Nonpharmacologic Treatments for Childhood Constipation:Systematic Review

OBJECTIVE: To summarize the evidence and assess the reported quality of studies concerning nonpharmacologic treatments for childhood constipation, including fiber, fluid, physical movement, prebiotics, probiotics, behavioral therapy, multidisciplinary treatment, and forms of alternative medicine. METHODS: We systematically searched 3 major electronic databases and reference lists of existing reviews. We included systematic reviews and randomized controlled trials (RCTs) that reported on nonpharmacologic treatments. Two reviewers rated the methodologic quality independently. RESULTS: We included 9 studies with 640 children. Considerable heterogeneity across studies precluded meta-analysis. We found no RCTs for physical movement, multidisciplinary treatment, or alternative medicine. Some evidence shows that fiber may be more effective than placebo in improving both the frequency and consistency of stools and in reducing abdominal pain. Compared with normal fluid intake, we found no evidence that water intake increases or that hyperosmolar fluid treatment is more effective in increasing stool frequency or decreasing difficulty in passing stools. We found no evidence to recommend the use of prebiotics or probiotics. Behavioral therapy with laxatives is not more effective than laxatives alone. CONCLUSIONS: There is some evidence that fiber supplements are more effective than placebo. No evidence for any effect was found for fluid supplements, prebiotics, probiotics, or behavioral intervention. There is a lack of well-designed RCTs of high quality concerning nonpharmacologic treatments for children with functional constipation. Pediatrics 2011;128:753-76

Value of Abdominal Radiography, Colonic Transit Time, and Rectal Ultrasound Scanning in the Diagnosis of Idiopathic Constipation in Children:A Systematic Review

Objective To perform a systematic review evaluating the value of abdominal radiography, colonic transit time (CTT), and rectal ultrasound scanning in the diagnosis of idiopathic constipation in children. Study design Eligible studies were those assessing diagnostic accuracy of abdominal radiography, CTT, or rectal ultrasound scanning in children suspected for idiopathic constipation. Methodological quality of the included studies was assessed with the Quality Assessment of studies of Diagnostic Accuracy included in Systematic reviews checklist. Results One systematic review summarized 6 studies on abdominal radiography until 2004. The additional 9 studies evaluated abdominal radiography (n = 2), CTT (n = 3), and ultrasound scanning (n = 4). All studies except two used a case-control study design, which will lead to overestimation of test accuracy. Furthermore, none of the studies interpreted the results of the abdominal radiography, ultrasound scanning, or CTT without knowledge of the clinical diagnosis of constipation. The sensitivity of abdominal radiography, as studied in 6 studies, ranged from 80% (95% CI, 65-90) to 60%(95% CI, 46-72), and its specificity ranged from 99%(95% CI, 95-100) to 43%(95% CI, 18-71). Only one study presented test characteristics of CTT, and two studies presented test characteristics of ultrasonography. Conclusion We found insufficient evidence for a diagnostic association between clinical symptoms of constipation and fecal loading on abdominal radiographs, CTT, and rectal diameter on ultrasound scanning in children. (J Pediatr 2012; 161: 44-50)

Pulmonary hypertension in extremely preterm infants:a call to standardize echocardiographic screening and follow-up policy

Pulmonary hypertension (PH) is a frequent complication in extremely preterm born infants that seriously affects outcome. We aimed to describe the prevalence of PH in extremely preterm infants and the policy on screening and follow-up in the ten Dutch intensive care units (NICUs). We performed a retrospective cohort study at the University Medical Centre Groningen on infants with gestational age <30 weeks and/or birthweight <1000 g, born between 2012 and 2013. Additionally, we carried out a survey among the Dutch NICUs covering questions on the awareness of PH, the perceived prevalence, and policy regarding screening and following PH in extremely preterm infants. Prevalence of early-onset PH in our study was 26% and 5% for late-onset PH. PH was associated with poor survival and early-onset PH was associated with subsequent development of bronchopulmonary dysplasia (BPD). All the NICUs completed the questionnaire and we found that no standardized policy existed regarding screening and following PH in extremely preterm infants. Conclusion: Despite the frequent occurrence of PH and its clinically important consequences, (inter-)national standardized guidelines regarding screening and following of PH in extremely preterm infants are lacking. Standardizing screening and follow-up will enable early identification of infants with late-onset PH and allow for earlier treatment. Additionally, greater clarity is required regarding the prevalence of early PH as are new preventive treatment strategies to combat BPD. What is known? center dot Pulmonary hypertension (PH) substantially impairs the survival of extremely preterm infants. center dot PH is associated with bronchopulmonary dysplasia (BPD): Early-onset PH predicts the development of BPD. Late-onset PH is prevalent in infants with severe BPD. What is new? center dot Pulmonary hypertension (PH) is prevalent in preterm infants. Its consequences for morbidity and mortality justify a standardized policy aimed at early detection to improve prevention and treatment. center dot No structured policy exists in the Netherlands regarding screening/follow-up for PH in extremely preterm infants

