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The intensity of turbidite sedimentation over long timescales is driven by sea-level change, tectonically driven rock uplift and climatically modulated sediment delivery rates. This study focuses on understanding the effect of sea-level fluctuations and climatic variability on grain-size variations. The grain size and environmental magnetic parameters of Arabian Sea sediments have been documented using 203 samples, spanning the last 200 ka, obtained from International Ocean Discovery Program (IODP) Site U1457. Grain-size end-member modelling suggests that between ~200 and 130 ka there was an increase in the coarse silt fraction caused by sediment transport following reworking of the Indus Fan and development of deep-sea canyons. The sediment size and enhanced magnetic susceptibility indicate a dominant flux of terrestrial sediments. Sedimentation in the distal Indus Fan at c. 200–130 ka was driven by a drop in sea level that lowered the base level in the Indus and Narmada river systems. The low sea-stand caused incision in the Indus delta, canyons and fan area, which resulted in the transportation of coarser sediment at the drilling site. Magnetic susceptibility and other associated magnetic parameters suggest a large fraction of the sediment was supplied by the Narmada River during ~200–130 ka. Since ~130 ka, clay-dominated sedimentation is attributed to the rise in sea level due to warm and wet climate.
Introduction: Abdominal pain is one of the most frequent reasons for an emergency department (ED) visit. Most cases are functional and no therapy has proven effective. Our objective was to determine if hyoscine butylbromide (HBB) (BuscopanTM) is effective for children who present to the ED with functional abdominal pain. Methods: We conducted a randomized, blinded, superiority trial comparing HBB 10 mg plus acetaminophen placebo to oral acetaminophen 15 mg/kg (max 975 mg) plus HBB placebo using a double-dummy approach. We included children 8-17 years presenting to the ED at London Health Sciences Centre with colicky abdominal pain rated >40 mm on a 100 mm visual analog scale (VAS). The primary outcome was VAS pain score at 80 minutes post-administration. Secondary outcomes included adverse effects; caregiver satisfaction with pain management using a five-item Likert scale; recidivism and missed surgical diagnoses within 24-hours of discharge. Analysis was based on intention to treat. Results: We analyzed 225 participants (112 acetaminophen; 113 HBB). The mean (SD) age was 12.4 (3.0) years and 148/225 (65.8%) were females. Prior to enrollment, the median (IQR) duration of pain prior was 2 (4.5) hours and analgesia was provided to 101/225 (44.9%) of participants. The mean (SD) pre-intervention pain scores in the acetaminophen and HBB groups were 62.7 (15.9) mm and 60.3 (17.3) mm, respectively. At 80 minutes, the mean (SD) pain scores in the acetaminophen and HBB groups were 30.1 (28.8) mm and 29.4 (26.4) mm, respectively and there were no significant differences adjusting for pre-intervention scores (p = 0.96). The median (IQR) caregiver satisfaction was high in the acetaminophen [5 (2)] and HBB [5 (1)] groups (p = 0.79). The median (IQR) length of stay between acetaminophen [235 (101)] and HBB [234 (103)] was not significantly different (p = 0.53). The proportion of participants with a return visit for abdominal pain was 4/112 (3.5%) in the acetaminophen group and 6/113 (5.3%) in the HBB group. The most common adverse effect was nausea (9% in each group) and there were no significant differences in adverse effects between acetaminophen (26/112, 23.2%) and HBB (31/113, 27.4%) (p = 0.52). There were no missed surgical diagnoses. Conclusion: For children with presumed functional abdominal pain who present to the ED, both acetaminophen and HBB produce a clinically important (VAS < 30 mm) reduction in pain and should be routinely considered in this clinical setting.
