Dried blood spot succinylacetone (SA) is often used as biomarker for newborn screening (NBS) for Tyrosinemia type 1 (TT1). However, false-positive SA results are often observed. Elevated SA may also ...be due to maleylacetoacetate isomerase deficiency (MAAI-D), which appears to be clinically insignificant. This study investigated whether urine organic acid (uOA) and quantitative urine maleic acid (Q-uMA) analyses can distinguish between TT1 and MAAI-D.
We reevaluated/measured uOA (GC-MS) and/or Q-uMA (LC-MS/MS) in available urine samples of 9 referred newborns (2 TT1, 7 false-positive), 8 genetically confirmed MAAI-D children and 66 controls.
Maleic acid was elevated in uOA of 5/7 false-positive newborns and in the 3 available samples of confirmed MAAI-D children, but not in TT1 patients. Q-uMA ranged from not detectable to 1.16 mmol/mol creatinine in controls (n=66), and from 0.95-192.06 mmol/mol creatinine in false-positive newborns and MAAI-D children (n=10). MAAI-D was genetically confirmed in 4/7 false-positive newborns, all with elevated Q-uMA, and rejected in the 2 newborns with normal Q-uMA. No sample was available for genetic analysis of the last false-positive infant with elevated Q-uMA.
MAAI-D is a recognizable cause of false-positive TT1 NBS results. Elevated urine maleic acid excretion seems highly effective in discriminating MAAI-D from TT1. This article is protected by copyright. All rights reserved.
This paper discusses the increasing interest in the territorial dimension of rural development in the Global South. Adapting the local development approach of the 1970s to the changing context of ...globalization and to the competitiveness discourse, mainstream development agencies and scholars currently see territorial development (TD) as an attractive model for the integration of rural regions into globalization dynamics. However, territory serves not only conventional mainstream ideologies, but also post-development thinking. It is shown that territory has turned out to be a crucial element for social movements in the defense of alternative visions of modernity and in the constitution of life worlds outside the conventional development path. The analysis of the meaning development actors give the term territory and the focus on the purposes for which it is mobilized allows a variety of possible development paths for the rural South to be identified, thus going beyond the prevailing modernist vision.
Coral reef degradation resulting from nutrient enrichment of coastal waters is of increasing global concern. Although effects of nutrients on coral reef organisms have been demonstrated in the ...laboratory, there is little direct evidence of nutrient effects on coral reef biota
in situ. The ENCORE experiment investigated responses of coral reef organisms and processes to controlled additions of dissolved inorganic nitrogen (N) and/or phosphorus (P) on an offshore reef (One Tree Island) at the southern end of the Great Barrier Reef, Australia. A multi-disciplinary team assessed a variety of factors focusing on nutrient dynamics and biotic responses. A controlled and replicated experiment was conducted over two years using twelve small patch reefs ponded at low tide by a coral rim. Treatments included three control reefs (no nutrient addition) and three+N reefs (NH
4Cl added), three+P reefs (KH
2PO
4 added), and three+N+P reefs. Nutrients were added as pulses at each low tide (
ca twice per day) by remotely operated units. There were two phases of nutrient additions. During the initial, low-loading phase of the experiment nutrient pulses (mean dose=11.5
μM
NH
4
+
;
2.3
μM
PO
4
−3)
rapidly declined, reaching near-background levels (
mean=0.9
μM
NH
4
+
;
0.5
μM
PO
4
−3
) within 2–3 h. A variety of biotic processes, assessed over a year during this initial nutrient loading phase, were not significantly affected, with the exception of coral reproduction, which was affected in all nutrient treatments. In
Acropora longicyathus and
A. aspera, fewer successfully developed embryos were formed, and in
A. longicyathus fertilization rates and lipid levels decreased. In the second, high-loading, phase of ENCORE an increased nutrient dosage (mean dose=36.2
μM
NH
4
+
;
5.1
μM
PO
4
−3
declining to means of 11.3
μM
NH
4
+
and
2.4
μM
PO
4
−3
at the end of low tide) was used for a further year, and a variety of significant biotic responses occurred. Encrusting algae incorporated virtually none of the added nutrients. Organisms containing endosymbiotic zooxanthellae (corals and giant clams) assimilated dissolved nutrients rapidly and were responsive to added nutrients. Coral mortality, not detected during the initial low-loading phase, became evident with increased nutrient dosage, particularly in
Pocillopora damicornis. Nitrogen additions stunted coral growth, and phosphorus additions had a variable effect. Coral calcification rate and linear extension increased in the presence of added phosphorus but skeletal density was reduced, making corals more susceptible to breakage. Settlement of all coral larvae was reduced in nitrogen treatments, yet settlement of larvae from brooded species was enhanced in phosphorus treatments. Recruitment of stomatopods, benthic crustaceans living in coral rubble, was reduced in nitrogen and nitrogen plus phosphorus treatments. Grazing rates and reproductive effort of various fish species were not affected by the nutrient treatments. Microbial nitrogen transformations in sediments were responsive to nutrient loading with nitrogen fixation significantly increased in phosphorus treatments and denitrification increased in all treatments to which nitrogen had been added. Rates of bioerosion and grazing showed no significant effects of added nutrients.