Metastability in the dilute Ising model

Consider Glauber dynamics for the Ising model on the hypercubic lattice with a positive magnetic field. Starting from the minus configuration, the system initially settles into a metastable state with negative magnetization. Slowly the system relaxes to a stable state with positive magnetization. Schonmann and Shlosman showed that in the two dimensional case the relaxation time is a simple function of the energy required to create a critical Wulff droplet. The dilute Ising model is obtained from the regular Ising model by deleting a fraction of the edges of the underlying graph. In this paper we show that even an arbitrarily small dilution can dramatically reduce the relaxation time. This is because of a catalyst effect---rare regions of high dilution speed up the transition from minus phase to plus phase.Comment: 49 page

De novo design of bioactive protein switches.

Allosteric regulation of protein function is widespread in biology, but is challenging for de novo protein design as it requires the explicit design of multiple states with comparable free energies. Here we explore the possibility of designing switchable protein systems de novo, through the modulation of competing inter- and intramolecular interactions. We design a static, five-helix 'cage' with a single interface that can interact either intramolecularly with a terminal 'latch' helix or intermolecularly with a peptide 'key'. Encoded on the latch are functional motifs for binding, degradation or nuclear export that function only when the key displaces the latch from the cage. We describe orthogonal cage-key systems that function in vitro, in yeast and in mammalian cells with up to 40-fold activation of function by key. The ability to design switchable protein functions that are controlled by induced conformational change is a milestone for de novo protein design, and opens up new avenues for synthetic biology and cell engineering

Climate Variability and Oceanographic Settings Associated with Interannual Variability in the Initiation of Dinophysis acuminata Blooms

In 2012, there were exceptional blooms of D. acuminata in early spring in what appeared to be a mesoscale event affecting Western Iberia and the Bay of Biscay. The objective of this work was to identify common climatic patterns to explain the observed anomalies in two important aquaculture sites, the Galician Rías Baixas (NW Spain) and Arcachon Bay (SW France). Here, we examine climate variability through physical-biological couplings, Sea Surface Temperature (SST) anomalies and time of initiation of the upwelling season and its intensity over several decades. In 2012, the mesoscale features common to the two sites were positive anomalies in SST and unusual wind patterns. These led to an atypical predominance of upwelling in winter in the Galician Rías, and increased haline stratification associated with a southward advection of the Gironde plume in Arcachon Bay. Both scenarios promoted an early phytoplankton growth season and increased stability that enhanced D. acuminata growth. Therefore, a common climate anomaly caused exceptional blooms of D. acuminata in two distant regions through different triggering mechanisms. These results increase our capability to predict intense diarrhetic shellfish poisoning outbreaks in the early spring from observations in the preceding winter