A cross-sectional study on six dairy farms was conducted to ascertain the occurrence of carbapenem-resistant Escherichia coli in calves. Two-hundred and seventy-nine isolates of E. coli were recovered from 90 faecal samples from apparently healthy (45) and diarrhoeal (45) calves. The isolates were screened for phenotypic susceptibility to carbapenems and production of metallo β-lactamase, as well as five carbapenemase resistance genes by PCR, and overexpression of efflux pumps. Eighty-one isolates (29.03%) were resistant to at least one of three carbapenem antibiotics [meropenem (23.30%), imipenem (2.15%) and ertapenem (1.43%)], and one isolate was positive for the blaVIM gene which was located on an Incl1 plasmid of a novel sequence type (ST 297) by multilocus sequence typing. The majority (83.95%) of isolates had an active efflux pump. Calves housed on concrete floors were approximately seven times more likely to acquire meropenem-resistant isolates than those housed on earthen floors (95% CI 1.27–41.54). In India, carbapenem drugs are not used in food animal treatment, hence carbapenem-resistant strains in calves possibly originate from the natural environment or human contact and is of public health importance. To our knowledge, this is the first report of blaVIM carbapenemases gene in calves from India.
The effect of sample granularity on diffracted x-ray intensity was evaluated by measuring the 2θ dependence of x-ray fluorescence from various samples. Measurements were made in the symmetric geometry on samples ranging from single crystals to highly absorbing coarse powders. A characteristic shape for the absorption correction was observed. A demonstration of the sensitivity of Rietveld refined site occupation parameters is made on CuAu and Cu50Au44Ni6 alloys refined with and without granularity corrections. These alloys provide a good example of the effect of granularity due to their large linear x-ray absorption coefficients. Sample granularity and refined thermal parameters obtained from the Rietveld analysis were found to be correlated. Without a granularity correction, the refined thermal parameters are too low and can actually become negative in an attempt to compensate for granularity, A general shape for granularity correction can be included in refinement procedures. If no granularity correction is included, data should be restricted to above 30° 2θ, and thermal parameters should be ignored unless extreme precautions are taken to produce <5 (μm particles and high packing densities.
The purpose of this study was to evaluate the dosimetric impact of multileaf collimator (MLC) positional errors on dynamic intensity-modulated radiotherapy (IMRT) treatments through planning simulation. Secondly the sensitivity of IMRT MatriXX device for detecting the MLC leaf positional errors was also evaluated.
Materials and methods
In this study five dynamic IMRT plans, each for brain and head–neck (HN), were retrospectively included. An in-house software was used to introduce random errors (uniform distribution between −2·0 and +2·0 mm) and systematic errors [±0·5, ±0·75, ±1·0 and ±2·0 mm (+: open MLC error and −: close MLC error)]. The error-introduced MLC files were imported into the treatment planning system and new dose distributions were calculated. Furthermore, the dose–volume histogram files of all plans were exported to in-house software for equivalent uniform dose (EUD), tumour control probability and normal tissue complication probability calculations. The error-introduced plans were also delivered on LINAC, and the planar fluences were measured by IMRT MatriXX. Further, 3%/3 mm and 2%/2 mm γ-criteria were used for analysis.
In planning simulation study, the impact of random errors was negligible and ΔEUD was <0·5±0·7%, for both brain and HN. The impact of systematic errors was substantial, and on average, the maximum change in EUD for systematic errors (close 2 mm) was −10·7±3·1% for brain and −15·5±2·6% for HN.
It can be concluded that the acceptable systematic error was 0·4 mm for brain and 0·3 mm for HN. Furthermore, IMRT MatriXX device was able to detect the MLC errors ≥2 mm in HN and >3 mm errors in brain with 2%/2 mm γ-criteria.
Shunt-related adverse events are frequent in infants after modified Blalock–Taussig despite use of acetylsalicylic acid prophylaxis. A higher incidence of acetylsalicylic acid-resistance and sub-therapeutic acetylsalicylic acid levels has been reported in infants. We evaluated whether using high-dose acetylsalicylic acid can decrease shunt-related adverse events in infants after modified Blalock–Taussig.