ENCORE has shown that reef organisms and processes investigated
in situ were impacted by elevated nutrients. Impacts were dependent on dose level, whether nitrogen and/or phosphorus were elevated and were often species-specific. The impacts were generally sub-lethal and subtle and the treated reefs at the end of the experiment were visually similar to control reefs. Rapid nutrient uptake indicates that nutrient concentrations alone are not adequate to assess nutrient condition of reefs. Sensitive and quantifiable biological indicators need to be developed for coral reef ecosystems. The potential bioindicators identified in ENCORE should be tested in future research on coral reef/nutrient interactions. Synergistic and cumulative effects of elevated nutrients and other environmental parameters, comparative studies of intact vs. disturbed reefs, offshore vs. inshore reefs, or the ability of a nutrient-stressed reef to respond to natural disturbances require elucidation. An expanded understanding of coral reef responses to anthropogenic impacts is necessary, particularly regarding the subtle, sub-lethal effects detected in the ENCORE studies.
High-dose chemotherapy (HDC) followed by autologous stem cell rescue (ASCR) is the only curative treatment for metastatic retinoblastoma, but its feasibility in developing countries is unknown. We ...report 11 consecutive children (six unilateral) treated in three South-American middle-income countries with HDC-ASCR. One patient had metastatic retinoblastoma at diagnosis and the remaining ones had a metastatic relapse. Metastatic sites included BM=6, bone=4, orbit=5 and central nervous system (CNS)=4. All patients received induction with conventional chemotherapy achieving CR at a median of 5.7 months from the diagnosis of metastasis. Conditioning regimens included carboplatin and etoposide with thiotepa in six or with CY in four or melphalan in one patient. All patients engrafted after G-CSF-mobilized peripheral blood ASCR and no toxic deaths occurred. Two children received post-ASCR CNS radiotherapy. Seven children have disease-free survival (median follow-up 39 months). CNS relapse, isolated (n=3) or with systemic relapse (n=1), occurring at a median of 7 months after ASCT was the most common event. In the same period, five children with metastatic retinoblastoma did not qualify for HDC-ASCR and died. We conclude that HDC-ASCR is a feasible and effective treatment for children with metastatic retinoblastoma in middle-income countries.
We report the results of an experimental study of the gas holdup,
ε
G
, and volumetric mass transfer coefficient,
k
L
a
, in a bubble column slurry reactor of 0.1
m diameter operated at ambient ...temperature and pressure conditions. The superficial gas velocity
U
was varied in the range 0–0.4
m/s, spanning both the homogeneous and churn-turbulent flow regimes. Air was used as the gas phase. The liquid phase used was C
9–C
11 paraffin oil containing varying volume fractions (
ε
S
=
0
, 0.05, 0.10, 0.15, 0.20 and 0.25) of porous catalyst (alumina catalyst support,
10
%
<
10
μ
m
;
50
%
<
16
μ
m
;
90
%
<
39
μ
m
). With increasing slurry concentrations,
ε
G
is significantly reduced due to enhanced bubble coalescence. For superficial gas velocities
U
>
0.10
m
/
s
the volumetric mass transfer coefficient per unit volume,
k
L
a
/
ε
G
, was found to be practically independent of
U
and has values in the range 0.36–
0.55
s
-
1
. From estimations of the sizes of the bubble size from literature correlation it is found that the “large” bubble mass transfer coefficient is about one order of magnitude higher than predicted by literature correlations.