An Investigation of Rotorcraft Stability-Phase Margin Requirements in Hover

A cooperative study was performed to investigate the handling quality effects from reduced flight control system stability margins, and the trade-offs with higher disturbance rejection bandwidth (DRB). The piloted simulation study, perform on the NASA-Ames Vertical Motion Simulator, included three classes of rotorcraft in four configurations: a utility-class helicopter; a medium-lift helicopter evaluated with and without an external slung load; and a large (heavy-lift) civil tiltrotor aircraft. This large aircraft also allowed an initial assessment of ADS-33 handling quality requirements for an aircraft of this size. Ten experimental test pilots representing the U.S. Army, Marine Corps, NASA, rotorcraft industry, and the German Aerospace Center (DLR), evaluated the four aircraft configurations, for a range of flight control stability-margins and turbulence levels, while primarily performing the ADS-33 Hover and Lateral Reposition MTEs. Pilot comments and aircraft-task performance data were analyzed. The preliminary stability margin results suggest higher DRB and less phase margin cases are preferred as the aircraft increases in size. Extra care will need to be taken to assess the influence of variability when nominal flight control gains start with reduced margins. Phase margins as low as 20-23 degrees resulted in low disturbance-response damping ratios, objectionable oscillations, PIO tendencies, and a perception of an incipient handling qualities cliff. Pilot comments on the disturbance response of the aircraft correlated well to the DRB guidelines provided in the ADS-33 Test Guide. The A D-3S3 mid-term response-to-control damping ratio metrics can be measured and applied to the disturbance-response damping ratio. An initial assessment of LCTR yaw bandwidth shows the current Level 1 boundary needs to be relaxed to help account for a large pilot off-set from the c.g. Future efforts should continue to investigate the applicability/refinement of the current ADS-33 requirements to large vehicles, like an LCTR

Trapped surfaces and symmetries

We prove that strictly stationary spacetimes cannot contain closed trapped nor marginally trapped surfaces. The result is purely geometric and holds in arbitrary dimension. Other results concerning the interplay between (generalized) symmetries and trapped submanifolds are also presented.Comment: 9 pages, no figures. Final corrected version to appear in Class. Quantum Gra

Children's International Polyposis (CHIP) study : a randomized, double-blind, placebo-controlled study of celecoxib in children with familial adenomatous polyposis

Objective: To evaluate the efficacy and safety of celecoxib versus placebo in the prevention and treatment of colorectal polyposis in children with familial adenomatous polyposis (FAP). Methods: In this Phase III, double-blind, randomized, placebo-controlled, multicenter trial patients aged 10-17 years with FAP were randomized to celecoxib (16 mg/kg/day) or placebo for up to 5 years. Patients underwent annual assessments, including colonoscopies, to detect the time from randomization to the earliest occurrence of >= 20 polyps (> 2 mm in size) or colorectal malignancy. The study was terminated early due to low rate of observed endpoints combined with a lower than expected enrollment rate. Descriptive results are provided. Results: Of 106 randomized patients, 55 were treated with celecoxib (mean age 12.6 years; 52.7% female) and 51 were given placebo (mean age 12.2 years; 54.9% female). Disease progression (>= 20 polyps, > 2 mm in size) was observed in seven (12.7%) and 13 (25.5%) patients, respectively. The median time to disease progression was 2.1 years in the celecoxib group and 1.1 years for placebo. No patient developed colorectal cancer. The rate of adverse events (AEs) was similar in both groups (75.5% and 72.9%, respectively). Three patients in the celecoxib group (none in the placebo group) experienced serious AEs. Conclusion: In children with FAP, celecoxib was a well-tolerated treatment that was associated with a lower rate of colorectal polyposis and a longer time to disease progression compared with placebo. Due to the low rate of observed endpoints, the long-term impact of these results could not be ascertained

Bottom and Suspended Sediment Backscatter Measurements in a Flume—Towards Quantitative Bed and Water Column Properties

For health and impact studies of water systems, monitoring underwater environments is essential, for which multi-frequency single- and multibeam echosounders are commonly used state-of-the-art technologies. However, the current scarcity of sediment reference datasets of both bottom backscatter angular response and water column scattering hampers empirical data interpretation. Comprehensive reference data derived from measurements in a controlled environment should optimize the use of empirical backscatter data. To prepare for such innovative experiments, we conducted a feasibility experiment in the Delta Flume (Deltares, The Netherlands). Several configurations of sonar data were recorded of the flume floor and suspended sediment plumes. The results revealed that flume reverberation was sufficiently low and that the differential settling of fine-sand plumes in the water column was clearly detected. Following this successful feasibility test, future comprehensive experiments will feature multi-frequency multi-angle measurements on a variety of sediment types, additional scatterers and sediment plumes, resulting in reference datasets for an improved interpretation of underwater backscatter measurements for scientific observation and sustainable management