Background Pre-cutting techniques have been used to gain biliary access at the expense of an increased complication rate. This may be because of the multiple attempts to achieve cannulation by using ...standard methods before pre-cutting and causing excess edema and papillary trauma. There are limited data on the early use of pre-cutting techniques. Methods We performed a prospective study of the early introduction of needle-knife techniques in patients with difficult biliary cannulation. Standard biliary cannulation was attempted with a sphincterotome and a guidewire. If this failed within 10 minutes or if there were more than 5 pancreatic cannulations, the needle-knife technique was used. Either a standard method of pre-cutting (below-upward) from the papillary orifice or the modified technique of pre-cutting (above-downward), stopping short of the papillary orifice, was adopted, as per the discretion of the endoscopist. If pre-cutting failed, the cannulation was reattempted 24 to 48 hours later. Results A total of 346 therapeutic biliary ERCP procedures were performed between April and August 2003. Of these, 70 patients (20%) (mean age, 54 years; 38 men) underwent needle-knife pre-cut sphincterotomy (16 with the standard technique). In 58 patients (83%), the procedure was successful with the initial pre-cutting, making the total success at initial ERCP 334/346 (96.5%). Nine patients in whom pre-cut failed, returned for a second-attempt ERCP, with 7 completed successfully. The total success rate of pre-cutting was 65/70 (93%). The overall success rate of biliary cannulation, after two ERCP attempts, was 341/346 (98.5%). Six patients had mild bleeding, and one had mild pancreatitis without any significant difference between the groups who underwent pre-cut with either of the techniques. Conclusions The early use of needle knife for difficult biliary cannulation is safe and effective, irrespective of the technique used.
Abstract Background Professional guidelines have reduced the recommended minimum number to an average of 50 percutaneous coronary intervention (PCI) procedures performed annually by each operator. ...Operator volume patterns and associated outcomes since this change are unknown. Objectives The authors describe herein PCI operator procedure volumes; characteristics of low-, intermediate-, and high-volume operators; and the relationship between operator volume and clinical outcomes in a large, contemporary, nationwide sample. Methods Using data from the National Cardiovascular Data Registry collected between July 1, 2009, and March 31, 2015, we examined operator annual PCI volume. We divided operators into low- (<50 PCIs per year), intermediate- (50 to 100 PCIs per year), and high- (>100 PCIs per year) volume groups, and determined the adjusted association between annual PCI volume and in-hospital outcomes, including mortality. Results The median annual number of procedures performed per operator was 59; 44% of operators performed <50 PCI procedures per year. Low-volume operators more frequently performed emergency and primary PCI procedures and practiced at hospitals with lower annual PCI volumes. Unadjusted in-hospital mortality was 1.86% for low-volume operators, 1.73% for intermediate-volume operators, and 1.48% for high-volume operators. The adjusted risk of in-hospital mortality was higher for PCI procedures performed by low- and intermediate-volume operators compared with those performed by high-volume operators (adjusted odds ratio: 1.16 for low versus high; adjusted odds ratio: 1.05 for intermediate vs. high volume) as was the risk for new dialysis post PCI. No volume relationship was observed for post-PCI bleeding. Conclusions Many PCI operators in the United States are performing fewer than the recommended number of PCI procedures annually. Although absolute risk differences are small and may be partially explained by unmeasured differences in case mix between operators, there remains an inverse relationship between PCI operator volume and in-hospital mortality that persisted in risk-adjusted analyses.
Background and Aims EUS-guided drainage using plastic stents may be inadequate for treatment of walled-off necrosis (WON). Recent studies report variable outcomes even when using covered metal ...stents. The aim of this study was to evaluate the efficacy of a dedicated covered biflanged metal stent (BFMS) when adopting an endoscopic “step-up approach” for drainage of symptomatic WON. Methods We retrospectively evaluated consecutive patients with symptomatic WON who underwent EUS-guided drainage using BFMSs over a 3-year period. Reassessment was done between 48 and 72 hours for resolution. Endoscopic reinterventions were tailored in nonresponders in a stepwise manner. Step 1 encompassed declogging the blocked lumen of the BFMS. In step 2, a nasocystic tube was placed via BFMSs with intermittent irrigation. Step 3 involved direct endoscopic necrosectomy (DEN). BFMSs were removed between 4 and 8 weeks of follow-up. The main outcome measures were technical success, clinical success, adverse events, and need for DEN. Results Two hundred five WON patients underwent EUS-guided drainage using BFMSs. Technical success was achieved in 203 patients (99%). Periprocedure adverse events occurred in 8 patients (bleeding in 6, perforation in 2). Clinical success with BFMSs alone was seen in 153 patients (74.6%). Reintervention adopting the step-up approach was required in 49 patients (23.9%). Incremental success was achieved in 10 patients with step 1, 16 patients with step 2, and 19 patients with step 3. Overall clinical success was achieved in 198 patients (96.5%), with DEN required in 9.2%. Four patients failed treatment and required surgery (2) or percutaneous drainage (2). Conclusions The endoscopic step-up approach using BFMSs was safe, effective, and yielded successful outcomes in most patients, reducing the need for DEN.
