from risk factors such as insulin resistance, inflammation and oxidative stress, via sub-clinical cardiovascular damage such as endothelial dysfunction and left ventricular dysfunction, to overt cardiovascular death. This thesis is based on two community-based cohorts of elderly, Uppsala Longitudinal Study of Adult Men (ULSAM) and Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS). The first study, show that higher insulin sensitivity, measured with euglycemic-hyperinsulinemic clamp technique was associated to improve estimated glomerular filtration rate (eGFR) in participants with normal fasting plasma glucose, normal glucose tolerance and normal eGFR. In longitudinal analyses, higher insulin sensitivity at baseline was associated with lower risk of impaired renal function during follow-up. In the second study, eGFR was inversely associated with different inflammatory markers (C-reactive protein, interleukin-6, serum amyloid A) and positively associated with a marker of oxidative stress (urinary F2-isoprostanes). In line with this, the urinary albumin/creatinine ratio was positively associated with these inflammatory markers, and negatively associated with oxidative stress. In study three, higher eGFR was associated with better endothelial function as assessed by the invasive forearm model. Further, in study four, higher eGFR was significantly associated with higher left ventricular systolic function (ejection fraction). The 5th study of the thesis shows that higher urinary albumin excretion rate (UAER) and lower eGFR was independently associated with an increased risk for cardiovascular mortality. Analyses of global model fit, discrimination, calibration, and reclassification suggest that UAER and eGFR add relevant prognostic information beyond established cardiovascular risk factors in participants without prevalent cardiovascular disease. Conclusion: this thesis show that the interaction between the kidney and the cardiovascular system plays an important role in the development of cardiovascular disease and that this interplay begins at an early asymptomatic stage of the disease process.

Hypoactivity of the central dopaminergic system and autistic-like behavior induced by a single early prenatal exposure to lipopolysaccharide

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Pharmacology of the glucagon-like peptide-1 analog exenatide extended-release in healthy cats

Exenatide extended-release (ER) is a microencapsulated formulation of the glucagon-like peptide 1-receptor agonist exenatide: It has a protracted pharmacokinetic profile that allows a once-weekly injection with comparable efficacy to insulin with an improved safety profile in type II diabetic people. Here, we studied the pharmacology of exenatide ER in 6 healthy cats. A single subcutaneous injection of exenatide ER (0.13 mg/kg) was administered on day 0. Exenatide concentrations were measured for 12 wk. A hyperglycemic clamp (target = 225 mg/dL) was performed on days 7 (clamp I) and 21 (clamp II) with measurements of insulin and glucagon concentrations. Glucose tolerance was defined as the amount of glucose required to maintain hyperglycemia during the clamp. Continuous glucose monitoring was performed on weeks 0, 2, and 6 after injection. Plasma concentrations of exenatide peaked at 1 h and 4 wk after injection. Comparing clamp I with clamp II, fasting blood glucose decreased (mean standard deviation = 11 8 mg/dL, P = 0.02), glucose tolerance improved (median [range] +33% 14%-138%], P = 0.04), insulin concentrations increased (+36.5% [-9.9% to 274.1%], P = 0.02), and glucagon concentrations decreased (-4.7% [0%-12.1%], P = 0.005). Compared with preinjection values on continuous glucose monitoring, glucose concentrations decreased and the frequency of readings <50 mg/dL increased at 2 and 6 wk after injection of exenatide ER. This did not correspond to clinical hypoglycemia. No other side effects were observed throughout the study. Exenatide ER was safe and effective in improving glucose tolerance 3 wk after a single injection. Further evaluation is needed to determine its safety, efficacy, and duration of action in diabetic cats. (C) 2015 Elsevier Inc. All rights reserved.