In this single-centre retrospective cohort study, we included infants ⩽1-year-old who underwent modified Blalock–Taussig placement and received acetylsalicylic acid in the ICU. We defined acetylsalicylic acid treatment groups as standard dose (⩽7 mg/kg/day) and high dose (⩾8 mg/kg/day) based on the initiating dose.
There were 34 infants in each group. Both groups were similar in age, gender, cardiac defect type, ICU length of stay, and time interval to second stage or definitive repair. Shunt interventions (18 versus 32%, p=0.16), shunt thrombosis (14 versus 17%, p=0.74), and mortality (9 versus 12%, p=0.65) were not significantly different between groups. On multiple logistic regression analysis, single-ventricle morphology (odds ratio 5.2, 95% confidence interval of 1.2–23, p=0.03) and post-operative red blood cells transfusion ⩾24 hours [odds ratio 15, confidence interval of (3–71), p<0.01] were associated with shunt-related adverse events. High-dose acetylsalicylic acid treatment [odds ratio 2.6, confidence interval of (0.7–10), p=0.16] was not associated with decrease in these events.
High-dose acetylsalicylic acid may not be sufficient in reducing shunt-related adverse events in infants after modified Blalock–Taussig. Post-operative red blood cells transfusion may be a modifiable risk factor for these events. A randomised trial is needed to determine appropriate acetylsalicylic acid dosing in infants with modified Blalock–Taussig.
Tardive dyskinesia (TD) is an often-irreversible movement disorder that may intensify the stigma of patients with psychiatric disorders and worsen quality of life. In two randomized, double-blind, placebo (PBO)-controlled, 12-week trials, ARM-TD and AIM-TD (‘parent studies’), deutetrabenazine (DTB) demonstrated statistically significant improvements in centrally read Abnormal Involuntary Movement Scale (AIMS) scores at Week 12 compared with PBO and was generally well tolerated.
To evaluate the long-term efficacy of DTB in an open-label safety study following double-blind treatment using site-rated efficacy measures: AIMS, the Clinical Global Impression of Change (CGIC) and the Patient Global Impression of Change (PGIC), which may be used in real-world clinical practice settings.
Patients with TD who completed the parent studies were eligible to enter this open-label, long-term extension (OLE) after completing the 1-week washout period and final evaluation in the blinded portion of the trial. This extension comprised a 6-week titration period followed by a long-term maintenance phase. Patients began DTB at 12mg/day, titrating up to a maximum total dose of 48mg/day based on dyskinesia control and tolerability. Efficacy endpoints included in this analysis are the change in site-rated AIMS score (items 1–7) from parent study baseline, and the proportion of patients who were “Much Improved” or “Very Much Improved” (treatment success) on the CGIC and PGIC from OLE baseline.
At the end of the parent studies (Week 12), patients treated with DTB had experienced greater mean (standard error) improvements in site-rated AIMS score (–5.0[0.40]) than patients given PBO (–3.2[0.47]). With long-term DTB treatment, both groups experienced improvements in site-rated AIMS scores (prior DTB, –7.9[0.62]; prior placebo, –6.6[0.64]) compared with parent study baseline. Similarly, at the end of the parent studies, a greater proportion of patients treated with DTB had treatment success on the CGIC (DTB, 51%; PBO, 32%) and the PGIC (DTB, 46%; PBO: 33%); whereas at Week 54 of the OLE study, treatment success on CGIC and PGIC were similar in both the CGIC (prior DTB: 66%; prior PBO: 68%) and PGIC (prior DTB: 62%; prior PBO: 62%) groups. DTB was generally well tolerated.
Patients treated with DTB showed improvements in abnormal movements, as measured by site-rated AIMS, CGIC, and PGIC scores, which may be used in real-world clinical practice settings. These results corroborate the previously reported efficacy of DTB as observed in the 12-week, double-blind ARM-TD and AIM-TD trials, in which central raters were used to evaluate AIMS scores.