Highlights • Rotavirus positivity reported from India is 26.4% (range 10.3–52.5%). • Children under the age of two years account for 69.7% of rotavirus positive diarrhea. • Maximum number of ...rotavirus related hospitalizations are reported between months, November to March.
•Fabricated non-toxic CZTS solar cell with ZnS buffer layer.•Investigated the effect of absorber layer thickness on the solar cell performance.•Prepared phase pure CZTS film by spin coating using ...non-toxic chemicals.•Structural refinement of CZTS was done using Rietveld refinement technique.
Cu2ZnSnS4 solar cell has been fabricated with a non-toxic buffer layer and Al doped ZnO transparent conducting layer. A detailed material study on each layer of the solar cell has been carried out independently. The precursor films prepared by spin coating were sulphurized at different temperatures to optimize the conditions to obtain phase pure CZTS films. X-ray diffraction, Raman spectroscopy and rietveld refinement studies confirmed the phase purity of the film sulphurized at 500 °C. The optimum CZTS properties like band gap of 1.45 eV, high absorption coefficient ~2 × 105 cm−1 and dense surface morphology were obtained for films sulphurized at 500 °C. Carrier concentration, mobility and resistivity of these films were ~1 × 1019 cm−3, 0.23 cm2 V−1 s−1 and 2.7 Ωcm, respectively. The efficiency measurements of the cells with device structure SLG/Mo/CZTS/ZnS/AZO/Ag were carried out using absorber films with three different thicknesses. The optimized CZTS absorber layer with thickness of ~1.8 µm exhibited solar cell conversion efficiency of 3.02% for an active area of 0.21 cm2 withopen-circuit voltageof 0.38 V,short-circuitcurrent density of 17.19 mA/cm2 and fill factor of 46%.
Diarrhoea is a leading cause of death and illness globally among children younger than 5 years. Mortality and short-term morbidity cause substantial burden of disease but probably underestimate the ...true effect of diarrhoea on population health. This underestimation is because diarrhoeal diseases can negatively affect early childhood growth, probably through enteric dysfunction and impaired uptake of macronutrients and micronutrients. We attempt to quantify the long-term sequelae associated with childhood growth impairment due to diarrhoea.
We used the Global Burden of Diseases, Injuries, and Risk Factors Study framework and leveraged existing estimates of diarrhoea incidence, childhood undernutrition, and infectious disease burden to estimate the effect of diarrhoeal diseases on physical growth, including weight and height, and subsequent disease among children younger than 5 years. The burden of diarrhoea was measured in disability-adjusted life-years (DALYs), a composite metric of mortality and morbidity. We hypothesised that diarrhoea is negatively associated with three common markers of growth: weight-for-age, weight-for-height, and height-for-age Z-scores. On the basis of these undernutrition exposures, we applied a counterfactual approach to quantify the relative risk of infectious disease (subsequent diarrhoea, lower respiratory infection, and measles) and protein energy malnutrition morbidity and mortality per day of diarrhoea and quantified the burden of diarrhoeal disease due to these outcomes caused by undernutrition.
Diarrhoea episodes are significantly associated with childhood growth faltering. We found that each day of diarrhoea was associated with height-for-age Z-score (–0·0033 95% CI −0·0024 to −0·0041; p=4·43 × 10−14), weight-for-age Z-score (–0·0077 –0·0058 to −0·0097; p=3·19 × 10−15), and weight-for-height Z-score (–0·0096 –0·0067 to −0·0125; p=7·78 × 10−11). After addition of the DALYs due to the long-term sequelae as a consequence of undernutrition, the burden of diarrhoeal diseases increased by 39·0% (95% uncertainty interval UI 33·0–46·6) and was responsible for 55 778 000 DALYs (95% UI 49 125 400–62 396 200) among children younger than 5 years in 2016. Among the 15 652 300 DALYs (95% UI 12 951 300–18 806 100) associated with undernutrition due to diarrhoeal episodes, more than 84·7% are due to increased risk of infectious disease, whereas the remaining 15·3% of long-term DALYs are due to increased prevalence of protein energy malnutrition. The burden of diarrhoea has decreased substantially since 1990, but progress has been greater in long-term (78·7% reduction 95% UI 69·3–85·5) than in acute (70·4% reduction 95% UI 61·7–76·5) DALYs.
Diarrhoea represents an even larger burden of disease than was estimated in the Global Burden of Disease Study. In order to adequately address the burden of its long-term sequelae, a renewed emphasis on controlling the risk of diarrhoea incidence may be required. This renewed effort can help further prevent the potential lifelong cost on child health, growth, and overall potential.
Bill & Melinda Gates Foundation.