Focal segmental glomerulosclerosis (FSGS) is a common cause of end-stage renal disease. Albuminuria is a risk factor for FSGS and is influenced by environmental, genetic, and sex-specific factors. ...Podocytes play a central role in the development of albuminuria, but the precise relationship between early glomerular and podocyte-associated damage and albuminuria is unclear. Furthermore, experimental findings demonstrate a sex difference in development of albuminuria and FSGS. We investigated the early glomerular changes in male Munich-Wistar-Frömter (MWF) rats, which spontaneously develop albuminuria, and male albuminuria-resistant spontaneously hypertensive rats (SHR). In addition, since female MWF rats are protected from overt proteinuria and progressive renal disease, we compared the phenotypic changes in podocytes during early development of albuminuria in male and female MWF rats. In male MWF rats, glomerular hypertrophy preceded the onset of albuminuria and was greater than in male SHR. Albuminuria developed starting at 6 wk of age and coincided with focal and segmental loss of podoplanin, increased expression of desmin, entrapment of albumin in affected podocytes, and focal and segmental foot process effacement at the ultrastructural level. Other podocyte-associated molecules, such as nephrin and zonula occludens 1, were unaffected. Early glomerular hypertrophy and podocyte damage did not differ between male and female MWF rats. Our data show for the first time that albuminuria in male and female MWF rats is preceded by glomerular hypertrophy and accompanied by focal and segmental loss of podoplanin when FSGS was not yet present.
The short-term effects of pulses of nutrients and jellyfishCatostylus mosaicuson planktonic assemblages were investigated in field-based experiments using 3 m³ mesocosms. Experiments ran for 5 d and ...were repeated in autumn and spring at Lake Illawarra, a coastal lagoon in New South Wales, Australia. Experiments consisted of 2 orthogonal treatments, addition/non-addition of nutrients and presence/absence of jellyfish, and were designed to determine how bottom-up (i.e. addition of nutrients) and top-down (i.e. predation by jellyfish) processes influence planktonic assemblages, both independently and in combination. During both experiments, nutrients stimulated primary production and caused changes in phytoplankton assemblages. Nutrients also stimulated production of large tintinnids, suggesting that bottom-up processes may influence 2 trophic levels. Mesozooplankton were consistently depleted in mesocosms containing jellyfish. Jellyfish also caused changes in microzooplankton assemblages, indicating that top-down processes also cascade to at least 2 trophic levels. In mesocosms to which both nutrients and jellyfish were added during spring, concentrations of the red-tide forming, heterotrophic dinoflagellateNoctiluca scintillanswere 20 times greater than in mesocosms to which nutrients were added alone. We hypothesize that addition of nutrients stimulated production of centric diatoms, the main prey ofN. scintillans, but that a bloom ofN. scintillansonly formed when jellyfish were also present because jellyfish grazed on populations of herbivorous mesozooplankton (particularly the calanoid copepod Gladioferens), which generally out-competedN. scintillansfor diatom prey. These data provide the first empirical evidence linking jellyfish to the formation of red tides.
The Cre/loxPsite-specific recombination system combined with embryonic stem cell-mediated technologies has greatly expanded our capability to address normal and disease development in mammals using ...genetic approaches. The success of this emerging technology hinges on the production of Cre-expressing transgenic lines that provide cell type-, tissue-, or developmental stage-specific recombination betweenloxPsites placed in the genome. Here we describe and characterize the production of a double-reporter mouse line that provides a convenient and reliable readout of Cre recombinase activity. Throughout all embryonic and adult stages, the transgenic animal expresses thelacZreporter gene before Cre-mediated excision occurs. Cre excision, however, removes thelacZgene, allowing expression of the second reporter, the human alkaline phosphatase gene. This double-reporter transgenic line is able to indicate the occurrence of Cre excision in an extremely widespread manner from early embryonic to adult lineages. It will be a valuable reagent for the increasing number of investigators taking advantage of the powerful tools provided by the Cre/loxPsite-specific recombinase system.