Presented at: American Psychiatric Association Annual Meeting; May 5–9, 2018, New York, New York, USA
Funding Acknowledgements: Funding: This study was supported by Teva Pharmaceuticals, Petach Tikva, Israel.
Tardive dyskinesia (TD) results from exposure to dopamine-receptor antagonists (DRAs), such as typical and atypical antipsychotics. Clinicians commonly manage TD by reducing the dose of or stopping the causative agent; however, this may cause psychiatric relapse and worsen quality of life. In the 12-week ARM-TD and AIM-TD trials, deutetrabenazine demonstrated statistically significant improvements in Abnormal Involuntary Movement Scale (AIMS) scores versus placebo and was generally well tolerated, regardless of baseline DRA use or comorbidities.
To evaluate the impact of underlying disease and current DRA use on efficacy and safety of long-term therapy of deutetrabenazine in patients with TD.
Patients with TD who completed ARM-TD or AIM-TD were eligible to enter this open-label, single-arm, long-term extension after completing the 1-week washout period and final evaluation in the blinded portion of the trial. Change in AIMS scores from baseline to Week 54 and patients “Much Improved” or “Very Much Improved” (treatment success) on the Clinical Global Impression of Change (CGIC) and Patient Global Impression of Change (PGIC) at Week 54 were analyzed by baseline psychiatric illness type, including mood disorders (bipolar disorder/depression/other) or psychotic disorders (schizophrenia/schizoaffective disorder), and presence or absence of current DRA use.
At Week 54, meaningful improvements from baseline in mean (standard error) AIMS scores were observed for patients with baseline mood disorders (–5.2[0.93]) and psychotic disorders (–5.0[0.63]), and in patients currently using DRAs (–4.6[0.54]) or not using DRAs (–6.4[1.27]). Most patients with mood disorders (73%) and psychotic disorders (71%) were “Much Improved” or “Very Much Improved” on CGIC at Week 54, similar to patients currently using (71%) or not using (74%) DRAs. The majority of patients with mood disorders (62%) and psychotic disorders (57%), as well as patients currently using (58%) or not using (63%) DRAs, were also “Much Improved” or “Very Much Improved” on PGIC at Week 54. Prior treatment in ARM-TD and AIM-TD did not impact the long-term treatment response. Underlying psychiatric disorder and concomitant DRA use did not impact the occurrence of adverse events (AEs). The frequencies of dose reductions, dose suspensions, and withdrawals due to AEs were low, regardless of baseline psychiatric comorbidities and DRAuse.
Long-term deutetrabenazine treatment demonstrated meaningful improvements in abnormal movements in TD patients, which were recognized by clinicians and patients, regardless of underlying psychiatric illness or DRAuse.
Presented at: American Psychiatric Association Annual Meeting; May 5–9, 2018, New York, New York, USA
Funding Acknowledgements: This study was supported by Teva Pharmaceuticals, Petach Tikva, Israel.
Normal odd-chain SFA (OCSFA), particularly tridecanoic acid (n-13 : 0), pentadecanoic acid (n-15 : 0) and heptadecanoic acid (n-17 : 0), are normal components of dairy products, beef and seafood. The ratio of n-15 : 0:n-17 : 0 in ruminant foods (dairy products and beef) is 2:1, while in seafood and human tissues it is 1:2, and their appearance in plasma is often used as a marker for ruminant fat intake. Human elongases encoded by elongation of very long-chain fatty acid (ELOVL)1, ELOVL3, ELOVL6 and ELOVL7 catalyse biosynthesis of the dominant even-chain SFA; however, there are no reports of elongase function on OCSFA. ELOVL transfected MCF7 cells were treated with n-13 : 0, n-15 : 0 or n-17 : 0 (80 µm) and products analysed. ELOVL6 catalysed elongation of n-13 : 0→n-15 : 0 and n-15 : 0→n-17 : 0; and ELOVL7 had modest activity toward n-15 : 0 (n-15 : 0→n-17 : 0). No elongation activity was detected for n-17 : 0→n-19 : 0. Our data expand ELOVL specificity to OCSFA, providing the first molecular evidence demonstrating ELOVL6 as the major elongase acting on OCSFA n-13 : 0 and n-15 : 0 fatty acids. Studies of food intake relying on OCSFA as a biomarker should consider endogenous human metabolism when relying on OCSFA ratios to indicate specific food intake.