Bacterial blight (BB) is a major production threat to Basmati, the aromatic rice prized for its unique quality. In order to improve the BB resistance of two elite, traditional BB-susceptible Basmati ...varieties (Taraori Basmati and Basmati 386), we utilized the strategy of limited marker-assisted backcrossing for introgression of two major BB resistance genes, Xa21 and xa13, coupled with phenotype-based selection for improvement of their plant type and yield. Improved Samba Mahsuri, an elite high-yielding, fine-grain-type BB-resistant rice variety served as donor for BB resistance. Backcross-derived improved Basmati lines at BC1F5 possessing a single resistance gene (i.e. either Xa21 or xa13) displayed moderate resistance to BB, while lines possessing both Xa21 and xa13 showed significantly higher levels of resistance. Two-gene pyramid lines (Xa21 + xa13) possessing good grain and cooking quality similar to their respective traditional Basmati parents, short plant stature (<110 cm plant height) and higher grain yield than the recurrent parent(s) were identified and advanced. This work demonstrates the successful application of marker-assisted selection in conjunction with phenotype-based selection for targeted introgression of multiple resistance genes into traditional Basmati varieties along with improvement of their plant stature and yield.
We used satellite-derived sea-surface-temperature (SST) data along with in-situ data collected along a meridional transect between 18.85 and 20.25°N along 69.2°E to describe the evolution of an SST ...filament and front during 25 November to 1 December in the northeastern Arabian Sea (NEAS). Both features were ~100km long, lasted about a week, and were associated with weak temperature gradients (~0.07°Ckm−1). The in-situ data were collected first using a suite of surface sensors during a north–south mapping of this transect and showed the existence of a chlorophyll maximum within the filament. This surface data acquisition was followed by a high-resolution south–north CTD (conductivity–temperature–depth) sampling along the transect. In the two days that elapsed between the two in-situ measurements, the filament had shrunk in size and moved northward. In general, the current direction was northwestward and advected these mesoscale features. The CTD data also showed an SST front towards the northern end of the transect. In both these features, the chlorophyll concentration was higher than in the surrounding waters. The temperature and salinity data from the CTD suggest upward mixing or pumping of water from the base of the mixed layer, where a chlorophyll maximum was present, into the mixed layer that was about 60m thick. A striking diurnal cycle was evident in the chlorophyll concentration, with higher values tending to occur closer to the surface during the night. The in-situ data from both surface sensors and CTD, and so also satellite-derived chlorophyll data, showed higher chlorophyll concentration, particularly at sub-surface levels, between the filament and the front, but there was no corresponding signature in the temperature and salinity data. Analysis of the SST fronts in the satellite data shows that fronts weaker than those associated with the filament and the front had crossed the transect in this region a day or two preceding the sampling of the front.
•We use satellite SST and in-situ measured data to describe a filament/front.•These features were ~100km long, lasted about a week.•They were associated with weak temperature gradients and high chlorophyll.•These mesoscale features were advected by the current.•Upward mixing of water from the base of the MLD was evident from CTD data.
A study on biogeochemical cycling in the west coastal Bay of Bengal was undertaken during the peak discharge period to understand the influence of enhanced stratification and primary production on ...the possible intensification of the oxygen minimum zone (OMZ). Our study reveals that oxygen concentrations were below the detection limits in the northwestern (NW) coastal Bay of Bengal between 100 and 500 m associated with strong stratification and high phytoplankton biomass. Such low oxygen concentrations have never been reported so far from the coastal Bay of Bengal. Despite the existence of an environment conducive to denitrification in the coastal Bay of Bengal, accumulation of neither secondary nitrite nor nitrous oxide (N
2
O) was observed. The absence of denitrification was reported to be caused by faster scavenging of organic matter and low bacterial respiration rates; in contrast, our results suggest that neither of these factors are potential reasons for the absence of denitrification in the coastal Bay of Bengal.
Genetic regulators and environmental stimuli modulate T cell activation in autoimmunity and cancer. The enzyme co-factor tetrahydrobiopterin (BH4) is involved in the production of monoamine ...neurotransmitters, the generation of nitric oxide, and pain
. Here we uncover a link between these processes, identifying a fundamental role for BH4 in T cell biology. We find that genetic inactivation of GTP cyclohydrolase 1 (GCH1, the rate-limiting enzyme in the synthesis of BH4) and inhibition of sepiapterin reductase (the terminal enzyme in the synthetic pathway for BH4) severely impair the proliferation of mature mouse and human T cells. BH4 production in activated T cells is linked to alterations in iron metabolism and mitochondrial bioenergetics. In vivo blockade of BH4 synthesis abrogates T-cell-mediated autoimmunity and allergic inflammation, and enhancing BH4 levels through GCH1 overexpression augments responses by CD4- and CD8-expressing T cells, increasing their antitumour activity in vivo. Administration of BH4 to mice markedly reduces tumour growth and expands the population of intratumoral effector T cells. Kynurenine-a tryptophan metabolite that blocks antitumour immunity-inhibits T cell proliferation in a manner that can be rescued by BH4. Finally, we report the development of a potent SPR antagonist for possible clinical use. Our data uncover GCH1, SPR and their downstream metabolite BH4 as critical regulators of T cell biology that can be readily manipulated to either block autoimmunity or enhance anticancer immunity.
PDF