•Benchmarking of standalone and coupled STH/CFD codes.•Experimental data from LBE (lead-bismuth eutectic) thermal-hydraulic loop.•Lessons learned from SESAME international benchmark exercise.
Design ...and safety analysis of the currently developed pool type liquid metal cooled fast nuclear reactors is currently impaired by limited operational experience for such systems and insufficient confidence in the predictive capabilities of the applied modelling. Understanding of pool-reactor thermal-hydraulics is crucial for assessment of reactor performance and passive safety systems reliability. Credibility of the analysis tools can be established in the process of code validation, which includes open and blind benchmarks against integral experiments.
TALL-3D is a lead-bismuth eutectic (LBE) loop built to provide experimental data for validation of standalone and coupled system thermal-hydraulics (STH) and computational fluid dynamics (CFD) codes. This paper summarizes the results of the open and blind benchmark exercise, performed using experimental data on natural circulation instability in liquid metal flows from the TALL-3D facility.
An approach for selection of experimental data for benchmark and tests for model input calibration is presented. A list of parameters, initial and boundary conditions are defined based on modelling limitations and sources of experimental uncertainty. A set of requirements and assessment criteria for the blind calculations were specified. Results of simulations are compared to experimental data. Implications of the benchmark test results for the codes validity and lessons learned are reported.
The rhizostome jellyfishes,
Catostylus mosaicus and
Phyllorhiza punctata abound in estuaries in New South Wales, Australia.
P. punctata contains symbiotic zooxanthellae but
C. mosaicus contains few ...or no zooxanthellae. Our experiment measured the rates at which NH
3, PO
4 and NO
x
were taken up or excreted by each species and in two controls: a “water only” control and a “mucus” control. Rates of uptake or excretion were measured as changes in the nutrient concentration of the water in the containers housing the animals over periods of 6 h. Experiments were repeated twice during the day and twice at night, under both ambient and enriched nutrient conditions. Under ambient nutrient conditions, the flux of NH
3 in the
P. punctata treatment did not differ from the controls but under enriched conditions
P. punctata excreted NH
3 during the night (49 μg kg
−1 WW (wet weight) h
−1) and took up NH
3 during the day (123 μg kg
−1 WW h
−1). In contrast,
C. mosaicus excreted NH
3 at a rate of 1555 μg kg
−1 WW h
−1 during the day and 1004 μg kg
−1 WW h
−1 during the night under both enriched and ambient nutrient conditions.
P. punctata neither took up nor excreted PO
4 but
C. mosaicus excreted PO
4 at a faster rate during the day than night (173 μg kg
−1 WW h
−1 cf. 104 μg kg
−1 WW h
−1). Both
C. mosaicus and
P. punctata excreted NO
x
and, although the rate of excretion for
P. punctata varied between the two experiments conducted during the day, the rate of excretion was consistently greater than for
C. mosaicus (52 and 80 μg kg
−1 WW h
−1 cf. 26 μg kg
−1 WW h
−1)
. Tubs containing
P. punctata had a much greater concentration of dissolved oxygen at the end of the experiments conducted during the day (152% saturation) than night (60% saturation) but tubs containing
C. mosaicus had a greater dissolved oxygen concentration during the night (47% saturation) than day (39%). Overall,
C. mosaicus appears to recycle more inorganic nutrients to estuaries than
P. punctata. Calculations of the importance of inorganic nitrogen excreted by this species during times of peak biomass in Lake Illawarra suggest that it can meet about 8% of the phytoplankton primary production requirements of N and that its inorganic N excretion rate is about 11% of measured inorganic ammonia fluxes from sediments in that system. Since the biomass of
C. mosaicus often exceeds several thousand tonnes, the contribution of inorganic nutrients by this species is substantial.
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