Stereotactic body radiotherapy (SBRT) is widely used for the treatment of stage-I non-small cell lung cancer (NSCLC). Patient-specific motion correlated with 4DCT could be essential for hypofractionated SBRT. All patients undergoing SBRT do not require motion management during the dose delivery. The objective of this study was to evaluate which patient may benefit from Gated SBRT.
Materials and methods
Treatment planning of 20 patients of stage-I NSCLC was analysed. Conventional and 4DCT scans were taken. Internal target volume as well as planning target volume (ITV and PTV) were determined in the CT data sets. PTVall phases created using 4DCT data sets and PTV15mm created using conventional CT data were compared. Also, ITVall phases were compared with ITV created from maximum intensity projections (ITVMIP). Suitability of patients for motion management-based treatment delivery was also evaluated.
The average ITVMIP to ITVall phases ratio is 1·06 indicating good agreement between them. Based on the ratio of intensity projections, 9 out of 17 patients were found suitable for our existing gated treatment.
4D CT is the main requirement in SBRT to identify the patients who can benefit from motion management during the dose delivery.
Grewia tenax locally known as ‘Gangerun’, is an important multipurpose underutilized shrub and potentially threaten species of the Thar Desert of India. Owing to its importance, naturally available germplasm was collected and evaluated for its sustainable utilization in future. Data on individual mother plant, seed characters and soil profile were investigated. Habitat occurrence of G. tenax was found in patches with dominant association of Euphorbia caducifolia across the four districts of western Rajasthan. Individual plant on unprotected area portrayed far lower average height (0.95 m) and canopy area (1.75 m2) than protected area (2.63 m and 13.89 m2) signifying level of browsing pressure on this species in Jaisalmer. Soil samples belonging to Pali region have high organic carbon and low electrical conductivity content than Jaisalmer and Jodhpur. The statistical analysis of seed characters revealed the presence of high coefficient of variation (%) in 100-seed weight (HSW; 27.36) followed by seed length (SL; 8.06) and least in seed breadth (SB; 5.85). The range and mean values of HSW, SL, SB and length:breadth ratio (LBR) were (2.02–7.00 and 3.34 g), (4.36–6.15 and 5.36 mm), (3.73–4.68 and 4.25 mm) and (1.11–1.44 and 1.27), respectively. Significantly positive correlation was observed between SL and LBR (0.73) followed by HSW and SL (0.66). Along with these findings, its economic importance, utilization and conservation are detailed in this paper as to hasten further research on its various aspects for its successful conservation and utilization.
The National Iodine and Salt Intake Survey (NISI) 2014–2015 was undertaken to estimate household iodised salt coverage at national and sub-national levels in India.
Cross-sectional survey with multistage stratified random sampling.
India was divided into six geographic zones (South, West, Central, North, East and North-East) and each zone was further stratified into rural and urban areas to yield twelve distinct survey strata.
The target respondent from each household was selected as per predefined priority; wife of the household head, followed by women of reproductive age, followed by any adult available during the visit.
Households (n 5717) were surveyed and salt samples (n 5682) were analysed. Household coverage of iodised salt (iodine≥5 ppm) was 91·7 (95 % CI 91·0, 92·7) %. Adequately iodised salt (iodine≥15 ppm) was consumed in 77·5 (95 % CI 76·4, 78·6) % of households. Significant differences in coverage were seen across six geographic regions, with North and North-East zones on the verge of achieving the universal salt iodisation target of >90 % coverage. Coverage of households with adequately iodised salt (adjusted OR; 95 % CI) was significantly less in rural households (0·55; 0·47, 0·64), lower/backward castes (0·84; 0·72, 0·98), deprived households (0·72; 0·61, 0·85) as assessed by multidimensional poverty index, households with non-diverse diet (0·73; 0·62, 0·86) and households using non-packaged salt (0·48; 0·39, 0·59) and non-refined salt (0·17; 0·15, 0·20).
India is within striking reach of achieving universal salt iodisation. However, significant differentials by rural/urban, zonal and socio-economic indicators exist, warranting accelerated efforts and targeted interventions for high-risk groups.
We report results of the studies relating to the development of the emerging nanostructured molybdenum trioxide (nMoO3)-based biocompatible label-free biosensing platform for breast cancer detection. The structural and morphological studies of the synthesized nMoO3 nanorods were investigated by XRD, SEM, X-ray photoelectron spectroscopic, and TEM techniques. This biocompatible one-dimensional (1D) nMoO3-based biosensing platform exhibited high sensitivity (0.904 µAmL/ng/cm2), wide linear detection range (2.5–110 ng/mL), and a lower detection limit as 2.47 ng/mL toward human epidermal growth factor receptor-2 detection. The results obtained using this sensor platform on serum samples of breast cancer patients were validated using ELISA.
The inefficiencies of the current pipeline from discovery to clinical approval of drugs demand a surrogate method to indicate adverse drug reactions, e.g. liver damage. Organ-on-chip (OOC) models would be an ideal, rapid, and human-specific alternate, which would render animal testing obsolete. The ground-breaking ability of OOCs and Multi-OOC constructs is the accurate simulation of the in vivo conditions of human organs leading to precise drug screens for cytotoxicity and/or drug efficacy at a faster pace and lesser cost. Here we discuss the innovation, architecture, and the progress of OOCs towards human body-on-a-chip.
In this paper, we present a model characterizing the interaction of a radiative shock (RS) with a solid material, as described in a recent paper (Koenig et al., Phys. Plasmas, 24, 082707 (2017)), the new model is then related to recent experiments performed on the GEKKO XII laser facility. The RS generated in a xenon gas cell propagates towards a solid obstacle that is ablated by radiation coming from the shock front and the radiative precursor, mimicking processes occurring in astrophysical phenomena. The model presented here calculates the dynamics of the obstacle expansion, which depends on several parameters, notably the geometry and the temperature of the shock. All parameters required for the model have been obtained from experiments. Good agreement between experimental data and the model is found when spherical geometry is taken into account. As a consequence, this model is a useful and easy tool to infer parameters from experimental data (such as the shock temperature), and also to design future experiments.
Iron deficiency chlorosis (IDC) is common among groundnut grown in calcareous and alkaline soils in India, China and Pakistan and causes considerable reduction in pod yield. To identify genetically diverse IDC tolerant accessions, the mini-core collection of groundnut representing geographical diversity was evaluated for IDC response over 2 years in iron-deficient calcareous soils. Enormous genetic variability was evident in the mini-core collection for IDC tolerance-related traits such as a visual chlorotic rating (VCR) and SPAD chlorophyll meter reading (SCMR) across five growth stages. Several IDC tolerant sources belonging to different botanical varieties such as hypogaea bunch (ICG # 5051, 6766, 5286, 6667, 4538, 14008, 5663, 9842, 11855), hypogaea runner (ICG 10479), fastigiata (ICG 10890) and vulgaris (ICG # 11651, 118) were identified. Among the six botanical varieties of groundnut, hypogaea bunch types were found most tolerant to IDC and this is the first report in groundnut. The IDC tolerant sources identified were irrespective of their country of origin. The principal component analysis based on VCR, SCMR, pod yield and its related traits revealed five major principal components that explained 80% of the total variation. The biplot generated using PC1 and PC2 revealed a distinct separation of IDC tolerant genotypes from the susceptible ones. The hierarchical clustering using five major principal components revealed seven major clusters that were mainly based on IDC response of the accessions.